Scientists Greater Than Einstein

Scientists
Sp
ec
ia
lE
Greater
di
tio
n
than
Einstein
Saved Over 2.0 Billion lives!
+
160 Winners of
Biological & Medical Sciences 1960-2020
Foege
Landsteiner Müller Sommer Borlaug
Nalin Endo Enders Florey
Banting
Billy Woodward
with Joel Shurkin and Debra Gordon
Abridged and enhanced by :
Srinivasa K. Rao Ph.D.
Krishnamoorthy Kannan Ph.D.
Padmavathi Anaparthi M.A.
Uma Devi Koduru Ph.D.
Bilikere S. Dwarakanath Ph.D.
Why should Indian students and scientists
read this book?
There are four revolutions in modern science so far. The first one is
the steam engine in engineering, the second one Benzene in chemistry,
the third one recombinant Insulin in biotechnology, and the latest one
computer.
All these did not happen in India. I think the next revolution in
science will be making man free from hunger, malnutrition, and disease,
and it should happen in India. Besides, there are a few thousand genetic
diseases present in man. There are viruses, bacteria, and several pathogens
causing harm to man either directly or indirectly. This is a big challenge.
It needs plenty of scientists! We have to prepare them to meet the
challenge to remove hunger and malnutrition. Scientists have successfully
removed several viral infections and some diseases so far. So, we can do
it!
Indian students and young scientists should be encouraged to pursue
science with this goal. They should be given confidence from the great
discoveries of the past. So the first experiment, to inspire them, is to
introduce this book - Scientist Greater than Einstein. This book presents
10 scientists who changed the world. They literally defeated death for
over two billion people. This book is truly international in scope.
This book shows science can occur not only in labs but also in
villages.
This book shows science can be developed in the real world for real
people.
It recorded the landmark discoveries in human health.
It celebrates those who saved the most lives in history.
Srinivasa K. Rao, Ph.D.
New York
2020
( ii )
Praise for Scientists Greater than Einstein
These remarkable stories of human achievement on a truly grand scale

are told with great sensitivity, yet fine precision. These are the gritty
details behind some of the greatest medical advances in human history.
Woodward’s story goes deep, showing us the personal lives of the players
involved and where they were when the eureka moment came, then
follows each researcher’s idea through to its full objective impact. The
hard core measure of human lives saved is the final irrevocable statement
of what can be accomplished in a human being’s lifetime.
—Dr. Jeff Wicker M.D.

St. Claire Regional Medical Center,
Morehead, KY, USA.
This engaging book is a fascinating read chronicling the genesis of

scientific curiosity, the travails and myriad failures, and, ultimately, the
triumphs of those researchers responsible for promoting the advancement
and survival of mankind. It should promote bountiful discussion and
would be an excellent library addition for students of science of all ages
who seek to understand the price and impact of scientific progress.
—Dr. Susan R. Campbell, Ph.D.

Chair, Chemistry Department,
Georgetown College Georgetown, KY, USA
( iii )
Scientists Greater Than
Einstein & Bhatnagar Award
Winners, India.
Copyright © 2009 by Billy Woodward
(Abridged) All rights reserved.
Printed in the United States of America.

Copyright © 2020 by
Published by
Srinivasa K. Rao, Ph. D Quill Driver Books,
an imprint of Linden Publishing
All rights reserved. 2006 S. Mary, Fresno, CA 93721
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Please contact Dr. Srinivasa Rao
Edited by Gabriel Popkin
at the above address or phone Library of Congress Cataloging-in-Publication
number. Data
+91 9885074764 Woodward, Billy, 1956-
srao@ drquinoa.com Scientists greater than Einstein : the biggest
lifesavers of the twentieth century / by Billy
Woodward, Joel N. Shurkin, Debra Gordon.
p. ; cm.
Includes bibliographical references and index.
ISBN-13: 978-1-884956-87-4 (hardcover)
ISBN-10: 1-884956-87-4 (hardcover)
1. Medical scientists--Biography. 2. Medicine--
Research--History--20th century. 3. Medical
innovations--History--20th century. I. Shurkin,
Joel N., 1938- II. Gordon, Debra L., 1962- III.
Title. [DNLM: 1. Medicine--Biography. 2.
History, 20th Century. 3. Research--history. WZ
112 W899s 2008]
R149.W596 2008
610.92’2--dc22
2008030163
eBOOK Rs. 100
( iv )
Dedication – eBook Edition
2020
In spite of great advancements in stopping viruses, more

than a million died, and millions are suffering. This
edition is dedicated to all of them.
—Srinivasa K. Rao,Ph.D. & Team (eBook 2020)
(v)
Dedication – Abridged Edition
2013
Despite strides made by many scientists, millions of people

like Padmaja Jagarapu die every year hoping and waiting for
a miracle. This book is dedicated to the Padmajas of the
world, who present challenges to the scientists with their life.
—Srinivasa K. Rao Ph.D.
( vi )
Dedication – First Edition
2009
Dedicated to the memory of Gertrude Elion and George

Hitchings, for their development of Allopurinol, which has
so greatly enhanced my life.
—Billy Woodward (2009)
( vii )
Acknowledgments - eBOOK Version 2020
It all started with a phone call from Dr. Yelloji Rao Mirajkar,
Convener, Global Indian Scientists and Technocrats Forum, New Jersey,
USA. Later he arranged a weekly meeting with Sri Jayant Saharsabudhe,
Mr. Nandakumar, Dr. Arvind Ranade, Dr. Prashant Kodgire, and their
associates. They help me to gain my fading confidence to work for India
and participate in the development of India. This eBook is a concrete step
in that direction.
Mr. Billy Woodward, the author, and Publishers Mr. Kent Sorsky
and Richard Sorsky encouraged us to take up the project. I appreciate
their interest in this project: Prof. Madhav Deshpande, Professor Emeritus
of Sanskrit, wrote a sloka comparing these scientists with the Risks of
India. I am thankful to him.
Mr. Qutub Bharmal, Alpha eBook, Rajkot, Gujarat, India, and his
team did all the necessary look to prepare the books to present as an
eBook for their professional support.
Srinivasa K. Rao, Ph.D.
New York,
December 2020
( viii )
Acknowledgments - Abridged Version, 2013
Several people helped us in bringing out this edition. Mr. Billy
Woodward, the author and Publishers Mr. Kent Sorsky and Richard
Sorsky encouraged us to take up the project. I appreciate their interest in
this project. I thank Mr. Vasu Prakash Chitturi, Director, his staff,
teachers and students of Sri Prakash Vidyaniketan, Visakhapatnam for
their interest in this book.
Dr. B. Sesikeran, MD, former Director of National Institute of
Nutrition, Hyderabad, India wrote the foreword in support of this book,
reflecting his commitment to the cause. We are indebted to him. Many
aspects of the book have to come out well in a short time, so we requested
the help of the following people for their reviewing and editing skills. We
are thankful to all of them - Mr. HardikYaji, Dr. Nirmala Devi Kanika,
Mr. Lakshman Kalasapudi, Dr. Bharati Kochar, Dr. Seshadri Thirumala,
Mr. Venkatesh Raghavendra, Dr. Vasundhara D. Kalasapudi, Prof.
U.N.Das, Mr. Surya Prakash Manapragada, Ms. Surekha Gottapu, Ms.
P.V. Purnima, Ms.Ananya Venkatesh, Ms. Avani Venkatesh,Mr. Venu
Thirumala. Ms. Vani Thirumala and Mr. Harshavardhana Yerramneni.
I thank the IIBT Books Project Team for their participation in
bringing out this book. I thank Mr. Prakash Konathala and Mr. M. Krishna
Kumar of Sathyam Printers for their active participation and professional
support.
—Srinivasa K. Rao, Ph.D.
( ix )
Acknowledgments – Billy Woodward
If the only prayer you said in your whole life was ‘thank you,’ that would
suffice.
—Thirteenth century German theologian Meister Eckhart
IT WAS a delight conversing with Al Sommer, Akira Endo, Bill

Foege, and David Nalin and I greatly appreciate the time and effort they
took to share their stories and photographs, and to read and make
corrections to their respective chapters.
The book would not have been completed with any degree of
professionalism without Gabriel Popkin. His help in researching the
subject from the germ of the idea to editing the last word was indispensable.
Most importantly, he insisted that the science be presented correctly.
I am grateful for the writing experience and enthusiasm Joel Shurkin
and Debra Gordon brought to the book. I wish to thank Amy Pearce for
her diligent work in calculating the numbers of lives each scientist saved
and Hiroko Hollis for translating three Japanese books for Akira Endo’s
chapter. I also would like to thank Chuck Wilson, Mike Tresenrider, and
Jeff Broughton for reading, editing, and discussing the chapters.
Finally, I would like to thank all the scientists presented in the book.
Their efforts in science and their compassion for the sick kept me
unflaggingly inspired year after year.
—Billy Woodward
(x)
Contents
Foreword by Dr. B. Sesikeran ........................................................ 1

Former Director, National Institute of Nutrition, India
Outstanding Scientific Discoveries ................................................ 2

Rama Haritha Pusarla, Ph.D.
Real Life-Savers ............................................................................. 5

T.A. Venkateswaran, Former Regional Manager, The Hindu, Visakhapatnam
About Authors ................................................................................ 7

Introduction .................................................................................... 9
PART I
1. Al Sommer—Over 9 Million Lives Saved

The Eye Doctor Who Discovered a Better Use
for Vitamin A ................................................................................ 15
2. Akira Endo—Over 10 Million Lives Saved

Statins: Life Extension for the Baby Boomers ............................. 43
3. Bill Foege—Over 169 Million Lives Saved

The Eradication of Smallpox ........................................................ 65
4. David Nalin—Over 71 Million Lives Saved

ORT: A Revolutionary Therapy for Diarrhea .............................. 87
5. Norman Borlaug—Over 320 Million Lives Saved

A Green Revolution to Enhance Nutrition ................................. 109
6. John Enders—Over 143 Million Lives Saved

The Father of Modern Vaccines ................................................. 129
7. Paul Müller—Over 22 Million Lives Saved

DDT and the Prevention of Malaria ........................................... 147
( xi )
8. Howard Florey—Over 94 Million Lives Saved
Penicillin: The Miracle of Antibiotics ........................................ 165
9. Frederick Banting—Over 18 Million Lives Saved

Insulin: The First True Miracle Drug ......................................... 187
10. Karl Landsteiner—Over 1.3 Billion Lives Saved

The Superman Scientist: Discoverer of Blood Groups .............. 205
Determining the Number of Lives Saved ................................... 229
PART II
Introduction to Bhatnagar awards winners ................................. 233

Award Eligibility ....................................................................... 234
Preface ........................................................................................ 235
Section 1 – Biological Sciences ................................................. 237
Section 2 – Medical Sciences ..................................................... 291
( xii )
Foreword
(For the 1st edition 2013)
We all know of Albert Einstein, who is a benchmark of extraordinary

scientific achievement. But there are several scientists who have made
achievements greater than any of Einstein’s. Their research, innovations,
discoveries, and astute logic have saved millions of lives and mitigated
the suffering of many more.
Scientists Greater Than Einstein presents the major scientific
advances that have made the health and nutrition of humankind
significantly better than what it was a hundred years ago. By calculating
the number of lives saved by these scientists’ work, Billy Woodward
gives the reader a clear idea of the importance of each scientific discovery.
To name a few of the remarkable scientists profiled in this book: Al
Sommer, whose Vitamin A treatment prevented millions of children
from dying or going blind; Bill Foege, who eradicated smallpox; Norman
Borlaug, who created the green revolution that saved the world from
starvation and death: Howard Florey, who pioneered using penicillin to
prevent infection-related deaths and disability; Frederick Banting, who
developed the treatment of diabetes with insulin; and many more great
discoveries and dedicated scientists.
The most interesting aspect of this compilation is the way it is written.
Each scientist’s life and struggle is captured in a highly personal way that
gives the reader insight into their personalities and tremendous
commitment to improve life on earth. This abridged English edition
makes this important book affordable to students, which will benefit
many young minds. This is really and enjoyable and emotional book to
read.
Sesikeran
Former Director
National Institute of Nutrition
Indian Council of Medical Research Hyderabad
(1)
Outstanding Scientific Discoveries
Reading this book “Scientists Greater Than Einstein: The Biggest

Life Savers of The Twentieth Century “ by Billy Woodward, Joel Shurkin,
Debra Gordon abridged by Srinivasa Rao Kalasapudi with Padamavathi
Anaparti, has been a great experience. Life is the most precious and
irreplaceable thing on the face of the earth. Bestowing good health or
preventing a premature death is the greatest accomplishment/ feat any
person can ever do. It is accompanied by a feeling of gratitude, which is
perhaps the noblest of all human emotions. All those discoveries that
have increased average life span or have averted premature deaths or
those that have sufficiently improved the quality of life are invaluable
gifts to humanity. All the scientists who lavished these gifts upon mankind
have rendered the greatest service.
The book briefly spans through the life of ten scientists who have
made a vast difference in the lives of billions of people. It is so inspiring
to read the lives of the scientists- Al Sommer (Vitamin A), Akira Endo
(Statins), Bill Foege (Smallpox), David Nalin (Oral Rehydration
Therapy), Norman Borlaug (Green Revolution), John Enders (Modern
Vaccines), Paul Muller (DDT), Howard Florey (Penicillin), Frederick
Banting (Insulin), and Karl Landsteiner (Blood Groups).
The life of an individual scientist is utterly unique. The backgrounds,
perceptions, and individual intelligence levels of all these scientists are
quite different. For some, it has been an inner call; for some, research has
been the pursuit of happiness. Some of the scientists had average
intelligence levels, but they believed in the great saying of Thomas
Edison, “Genius is 1% inspiration and 99% perspiration”. Each of them
had ardently dedicated themselves to their research goals. What is striking
is their unbelievable conviction and aspiration towards their goal and the
undaunted will and courage to pursue their objectives.
After reading the book, certainly, each of us would be marveled by
the simplicity in their scientific strategy, execution, and planning. Science
(2)
doesn’t necessarily translate into working with sophisticated gadgets.
The keen interest in a change or a deep passion or being sentimentally
getting attached to an objective, conviction, teamwork, above all, an
intuition. It is a guiding force that often results in obtaining a path
breaking-groundbreaking discovery.
Further, the book makes us realize that often simple interventions
with commonsense and careful formulation thereafter can do the miracle.
Sometimes neatly thought out and executed strategy would bring the
necessary change in the existing plan, and a stage is set for unraveling a
new discovery. A peek into the lives of these scientists gives an insight
into science and, more appropriately, natural science, which goes hand in
hand with other branches of science. With gradual progress and
developments in allied branches of science like Chemistry, Biochemistry,
Microbiology, etc., the discoveries in life sciences have hastened. The
culmination and better coordination of all these fields of science resulted
in significant changes, thus leading to groundbreaking discoveries.
Particularly the discoveries that spanned the early 20thcentury would
give us a glimpse of the great power of intuition and the common sense
displayed by the scientists. Science was not fancied with superior gadgets
during that period. Hence what appears to be a simple experiment as per
present standards is the result of painstaking years of research of those
pioneers. Especially the effort incurred in converting a serendipitous
experiment in the case of Penicillium mold into a panacea of all ailments
is worth recalling.
The last chapter of the book sums up the importance of health and
raises relevant issues concerning funding medical research and the
callous attitude of the governments in diverting necessary resources to
health. I wish people in general, and nations in specific, treasure the value
of life. Science can do miracles, and if endowed with better facilities and
resources, both the quality of life and the lifespan of people can be
increased. General view of a population explosion being viewed as a
drain on natural resources be discarded.
(3)
Perhaps this is one of the best reads for youngsters who are at the
crossroads of their life and want to plunge into the depths of science.
— Rama Haritha Pusarla, Ph.D.
(4)
Real Life-Savers
Inter-dependence is the core message of creation. On earth, it cannot

be different. The mineral, the plant, the animal and the human kingdoms
are inter-dependent on one another. In creation, there is no disharmony;
in human life, there is. In cosmos, there is no confusion; in our minds,
there is. If I think that I am not connected to you, it means that I have
missed a golden opportunity called life. If I realize that your health is
important to me and my conduct vital to you, then, I gain a grand reason
to cherish life every moment.
Those who realize this beautiful message of inter-dependence do not
find life mundane and meaningless. They find it interesting, sweet and
something to strive for. Some among those understand that the individual’s
well being is squarely dependent on every individual’s welfare. They
pursue avenues which would benefit the society in some way or other.
The spirit of brotherhood and world citizenship has its origin in this
understanding.
“Scientists Greater than Einstein’’ is a brilliant book, absolutely
unputdownable. It takes us into the lives of ten great men who made
phenomenal life-saving contributions to science. While the title might
seem provocative, the message behind it is profound. It is the responsibility
of the general populace to keep abreast not only of significant progress in
science, but also understand the remarkable men and women who drove
that progress. To place Einstein as the only luminary within our easy
recall is unfair and beyond a point, ungrateful.
But this travesty is easily remedied, through this book, where you
will meet a few awakened ones who go farther and look beyond. They
seek to find solutions to problems that afflict a society as a whole. They
become Rishis, or Seers. It is their quest to find solutions that enable them
to look beyond. Looking beyond becomes possible only when one has a
clear understanding of the past and present, governed by the love for the
welfare of humanity as a whole.
(5)
The modern name for such Seers or Rishis is Scientists. Like there
are no temples for the Rishis whose prowess was equal to that of Gods,
the Scientists’ contribution is also not well recognized. We do not even
know the names of the milk vendor, the paper boy, the children of the
servant maid and so many people on whom we are dependent for our
daily living. How would we know the role or the names of the Scientists
who strive to enhance the quality of our life by trying to prevent death as
much as possible, from snatching the lives of fellow humans.
In this book, we walk along with them. We glean their beautiful
psyche – always ticking, curious and concerned about the welfare of the
society.
Authored by Billy Woodward with Joel Shurkin and Debra Gardon,
it was brought into India as an abridged version by Srinivasa K. Rao with
Padmavathi Anaparthi. The language is deliberately simple and the style,
captivating.
When we complete the book, the immensity of their work and their
greatness hit us and leave us dumbstruck. We feel sad and severely
embarrassed that we did not know these great personalities who have
been vital to our very existence.
As I turned the last page, I stood in the balcony, looked up and saluted
them with gratitude, admiration and respect. With the same feeling, I
salute Srinivasa K. Rao.
May we have an expanded version of this extremely necessary book!
May this be made compulsory in every school and college! May we have
many such books from Rao!
— T.A. Venkateswaran, Former Regional Manager,

The Hindu, Visakhapatnam
(6)
About the Authors:
Billy Woodward is a University of

Kentucky graduate and successful businessman
whose ardent interest in science led him into
writing. An accomplished team builder, he
chose the award-winning writers Joel Shurkin
and Debra Gordon, statistical expert Amy R.
Pearce, and editor Gabriel Popkin to contribute
to this sweeping project. Woodward lives in
Lexington, Kentucky, where he currently has a team extending the list of
lifesavers on a dynamic website, ScienceHeroes.com, which also
promotes an innovative form of science education for students.
Srinivasa K. Rao received Ph.D. from University of Paris, Paris,
France. He worked as a scientist at Albert Einstein College of Medicine,
Bronx, New York and taught as an adjunct faculty at Queens College,
City University of New York. He established the Indian Institute of
Biotechnology Private Limited company and runs it at present. He divides
his time between New York and Hyderabad.
Prof Krishnamoorthy Kannan has played a key role in producing
quality Biotechnology manpower. His research established extracellular
role of Ubiquitin in Haematopoietic Stem Cell homing and adhesion in
the bone marrow. Has held very senior positions in Universities, the
Diagnostic and pharmaceutical Industry, popularised Biotechnology,
IPR, and Stem Cell Biology as an integral part of the academic program
of schools and Universities. Late Dr. A P J Kalam appointed him as Vice-
Chancellor of Nagaland Central University, Nagaland, India (2006-
2011).
Anaparthi Padmavathi, received M.A. English and Economics
from Andhra University, Waltair and B.Ed. from Annamalai University.
She is a teacher and lives in Bobbili. She is a National Resource Person
for Professional Development Program for Primary Teachers and State
Resource Person for English teaching.
(7)
Prof. Uma Devi Koduru, Ph.D., Andhra university. She Has over
30 years of teaching and research experience at Andhra University.
Research area: Microbial Molecular Biology and Biotechnology.
Awarded ‘Best Researcher ‘by Andhra University. Authored a textbook
– General Course Biology for Engineers
Bilikere S. Dwarakanath obtained his Ph. D degree in Biophysics
from Bangalore University and was a post-doctoral fellow at the Wake
Forest University, North Carolina, USA. He served at NIMHANS,
Bangalore, INMAS, DRDO, Delhi, SRIHER, Chennai, and SPHIC,
Shanghai He has guided and mentored several students. He serves on the
editorial board of seven international journals and as a reviewer for more
than 50 journals.
(8)
Introduction
In 2004, after two years of having gout, a drug - allopurinol -

alleviated my pain. To sit outside without constant pain and feel the wind
on my skin was extraordinarily sensual. I could take walks again; I could
pet a dog. To be pain-free was so exhilarating; to be alive was once again
such a joy, that I came to call my cure a miracle. I was living a miracle.
Life was wonderful.
It took months for me to become aware of how oblivious I was in my
happiness. It slowly dawned on me that the drug I toasted each morning,
my elixir, did not spring from a pharmacy. Someone created it. But who?
Someone saved me from a life of constant pain and I hadn’t even bothered
to learn their name. My shame prodded me to research. I learned that
drugs are created through arduous experimentation and investigation,
over many years – often decades. Someone had dedicated her life to
making a drug that gave me back my life, and I didn’t even know my
hero’s name.
Trudy Elion was an admirable woman who fought through much
adversity. She never married – her beloved fiancé died from an infection
only a few years before the development of penicillin, which could have
saved him. Instead, Elion devoted her life to science. But coming of age
in the 1930’s, women were not supposed to obtain doctorates or go into
scientific research. Only the shortage of men resulting from World War
II made it possible for Elion to enter the laboratory. Once there, her
scientific production was prodigious. Working with George Hitchings,
she discovered numerous drugs, two of which save lives to this day – one
for childhood leukemia and one that prevents the rejection of kidney
transplants. Hitchings and Elion even won the Nobel Prize. It is to them
that I owe tremendous thanks for developing allopurinol.
It isn’t much of a leap, once you are contemplating someone saving
the quality of your life, to realize the importance of someone saving your
mortal life itself. In fact, before allopurinol was discovered gout killed
(9)
10,000 people a year. This made me wonder - who saved the most lives
in history? Surprisingly, there was no answer to be found. This book and
the website ScienceHeroes.com answer that question.
Modern Medicine is New

The number of lives saved is truly remarkable. They add up into the
billions. In some respects, the vast numbers make sense. The life
expectancy in 1900 in the United States was 45 years of age. By the year
2000 it was 77. An immense number of lives were saved to account for
such a colossal increase. One of the reasons I hadn’t recognized the
implication of this monumental advance in life span was that, growing up
in the latter half of the twentieth century, I had assumed that the medicines,
vaccines, and nutrition available to me had also been available to my
parents and grandparents.
But this was not true – in fact, modern medicine is remarkably new.
The reason doctors made house calls until the 1940s is that they couldn’t
fix much and could fit most of their medical tools into a little black bag.
In practice, doctors were more like hospice workers than healers. Outside
of setting broken bones, most of what they did was to provide comfort in
the form of painkillers until nature took its course, for better or worse. My
generation was the first to grow up with modern medicine that could
actually cure many diseases.
Doing the research, my biggest surprise was that I had never heard of
any of the scientists who saved the most lives. None were on Time
Magazine’s list of the 100 most important people of the twentieth century
or on various lists of the top 100 scientists who have shaped world history.
Yet based on the evidence, these scientists have had the most impact on
humanity. Six of the scientists chosen for the book have never had more
than cursory accounts written about them in the popular press. Remarkably,
four of the ten are still alive.
( 10 )
A Culture Can be Judged by Where it Places its Gratitude
The thirteenth-century German theologian Meister Eckhart said, “If
the only prayer you said in your whole life was, ‘thank you,’ that would
suffice.” Gratitude is important because it acknowledges those who
contribute to our well-being, but also because it can influence how we
invest our resources. If a society devotes all of its resources to building
giant statues, as on Easter Island, it might collapse. In contrast, if a society
invests its resources in developing life-saving techniques, it will thrive.
Gratitude toward these scientists can inspire children to grow up to be
scientists and inspire us to encourage more scientific research.
Recognizing the power of science can lead a society to dream of a
much better future, even a utopia. Before researching this book I would
have dismissed any discussion of a future utopia with jaded cynicism.
But after having my eyes opened to the power of great scientists to
literally remove the specter of death from one quarter of the earth’s
population, I realize I am living in the beginning years of a utopia. Such
optimism opens up a society to the possibility that premature death need
not occur.
Think of taking gratitude to an international level. What if every
nation, instead of bragging about how many nuclear weapons it has,
paraded before the world the number of lives of other nations’ its scientists
had saved? How different a world would that be?
It is a delight to introduce you to the ten hardest-working, most
intelligent, most productive people of the Twentieth Century.
( 11 )
Scientists
Greater
than
Einstein
Part I
1
Alfred (Al) Sommer
(1942-
The Eye Doctor Who

Discovered a Better Use for Vitamin A
Over 9 Million Lives Saved
ALFRED SOMMER was

hanging onto his seat as he rode the
rugged roads into the highlands of
Indonesia. His family was wide-
eyed at the new sights. The barely
two-lane road was crooked and
cramped, much too narrow for the
comfort of a doctor who knew the
carnage that can litter rural roads. Al Sommer in the mountains of
They rose in altitude, with a 2,000- Indonesia.
Photo courtesy of Al Sommer.
foot drop on one side and a blind
switchback up ahead. A car raced past them with nowhere to escape if
another vehicle appeared ahead—Sommer grimaced and shut his eyes,
but there was no crash of metal, just the laboring of the engine as it
chugged on up the mountain. The vegetation had been incredibly profuse
in the rainforest of the lowlands—bamboo and orchids and palm trees—
and it was green and lush here, too. The road leveled out for a while, then
climbed some more, then flattened as they rode past rice paddies, past tea
plantations, past tall cinnamon trees. It grew cooler as they rose, slowly
heading southeast, toward Bandung, the Flower City, Indonesia.
It was 1976, and Sommer, an ophthalmologist—an eye doctor—who
Alfred (Al) Sommer
had come to Indonesia to spend three years investigating nutritional

blindness. He had been working as a medical doctor with a lot of
children—cholera and smallpox patients—looking into their big, innocent
eyes that implored him to give them life, to heal. Looking into the eyes
of children who have nutritional blindness, diseases with no fatality rate
decided to fight that blindness on a war footing.
Beer Soup
For a mother, the first symptom of nutritional blindness in her child
is often night blindness. The inability to see well in the dark was described
in ancient times, as was the cure. Hippocrates recommended eating
animal liver, which actually helps, although we don’t know how he or
others learned this.
By 1816, scientists knew there was a direct relationship between
blindness and other eye disorders and nutrition. Dry eyes appeared to be
a precursor to blindness. The cure, discovered, Cod Liver Oil, in 1881,
became the boon of children everywhere.
In 1913, Elmer McCollum and Marguerite Davis at the University of
Wisconsin isolated the substance, still without a formal name. In a famous
1917 study, Denmark’s Carl E. Bloch determined much of the substance’s
health benefits.
Gowland Hopkins, in 1912 gave the first clear evidence that a lack of
particular components of the diet could be harmful. He fed young rats on
casein, lard, sucrose, starch, and minerals. Half of the rats also received
milk daily. Those receiving the milk grew well, and after two weeks, the
group receiving the milk was switched. He found that those receiving the
milk grew normally, and those now lacking did not continue to develop
well. He explained this by the basic diet was lacking in some essential
organic nutrient and felt that similar problems might be present in human
diseases related to diet. Hopkins did not investigate his “milk factor”
further. In the year 1912, Casimir Funk, a Polish scientist, was studying
nutrition from the top down by starting with human diseases and published
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Scientists Greater than Einstein
the “Vitamin Hypothesis.” He called them Vitamins, linking the word

VITAL with the word AMIN, the scientific term for Proteins. Building
upon decades of medical research showing that diseases such as scurvy
could be cured by diet changes, Funk named this class of maladies the
“deficiency diseases.”
During the early 20th century, the cutting edge of nutritional chemistry
was “purified food” ---processing food to measure the exact amount of
protein, carbohydrate, and fat. But the stunted, blind cows in the barns in
Madison clearly demonstrated that diet was not that simple; something
important was missing. Madison’s economy depended on healthy cows.
Elmer McCullum, a young researcher, a first great idea was to study
nutrition using lab rats instead of cows. Fed on the processed, purified
diets, the rats failed to thrive. The process-of -elimination experiments to
identify the missing component was long drawn. He was joined by a
young Lady volunteer Marguerite Davis, who not only took care of and
feeding the rats and keeping careful notes on the process. They tested rats
on three different fats ---milk, olive oil, and lard. The milk-fed rats
continued to grow and thrive, while the rats receiving olive oil and lard
started out well but then stopped growing, becoming sick and stunted.
The work was published in 1913.
The news that milk fat appeared to have protective power over the
health of rats was greeted enthusiastically by McCollum’s boss Stephen
Babcock as Madison, Wisconsin, was America’s Dairyland. To prove
that the growth-promoting nutrient was real, McCollum and Davis used
a chemical technique to extract the fat-soluble compound from milk fat.
They mixed the extract into Olive oil and lard. Rats that ate the treated
olive oil and lard grew to be as healthy and happy as rats that drank the
milk. Independently Yale group demonstrated that casein-free milk, also
called Whey, could support the healthy growth of rats. Other sources are
leafy greens rich in the fat-soluble factor.
In a famous 1917 study, Denmark’s Carl E. Bloch characterized the
likely substance’s health benefits. Researching the problem, Bloch zeroed
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Alfred (Al) Sommer
in on fat in the diet and concluded that the key factor was the “fat-soluble
accessory factor A” in the milk, soon to have its name simplified to
“vitamin A.” As a result of Bloch’s work, the Danish government rationed
butterfat, guaranteeing access at affordable prices to all Danish children.
The problem disappeared in Denmark. Bloch’s published research had a
brief impact, then was largely forgotten.
Following in Forrest Gump’s Path

Forrest Gump, of movie fame, had a propensity for being present
when historically significant events occurred, such as Elvis learning to
dance, John Lennon writing the song “Imagine,” and the Watergate
break-in. Alfred Sommer never met Elvis, and his IQ is on the opposite
end of the spectrum from Gump’s, but he has happened to be on location
for three of the biggest medical advances of the twentieth century.
Meeting Dr. Sommer leaves quite an impression. It isn’t his
appearance that is so remarkable—he wears professorial glasses and has
a recessed hairline—rather, it is his personality that is memorable. Known
as Al to his friends, when he meets someone, he flashes an easy smile and
starts talking. And, boy, does he have stories to tell. To Al Sommer,
medicine is an adventure, not a job. He has traveled around the world for
the United States Centers for Disease Control (CDC), the World Health
Organization (WHO), and Johns Hopkins’ illustrious school of public
health (now the Johns Hopkins Bloomberg School of Public Health),
often living in rough, sometimes even dangerous conditions, and usually
taking his family along. When something new interests him, he seems
just to decide it’s time for another adventure, and off he goes.
Sommer began his life in Brooklyn in 1942 and moved with his
family to Queens as a teenager. He had a great interest in history, so he
didn’t bother with New York City’s famed science high schools. He liked
to draw maps, and sometimes as he sat drawing them, he could picture
himself as a professor in a little New England college town. The sixties
were just starting when he headed off to Union College, a small, then
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all-male college in upstate New York. He chose it because a friend was

going there, and he knew if he went to a small boys’ school, “it would
keep my raging hormones in control, and I could get some work done.”
Graduation for Sommer was just a way station, for he had always
known where his future lay. “My becoming a doctor in the first place was
very easy,” he says. “I truly believe that my grandmother, on the day of
my birth, imprinted it somehow on my soul and, in fact, I can never
remember a time when I did not want to be a doctor. She was somebody
who had been an immigrant to the United States from Eastern Europe and
thought that physicians were people who did good and did well while
doing good, and thought that her grandson couldn’t choose a better career
for his life. And it was never a tussle. Nobody ever repeated it. I was
never threatened or bludgeoned into doing this, but as I grew up and met
physicians, as we all encounter our pediatricians and our internists, I
couldn’t think of anybody who was having more fun because they were,
in fact, respected, they were thoughtful, they were intelligent, they were
knowledgeable, and they were helping people.”
Sommer married his high school sweetheart, Jill, three weeks before
entering Harvard Medical School. They shared the optimism of the early
1960s: “I received my MD training at the time that Kennedy had been
president. We were all, of course, traumatized, and we can all remember
where we were the day that he was killed, but we had been inspired. I
remember his inaugural address, as does my wife: ‘Ask not what your
country can do for you, but what you can do for your country.’ That was
inspiring to young people in those days.”
Sommer and his wife both wanted to join the Peace Corps, but there
was a problem—a change in the draft laws that would have pulled him
out of the Peace Corps. His friends and colleagues suggested that instead,
he applied to work with the Centers for Disease Control and Prevention,
an alternative form of service. He was accepted into the Epidemic
Intelligence Service and was soon off to the CDC’s Atlanta headquarters
for the one-month introductory course. He was assigned to an office for
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Alfred (Al) Sommer
vaccine trials, then engaged with new rubella (measles) vaccine.

Sommer was, he said later, unimpressed with many of his colleagues,
who, it seemed, were far too interested “in the price of eggs in the
commissary.” He started firing off proposals for initiatives he thought the
office should launch. The torrent of requests made everyone nervous.
“Al,” his boss said, “we have all voted for you to go home for two
weeks and relax.” He went home to his pregnant wife and made baby
furniture. After he returned, a group of CDC employees who were
working in East Pakistan on cholera research came through, looking for
an additional person to join the group. Except for two things, East
Pakistan sounded to Sommer like a good adventure: “The two things I
really don’t like in life are hot, humid conditions and rice. And then I
looked up in the back of the National Geographic Atlas—they always list
the humidity and the temperature—and it was 120 degrees, it seemed to
me on average, in the shade, and 100 percent humidity and I said,
hmm….” But he realized the people “were excited about what they were
doing”—they were his kind of doctors—so he signed on.
Introduction to Epidemiology
Al and his wife Jill Sommer went off to Dacca, East Pakistan (soon
to be renamed Bangladesh) with their five-month-old baby. On November
8, 1970, a cyclone darkened the sky over the Bay of Bengal, devastated
the country. The Cholera Research Laboratory helped out in any way it
could. After initial aid had been dispensed, Mosley, the center’s director
of epidemiology, assigned Sommer to do a study on the impact of the
disaster.
Sommer coordinated ten two-person teams that went door-to-door,
visiting 2,973 families beginning two months after the storm, recording
mortality, injury, shelter, and food conditions. They found a staggering
240,000 people had been killed by the storm, including more than 29
percent of all the children under age four and 20 percent of all seniors in
the affected area. After two months, one million people were still
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dependent on outside food relief for survival. It was the biggest

epidemiologically documented natural disaster in history.
Sommer loved the work. He says it was “an area of medical research,
investigation, and endeavors that I didn’t know very much about and
literally fell in love with—epidemiology—which, in its best sense, is
medical detective work. In 1971, a civil war broke out in East Pakistan—
the Bangladesh Liberation War.
Compulsively Driven to Collect Data

The war lasted nine months, resulting in the new, independent nation
of Bangladesh, which was almost immediately confronted with a
smallpox outbreak. The (WHO) requested assistance from the CDC, and
Sommer joined the hastily assembled team. He was told to organize
containment activities, which meant vaccinating people around local
outbreaks to isolate the virus.
Sommer was ever-observant while the epidemic festered: “Since I
am compulsively driven to collect data without thinking about it, I had
these teams not only vaccinate but collect data. I was able to demonstrate
that if you got vaccinated within five days of exposure, you were
completely protected from smallpox, and if you are inoculated within
eight days, you won’t die of smallpox.” Along with thousands of
healthcare workers, Sommer helped to wipe smallpox from the face of
the earth.
Challenges of measurement of Malnutrition

Bangladesh has a way of changing people. Sommer says of the
experience: “It was fantastic, even though we had a cyclone disaster, a
civil war, a smallpox epidemic, one thing after the other. I went overseas
and had this marvelous experience working in the field and literally
having millions of people’s welfare and lives hinging upon decisions that
I made and investigations that I carried out. I found that extraordinarily
exhilarating—that the amount of leverage, the amount of impact I could
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Alfred (Al) Sommer
have was so much greater than I could on a one-to-one patient-physician

basis. Public health research is an area where I knew that I was going to
enjoy myself.”
Nutritionists had long sought a way to measure Malnutrition in
children. Some obviously effective methods, like measuring body fat or
protein content of blood, were too technically difficult for widespread
application in the developing world. The most widely accepted method
at the time was comparing a child’s weight to his age, but the exact age
was often unknown and frequently impossible to estimate. A weight-to-
height ratio would also work, but how do you get scales to rural areas in
the developing world? In the 1960s, Quaker medical missionaries in
Nigeria had developed a physical test by which they measured the
circumference of a child’s upper arm (a good indirect measure of muscle
mass) against a height table to determine who might be undernourished.
Nothing had to be recorded—they could put the height table on a stick so
that analysis could be instantaneous.
Health workers in East Pakistan a decade later had accumulated arm
and height measurements for 8,292 Bengali children as part of a study,
but there was no follow-up. In his spare time, Sommer wondered what
had happened to those children. He tracked down as many as he could.
Combing through death records, he found that 2.3 percent had died, and
in a taste of what would follow years later, he made a startling discovery:
During the first month after the children had their arms measured, 1- to
4-year olds in the lowest nutritional category (based on the ratio of arm
circumference to height), were at almost 20 times greater risk of dying
than their peers whose ratio was considered normal.
Predicting the mortality of children could be as simple as measuring
their arms! Sommer had trouble convincing anyone to believe his finding
and even had a difficult time getting his study published. It was too
simple, and his data set was too good to be believed. “They never
thought of clinical issues like death,” he said of doubting nutritionists. It
took a while before anyone bothered to replicate the work. Today, arm
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circumference is a standard measurement.

Bangladesh has a way of changing people. Sommer says of the
experience: “It was fantastic, even though we had a cyclone disaster, a
civil war, a smallpox epidemic, one thing after the other. It was fascinating.
Another culture. Other people. To be fascinated with what you’re
doing—I went overseas and had this marvelous experience working in
the field and literally having millions of people’s welfare and lives
hinging upon decisions that I made and investigations that I carried out.
I found that extraordinarily exhilarating—that the amount of leverage,
the amount of impact I could have was so much greater than I could on a
one-to-one patient-physician basis. As fulfilling as that is in its own right,
I then made the commitment to public health. Public health research is an
area where I knew that I was going to enjoy myself.”
Chance Favors the Prepared Mind

Some people go down well-planned paths and can see their life
unfolding far into the future. Others, like Sommer, take a different
approach. “I ought to provide a disclaimer,” Sommer says, “some people
are far more directed and deliberate than I am; I have lived most of my
career by doing whatever seemed most interesting at that particular
moment. So, I have not said, gee, I ought to do this because that’ll best
position me for the future.”
He had intended, on returning to the United States, to become an eye
doctor because it was a wide-open field with very few full-time
academicians. “I was supposed to begin my training in ophthalmology
but decided that since I had been doing epidemiology for three years, I
really ought to learn something about it. And so, I again postponed my
residency training for an additional year to pursue a master’s degree in
epidemiology at the Johns Hopkins School of Hygiene and Public Health.
And that, indeed, made a large difference because I came to ophthalmology
with a whole different perspective in which I would think about
populations of people and populations of eyes—much more so than the
variation you see with one individual.”
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Alfred (Al) Sommer
While there, Sommer’s favorite saying of Louis Pasteur’s—”Chance

favors the prepared mind”—played a hand. A professor hooked him up
with Susan Pettis, “a remarkable woman.” Pettis didn’t get her doctoral
degree until she was in her fifties, after which she became the director of
prevention for the American Foundation for Overseas Blind (now Helen
Keller International). The organization was looking to widen its research,
and an energetic young “whippersnapper” fit the bill. Pettis’ ideas
interested Sommer, and soon he was hooked. While he was completing
his residency, he began helping to design programs and evaluate issues.
Sommer set up small studies in Haiti and El Salvador, and he began
learning about night blindness.
What’s So Important About Vitamin A Anyway?

At the time Sommer began studying the problem, as many as half a
million kids a year were losing their sight. It was well known that vitamin
A deficiency caused nutritional blindness, so some scientists had
recommended biannual vitamin A supplementation as a preventative
measure—but this had never been proven in controlled trials. When a
child with symptoms was presented to the medical community, a shot in
the arm of vitamin A was the accepted treatment, and it worked very well
if administered before the cornea was permanently damaged. In fact,
nutritional blindness responds to a dose of vitamin A within 24 hours.
Unfortunately, this treatment was rare.
The short answer—everything. As Sommer would later describe it,
“A child who is night-blind in a village in India or Bangladesh or Nepal
literally can’t fend for him or herself. While other kids are walking
around the village or playing with toys, these children huddle in a corner.”
Infants rarely show signs of night blindness, but in older children, it is
obvious to all—their behavior changes drastically at dusk. And the
consequences of leaving the condition untreated could be tragic: “The
children will go truly blind because what happens is the cornea, that clear
front of the eye, just melts away. And it can melt away in the course of
one day.”
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Night blindness is one of the first symptoms of a condition formally

known as xerophthalmia, which is Greek for “dry eyes.” (The term is
often simplified to “nutritional blindness.”) The eyes dry out. Then, waxy
spots known as Bitot’s spots appear on the conjunctiva, the membranes
that cover the whites of the eyes. The dryness spreads over the cornea,
causing it to ulcerate and shrivel. The victims are consequently blind for
life.
Vitamin A is not one substance but a generic term for a variety of
related compounds. Briefly, they include the active forms retinol and
retinal, and retinoic acid, which can be produced from retinal. Vitamin A
is found in animal products, including meat, fish oil, and milk.
Vegetables can also provide vitamin A, but only through precursors
such as carotenoids, which are named after their most famous source, the
carrot, and include the well-known molecule beta-Carotene. They are
broken down to form the retinal in the intestine. The ability of the body
to absorb carotenoids from food varies widely depending upon the way
the food is prepared and consumed. Because carotenoids are fat-soluble
and often strongly bound in raw vegetables, absorption increases
significantly when vegetables are cooked in fat. Normally, more than 90
percent of vitamin A is stored in the liver, which is why fish and animal
livers, and foods prepared from them, such as cod liver oil, are such good
sources of the vitamin.
Vitamin A then, in its different forms, has many functions in the
body. Retinal, for example, in the form in which the vitamin plays its
well-known role in promoting night vision. Retinoic acid has been shown
to play a crucial role during embryological development. In all its active
forms, vitamin A acts as a hormone that regulates the expression of over
300 genes, including many that play a role in cellular growth and
differentiation. This regulatory role is most evident in its effect on the
mucous membranes of a number of organs, including those of the
genitourinary tract and respiratory system (there is some indication of
malabsorption of vitamin A in cystic fibrosis patients), and the membrane
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Alfred (Al) Sommer
over the cornea of the eye—hence the correlation between vitamin A

deficiency and dry eyes.
Immersed in Indonesia
In 1974, the first international conference on nutritional blindness
was scheduled for Indonesia. Sommer, a virtual unknown, had no reason
to go. But Susan Pettis had different ideas and wrangled him an invitation.
Friends who knew Indonesia’s culture cautioned him to curb his tendency
to talk too much—it was a culture that respected somber dialogue.
Perhaps they were improperly characterizing the people, but quieting
Sommer was an impossible task anyway. He quickly formed the opinion
that it was a “wonderful country” where “the people seem marvelous,”
and soon he was as effusive as ever, meeting and befriending numerous
people, including those at the Ministry of Health. They accepted his
loquacious personality and invited him to come to work with them on a
serious problem that his background, both in epidemiology and
ophthalmology, seemed perfectly suited for: Due to some unknown
reason, nutritional blindness was more prevalent in Indonesia than in
most other places in the world.
Back in Baltimore after the conference, Sommer was invited to join
the faculty at Johns Hopkins, but he was not the conservative, academic
tenure-track type of doctor. When he told them of the opportunity to do
research in Indonesia, colleagues warned him that he would lose his place
on the faculty and be forgotten. Sommer told them, “No, I have this
wonderful opportunity to go overseas and work with people in another
culture. I have something to contribute, and it is intrinsically a very
interesting series of questions that need to be answered.” And so, Sommer
headed up that mountain road in the Indonesian spring of 1976
The Nutritional Blindness Prevention Project would largely do
research that Sommer planned. He cleverly chose Bandung for a variety
of reasons. While it was a modern city with a population of more than a
million, it was far away from outside influences. Epidemiology, one of
( 26 )
the most powerful concepts in medical science, is the study of all aspects
of disease in populations rather than in an individual. It ferrets out the
causes of diseases and codifies the best treatments by using one of the
basic tools of science—measurement. This concept may seem trivial to a
scientist but is often ignored by nonscientists, as evidenced by whole
industries of “alternative” medicine that rely on anecdotal stories or
studies that do not measure statistical significance. An epidemiologist
uses accurate measurement to discover hidden causes of disease or death
by isolating both the many variables in a population and the various
outcomes a disease may present.
Sommer’s epidemiological plan was to do three integrated studies
over three years to try to determine the risk factors associated with night
blindness. He would then have one year to study the data.
The studies, however, were not simply about amassing and tabulating
data. There was a personal and cultural aspect to them as well, for it was
important to understand the people whom the disease affected. By now,
both Sommer and his wife had learned to speak Malay. They put their
knowledge to use listening to mothers whose children had eye disorders.
An early problem had been how to define night blindness objectively.
Sommer learned that “a mother’s history that her child could not see at
dusk or dawn was as accurate or more accurate than our objective tests.
And the reason we know that is that if we compared our objective tests
with what she said, her history had a better correlation with the serum
vitamin A levels than our objective test had. So, in this population, we
were able to know precisely what a child was getting simply by asking
the mother.”
There were folk remedies worthy of study as well. One widely used
in Java on children with either night blindness or Bitot’s spots consisted
of dropping the juices of lightly roasted lamb’s liver into the eyes of
affected children. Sommer relates, “We were bemused at the
appropriateness of this technique and wondered how it could possibly be
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Alfred (Al) Sommer
effective. We, therefore, attended several treatment sessions, which were

conducted exactly as the villagers had described, except for one small
addition—rather than discarding the remaining organ, they fed it to the
affected child. For some unknown reason, this was never considered part
of the therapy itself.” Sommer and his associates were bemused but now
understood why the folk remedy had persisted through the centuries. The
liver, being the organ where vitamin A is stored in a lamb or any other
animal, is the best food to eat to obtain vitamin A.
The Studies of Children’s Eyes

Sommer’s team’s first formal study was a countrywide survey of
36,060 preschool-aged children from areas of the country that were
thought to represent 96 percent of the urban slum and rural population of
Indonesia. The parents of any child with symptoms of nutritional
blindness were asked dietary questions, as were the parents of 20 percent
of all children examined. Children in need of treatment were provided
free of charge. This study would set some baseline statistics to compare
the other studies too, but its most important purpose was to quantify the
scale of the problem so that government and international aid agencies
might be informed of how aggressively the problem needed to be attacked.
The second study was set up in the biggest eye hospital in Bandung—
the Cicendo Eye Hospital. The plan was to follow every case of nutritional
blindness that presented itself so that the researchers could describe the
progression of the blindness as the disorder was treated. Over the course
of the three years, about 350 children came in who was going blind, and
another thousand came in with precursor symptoms. A pediatrician, an
ophthalmologist, and a nutritionist, each of whom gathered data, saw
every child. The researchers took photographs of their patients’ eyes,
examined blood specimens, and then treated the children.
Because they conducted their study in a tightly controlled
environment, Sommer and his colleagues could do specific randomized
studies on different aspects of the disease. For controls, they would head
( 28 )
out to the children’s homes and examine other children residing in

surrounding houses, finding children who were the same age and sex as
each sick child. Some of these children were also found to have nutritional
blindness and so were switched from the control group to the nutritional
blindness group and treated.
The studies were dynamic. If the researchers couldn’t proceed due to
unplanned events, they had to adapt. Sometimes this led to new
discoveries.
They ran into one roadblock as soon as they began. The accepted
treatment, endorsed at the time by the World Health Organization, was to
inject children with shots of vitamin A. Vitamin A is naturally fat-soluble,
but animal testing showed that using it in a fat-soluble form wasn’t
effective. As Sommer says, the vitamin A “sat there like a lump and
didn’t get out” into the blood. Processing the vitamin to make it water-
soluble seemed the answer.
The process resembled that of homogenizing milk—the fat-
containing vitamin A is distributed in the liquid instead of sitting like
cream on the top. The problem, he immediately discovered, was that
there was no water-soluble vitamin A available—no one had bothered
to make any. It would take months before the pharmaceutical company
Roche could produce some and ship it to Bandung. “What am I going to
do in the meantime?” Sommer asked.
Sommer had worked in Bangladesh, where it was shown that
dehydration from cholera was fought more successfully by patients
drinking fluids (oral rehydration therapy) than by having fluids injected
intravenously. So, he wondered what would happen if he took the fat-
soluble vitamin A and, instead of injecting it, squirted it into the children’s
mouths? He found that it worked remarkably well.
When the shipment from Roche finally arrived, Sommer was
presented with a dilemma—keep using the method that worked, or revert
to the book treatment. Sommer is one of the more prominent members of
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Alfred (Al) Sommer
a movement to bring evidence-based science into modern medicine.

This movement seeks to base medical conclusions on real, statistically
significant, verifiable evidence—not guesses, not anecdotes, not
traditional methods. Hard as it is to believe, there is no statistical support
for many of the cookbook treatments doctors use or believe in, even to
this day.
So, Sommer set up a controlled study. He established a trial in which
sixty-nine children with corneal symptoms of nutritional blindness were
given 200,000 IU of oil-based vitamin A by mouth, and a matched group
of forty-five children were given the book dose of 100,000 IU of water-
based vitamin A injected by a shot into a muscle. All were given another
oral dose the next day. There was no detectable difference in the children’s
clinical response to the two methods of delivery. This was a monumental
change in protocol. A child who comes down with night blindness or
other symptoms of nutritional blindness is in a state of emergency—time
matters. But to receive an injection of the vitamin, an Indonesian child
had to be transported, sometimes for days, to a healthcare center, and
once the child got there, a healthcare worker had to provide the injection
using needles and syringes, which introduced an associated risk of
hepatitis infection. But anyone could squirt the vitamin into a child’s
mouth, and it only cost two cents a dose. Thanks to what at first had
seemed to be a serious hindrance, Sommer had found a way to bring
healing directly to the patient.
The third study would isolate one geographical area and examine as
many factors as possible that might cause nutritional blindness. Sommer
and his team decided to locate this study in Purwakarta Regency, West
Java, a two-hour drive north from Bandung. The area was chosen because
there seemed to be a high incidence of nutritional blindness in the region.
A census was performed on six villages, involving a total of 6,598
preschool-aged children, who were then categorized by neighborhoods.
Teams consisting of eight enumerators, two nurses, an ophthalmologist,
a pediatrician, and a nutritionist measured and examined the children.
( 30 )
Because of local taboos, many parents refused to allow the examination

of babies under three months old, so that data set was substandard.
Otherwise, parents were very cooperative—only 1 percent refused to
participate.
Those with nutritional blindness symptoms were discovered, and
controls for each of the sick children were found nearby, matched for age
and sex. Blood samples were taken from all children with symptoms,
from the chosen controls, and from 5 percent of the entire population of
children.
Then the children were divided into three groups. Children with
advanced symptoms of nutritional blindness (corneal symptoms) were
treated and removed from the study. That left two groups—those with
mild symptoms and those with no symptoms. The number of children
who had mild symptoms rose dramatically with age from zero percent
under the age of 1- 7 percent of those four years of age.
A major goal of the study was to find out why some children got
nutritional blindness and vitamin A deficiency, and others didn’t. To
accomplish this, the study was designed to be longitudinal, meaning that
all the children were reexamined every three months for eighteen months.
All such large epidemiological studies deal with the vagaries of human
beings, so some children would not be at home when the examiners
returned, and others developed symptoms of serious nutritional blindness
and had to leave the study for treatment. In the end, 3,481 children
completed the whole program. The team conducted a total of 20,885
child-interval examinations.
With the three-year study complete and the data piled in boxes,
Sommer moved to London for a year and began analyzing the data and
writing up the significant conclusions readily apparent. This is what had
drawn Sommer into epidemiology: “As you peel back the layers of the
onion one at a time, there’s always another mystery behind it, another
medical detective story.” And sometimes, the answers didn’t jump off the
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Alfred (Al) Sommer
page at him. “Often, the answers come at odd times,” Sommer says. “You
don’t get the insights you need—either the answer or how you are going
to approach a question—while you are actively thinking about it.”
Sometimes they came to him while he slept. “I’ll wake up at two in the
morning, and I’ll say, ‘Aha, I know how I’ll approach that now.’
Unfortunately, a lot of times in the morning, what I wrote makes no
sense.”
It was a typical epidemiology. For the first time, the disease of
nutritional blindness had been thoroughly studied in the field, and a lot of
its factors could be explained.
He found that:
• The incidence of nutritional blindness was 2.7 per 1,000 children in
Indonesia per year.
• That meant that 63,000 cases of nutritional blindness occurred per
year in Indonesia.
• If the data were extrapolated to the Philippines, India, and
Bangladesh, which had similar dietary and related conditions, there
could be 500,000 cases of nutritional blindness per year in these
four countries.
• Half of untreated cases of nutritional blindness lead to blindness, so
potentially 250,000 children a year could go blind in these four
countries if the problem was not addressed aggressively.
• Half the population of seemingly normal rural Indonesian children
had low levels of vitamin A in their blood—this explained why
night blindness was a big problem there.
• Breastfeeding provides an important source of vitamin A—children
at age two who were not being breastfed were at eight times the risk
of developing Bitot’s sports compared to those who were being
breastfed.
• Children with nutritional blindness ate fewer eggs, carrots, mangos,
papaya, dark leafy vegetables, and fish than the control children.
( 32 )
• Vitamin A deficiency was a neighborhood phenomenon and rarely

occurred in isolated cases. Thus, treating whole neighborhoods of
children at once might be beneficial.
• Children with the corneal disease were shorter than children who
had Bitot’s spots, who were themselves shorter than the healthy
controls.
• The discovery with the greatest potential impact was that children
could take vitamin A by mouth. This meant that treatment was
cheap and could be made available even in remote, undeveloped
parts of the world.
Living Inside the Data
His research program finished, Sommer moved back to the United
States and finally became a full-time professor at Johns Hopkins. He
continued his vitamin A deficiency research but also did research on
glaucoma; in addition, he saw patients and performed surgery one day a
week. It was Christmastime, 1982, and things were slow at the Wilmer
Eye Clinic at Johns Hopkins, where Sommer was based. No one comes
in for cataract surgery over the holidays; it’s an elective procedure. It
seemed to him to be a good time to take another look at his Indonesian
data. Sommer doesn’t believe an epidemiologist should simply ask a
question and then have a statistician or computer program determine the
answer. “I say ‘data, talk to me, tell me what you have to say? You have
to know your data. You have to smell it. You have to be in it. If you’re
not living inside the data, you are going to miss the most interesting
things because the most interesting things are not going to be the questions
you originally proposed; the interesting things are going to be questions
you hadn’t thought about.”
The week after Christmas, Sommer was going over the longitudinal
study data that examined every child in a village every three months for
eighteen months. He was “peeling back the next layer of the onion, as it
were. And as we had anticipated, children who had the respiratory disease
a month ago were more likely to become vitamin A deficient. Children
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Alfred (Al) Sommer
who had diarrhea were more likely to become vitamin A deficient.

Children who had a diet that was poor in vitamin A or provitamin A
carotenoids were more likely to become deficient.”
This was before the desktop computer age, and Sommer was looking
through massive, old-fashioned printouts—the kind with alternating light
green and white horizontal columns; he was looking at each cell of
information in tables. There were lots of ways of looking at the data: He
could group it by age; he could group it by sex. He was living the data,
looking for questions as well as answers. What proportion developed
night blindness or the white Bitot’s spots in the next round? How many
had night blindness in one examination and still had it in subsequent
examinations? He began thinking of the children, tracing what happened
to each child with their big, dark eyes, seeing their eyes change as the
intervals went by. Many eyes cleared up completely. Others appeared
with Bitot’s spots for the first time—sad, innocent, imploring eyes
looking for a healer.
As he immersed himself in the information, “It became apparent that
something very funny was going on with the data.” Children who had
night blindness seemed to disappear from the study. They wound up in
the “don’t know” category far more frequently than did kids who had
normal eyes. What happened to those children with their big eyes? Why
did they leave the study?
Usually, 90 percent or more of the children showed up for the next
examination, although occasionally, children were in the fields or
traveling with relatives. But these missing kids were not kids with healthy
eyes. Their parents knew that another free examination was scheduled.
Wouldn’t they have made sure their child showed up? “Was it because
they were too sick to show?” Sommer wondered. “No, their mothers
would want to get them to help if they were sick. Were the parents of the
blind too uncaring, too busy to show?” Not hardly—Indonesians were
wonderfully loving parents. Where had the sick children gone?
( 34 )
“Holy cow!” Sommer exclaimed. He suddenly realized the children

were not doing the same thing the controls were doing when they missed
examinations. The missing children weren’t out working in the fields.
Sommer realized the children weren’t showing up because they were
dead! “I got really excited and, using my little hand calculator, I redid the
data by hand, going from cell to cell. What was the risk of kids with night
blindness dying? What was the risk of kids with Bitot’s spots dying?
How about kids with spots and night blindness? Kids with normal eyes?
I checked them through six intervals.”
Night blindness wasn’t a fatal disease, so the team hadn’t been
measuring death as a variable. Sommer called in a statistician to rerun the
data and make sure his results were correct. They were.
But Sommer knew not to leap to conclusions. Data sets are full of
variables, so he began to examine the data to see if causes other than
vitamin A deficiency might be the fatal culprit. He ruled out respiratory
and diarrheal diseases, which were common among the children. Age
wasn’t the causative variable either. Nor was wasting due to
malnourishment. In fact, malnourished children with adequate vitamin A
were less likely to die than well-nourished children who were deficient in
vitamin A. The only consistent cause of death, no matter how he grouped
the children, was vitamin A deficiency.
It was obvious that he had found something new: “When you summed
it all up, the kids who had night blindness were dying at three times the
rate of kids who had normal eyes. The kids with spots died at seven times
the rate, and the kids who had blindness and spots were dying at nine
times the rate.” Evidently, the whole paradigm they and the worldwide
medical community had worked under had been wrong. It wasn’t at all
that changes in the eye were the early symptoms of vitamin A deficiency.
Nutritional blindness was, in fact, a sign of advanced deficiency that was
causing the children’s immune system and organ tissues to deteriorate
and thereby allowing them to die of other causes. It was likely that
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Alfred (Al) Sommer
vitamin A deficiency affected health long before it became manifest in

the eyes.
The Medical Establishment Turns a Blind Eye

Sommer’s finding became the lead article in Lancet, the prestigious
British medical journal. “Nobody paid any attention to it. In the lead
article,” Sommer says, “no attention. Not one letter to the editor. Nothing.”
According to the historian of science Thomas Kuhn, scientists are
mostly a conservative lot who have set ideas about how things work.
Kuhn popularized the use of the word “paradigm” to describe this
common wisdom, which is what everyone “knows” or assumes to be true.
A virus causes smallpox; the sun revolves around the earth; gravity
makes apples fall—things like that. Of course, the sun doesn’t revolve
around the earth, so sometimes the common wisdom is wrong—even if
people have accepted it for 500 years. Kuhn calls that realization a
“paradigm shift,” a rare but crucial concept for the advancement of
science. Paradigm shifts come with significant disruption. Doctors are
reluctant to embrace them because, in medicine, the wrong paradigm can
kill you, so doctors often find it safest to repeat the past.
The same thing had happened with Sommer’s other big discovery—
that prescribing oral vitamin A to heal nutritional blindness is as good as
an injected shot. The medical community continued to recommend an
injection even though a vitamin A pill cost only two cents and, being an
oral application, could be easily supplied to a child by an adult. Sommer
recalls, “They said, ‘Oh no, we can’t change the recommendation.’ I
asked why we can’t change the recommendation, and they said, ‘People
like to get injections.’ I said that was a pretty stupid reason.” Sommer’s
finding was still being ignored and would take another five years to
become accepted practice.
The nutritionists had their own paradigm, too—that children were
protein-energy-malnourished. They even had an acronym to encapsulate
all the research they had conducted on it—PEM. It wasn’t possible that
( 36 )
an outsider to the profession could come in with a magic bullet, a simple

vitamin pill that would save children’s lives. But the nutritionists hadn’t
read the history of nutrition, including Carl Bloch’s work in Copenhagen
with the beer soup. According to Sommer, “A profound amnesia appears
to have settled over the broader context of vitamin A deficiency once it
ceased to be a major concern of wealthier nations.” There were plenty of
animal studies and clinical observations that delineated its important role
in the immune system and organ tissue growth, but everyone thought that
vitamin A only affected the eyes.
Bury Them in Data

Sommer was disappointed in the reception of his discovery, but he
isn’t the type to sit on his hands. So, he did another study, this one in
Aceh province, Indonesia, which later would become famous for the
2004 tsunami. Four hundred and fifty villages on the northern tip of the
island of Sumatra were randomly assigned to participate in a vitamin A
supplementation scheme for one year. Two hundred and twenty-nine
villages would have all of their children given 200,000 IU of vitamin A,
then six months later, the children would get another capsule. Two
hundred and twenty-one villages would act as controls and would receive
no vitamin pill. A total of 25,939 children were examined at the beginning
of the study and again a year later. This time, the findings were even more
dramatic. Those receiving the vitamin A pill had a decrease in mortality
of 34 percent. Again, Lancet published his study, this time with an
editorial of support.
“Now everybody noticed,” he said, “but they were all angry. There
is this thing about when something new comes along, totally unexpected;
it’s almost the equivalent of getting bad news, like being told you are
dying. First, you go into denial, then anger, and eventually, you are
reconciled. That’s what happened; we went through those stages. People
should have run out to replicate the findings—do a randomized trial.”
One problem was that Sommer’s data sets were too good. One critic
suggested that if Sommer had only claimed a 10 percent impact, perhaps
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Alfred (Al) Sommer
more people would believe him. Then there was the placebo problem.
Sommer had refrained from using placebos at the Indonesian government’s
request. He says, “I didn’t have difficulty with that because placebos, for
the most part, counter the potential for subjective bias, where the patient
feels better because they’ve got the medicine. But in this instance, death
is a pretty hard endpoint, and Nobody is going to fake death because they
received the placebo. They didn’t receive those placebos, so, to me, it did
not detract from the rigor of the study. But, I must tell you that from a
political point of view, many scientists and certainly all policymakers,
who had to make decisions whether they were going to use and divert
some of their limited resources to controlling vitamin A deficiency, made
a big thing about the lack of placebo and said they didn’t believe the
results of this study because it did not have a placebo control.” Others
said that vitamin A supplementation might not be safe. But studies
showed that side effects are transient and very rare.
There was one party that did not join the chorus of criticism. The
Indonesian policymakers had seen enough—they immediately drew up
plans for a nationwide vitamin A intervention program.
A wise colleague pointed out that these were the normal reactions to
any unexpected research finding. He advised Sommer he needed to “bury
them in data.” That’s what Sommer did. He started another study in the
Philippines, but after he had put in years of work and $2 million had been
spent, a local guerilla movement forced his team to abandon the area.
Sommer moved the operation to Nepal. At the same time, he encouraged
other researchers in other countries to try to replicate the findings—
sometimes providing direct support.
The study in Nepal showed a 40 percent reduction in mortality. A
study in India, where the children were given vitamin A once a week,
showed a 50 percent reduction in preschool mortality. Ghana showed 23
percent. Sommer thought that vitamin A might help fight measles as well
as night blindness since “measles is a viral disease that infects and
damages epithelial tissues throughout the body.”
( 38 )
Vitamin A, in the form of retinoic acid, is known to be important in

the maintenance of these tissues, which form the mucous membranes in
the intestine, lungs, and eyes that provide the first line of defense against
infection. Vitamin A also plays a role in the development of white blood
cells, crucial to the maintenance of a strong immune system.
In Tanzania, Sommer found a missionary physician who reported
that significant numbers of children with measles were going blind. Their
corneal ulcers were easily fixed with the little pills, but it was the perfect
opportunity for a study on vitamin A’s effect on children with measles.
In a randomized trial, half the children brought in with severe measles,
and without eye lesions were given vitamin A on two successive days,
while the other identical half received standard treatment alone. The little
pills cut the mortality rate in half.
That paper was published in the British Medical Journal, and this
time the world was paying attention. A colleague who had earlier debated
Sommer publicly, claiming that vitamin A treatment was “too good to be
true,” soon wrote an editorial in The New England Journal of Medicine
titled “Vitamin A—Too good not to be true.” Within months, the WHO
and UNICEF issued a recommendation that all children with measles get
vitamin A as part of their treatment. The vitamin works so fast it’s
effective even if measles is already raging in the child.
Other studies showed that vitamin A deficiency also increased the
severity of diarrhea, another major cause of childhood death and that the
little pills reduced mortality from this affliction as well. There were still
critics, but by this time, Sommer believed that any further dickering was
unethical. Clearly, the little pills worked, and anything that interfered
with the treatment was morally unacceptable. He called a meeting at the
Rockefeller retreat center in Italy, where he posed three questions. Is
vitamin A deficiency bad for kids’ health and survival? Is vitamin A
deficiency bad for kids with measles, in particular? If you gave kids
vitamin A, would you reduce their overall mortality rate and their
measles-case mortality rate?
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Alfred (Al) Sommer
Everyone agreed the answer was “Yes” to all three questions, and the
attendees published the results in their favorite medical journals. That
turned the tide.
According to Sommer, there are three ways of getting vitamins for
children. The “politically correct” method is to improve their diets, but
this is difficult to do. Scientists have recently genetically engineered rice
to produce more vitamin A and are attempting to crossbreed it with rice
strains native to vitamin A-deficient areas, much as Norman Borlaug
once crossed his high-yielding (though not genetically engineered) wheat
strains with native germ lines. The idea is that since rice is the staple in
much of the world where vitamin A deficiency is rampant, genetically
modified rice could mitigate the deficiency problem. This so-called
“golden rice” is controversial because it is genetically engineered, and
there are doubts as to whether it can provide the amount of vitamin A
necessary for children.
Food fortification is another mechanism for introducing vitamin A to
the diet, and bread, milk, and margarine have been fortified with vitamin
A for decades in Europe and the United States Countries in Central
America fortify sugar with vitamin A. Fortification allows vitamin A to
be distributed to virtually 100 percent of the population, regardless of
socioeconomic status.
But for much of the developing world, the answer has been
supplementation vitamin A pills are now standard treatment for children
in seventy countries. UNICEF supplies the pills, the Canadian government
pays for most of it, and 600 million doses—half of what is needed—are
distributed annually. Still, more than 100 million young children don’t
get the pills and suffer from vitamin A deficiency. But the inexpensive
pills make a huge difference for those children who do receive them.
According to UNICEF, half-a-million children are saved from death
every year, which means more than six million lives have been saved
since the pills became policy in the 1990s.
( 40 )
The Good Part of Being a Doctor

Sommer hasn’t stopped with vitamin A research. New research,
based on a huge study he and his colleagues have led in Nepal, shows that
supplementing pregnant women with vitamin A or beta-carotene can
reduce maternal mortality by 45 percent. It also finds that giving a
newborn child a slightly smaller amount of vitamin A within hours of
birth dramatically reduces neonatal mortality when childhood deaths are
at their highest.
The story of vitamin A deficiency is a wonderful illustration of the
development of scientific understanding over the course of the twentieth
century, especially because it brings together findings from seemingly
disparate fields of study. It began as a chemistry problem, as Elmer
McCollum and Marguerite Davis discovered vitamin A—the hidden
ingredient in fat. Then it became a nutrition problem as Carl Bloch
showed how a diet that lacked it was the cause of night blindness.
Then Alfred Sommer, who obtained his scientist’s credentials
refining the work on cholera and its solution, oral rehydration therapy, as
well as on smallpox eradication, brought to the problem of vitamin A
deficiency. not only the specialized knowledge of ophthalmology but
also an epidemiological perspective. With it, he discovered a whole new
paradigm—that vitamin A deficiency is not primarily an eye disorder but
is a life-or-death nutrition disorder. Finally, he realized that being a
scientist wasn’t enough to begin saving lives. He became an advocate for
his own research and for the research of others until he could convince
scientists and policymakers of the life-giving benefit of spending a nickel
a year so that each child in the developing world can take two vitamins a
year and see into a future.
In 2004, the Johns Hopkins Bloomberg School of Public Health
established a $22 million scholarship program in honor of Dr. Sommer
called the ‘Sommer Scholars.’ The program aims to recruit the next
generation of public health leaders to devise new, effective interventions
to improve global health.
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2
Akira Endo
(1933-
Statins: Life Extension

for the Baby Boomers
EVERY SPRING, the Japanese

follow the sakura zensen—the
cherry blossom front—as it moves
northward week by week. It takes
months for the cherry trees to bloom
over the length of the country,
ending in the north where the snow
has just melted, and the mountain
clearings have greened with
rejuvenated growth. Akira Endo
was born on November 14, 1933, in
northern Japan, and every spring, he
saw his family’s backyard cherry
Akira Endo in the lab, pictured soon
tree bloom. The trees were such an after graduating college.
important harbinger of spring that Photo courtesy of Akira Endo.
they came to symbolize much of

Japanese culture. For a boy growing up in rural Japan during World War
II, the evidence of war was not so much what came into the region as
what was taken from it. There were no bombs, no invading army, no war
factories. But sucked from the region were men, food, and carefree youth.
Akira Endo was nine years old when America first bombed Japan, and in
Akira Endo
his autobiography, he remembers the effect the shortage of working men

had on children: “When I was in the upper grades of elementary school,
we took part in labor service projects called kinrou houshi to help the
local farmers. At the labor service, all the classmates helped the farmers
and picked edible wild plants from the fields and mountains near the
farms.”
In the autumn, when Endo was in the fourth grade, his beloved
grandmother became sick. At night, she took his hand and said,
“Grandma’s disease is the one which cannot be cured,” and made him
touch her belly. He would place his fingertips gingerly on her abdomen
and feel a small crunchy thing. Day by day, the crunchy thing got bigger,
and Endo’s grandmother got thinner.
That May, the double cherry blossom tree in Endo’s backyard
bloomed gloriously, and his grandmother was released from the pain of
cancer. He thought, “I want to become a doctor to help people who are
suffering from diseases.”
Japan’s total surrender at the end of World War II eroded much of
the country’s national pride. Arising from the ashes, the young generation
would need to build a new Japan. Akira Endo grew up to embrace a
modern way of thinking, embodied by science, and with it, he crafted a
gift to the world that would rekindle Japan’s pride in what it could
accomplish and that people from all nations could celebrate.
A Student of Fungi
Bookending the cherry blossoms of spring, the northern Japanese
autumn produces a kaleidoscope of color across the mountain vistas. In
the forests of falling beech and oak leaves, what most attracted the young
Endo lay underneath the trees, beneath the damp, speckled forest floor.
Endo recalled, “When I was in junior high school, my grandfather, who
had an interest in medicine and science, often took me to the mountains
near my house to pick mushrooms in the autumn. He was my home
teacher for seventeen years taught me how to tell the difference between
( 44 )
mushrooms and toadstools [in some cultures, poisonous mushrooms are

called toadstools]. Almost all the poisonous ingredients of toadstools are
water-soluble, which means that if you boil them, the poisonous
ingredients dissipate into the water. So, you can actually eat most
poisonous toadstools if you really wash them after you boil them and get
rid of the broth.” Mushrooms were eaten at almost every meal in the Endo
household. Thanks to his influence, Endo became fascinated with
mushrooms and other molds. He dreamt of becoming a scientist, much
like the renowned Japanese scientist Hideyo Noguchi, who, in 1900 at the
age of 24, went to the USA and studied syphilis and yellow fever at the
Rockefeller Institute in New York.
Endo began attending a work-study school, which met only on
weekends. It was a two-hour walk each way and was not advanced
enough to prepare him for college. Fortunately, his uncle moved to the
city of Akita and accepted Endo into his household, where he could
attend a real high school.
There Endo learned more about fungi, including the microscopic
molds that he found on mandarin oranges and koji (steamed rice that is
cultured with mold spores so that it can be used to make sake, a sweet
wine). He also retained his interest in the larger fungi—the poisonous
mushrooms his grandfather had taught him. One type killed both flies and
humans. Another, called the fly-catching mushroom, had evolved a
subtlety that Endo found fascinating. Lemon yellow in color, people cut
it up and placed it on plates throughout their homes. Flies were attracted
to it and later died, yet it was not poisonous to humans.
It was so mysterious to Endo that during the summer break, he
devised his own experiment. He confirmed that the poisonous ingredient
of Tricholoma muscarium Kawamura [which kills flies, not humans] is
water-soluble. Endo loved chemistry, and his principal encouraged him
to take the entrance exams to Tohoku University’s College of Agriculture
in Sendai. Endo’s principal helped him get a scholarship. Here he was
inspired by the biography of Alexander Fleming, who discovered
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Akira Endo
penicillin in the blue-green mold belonging to the genus Penicillium in

1928. The work of Howard Florey, E.B. Chain, Abraham, Selman
Waksman had made a deep impression in the mind of Endo as antibiotics
had saved the lives of many patients with infectious diseases.
Steaks the size of Sandals

Endo lived in the college dorm with three other students. Though the
food was lacking, the knowledge Endo gained was ample and nourishing.
After graduating from college, Endo moved to Tokyo and was hired by
the Sankyo Corporation, a pharmaceutical company with products
ranging from medical to agricultural. Endo was assigned to one of the
applied microbiology group. He worked toward developing a new
pectinase that hydrolyzed viscid pectin contaminated wines and ciders. In
1958, he found a grape-parasitic fungus, coniothyrium diplodiella, to be
a potent producer of such an enzyme. Pectin is a type of fiber produced
in fruits such as apples and grapes, which causes their juices to be cloudy.
One year later, this new enzyme was commercialized by a process to
make great quantities of pectinase. He then purified this enzyme and
characterized it. It became very profitable for the company as a clarifying
agent.
His stellar research and acclaim from the commercial success of his
pectinase production earned him a reward—the opportunity to study in
the United States for two years.
He could now spare himself time for something more altruistic. Endo
thought, “Since I was born as a human in this world, I want to leave my
mark before I die.” Remembering his grandmother’s sickness, he turned
to medicine. Endo says, “At that time, doing research on nucleic acids
and proteins was very popular among other researchers, so I avoided
researching those topics. I chose the biochemistry of lipids [cholesterol
and fatty acids] as my research theme. The reason why I chose this theme
was that not so many researchers were researching it. This meant I did not
have much competition.”
( 46 )
Endo wished to study at Harvard under Konrad Bloch, who had just
won a Nobel Prize for his research on cholesterol metabolism.
Unfortunately, Bloch’s student load was full. Consequently, in the
autumn of 1966, the 32-year-old Endo, with his wife Orie and his two-
year-old son Tadasu, moved to New York City to attend Albert Einstein
College of Medicine.
The day Endo and his family stepped off the plane, they were
confronted with the proportions of everything American. Everything was
bigger. At restaurants, Endo watched with amazement as people ordered
steak “the size of a sandal”—enough to feed a family in Japan. Although
Endo was studying phospholipids, which are the principal component of
biological membranes, he also sought out Bloch, who became one of his
most important mentors.
The Culprit Was Cholesterol, and It Was Big News in

America
Endo learned that a high blood cholesterol level was thought by some
to be a major risk factor for heart disease. Cholesterol is a fatty, wax-like
substance found in the cell membranes of all tissues. Its name is derived
from the Greek chole, meaning bile, and stereos, meaning solid. It is
essential to animal life, providing structure and fluidity for cell membranes
over a range of temperatures. Cholesterol also plays a crucial role in the
production of bile, which helps in fat digestion, and of various steroid
hormones such as estrogen and testosterone. It plays other roles as well,
including the metabolism of the fat-soluble vitamins A, D, E, and K.
Ninety-three percent of all the cholesterol in the body is in cells, most
of which can manufacture their own supply. Only about 7 percent is
circulating in the blood at any given time. The cholesterol that circulates
in the blood comes from the diet or from the liver. Cholesterol is water-
insoluble and swishes through the arteries, veins, and heart by hitching
rides on proteins called lipoproteins to get where it needs to go. Low-
density lipoproteins (LDL) carry cholesterol from the liver to the rest of
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Akira Endo
the body. It is called ‘bad cholesterol,’ a misnomer because LDL serves

an absolutely necessary function; only when there is too much of it is bad.
The second type, high-density lipoprotein (HDL), is the ‘Good cholesterol’
because it carries excess or unused cholesterol from the arteries, where it
might do damage, back to the liver, where it is broken down and sent for
excretion.
Total cholesterol count includes both LDL and HDL. If it is less than
190mg/dl, everything is fine. If it is between 190 and 240, it is considered
borderline high. If it is above 240, it is considered high, and the
development of atherosclerosis is considered probable.
If there are too many LDL particles in the blood, cholesterol can stick
to the walls of the coronary arteries, triggering an inflammatory response,
causing pimple-like lesions to form on the artery walls, and eventually
blocking the free flow of blood—essentially building a dam in the
arteries. This buildup is called atherosclerosis. Calcification with plaque
and scar tissue occurs, and the arteries become less flexible, more rigid,
and resistant to the life-giving pulse of the pumping heart.
This buildup of plaque begins early in life. If left unchecked, the
reduced flow of oxygen-rich blood can eventually lead to pain in the heart
called angina. In addition, if the plaque breaks off, it can lead to blood
clots. If a blood clot cuts off enough blood, the heart is starved, heart
muscle dies, and a heart attack occurs. The same mechanism causes
strokes. A clot forms and blocks the flow of blood to the brain, which
causes cells to die due to lack of oxygen.
Endo learned that the culprit was cholesterol, and it was big news in
America. At that time in the United States, heart disease was the leading
cause of death. Inspired by Bloch, Endo began dreaming of discovering
a drug to treat high cholesterol.
According to Endo, Cholesterol is supplied to the body through two
routes: either through the intake of food where it is absorbed by the
gastrointestinal tract or through synthesis by the body, mainly by the
( 48 )
liver. When the former supply is unable to meet the required amount, the
latter compensates. However, when the supply is adequately met by the
former, the synthesis of cholesterol by the liver is suppressed. In this way,
the body has a mechanism to prevent cholesterol from becoming
excessive. By the end of the 1960s, it was already known that the synthesis
of cholesterol was controlled by HMG-CoA reductase.”
Bloch, along with Fyodor Lynen, had unraveled many of the details
of how the body synthesizes cholesterol for most of human history.
Obtaining enough dietary fat to survive was a problem for the vast
majority of people, and high cholesterol was not a significant concern.
Only in the last 100 years have countries’ entire populations had ample-
enough food resources to have too much fat in their diets. Through a
mechanism that is not clearly understood, about two-thirds of people in
industrialized countries have genes that cause the body to repress the
LDL receptor gene when they consume a high-saturated fat diet. With a
diet that encourages the synthesis of cholesterol but with no increase in
LDL receptors to remove the excess, cholesterol levels for two-thirds of
the population remain at a high enough level to make clogging of the
arteries epidemic.
People can’t change their genetics, but they can change their diets,
which influence cholesterol levels. However, managing cholesterol isn’t
simply a matter of will-power. Removing cholesterol from the diet often
results in a minimal decrease in blood levels of LDL. Removing saturated
fats has more of an effect, but many people possess a genetic makeup
such that even on a low-fat diet, they can’t cut their LDL cholesterol by
more than 10 percent, which is not always enough to prevent
atherosclerosis.
A Brilliant Hypothesis
Endo returned from America excited about doing research on a drug
to lower cholesterol. Then Sankyo made Endo as a group leader and had
complete freedom in research. He learned as many of the aspects of the
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Akira Endo
basic science as possible, then analyzed comprehensively. His thinking

was deliberate and clear, and he was exceedingly logical.
Endo did not know about the LDL receptors that removed cholesterol
(the role of LDL receptors was later discovered by Michael S. Brown and
Joseph Goldstein, for which they won the Nobel Prize in Medicine in
1985). However, he did know that the drugs used at the time to lower
cholesterol did so by increasing the removal of cholesterol from the body
or by inhibiting its absorption from food, that neither method was very
effective, and that both had severe side effects.
Endo wasn’t the first to think about inhibiting HMGCR, the crucial
enzyme in the cholesterol synthesis pathway. His brilliant insight was
developing a hypothesis as to where he might find a substance that would
target the enzyme.
Endo knew a lot about microbes. There was a theory that microbes
make antibiotics to kill other microbes that were foreign enemies or to
inhibit their growth. He thought it was possible that a microbe existed
which could inhibit cholesterol synthesis.
How do you set about finding a substance that has what must be a
rather rare trait—cholesterol synthesis inhibition? There were literally
tens of thousands of candidates, so Endo culled the less promising ones
in his mind. He needed an active substance that was safe enough for
continual ingestion because he realized that maintaining low cholesterol
might require lifelong therapy for many individuals.
There had been safety concerns with some antibiotics made from the
Actinobacteria. In contrast, some molds and mushrooms are edible.
While they had yielded considerably fewer antibiotics, the ones they had
produced, such as penicillin, were remarkably safe. Endo says, “I chose
to mold and mushrooms as microbes which had a strong possibility to
produce a cholesterol synthesis inhibitor; I did not choose actinomycetes,
although it was against the trend of those days.”
( 50 )
Ever logical, Endo remained pragmatic. “With that said, there was no
guarantee that I would be able to discover an HMGCR inhibitor, so I
decided to study a few thousand strains of fungi over a two-year period.
It was the research that was like a bet, and if I were unable to discover the
substance, I set out to find, I would then terminate my research.”
Treasure Hunting
While Sankyo’s Fermentation Research Laboratory director was on
Endo’s side, he made it clear there were financial constraints. He said,
“The key was constructing an experimental method to examine more
than 100 specimens at once and to reduce consumption of expensive
radioactive material as much as possible. I solved these two problems by
constructing a method which scaled-down an existing method, which
ordinarily took two days to finish, to be able to finish in one day.”
The First Run

There was no shortage of molds to investigate. Sankyo kept around
2,000 molds and mushrooms at the fermentation laboratory, taken from
the soil, dead leaves, and fruit. The lab continuously collected molds, and
Endo could buy additional ones from research institutes around the world.
Getting the molds would not be the problem. Analyzing them would be.
Step 1: Grow one hundred culture broths.
The first step was to culture a hundred species of fungi in separate
flasks for a week. Soon cloudy culture broths were everywhere.
Step 2: Mix and test radioactivity.
The first test was to see if any of the cultures inhibited cholesterol
synthesis.
Endo was pleased to find quite a few molds that inhibited cholesterol
synthesis. His hypothesis was correct:
Step 3: Discard molds that have logistical problems.
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Akira Endo
Not all the substances that demonstrated cholesterol inhibition were

potential drugs. There are numerous prerequisites for a potentially
therapeutic substance to be considered for actual human use. Obviously,
it must be safe. It must also be easily and cheaply reproducible.
Step 4: Discard broths that do not show early-stage cholesterol
synthesis inhibition.
Cholesterol synthesis is a multistage process. The active culture
broths were therefore tested for their ability to inhibit lipid synthesis from
mevalonic acid. If they did, they were acting on a later stage of the process
so that they could be discarded.
Step 5: Test for HMGCR enzyme inhibition.
Each potential broth was added to a solution containing the precursor
molecules that the HMGCR enzyme acts upon, mixed with rat liver
enzymes. To see if the broth had inhibited the HMGCR enzyme.
Step 6: Purify the active substance in the broth.
To isolate and purify the active substances in the molds, Endo used
various organic solvents as well as various chromatography techniques.
Organic solvents are stable carbon-based chemicals that, when added to
mixtures, can separate out various substances. Chromatography passes
solutions in one state (liquid or gas) through rows of chemical filters of a
different state. Substances pass through these media in different amounts
of time, allowing them to be isolated from each other.
Step 7: Discard known substances.
Some of the active substances Endo and his team isolated could be
identified as known substances. They usually discarded these since their
properties were generally known and could be looked up in books. They
focused their investigations on novel substances.
Step 8: Measure the inhibiting potency of the novel substances.
Endo and his team selected for further research only novel substances
( 52 )
that greatly inhibited the HMGCR enzyme. They measured potency by

the inhibitory effect per unit of weight.
Step 9: Test the substances for toxicity.
No matter how much a substance inhibited the HMGCR enzyme, if
it was unsafe, it could not be a drug. They tested all remaining substances
for toxicity by administering them to mice.
After 2,600 culture broths, three potential substances.

From May 1971 to January 1972, Endo’s team investigated 2,600
culture broths. “We were working hard every day until we got sick of it,”
Endo recalled. The lab was now cold, and they taped the windows with
packing tape to keep out drafts. They had found three strains of mold that
passed the first five tests. But when they isolated the active substances,
they found they had isolated oxalic acid and maleic acid. Endo said, “It
had been known for a long time that many fungi produced organic acids,
including oxalic, maleic, citric, and gluconic acids and a similar level of
inhibitory activity was recognized in all of these organic acids.”
In other words, it was a dry run. Endo recognized that their tests were
too broad; they needed to eliminate these known active substances before
running all the tests. Endo changed the team’s procedure by using
“extracts from which the organic acids had already been eliminated.”
The Second Run Via an Improved Method

Throughout the spring of 1972, Endo and his team went through
another 1,222 fungal strains using the improved method that eliminated
organic acids. They found four strains that had inhibitory activity, of
which two seemed promising. One of these came from parasites found on
rice and cucumbers. It turned out to be a known substance—citrinin.
However, as previously known, kidney toxicity was observed, and the
research was halted.
Endo and his team kept growing more of the blue mold, from which
they got a compound 1400 times stronger than oxalic acid and 300 times
( 53 )
Akira Endo
stronger than citrinin. They named it as ML236C, and by February of

1973, they had 162 mg of the purified substance. When tested on mice, it
showed low toxicity. The next step was to test it on rats but to perform
adequate tests; they needed 5 grams. At their current rate of production,
an impossibility. While the team continued its regimen of examining
other fungi (with 2,570 more possibilities chosen), they confronted the
entirely new problem of obtaining mass amounts of their promising
candidate. By that fall, they were brewing great quantities of the broth,
and when they analyzed it, they found two new active substances besides
ML236C—ML236A and ML236B. Endo and his group decided they
would develop ML236B. In two-and-a-half years they had analyzed
6,392 strains of fungi. Would the single isolated substance left, ML236B,
later to be named Compactin, prove useful?
The Cholesterol of Rats Does Not Fall Down

Some people ascribe the mental qualities of open-mindedness,
nimbleness, even childishness to scientists. Scientists themselves often
use the term “playfulness” to describe their approach. When confronted
with these descriptions, Endo thought of one playground toy to describe
his experiences in science—the seesaw. By now, Endo felt like a kid
riding a seesaw on the rise, looking up at the clouds floating by,
anticipating the instant of weightlessness just ahead of when the seesaw
would fling him upward toward the blue sky of success.
Discovering a new drug in medicine differs from discoveries in other
sciences in that the work is only half done when the discovery is made.
Most of the discovery work occurs in test tubes, so any new drug must be
proven to work in real living organisms. After that, it has to work in
humans. And, finally, it must be safe.
In January of 1974, Endo sent five grams of Compactin to be tested
for toxicity and efficacy. He was informed that there were no toxicity
problems. But it had not lowered the cholesterol levels in the rats at all.
Endo reeled unsteadily and could not believe what he was told. He said,
( 54 )
“The next moment, I was struck with deep sorrow that our research of the
past three years may have amounted to nothing.”
The next two years were difficult for Endo—his life’s work seemed
to be on the line. If that work was going to be revived, it was completely
up to Endo’s lab to do so, for everyone else at Sankyo was in favor of
abandoning Compactin. There was no question in his mind that the
studies had been performed correctly, so why had the rats’ cholesterol not
been lowered? “It was a basic assumption at that time,” Endo recalled,
“that what would not work on rats also would not work on humans.
However, after a short time, I started to have doubts about this basic
assumption.” Searching the literature, Endo learned that another
cholesterol-lowering drug worked on humans and dogs but also did not
work on rats. Endo said, “This gave us a ray of hope.”
While he and his associates confirmed that Compactin did not reduce
the cholesterol of young rats at all, they found it did reduce the cholesterol
of middle-aged rats by 20 to 30 percent for the first eight hours. But after
that, even if it was re-administered, Compactin had no effect on cholesterol
levels.
By January of 1976, two years after their triumphant discovery, Endo
and his team finally understood why Compactin did not work in rats.
Their five years of work looked fruitless; the prospects for Compactin
becoming a drug seemed remote. It was time to face giving up.
On the way home from the lab, one day, Endo stopped at Yomogi, a
restaurant, and a bar. At the bar, he recognized another Sankyo associate,
Noritoshi Kitano, a veterinary surgeon. Kitano was conducting
pathological research using laying hens. Endo, his mind ever at work,
quickly realized that if the eggs hens lay are so rich in cholesterol, it
meant they had to synthesize a lot of it. That meant they should have a lot
of cholesterol in their blood, just like humans.
“Kitano told me,” Endo said, “that he was going to clean up [kill] the
laying hens after the examination, which would end in the middle of
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Akira Endo
February. I asked him after I told him about the plight of Compactin,
could you administer Compactin to the laying hens before you clean them
up?’ Kitano, who enjoyed drinking and had a pleasant nature, promised
his cooperation on the spot.
Said Endo, “We fed commercial feed to the control group, and
commercial feed added with 0.2 percent of Compactin to the medication
group. My prediction hit the nail on the head, and within a period of two
to four weeks, the blood cholesterol of the hen fell by close to 50 percent.
During this period, a reduction of more than 10 percent was observed in
the yolk cholesterol. The laying hens stayed healthy during the
administration of the Compactin, and after the administration was halted,
no pathological abnormality was observed. My team and I shouted with
joy and toasted our success when we discovered the dramatic effect of
Compactin!”
In August, Sankyo put Compactin, the first of a class of drugs now
known as statins, back on track to become a drug. The seesaw had risen.
Research moved to dogs, which received different doses of Compactin.
The studies proved it to be completely safe up through doses of 250 mg
of Compactin per 1/kg of a dog’s body weight, but at 500, 1,000, and
2,000 mg/kg, some of the dogs’ liver cells developed minute crystals.
This did not alarm Endo because he predicted the dosage for humans
would be around 1 mg/kg. However, upper management at Sankyo
wanted only risk-free drugs, and the discontinuation of Compactin again
seemed inevitable.
A Clandestine Human Trial

Dr. Akira Yamamoto heard Endo speak about Compactin at the
annual meeting of the Japanese Conference on the Biochemistry of Lipids
in Kyoto in June 1977. Yamamoto had an 18-year-old patient with
homozygous FH who had severe symptoms of blocked arteries,
cholesterol deposits in her skin, and angina. She could not live a normal
life and, without treatment, would almost certainly die young. Desperate
( 56 )
for a better treatment, Yamamoto, of Osaka University Hospital,

buttonholed Endo. “My intention was not to test the efficacy of the drug,
but to cure the patient,” he later said.
Endo discussed the proposal with his supervisor, Arima. Arima
decided to provide a sample of Compactin to Yamamoto. Thus, began a
clandestine month of late-night telephone calls that originated only from
Endo’s home to avoid any overheard conversations.
The drug was effective, dropping her serum cholesterol by 20
percent. But after three weeks, she had muscle pain so severe that she
couldn’t walk, so the drug was stopped. Endo held on as the seesaw
swung down again. There were, however, some positive signs. A test that
listened to the noise in her carotid arteries (a means of discerning blocked
arteries) indicated less blockage, and her skin xanthomas, which are fatty
deposits caused by too much cholesterol, had begun to recede. He also
gave small doses to eight other patients for several months. Their
cholesterol fell by 30 percent on average. By that fall, they had begun
Phase I clinical testing. Compactin seemed on track to become a
commercial drug. It was a natural substance, and most people did not
exhibit the side effects the first patient had.
Japanese Corporate Ostracism

With the clinical testing begun, Endo thought he could finally relax
and turn toward new horizons. He moved to Tokyo University of
Agricultural and Technology. At that time, Japanese corporate culture
was very conservative. Many corporations viewed anyone who halfway
resigned (the Japanese term for retiring by one’s own choosing before the
traditional retirement age of 55) as disloyal. Endo said, “I had wished that
I would not have received the cold shoulder from my company because
of the significant contribution I had made in the development of statin.
My company’s prohibiting my fellow workers from helping me clear my
belongings from the office was just one example of this ostracism.”
The lonely Endo carried his own boxes out of his office after working
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Akira Endo
21 years and eight months for Sankyo. His retirement allowance came to
about $2,000 a month, the same as any other worker of a comparable
position. As Endo said, “I never received any reward from Sankyo for the
development of statin.”
I Doubted an Ear for an Instant

The commercialization of statin drugs makes for a great case study
in two entirely different business school courses. How a pharmaceutical
company, Merck, obtained its version of the bestselling, most profitable
drug in history would be a great study in how to maximize profits and
completely change an industry. It also would be a great study in business
ethics.
As Endo told the story, “In April 1976, the head office of Sankyo
received a letter from Mr. H. B. Woodruff, the executive administrator of
Merck [then Merck, Sharp, and Dohme] Research Laboratories. In
summary, the brief letter more or less said: We have read the announcement
of your patent application for Compactin. The biochemists at Merck
Research Laboratories have shown a keen interest and appreciate the
opportunity to make an evaluation.” The letter from Woodruff also
included the following leading statement: “We hope that as a result of
these exchanges, a product will be found which is suitable for license and
royalty return.”
Over the next two years, Sankyo sent Merck much of its research.
Endo said, “In the middle of August 1978, we received results: that the
testing of Compactin on dogs was extremely favorable. We also thought
that perhaps Merck was seriously considering joint development of
Compactin.”
As soon as they had seen the first contract with Merck, Endo and Dr.
Hiroshi Okazaki, his supervisor, warned the top brass at Sankyo that the
written agreement providing Merck with samples of Compactin was full
of loopholes. They were providing Merck with an immense wealth of
information. The discovery of penicillin had proved decades before that
( 58 )
one great drug idea can lead to the development of many similar drugs.
But the top brass at Sankyo trusted Merck. Merck informed Sankyo that
it had tested Compactin in combination with cholestyramine, another
drug, and hinted that it might patent the combination as the invention of
Merck alone.
Endo said, “The concomitant use test of Compactin and
cholestyramine would not have been a test for Merck to take the liberty
to conduct under normal circumstances. Even if the test had been
approved, the rights should have been shared between Sankyo and Merck.
However, due to the details of the confidentiality agreement, Sankyo
could not have made a complaint even if Merck kept the rights to itself.”
Then, completely full of aplomb, Merck asked for 300 g more of
compactin crystals. Endo felt as though his stomach were falling through
his feet. Here he was in the process of leaving Sankyo, and rather than
reaping the rewards for two decades’ worth of discoveries, he was being
tormented for doing so, and now he was learning that his drug might be
commercialized without Sankyo getting any monetary benefit for all his
years of work on it.
Within a month, his research at Tokyo University yielded another
statin. Monascus purpureus, a mold found in red yeast rice (red koji), was
found to contain a substance that was similar to Compactin. Endo named
it monacolin K. On February 20, 1979, he filed for a patent on it.
Later that year, Endo submitted an article about monacolin K to an
academic journal. Then on September 11, 1979, right after the article was
published, Boyd Woodruff of Merck showed up at Endo’s laboratory.
Endo related, “He said, ‘I read the article on Monacolin K. It is very
similar to what the researchers of Merck have discovered. I would like
you to offer us a small amount of crystal of Monacolin K to identify
whether they are the same substance.’ So, I doubted an ear for an instant.”
(Doubting an ear is a Japanese saying meaning I can’t believe my ears!)
Endo was stunned. Merck had already said that if it developed Compactin,
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Akira Endo
it would likely do so in combination with another drug, circumventing

any royalty payments. Now Merck was claiming that they had already
invented the drug Endo had been first to patent. Endo was a man of honor.
He composed himself. “I took to heart and handed him a few milligrams
of crystal.”
A month later Merck, wrote to tell Endo that its tests indicated it had
already discovered monacolin K before Endo had discovered it, although
they had not applied for a patent until four months after Endo had applied
for his. Merck had named it lovastatin.
Patent law differs between countries. Japan is one of about thirty
countries where the date on which the first patent is filed takes precedence
over the date of discovery. However, in the United States and some other
countries, the date of discovery is deemed as more important. In the end,
Merck did not commercialize Compactin. But it did commercialize
lovastatin in 1987 and profited from selling it as the first commercial
statin drug in countries that had favorable patent laws, under the brand
name Mevacor.
Endo summed it up: “Merck signed the nondisclosure agreement,
and they not only got secret information/documents and crystals of
Compactin repeatedly but also received our guidance for more than two
years. Furthermore, they discovered mevinolin [lovastatin] without
permission and have monopolized the right. It is as if we believed the
proposal and dated for more than two years but were betrayed.”
Statins Prove Cholesterol’s Role in Atherosclerosis

The idea that cholesterol was a risk factor for coronary heart disease
was controversial throughout the 1970s and 1980s. The evidence that
people with FH (familial hypercholesterolemia) had clogged arteries and
heart attacks as early as childhood was based on too small a data set to
suit many scientists. It would take large, long-term studies to prove that
high cholesterol causes the slow buildup in the arteries—atherosclerosis—
that leads to heart attacks and strokes. Endo’s statins were the first drugs
( 60 )
that had few side effects, and therefore could be given to people with
elevated but not immediately dangerous levels of cholesterol. The
breakthrough study was the Scandinavian Simvastatin Survival Study
(4S). It followed 4,444 patients with high cholesterol, some given a statin,
others not, in a double-blind trial, lasting more than five years.
Cardiologists all over the world awaited its outcome. The lipid study
provided significant evidence that lowering cholesterol saves lives.
What’s more, there was no increase in non-cardiovascular deaths,
meaning that statins had not harmed anyone. While there is still some
controversy about the importance of lowering cholesterol, there is
overwhelming evidence that statins are lifesaving drugs when given to
patients with a high risk of having a heart attack.
In the 1970s, Michael Brown and Joseph Goldstein discovered that
the liver removes cholesterol from the blood by way of LDL receptors.
Endo’s statin drugs were perfect for increasing LDL receptors.
In 1985, before statins were commercialized, Brown and Goldstein
received the Nobel Prize for their work on LDL receptors. In fact, thirteen
scientists who have devoted major parts of their careers to the study of
cholesterol have won the Nobel Prize. To Endo, there must have been a
sense of irony in the announcement of the award to Brown and Goldstein.
The Nobel Committee’s press release praised Brown and Goldstein for
finding new treatments for high cholesterol—with statins. It is as if the
person who describes a problem gets all the credit, while the person who
solves the problem is forgotten.
Brown and Goldstein are longtime fans of Endo and have said, “The
millions of people whose lives will be extended through statin therapy
owe it all to Akira Endo.”
Big Pharma
Endo and his team knew the molecular shape of Compactin thanks to
tests such as Nuclear Magnetic Resonance (NMR) and mass spectroscopy,
( 61 )
Akira Endo
amongst others. The shape consists of four parts: a head, a neck, a trunk,
and an arm. Their analysis had shown that the head is the part that binds
to and inhibits the HMGCR enzyme. They knew that changing the arm
part could limit the inhibition because when they initially discovered the
three similar compounds, the main difference between them was in the
shape of the arms. Drug companies had the tools to examine Endo’s
statins with just such precision. Soon, companies all over the world were
trying to synthesize statins, tweaking them just enough to obtain a patent.
Novartis developed Fluvastatin, Warner-Lambert developed atorvastatin,
and Pfizer developed atorvastatin (Lipitor). Sankyo and Merck each
developed lovastatin, calling them different names due to the patent
disagreement. Continued research allowed Merck to get around the patent
problems that prevented lovastatin from being sold in all countries. It
synthesized another statin—simvastatin—and named it Zocor.
Statin drugs were so popular that they transformed drug companies
into behemoth corporations. Profits could go not only to shareholders but
also into research laboratories, which churned out still more lifesaving
drugs. In 2005, of 10,000 drugs sold in the world, the best- and fifth-best-
selling drugs were Lipitor with $12 billion in sales and Zocor with $4
billion in sales. Merck’s stock price more than doubled in the seven years
after it introduced the first commercial statin.
Worldwide sales of statin drugs have far surpassed $100 billion.
Endo, ever riding the seesaw, never received any money from Sankyo or
any other corporation for any statin drug. Japanese ostracism has a long
memory. Endo’s name is not mentioned on Sankyo’s website to this day.
Statin drugs only became widely prescribed in the late 1990s. Their
full effect is years, perhaps decades, incoming, so they haven’t yet saved
the number of lives that other discoveries in this book have. Even so,
Amy Pearce estimates that they have already saved more than five million
lives from death by heart attack or stroke.
Today, millions of World War II veterans extend their lives with
( 62 )
statins, a drug discovered by a child of the new Japan they helped create.
Not only has Endo received no money for his discovery, but virtually
none of the old soldiers know his name.
Like a Seesaw
Endo and his wife raised three children. Today he is retired, living in
Tokyo. Through it all, Endo has kept good humor. In 2004, a Festschrift
(a German word meaning “celebration publication”) was held in Japan to
honor Endo. Many relevant scientific articles and memoirs of people with
whom he had associated were put together and published, and a dinner
was held in his honor. When it was Endo’s turn to speak, he said, “Today
I have good news and bad news. The bad news is that my cholesterol
levels have reached 240 mg/dl. The funny thing is that the doctor said,
‘Don’t worry! I know some very good drugs to lower your cholesterol.
Obviously, the doctor did not know the drug’s creator. He was awarded
the 22nd Japan Prize in 2006. Later he received the Lasker Award,
sometimes referred to as ‘America’s Nobel’ in 2008.
Through the years, Endo has become philosophical about his lack of
money. Endo recalled his goal beginning the research: “I did not start the
research to make money or become a big man. Since I was born as a
human in this world, I wanted to leave my mark before I die. I want to die
after I do at least one thing useful for the world. I could start the research
because I had such a thought. Therefore, we cannot measure the
contribution which statins made toward saving precious lives. Maybe we
should not simply convert ‘to be useful for the world’ into money. It is
something we cannot convert.”
Endo continued, “Nowadays, it is said that money is important.
However, we can discover the pleasure and value of life when we do
something for the world with a sense of mission. What I have done was
rather for the world than a Japanese company or Japan. It was needed all
over the world, so I was challenged for it. Especially now, it is called the
time of globalization. I want to tell young people the message that the
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Akira Endo
philosophy and sense of the value of doing something for the world are
more important than making money.”
( 64 )
3
William (Bill) Foege
(1936 -
The Eradication of Smallpox
BILL FOEGE grasped an arm above the elbow, held it firmly, pressed
the gun to the skin, angled it until it was still, pulled the trigger, and
released the arm. Then he pressed a hydraulic pedal with his foot and
grabbed another arm. The black gun he used was the size of a 9mm Luger.
A hose fell from it to the foot pedal, and a bottle was attached to the top,
ensuring that what came out of the gun saved lives rather than spent them.
It was 1964, and the 28-year-old Foege
(pronounced FAY-ghee) was on the South
Pacific island of Tonga. He was vaccinating
a long line of people with the Ped-O-Jet
gun.
But it was vaccination, he knew, that
was the key to preventing smallpox. Some
even held the audacious view that smallpox
could be eradicated. It was certainly a
disease worthy of elimination. Smallpox
had destroyed the Incas, the Aztecs, and
other American Indian nations, killing as
much as 95 percent of their populations. It Bll Foege and his wife in
had raged through Europe and America in Nigeria in 1966, dressed to
attend the wedding of a friend.
the 1800s. Even in 1964, it was still striking
Photo courtesy of David M.
an estimated ten to fifteen million people a Thompson, MD, who also worked on
the eradication effort.
year in forty-three countries, killing more
than two million. In thirty-three of those countries, it was endemic,

continually present in the population.
Smallpox is a poxvirus, one of a family of related diseases named
after the creatures most likely to contract them: camelpox, raccoon pox,
mousepox, monkeypox. There are two clinical forms of smallpox—
Variola minor, which is the less lethal form, but which scars many of its
victims: and Variola major, the most common form and the big killer. It
slays 30 percent of its victims, blinds 10 percent of the survivors, and
scars almost everyone. The viruses, which sometimes look like a dumbbell
under an electron microscope, are among the largest and most complicated
known.
Yet, the disease is entirely preventable thanks to the work of Edward
Jenner (1749-1823). He was a practicing physician at the age of 23,
already dedicated to understanding how to control the high mortality due
to smallpox (Variola) virus. His use of the technique of “variolation,” in
which live samples of this variola virus were used as inoculants and
already practiced in many areas of the world despite the high death rate
(10-30%) associated with the procedure, was taken by Jenner to the
empirical science over the next 40 years. His acute observational skills
and extensive knowledge of animal and plant biology led him to question
why cow maids exposed to the cowpox virus believed they were protected
from smallpox infection. In the now-famous example, in 1796, the local
boy James Phipps was inoculated with “matter” from the cowpox
secretions of cow maid Sarah Nelms and subsequently challenged with
the smallpox virus. By this early clinical trial, Jenner demonstrated
beyond doubt that exposure of humans to a related but benign virus
(Cowpox) could substantially reduce the risk of a later encounter with a
more virulent cousin(smallpox). Thus, vaccination was born. The term
virus as used by Jenner and others later should not be confused with the
modern understanding of viruses. At that time, the term was used to
describe an infectious agent that was extremely small and not visible in
the ordinary light microscope, as in the Latin virus and virulent, which
( 66 )
referred to poisons or toxins that cause disease or illness. Unknown to

Jenner, but providing the foundation for later hypothesis on infection and
immunity, the initial challenge with the cowpox virus would have
triggered a primary response leading to low- affinity antibodies that were
capable of cross-reacting with the smallpox virus. To gain extended
protection against smallpox, however, the individual had to be
subsequently challenged with the smallpox virus itself. This critical
insight of Jenner separated him from variolation “Folklore.” We now
know that this second inoculation would have invoked a secondary
antibody response and an associated antibody affinity maturation process
that would have targeted specific smallpox antigens, along with the
production of memory B cells, events that were necessary for conferring
early protection from life-threatening smallpox virus and for ensuring
lifelong immunity. Jenner’s cowpox virus had been passed down all the
way to Foege, mutating along the way into a slightly different virus but
still making whoever received it immune to its killer cousin, the smallpox
virus.
Nevertheless, many experts thought it was impossible to eradicate a
disease from the entire earth. After all, it had never been done before.
How can you go after a germ as small as a virus and destroy every single
one on earth? It would take vaccinating the masses of humanity to
eradicate a disease, but how do you freeze people in place so that you can
walk up to them and give them a vaccination? Children are constantly
being born; nomadic people are moving around; a small percent of any
population keeps its distance from the rest—itinerant workers and street
people, criminals and drifters, all fervently fleeing authority figures,
furtively existing underground. In addition, some countries have political
leaders who have no concern for their people and so refuse vaccination
programs, and in every country, there are groups who fear or don’t believe
in vaccination itself.
However, the cockeyed idealists argued smallpox was eradicable
because it infects no other species, only humans. If for a single two-
( 67 )
month period, no one on earth caught smallpox, then the disease would
either kill or run its course in whatever humans were already infected,
and that would be it—the virus would cease to exist. This had happened
in North America and Western Europe, so why not the whole world? The
key in the smallpox-free areas was mass vaccination. 1964 WHO advisory
committee concluded that vaccinating 80 percent of a population would
fail to eradicate smallpox. It recommended a 100 percent mass vaccination.
The Son of a Lutheran Minister

If anyone was an idealist, it was Bill Foege. He read the books of
Albert Schweitzer and imagined a life in the jungles of Africa. Foege
grew up in the Pacific Northwest to be a rail-thin, unintimidating six-
foot-seven-inch lover of humankind.
After medical school at the University of Washington, he went into
the Epidemic Intelligence Service at the Centers for Disease Control,
which sent him to India with the Peace Corps, and then to Tonga in the
South Pacific.
Following in Schweitzer’s Footsteps

When his Tonga tour ended, Foege immediately applied to Harvard.
He got in and, mentored by Weller, received a Master’s Degree in Public
Health. He came out as an epidemiologist, and even more of an idealist,
believing more strongly than ever in global health.
Still, under Schweitzer’s spell, Foege, along with his wife Paula and
their infant son David, boarded the Aurel—to Africa to work in a Christian
mission. The ship turned east toward the Bight of Benin and then coasted
to a stop in Lagos, Nigeria. The Foeges departed and drove inland. The
Lutherans had set up the clinic to serve the surrounding villages. The
clinic needed the Foeges to learn a minority language, Yala.
Foege’s work as a doctor at the clinic reinforced what he had learned
in India, that most people in the world do not present a single medical
problem. Whatever brings them to the hospital or clinic brings with it a
( 68 )
background of malnutrition, roundworms, hookworms, and a half-dozen

other conditions.
While Foege was far away in Nigeria, the Nineteenth World Health
Assembly voted in May 1966 to institute a worldwide smallpox
eradication campaign. The C.D.C. sent Henry Gelfand, a prominent
public health physician, to Africa to lay the groundwork for the eradication
campaign. West Africa had the highest rates of smallpox on earth and so
would need strong direction. Gelfand met Foege. It didn’t take him long
to recognize that Foege was highly intelligent, had wonderful people
skills, and was full of energy.
Ogoja
Sunday morning, December 4, 1966, was sunny and warm. The
fronds of the African oil palm trees were still except when a grey parrot
alighted on a branch, searching for fruit. People walked back from church,
their children running ahead. Foege was in the clinic when he was called
to the radio.
It was Hector Ottemiller, a missionary.
He put his medical gear into a leather shoulder bag, tucked himself
into the mission’s V.W. Beetle, and drove northeast through Ogoja
Province. When they arrived in Alifokpa, where the road ended, they
parked. It was twelve kilometers on to the village of Ovirpua, where the
smallpox cases were.
They arrived in the village of forty mud-walled houses covered by
drooping, thickly-thatched roofs. They were led to a hut, and a woman
came to the door. A couple of minutes later, a man emerged into the light.
His shoulders were slumped, and he moved with the hesitant gait of the
sick. It was immediately evident to Foege that the man had smallpox.
There were between 100 and 200 pustules on his face. He didn’t need to
look at the man further. The pustules were hard and were all at the same
stage of development, two of the major criteria for diagnosing smallpox.
Then Foege confirmed the man had smallpox; there was no treatment.
( 69 )
Foege knew well the course the disease had taken and what would
follow. The virus had entered through the man’s nose or mouth as he
breathed in virulent droplets from an infected person’s cough or sneeze.
A week, possibly two had passed with no symptoms, as the virus incubated
in the man’s cells. Then his body began to ache, maybe he vomited, and
then he developed a high fever of 101 to 104 degrees F. At this point, he
might have thought he had the flu. But then a rash with small red dots had
developed in his mouth and on his tongue. The sores had grown and
broken up, spreading the virus further into his mouth, beginning the most
contagious phase. Then the fever had subsided, and the man probably
thought he was getting better. But the rash spread to his face, then down
his arms and legs, and onto his hands and feet. By the third day of the
rash, the red dots had started rising. Maybe he had chickenpox? The fever
returned. Now the man’s bumps were turning into pustules, sharply
raised, a small indentation like a belly button in the middle, firm and
round. To the touch, it felt as though B.B. pellets lay beneath them. It
wasn’t chickenpox.
The next couple of weeks would be horrible. In addition to the fever,
the pustules would remain, slowly scabbing over. If the man lived, most
of his scabs would fall off during the third week, leaving pockmarks,
scars for life. He would be contagious until they were all gone. If there
were so many that they ran together so that they were confluent, survival
chances were diminished. In Africa, the mortality rate was typically 20 to
25 percent.
Quickly they surveyed the village—there were three other smallpox
cases. Foege began vaccinating the villagers.
David Thompson, also a young, idealistic doctor bent on saving the
world, and also a future Christian missionary, and Paul Lichfield, a
Mormon, had joined Foege. The three made up the smallpox eradication
advisors to the Ministry of Health for eastern Nigeria. They had radioed
out and learned there was no extra vaccine, immediately thwarting the
standard response they had been trained to put into effect when smallpox
( 70 )
was found—mass vaccination. The eradication effort was not scheduled

to begin until the next year, so ample supplies had not yet arrived.
They had to face the grim possibility of an epidemic.
“What do we do with the insufficient vaccine?” one lamented.
“What else can we learn about this outbreak?” another suggested.
They considered what they knew. One option was to dilute the
vaccine they had on hand. This had been tried a decade before in Liberia.
But they knew the take rate, the number of those who incurred an immune
reaction when vaccinated had been low. If they diluted their vaccine,
many supposedly vaccinated people would be unprotected.
Perhaps their vaccine was stronger? Doubtful. They decided they
would not dilute their preventative medicine. “If we were smallpox
viruses, bent on immortality, what would we do next to survive?” Foege
asked. They began imagining; they were the virus. The obvious answer
was to find someone else to infect, thereby ensuring reproduction.
How well did they know the virus? The first thing to do was find out
where it was, but they were in the heart of Africa. Communication was
poor.
The missionaries had other means of communication. They use ham
radios. There were fifteen missionaries in the surrounding area. The three
eradication officers laid out maps of Ogoja, and when the radio crackled
to life, they were relieved. They could now take their first action. They
asked the other missionaries if they would help, and one after another
agreed. The plan quickly coalesced. Each missionary would send
someone, generally by bicycle, to the villages around them to record if
any village people were sick with smallpox.
In one day, they had surveyed a large area, each recording the
smallpox incidence in two to seven villages (totaling almost a hundred
villages), representing some 20-25,000 people. The missionaries had
found six cases. The next day, vaccination teams were sent out to
( 71 )
vaccinate the people close to each case.

The three advisors knew that smallpox was highly contagious, and
feared that the cases found so far might be the first of a mushrooming
epidemic, so they kept strategizing. Now that they knew where the virus
had been several weeks earlier when the sick had to have been exposed,
could they draw its vector on a map and predict where it might go next?
Talking with both missionaries and the villagers, they ferreted out
two important means of transmission. The virus would most likely travel
toward family members and marketplaces, where people in African
village life connected.
Every night at 7 PM, the missionaries reported in. Over the week,
only four new cases were reported, and they began to feel more confident.
During the second week, an additional twelve cases were found—not so
good. The third week brought nine new cases. What’s more, the cases
appeared in two of the three areas they had vaccinated. They had guessed
right. Now they had to wait to see if they had reached the villages in time
to stop the virus’s spread throughout the populations.
During the fourth week, one missionary after another reported no
cases. With each day, hope grew brighter. There was no epidemic. As
more weeks passed and additional vaccine supplies came in, they stepped
up vaccination in the area. Then Foege had an interesting insight: ‘We
might feel very good about every vaccination we were doing, but in the
absence of the smallpox virus, it was a wasted effort.’ The vaccines might
be important when smallpox came through in later years, but in the short
term, they were throwing water on the ground that was not on fire.
Foege had been trained in epidemiology and was not about to let this
data set go unexplored. He kept records and pored over the results. He
calculated the number of people they had vaccinated in order to stop the
first outbreak—7 percent. That was hardly mass vaccination. No herd
immunity could have been conferred by what they had done. Foege
enjoyed data and loved elucidating patterns. He believed in a cause-and-
( 72 )
effect world. What they had accomplished was no fluke. There had to be
a reason. And the first man with smallpox Foege had seen in Ovirpua? He
lived.
A Firefighter Discovers a 6 Percent Solution to a

100 Percent Problem
Over the following weeks, Foege devoured all the information he
could find on smallpox. One thing, in particular, he found curious was
that the number of smallpox cases they had seen was small. “Why was
this,” Foege wondered, when “folklore and the textbooks presented a
disease of rapid transmission.” He explained, “The textbooks kept saying
that this was one of the most contagious diseases. We believed them until
we started the epidemiology. We went to villages where smallpox had
broken out and found that there hadn’t been a case for fifteen or twenty
years. This is unlike measles, where every other year, you expect an
outbreak. So gradually, we developed the idea that smallpox really
comprises islands of infection that move around slowly but is not
something that covers an extensive area like a country all the time. During
the smallpox season in West Africa, maybe only one percent of the
villages contain cases at any one time.”
Parasitic pathogens evolve clever tactics to survive. If they kill their
hosts too rapidly, they will not have any place to live. It is, therefore, to
their benefit to allow a host to survive long enough that they can multiply
and then jump to another host. When syphilis first appeared in Europe in
the 1490s, it killed within months. But over time, it evolved into a
pathogen that took decades to kill. To survive, it only needed to pass itself
on to two or three other people and could do so slowly. Foege realized
that the tenacity of the virus in continuing to infect new generations
within a household was confused with high transmissibility.
Foege had spent his college summers fighting fires in the Colville
and Wallowa National Forests in the Pacific Northwest. His trainers had
pounded into him and his fellow firefighters the principle that a fire
( 73 )
can’t burn without oxygen or fuel. He drew upon that analogy now.
During forest fires, dirt was shoveled on flames to block oxygen, and
firefighters built a perimeter of scraped dirt around fires to block
access to fuel. Foege wondered if he and his colleagues could not do
the same with smallpox. Susceptible people were the fuel of smallpox,
and if they could vaccinate enough people, the virus would be snuffed
out. They could also scrape away a perimeter of fuel around the islands
of smallpox, leaving the virus to burn out, with nowhere to spread. In
fact, the perimeter they needed to scrape only had to be a few feet wide.
Studies would show that smallpox was usually transmitted due to close
range (within six feet), prolonged contact, usually of more than seven
days. Foege realized, “It was necessary, of course, to prevent the virus
from traveling out of that protection bubble on contaminated clothes, as
when a fire crosses a fire line. The basics for breaking transmission of the
virus were remarkably simple and similar to fighting forest fires.”
Foege had in mind a radically different strategy to deal with smallpox.
If smallpox was not ferociously contagious—even if it was extremely
dangerous—then there was time for teams of smallpox vaccinators to
react. And, if outbreaks of smallpox were treated as islands in a population
rather than as endemic in the populations, mass vaccination would not be
necessary.
Foege studied smallpox outbreaks in eastern Nigeria and discovered
he could draw maps that showed smallpox spreading seasonally from the
north to the south each year. Outbreaks decreased in wet months and
increased in dryer months. This suggested that vaccinating when the
incidence of transmission was lowest might break most of the chains
of infection, drastically shrinking the potential islands of smallpox.
Foege’s analysis was spot on, and later studies would provide ample
evidence to back up his conclusions. They would show that all over the
world, “at any one time a very small percentage of villages (often 1
percent or below) was actually harboring the disease.” Smallpox really
was a disease of isolated islands in a population. Studies would also
( 74 )
show that vaccination on the day of exposure, or even a day or two

afterward, could still provide protection. This was because the
incubation time of the virus in the vaccine was faster than that of the
pathogenic smallpox virus. So, the race to infect could be won by the
vaccine virus, conferring immunity before the deadly virus became
full-blown. It is easy to think that science only occurs in laboratories or
behind desks. And indeed, the eradication of smallpox did reflect some
of that. Historians highlight four scientific advances that made the
eradication of smallpox a real possibility. The first was the development
of an adequate vaccine. While a smallpox vaccine had been used for
more than a century-and-a-half before the eradication effort began,
it was not portable or stable in hot climates, where many people
needing vaccination lived. Transporting refrigerated vaccines to
much of the world was a logistical nightmare. The answer was the
freeze-dried vaccine, which had been developed in the 1920s.
Unfortunately, it was often contaminated by bacteria. Phenol had been
added to it, which destroyed the bacteria, but often damaged the virus
making up the vaccine as well. Leslie Collier, of the Lister Institute in
England, solved this problem by developing a stable unrefrigerated
vaccine. He added peptone, a soluble half-digested protein, which
prevented damage to the virus. The resulting freeze-dried vaccine
could remain stable for years at temperatures of up to 113 degrees F.
The dry powder was suspended in a 40 percent solution of liquid
glycerin when it was time to be used.
Engineering advances were also necessary in order to deliver the
vaccine effectively and efficiently. Before the invention of the jet
injector, such as the Ped-o-jet Foege used, the vaccine was scratched
into a person’s arm using a needle or a rotary lancet. This meant it
was not precisely administered, so it often failed to cause an immune
reaction. The jet injector Ismach developed provided vaccine take rates
of close to 100 percent and was to be used throughout the Western Africa
campaign. In 1961, Benjamin Rubin, a researcher for Wyeth
Laboratories, had the ingenious idea of turning a sewing needle
( 75 )
upside down and cutting into the eye of the needle, leaving two sharp
prongs. The prongs were just far enough apart to hold the exact
amount of liquid vaccine needed due to capillary action. The
bifurcated needle, as it became known, also had carefully shaped
prongs that prevented it from being stabbed too deeply beneath the
skin. Virtually anyone could be trained to pick it up, dip it into a
solution of vaccine, then insert the vaccine under the skin of another
person. The bifurcated needle was the perfectly engineered solution
for worldwide vaccination in any environment since it was completely
mobile, inexpensive, and could be used with no instructions.
Science can, however, occur outside of a lab as well, and the fourth
scientific advance was the development of an effective strategy for
vaccinating populations at risk. At its heart, science is based on inductive
logic—the examination of detailed data to find general principles.
Epidemiologists take vast arrays of information about a disease and its
presentation in people and seek out patterns in that information. Foege
was doing just this in the field in rural Nigeria. However, it wasn’t as
simple as sitting at a desk and going through the data because he didn’t
have complete data when he started his analysis. One principle of using
inductive logic is always to seek out more data. Old data might be wrong
or may leave out important variables, so look, learn, iterate: look, learn,
iterate. Foege had identified some incorrect assumptions about smallpox
and had also discovered some new variables. He was a powerful,
unceasing learner, and he would continue to look for more clues about
smallpox as time passed.
While Foege thought his new containment strategy might be more
effective than mass vaccination, he understood that just as deductive
logic has logical fallacies, we are all familiar with, such as contradiction,
inductive logic also has its fallacies. The most common one is basing
conclusions on anecdotal evidence—on one or two isolated incidents.
This is a common fallacy of groups opposing vaccination. Vaccines did
not spring up as perfect preventative medicines. Many early vaccines
( 76 )
were flawed and caused a small amount of sickness and even death. The
question a parent must face is: Should their child get vaccinated when
there is a one-in-several-million chance of dying from vaccines?
Based on the anecdotal evidence of those few occurrences, some
parents refuse vaccinations. Others recognize that those odds, while
real, must be compared to the chance of sickness and death from the
diseases vaccines protect against, which can kill at a substantially
higher rate. Nationwide, the few deaths that occur due to vaccines pale
in comparison to the number of deaths the vaccines prevent. This is an
example of how statistics have come to be so important in science.
Statistics allow us to measure risk based on data sets that are
imperfect or incomplete, as so many of life’s data sets are.
The epidemiologist in Foege understood that his new strategy, which
he named ‘Surveillance and Containment.’
Surveillance and Containment Is Tested

The leaders of the smallpox eradication campaign had already
divided Nigeria into regions. Eastern Nigeria was to be coordinated by
Foege, Thompson, and Lichfield, who would work with a team of
Nigerians from the eastern Ministry of Health. As January came and it
became clear they had stopped smallpox in Ogoja, Foege could not get it
out of his mind how well their very different strategy had worked. He
became more and more convinced that mass vaccination was not the
correct strategy. Vaccinating the 12 million individuals in their territory
would be a huge challenge. It seemed quite plausible that the 20 percent
they were predicted to miss would be the most likely harborers of the
virus. If so, the next year’s smallpox caseload might well be the same as
the previous year’s.
Foege and his colleagues began discussing their new strategy of
surveillance and containment with Dr. Anezanwu, the director of
smallpox for eastern Nigeria. Foege said, “We talked about trying a
surveillance approach of figuring out where the smallpox was and then
( 77 )
concentrating on those areas. It’s to the credit of the Ministry of Health

people that they were willing to try something new.”
There was definitely risk involved for those in the Ministry of Health.
If the Americans were wrong, they could simply leave the country. If
Anezanwu were wrong, he would have to live with the results. It might
ruin both his career and his reputation if his decision set back smallpox
control. Eventually, it was agreed that the eastern Ministry of Health
would use Foege’s surveillance and containment strategy. When an
outbreak was discovered, the three team members, along with the
Ministry of Health officers, would race to the site, verify the presence of
the disease, and then train the local people how to record cases, vaccinate
people, and search out more cases. The three-team members played the
role of military generals, spreading out maps and drawing circles where
they predicted the virus might go so that they could vaccinate people in
these places in advance.
Sometimes a single smallpox case was reported; sometimes, there
were many. One-time Foege saw 1,000 cases in one week.
When smallpox hit the state capital Enugu, a decision had to be
made. All the trained teams were busy vaccinating in the east. Should
they pull teams out to treat Enugu or finish the jobs they were doing?
Thompson remembered the argument and Foege’s position: He wanted
to pull the teams out of Ogoja to vaccinate Enugu, which I was reluctant
to do. But we did just that. Foege insisted on hitting every outbreak. If a
cinder escapes from a forest fire, it must be chased down before it can
start another big fire.
They continued to use a regimen of surveillance and containment,
and the vaccinations went forward.
In western Nigeria, the Ministry of Health had barely gotten
organized—officials were still preparing for a mass vaccination effort. In
comparison, workers in the eastern region were racing all over the
country, throwing vaccines at every little outbreak. The national
( 78 )
government had barely used any of their supply of vaccine, while the east
was quickly doling theirs out.
What is a military without bullets or a doctor without medicine?
They had been making such rapid progress, and now suddenly, they had
to quit. When a new outbreak of smallpox sprang up, they had no vaccine.
Smallpox would retain its reservoir in the population, grinding out deaths
for another year.
A Strange Mission for a Missionary

This was not acceptable to Foege. He had a new vaccination strategy
to prove. He knew it was working—if they stopped now, how would they
ever prove their method was effective? Foege and a colleague had an
idea.
It was 451 kilometers to Lagos, and the drive there was fraught with
tension. Their intended mission was something Foege would never have
imagined doing when he first arrived in Africa two years before. That
night they mapped out a plan. The next morning, they returned to the
warehouse, and while one of them kept the guard busy, the other slipped
back to the vaccine supplies and requisitioned an order, loading their
truck full of boxes. The one-time missionary had resorted to stealing.
Suddenly a roadblock confronted them. Tanks and trucks were lined
up in a show of power. Was it the West or the East manning the roadblock?
Foege and his colleague pulled up, and a guard approached them. He was
Ibo, from the East. No one got over the bridge at night; no arms would
cross the river. The guard got his boss, who got his boss, and slowly they
moved up the chain of command. Finally, they talked to the commanding
officer. They explained they had supplies for smallpox vaccination to
take into Enugu. The boxes were examined and found not to contain
arms. And the two smallpox warriors drove triumphantly across the
bridge, back into the east, carrying vaccines that would soon save lives.
But the vaccine did get through and made it to the last outbreak of
smallpox. There was no communication with the eastern Ministry of
( 79 )
Health for a long time, and no one was checking on smallpox cases. Later
they did learn, though, that there were no more smallpox cases in the east.
The last supply of stolen vaccine had done the job. In only six months’
time, using the new strategy of surveillance and containment, Foege and
his colleagues had wiped smallpox completely out of eastern Nigeria by
vaccinating only 6 percent of the population.
Back at the C.D.C.

Back in the U.S., in Atlanta, Foege had confirmation of his
surveillance and containment strategy. Foege had no trouble selling it to
the C.D.C.
The program began in September of 1968. In one country after
another, within nine months of implementing the surveillance and
containment strategy, smallpox disappeared. The success propelled
Foege to become the director of the C.D.C.’s smallpox unit.
Colossal India
By 1973, the thirty-three countries with endemic smallpox had been
cut to four: India, Pakistan, Bangladesh, and Ethiopia. India was the most
vexing. With a population of 600 million—India had over a half-million
villages and 2,641 cities. A concerted mass vaccination effort was begun
in 1962, yet five years later, more smallpox was being reported than at
any time since 1958. How could mass vaccination work when every day
there were another 70,000 infants born?
From Atlanta, Foege wanted to suggest new tactics of surveillance
and containment for India but found himself too far away. “For several
years, I found myself very frustrated,” he says. “We just couldn’t seem to
get a foothold in India that would work. Some of our best people from
Africa went there. They came away so discouraged, telling us that it’s
never going to work there. I finally went to Dave Sencer, director of the
C.D.C., and I said, ‘I don’t know if it’ll work or not, but I do know I can’t
be criticizing from the sidelines. So, I asked him if he would assign me
to India, and he did.’
( 80 )
In August of 1973, Foege joined the WHO team. “I lived in New

Delhi,” Foege said. “The two states that I took primary responsibility for
were Uttar Pradesh and Bihar. They had by far the highest concentration
of smallpox in India. It was a daunting project. Four states, cutting a
swath across India’s northern border with Nepal, provided more than 90
percent of India’s smallpox cases. Twenty-two surveillance teams would
organize searches city by city, village by village, each team covering 10
million people.
Foege said, “When we did our first big search in India in October
1973, in six days’ time, our search in four states found ten thousand new
cases of smallpox that no one knew existed.
The Indians had their best minds working on the problem, too. These
included M.I.D. Sharma, a premier epidemiologist who had not taken a
vacation in twenty years and had connections all the way to the health
minister in the government. Also assisting were C.K. Rao, R.N.Basu,
R.R. Arora, Mahendra Singh, and Mahendra Dutta.
One of the big lessons they learned was psychological. “To start
with,” Foege said, “it seems to make sense that the searchers should
always have vaccine with them, and when they find a case immediately
vaccinate around them. We found out that it doesn’t work. The reason is
that approach biased a searcher to feel they had to do more work if they
find a case than if they didn’t find a case—you’re inducing them not to
find a case. You actually have to divide the workload. Searchers only
search and report on cases, and then containment teams go in to vaccinate.
Initially, Foege and his team instructed the vaccinators to vaccinate
the family of each infected person and twenty households around the
outbreak. But that didn’t work, and the number of cases kept growing.
They could barely get to a case before they needed to go on to another.
In May of 1974, there were 11,600 new cases in one week in one
state, resulting in 4,000 deaths. In the state of Bihar alone, there were
8,664 infected villages. It was the same month India detonated its first
( 81 )
atomic bomb, and plenty of pundits noted the irony that they could smash
the atom but could not smash smallpox.
The surveillance and containment effort came dangerously close to
imploding. At one meeting, a minister of health insisted on giving up on
surveillance and containment and going back to mass vaccination. An
Indian doctor stood up and said he had grown up in a poor village: “When
there was a fire, the villagers poured water on the burning hut, not
on all the houses.” Minister relented and gave them one more month.
Finally, in June of 1974, there were fewer cases than in the previous
month. In July, fewer still. The numbers began reflecting the effects of all
of their work. Then the numbers really started dropping. In late 1974, the
active search program was expanded, eventually including 33,000 district
health personnel and more than 100,000 field workers going house to
house, searching for smallpox cases. They began offering monetary
rewards for anyone finding a smallpox case. This brought the public into
the program, and they reported 11 percent of all the remaining cases.
January 1975 only turned up 1,010 smallpox cases in all of India. In
February, there were only 212.
The last case of smallpox in all of India occurred in May of 1975.
“I think the story is so incredible in India,” I don’t think the Indian
government would have ever have made a major decision without those
of us who were now assigned through WHO agreeing, and we from
WHO would never have made a decision without the Indians agreeing. It
was simply a unit working together.”
Bangladesh was the next country to be attacked with surveillance and
containment, and then finally Somalia. The last case of naturally occurring
smallpox in the world was recorded there on October 26, 1977. Ali Maow
Maalin, a 23-year-old man, recovered—but the virus was dead.
Bill and Melinda Gates

After India, Foege returned to the C.D.C., eventually directing it
( 82 )
from 1977 to 1983. He moved on to Emory University in Atlanta as a

distinguished presidential professor and served as executive director at
the Carter Center, formed by former President Carter to support
humanitarian efforts globally. In 2000, when Bill Gates, the richest man
in America, and his wife Melinda were setting up a foundation, Foege
was asked to be a consultant.
The Bill and Melinda Gates Foundation chose as its goal to “bring
innovations in health and learning to the global community.” Warren
Buffett later joined in, giving substantial sums to the foundation—
together, they have contributed more than 38 billion dollars. Foege has
been an advisor and cannot be more complimentary of the role the Gates
is playing in global health: “I think a hundred years from now when the
history of global health is put into some perspective, it’s going to be clear
that the tipping point was about 2000. It’ll be due to Bill & Melinda
Gates. They’ve changed everything. They’ve made it possible for people
to think in terms of better tools, delivery of those tools, and finding the
right resources. And they’re absolutely serious about the fact that
everyone should have the same chance at health no matter where they’re
born.”
Back on the Streets of New Delhi

Other historians might conclude the tipping point occurred three
decades earlier. The eradication of smallpox showed what humankind
can accomplish when people care enough for their neighbors to use
science to help every human on earth and every human who will ever be
born.
There were economic benefits, as well. The U.S. was spending 150
million dollars a year to keep smallpox out of the country in the 1970s.
Ever since smallpox was eradicated, that money can go to other uses. In
fact, those savings have virtually paid the U.S.’s contribution to the WHO
every year since. Dr. Halfdan Mahler, the director-general of the WHO
when smallpox was eradicated, said that the eradication program was a
( 83 )
two-billion-dollar gift from the poor nations to the rich because it was the
latter that benefited the most financially. With smallpox eradicated, the
wealthy nations could pursue global markets with abandon. Amy Pearce
estimates that more than 122 million lives have been saved by the
eradication of smallpox—lives that also contribute to economies around
the world.
How big a deal was the eradication of smallpox? When a young
beauty contestant is asked what she wishes for in the world and answers
‘peace on earth,’ her naiveté is laughed at. Yet many of the same people
who laugh sincerely believe that if someone had stopped World War I,
World War II, the Vietnam War, the Holocaust, and all genocides, that
individual would be celebrated all over the world. Or would they? To put
the eradication of smallpox in context, smallpox killed more people in the
twentieth century (300 million) than all of the wars, terrorist acts,
genocides, and political famines in the entire world combined (188
million, a figure which includes both combat and non-combat deaths).
The eradication of smallpox, by measurement, was one of the single
greatest achievements by humankind in history. Yet, how many know
the names of the scientists who contributed the key insights that made it
possible?
Most accounts credit the eradication to five scientific advances:
cowpox vaccination, pioneered by Edward Jenner; freeze-dried
vaccine, perfected by Leslie Collier; the jet injector, engineered by
Aaron Ismach; the bifurcated needle, engineered by Benjamin
Rubin; and the surveillance and containment vaccination strategy,
developed by Bill Foege.
Ask him about his own personal satisfaction. Then sit quietly and
listen to the poetic image he conveys: “I’ve been going to India now for
40 years.” Speaking of when he first went, he says, “I was very conscious
of how many people on the streets had pockmarks.” A decade later, when
he was running all over the country trying to eradicate smallpox, he still
saw pockmarks, the telltale markings of those who had survived smallpox.
( 84 )
Then ten more years passed, and he returned to New Delhi. Vividly, he
remembers standing on the street and watching the people pass (India is
a country of people; people are everywhere). As he watched children go
by—some laughing, others quietly serious—not a single one had a
pockmarked face. Then later still, in the 1990s, he returned to New Delhi
and again stood on a street and watched the masses of humanity pass—
now not a single person under the age of twenty had the pockmark scars.
Just recently, he was there again, standing on the streets, looking at the
faces, and now no one under the age of thirty had pockmarks. “I think to
myself; this is a change that almost everyone walking down the street is
unaware of. There is just no memory. Isn’t that great? It’s fun to see, and
I still get pleasure out of seeing the tangible results.”
( 85 )
4
David Nalin
(1941 –
ORT: A Revolutionary
Therapy for Diarrhea
IT WOULD be hard to find a

humbler, more ghastly way to die
than by cholera. The typical cholera
patient, usually a child, dies amid
vomit and excrement in pain and
stupor. Diarrhea—watery and fishy
smelling—is the most important
symptom. The disease is usually
Dr. David Nalin turning off an IV so
found in South Asia, with the cholera patient can begin drinking
communities in India, Pakistan, and the ORT soution (at a trial in Dhaka,
Bangladesh, which are often the Bangladesh).
Photo courtesy of Dr. David Nalin.
centers of epidemics. Even in
modern times, it can be a gruesome killer. In the 1980s and 1990s, cholera
struck refugee camps in Africa and returned to South America after a 70-
year absence. Caused by a bacterium, V. cholerae, which attacks the
small intestine, it has the distinction of being one of the fastest killing
diseases known. It is possible to have the first symptom of cholera,
diarrhea, and, then, be dead three hours later. Usually, however, it takes
several awful days for death to come.
Cholera is only one of many causes of diarrhea (from the Greek word
for “flowing through”) but, whatever the agent, the symptoms can rapidly
David Nalin
lead to dehydration and death. In the early 1900s, before chlorination of

water and the installation of sanitary sewers, diarrhea was the fourth-
leading killer in the United States and the principal cause of death among
children. According to the CDC, there are 1.5 billion episodes of diarrhea
worldwide annually, and more than 1.5 million deaths, each year, are
caused by this very human indisposition. The standard treatment, until
recently, relied on injecting intravenous (IV) fluid to replace lost bodily
fluids and salts, but this was cumbersome, expensive, and rarely available
in the tiny villages of Pakistan or the slums of Dacca. Little could be done
in these places for the children afflicted by cholera and other diarrheal
illnesses. Then, the young American researcher David Nalin and his
colleagues developed a simple, effective treatment that could be used
anywhere, by ordinary people with no special training. Their treatment
completely changed the landscape of public health in the developing
world in a way that almost no other discovery has.
The Philadelphia Buddha

David Nalin lived in a modern house tucked away in the
hills west of Philadelphia, USA. Traveling throughout the world
in the service of science and public health, he filled his house
with shelves of brass and copper pots and statues and covered his
walls with old photographs of Indians, Thais, and Tibetans. One
of the statues, in particular, reflected the spirit of Nalin. It was of
a Bodhisattva, a Buddhist saint who postponed Nirvana to help
others through adversity.
Nalin was instrumental in making death by cholera and other diarrheal
diseases unnecessary in much of the world. His was a story of human
fallibility, brilliant research, and people who refused to take “no” for an
answer. It is of discovery, so big that a UNICEF’s special report, in 1987,
had said: “No other single medical breakthrough of the twentieth century
has had the potential to prevent so many deaths over such a short period
and at so little cost.” It is also one of the science’s least-known major
discoveries—few have heard of it—and goes by the acronym ORT.
( 88 )
The enormous success of vaccination approaches to disease

prevention and cure enabled through the frontier-pushing work of Jenner,
Koch, Pasteur, and others was to have a major impact on mortality in
domestic animals and, more importantly, the human population,
particularly the fighting soldier, in the early 20th century. In 1854, John
Snow, known as Father of Epidemiology, linked cholera and contaminated
water when hand pumps were set up in the Soho area in London to supply
drinking water. Three decades later, the German physician Robert Koch
tracked the disease with his microscope to the villain—the bacterium
Vibrio Cholerae. Koch also set up the sanitation rules that are still used
today for controlling epidemics. Thanks to Koch’s protocol, the sixth
pandemic that began in 1899 had little effect in Europe, although cholera
remained endemic in Asia. Before modern medicine, there was no
treatment for cholera other than to treat dehydration.
Treatments
Just hearing the word cholera sends shivers through people all over
the world, and every time a natural disaster like a tsunami causes mass
flooding, newspapers warn of the threat of cholera due to water
contaminated by the corpses. Nalin explains that this is a myth—outbreaks
usually begin in coastal estuary areas simultaneously with zooplankton
blooms, which contain the bacteria. Animals eat the plankton and,
humans eat animals or drink contaminated water and become deathly ill.
The bacteria then ride human feces into the sewers. If the sewage
contaminates water systems, cholera can spread rapidly. It is rare for the
disease to be transmitted from one person directly to another, as it is not
generally contagious.
Essentially, cholera was and is an Asian disease, but

sometimes it escapes
In 1831, while Europe was reeling from a cholera pandemic, the Irish
doctor W. B. O’Shaughnessy told the participants at a medical meeting
that the potpourri of treatments being used at the time didn’t work. The
death rate for cholera ran as high as 70 percent.
( 89 )
David Nalin
By analyzing the blood of a cholera patient, O’Shaughnessy found

that the patient had lost not only much water but much of the salt required
for life, blood being a saline solution. His recommendation, published in
The Lancet, was to insert a goose quill needle into a vein and inject a
tepid saline solution.
The medical profession largely ignored O’Shaughnessy’s suggestion
for fifty years, but by the late 1800s, medicine began to lay down a
scientific foundation, and intravenous saline solutions proved their worth
repeatedly, cutting the death rate of cholera to 40 percent. In the early
1900s, further refinements to the IV solution dropped the death rate to 20
percent. Intravenous therapy worked because fending-off dehydration for
enough time allowed the body’s immune system to rev up and eliminate
the infectious agent.
With the arrival of antibiotics in the 1940s, doctors thought they
finally had a way to fight the disease itself, rather than the symptoms.
Antibiotics did kill the bacteria that caused cholera. Unfortunately,
people with cholera could become dehydrated so fast that antibiotics
alone could not save the patient. A vaccine was also tried but did not
prove to be very effective.
In the 1940s, Daniel Darrow of Yale became the leading expert on
the use of IV solutions for dehydration. He came up with a good
approximation of what the body was losing and what needed to be
replaced. In a series of experiments, he showed that the IV replacement
solution should include sugar, glucose, salts, potassium, and sodium
chloride.
In 1948, Robert A. Phillips, a Navy doctor, successfully used
Darrow’s formula to cut the mortality rate of cholera to below 5 percent.
The problem was that IV therapy required doctors, nurses, equipment,
and sterile procedures to prevent infection, and in most of the places
where cholera was endemic, that was not practicable or even possible.
What was needed was a way to rehydrate patients without using modern
( 90 )
medical technology. Myriad concoctions—vegetables, fruits, carob flour,

bananas, saltwater—were devised to rehydrate patients orally in parts of
the world without hospitals. But, most of what went down came right
back up again or got excreted in the flow of diarrhea, so they worked no
better than drinking water. Cholera epidemics in the developing world
continued to be devastatingly deadly.
Sambunath Dey (1915-1985) was an Indian medical scientist and
researcher who discovered the cholera toxin, the animal model of cholera,
and successfully demonstrated the method of transmission of Cholera
pathogen Vibrio cholerae. The seminal work of De in Calcutta, during
1950-1960, breached several qualms pertaining to the enteric toxin
produced by bacteria, including Vibrio cholerae and Escherichia coli. His
major discovery of cholera toxin in 1959, in the cell-free culture filtrate
of Vibrio cholerae, stimulated a specific cellular response leading to
severe water and salt loss. This discovery promoted research to find a
treatment aimed directly at neutralizing the cholera enterotoxin. Research
has been redirected to find a vaccine that would spark the immune system
to fight the enterotoxin specifically, rather than the bacteria.
David Nalin, born on April 22, 1941, is a New York native and one
of the long lines of illustrious graduates of New York City’s legendary
Bronx School of Science. Nalin went to Albany, NY, Medical College,
where he was one of the youngest medical students at the age of 20. On
a cross-cultural clerkship, he went to Guyana, in South America, and
quite suddenly, his life changed. It was in Guyana that he learned about
practicing medicine in different cultures. “It was an eye-opening, life-
changing experience,” he recalled. My experience in Guyana led me to
choose a laboratory focusing on tropical, particularly infectious diseases.
Having completed the first year, only, of his medical residency, the
twenty-six-year-old Nalin found himself signing on to the Pakistan-
SEATO Cholera Research Lab in Dacca. He learned that the bacteria
responsible for cholera is not very robust critters. Indeed, research has
found that healthy people rarely get cholera. Researchers have even fed
( 91 )
David Nalin
billions of bacteria to healthy, well-nourished subjects, and none of them

became ill. However, if the subjects are given an antacid, they immediately
become susceptible to cholera. The body’s natural defense against the
cholera infection is stomach acid, which destroys before it can reach the
small intestine to do its deadly work. Most cholera victims have other
pre-existing gastrointestinal infections or suffer from malnutrition, which
can compromise stomach acid production and render them susceptible to
V. Cholerae.
No One Believed an Oral Solution Could Work

Before leaving the U.S., Nalin and Richard Cash, another twenty-
six-year-old who had also signed on to go to East Pakistan, attended a
cholera symposium in California where they heard Dr. Bert Hirschhorn,
who had just left the Cholera Research Lab, describe his work. Hirschhorn
told them that the current director, the noted cholerologist Phillips, held
the hypothesis that cholera poisoned the sodium pump in the human gut,
shutting down the transport of sodium through the intestinal wall and
making oral therapy impossible. Just the year before, another scientist
working in Dacca, David Sachar, had disproved this hypothesis,
prompting Hirschhorn and others to speculate on the possibility of an oral
solution. The idea was that a solution with glucose might reduce or stop
diarrhea. Hirschhorn performed an experiment that pumped a digestible
solution into eight cholera patients’ stomachs who were on IV solution.
There was a positive result from the study.
Hirschhorn’s trial confirmed Phillips’ observation that cholera
patients could absorb water, salt, and glucose in a single solution. But
because diarrhea did not stop, and because Phillips had told him of his
very dark secret (which he did not dare divulge), Hirschhorn “was not
optimistic that ORT [oral rehydration therapy] was feasible as a routine
treatment.” Nalin’s impression was that there was “absolutely no one
who believed that an oral therapy could work as a practical thing in rural
areas or even in hospitals.” Everyone was a skeptic. What formula would
you use? How much solution should you give? Physicians doubted there
( 92 )
could be a universal formulation, and creating a customized mixture for

each patient seemed logistically impossible. Besides, no one believed
that cholera victims could drink the amount of fluid that they effuse. How
do you get a cholera patient in shock to drink a liter of hydration fluid
every hour for twenty-four hours? Additionally, cholera patients often
vomit up whatever is in their stomachs.
A Young American in Dacca

Bangladesh, then East Pakistan, is the most densely settled rural
nation in the world. Draining much of northern India and the Himalayas,
the Ganges produces the largest delta on earth, and a great site for cholera
research, for the Bay of Bengal, is thought to be a natural reservoir for the
bacteria that cause the disease. Cholera has always been endemic there,
typically starting when the flooding recedes after the summer monsoon
season (which can dump sixty inches of rain on the country in a few
months), and whose cyclones cause tidal surges that wash seawater
inland.
The Dacca that Nalin arrived in on August 17, 1967, was an old,
multiethnic city. “My initial impressions of Dacca were wondrous,
sometimes bewildering and spellbinding,” Nalin says. The cholera center
was located on the outskirts of the city. Behind it was a waterway that
could be navigated all the way to the Buriganga River in old Dacca. Nalin
recalled, “Within a few weeks, I was taken by boat out on the Buriganga
River for the Independence Day boat races. The Provincial Governor,
Monem Khan, stood at the head of a yacht, while dozens of wooden
launches raced one another, their crews often rowing themselves
underwater and capsizing. It was a scene of chaos presided over by
officialdom, which proved emblematic of subsequent history.”
No Detectable Pulse
Nalin’s first experience with a cholera epidemic was not long in
coming. In September, cholera broke out in the Chittagong Hill Tracts,
along the eastern Burmese border. Chittagong is Bangladesh’s largest
( 93 )
David Nalin
port city. Nalin recalls that when he had arrived “patients were dying in
their villages because the only hospital was run by the Christian
missionaries, and the local mullahs had preached that any Muslim who
went there would be branded with the sign of the pig. So, we had to go
out to these remote villages with our intravenous solutions and try to coax
parents to let us use them in the huts. A few, finally, let us do this, and the
results were so dramatic that rumors circulated that this could not be
cholera after all because they had never seen a cholera outbreak where
anyone survived!” Soon patients began to arrive at the hospital in droves.
Cholera does its damage in the gut, specifically, the small intestine,
where the stomach deposits a mixture of partially digested food and water
known as chyme. In the small intestine, chyme receives an additional six
or seven liters of fluids from the ordinary bodily secretions. All this fluid
is necessary to maximize contact with the intestinal lining so that nutrients
can be absorbed into the bloodstream. By the time the chyme moves
through the twenty feet of the small intestine in a healthy individual, 80
percent of the water is reabsorbed and goes back out, through the
bloodstream, to hydrate the body. What is left enters the colon, where
most of the unabsorbed water is reabsorbed, leaving semisolid feces.
It takes about a million V. cholerae bacteria to make someone sick.
Those that survive the acidic stomach descend into the small intestine
with the chyme. Little propellers pop out of the bacteria that allow them
to push their way through the mucus lining the intestinal wall, where they
begin to produce a poison known as cholera toxin. It forces the cells of
the intestinal wall to expel chloride ions, causing an electrolyte imbalance
in the intestine that leads to dehydration.
An ion is an atom or molecule that has lost or gained one or more
electrons, making it electrically charged. Electrolytes are simply ions
dissolved in water. In our bodies, electrolytes come mainly from dissolved
salts such as sodium chloride (table salt), which contains equal amounts
of positive sodium ions and negative chloride ions. These electrolytes
play vital roles in many cellular processes, and our bodies regulate, very
( 94 )
carefully, the concentrations of different ions inside and outside our cells,
using highly specialized ion channels located in our cell membranes. For
instance, virtually all our cells have hundreds of thousands, or even
millions, of sodium-potassium pumps that are constantly at work,
exchanging three sodium ions, inside the cell, for two potassium ions
outside the cell. As cells in the intestinal wall pump out sodium ions into
the bloodstream, more sodium ions enter the cells from the intestine.
Nature has its tendency to create equilibrium, to balance the concentration
of electrolytes/ions/salt on either side of a semi-permeable barrier such as
a cell membrane.
Cells also have chloride ion channels, and these are what the cholera
toxin goes after. When negative chloride ions flood the intestine, sodium
can no longer easily move into the intestinal wall cells because of another
simple natural tendency—to avoid the concentrations of electrical charge.
Positive sodium ions are needed in the intestine to balance all the negative
chloride ions, and this, in turn, causes a massive volume of water to travel
across the intestinal lining due to a principle called osmosis, by which
water moves to balance the concentrations of both types of ions. The
chemical imbalance literally sucks water out of the body, the excess
liquid cascading into the colon, which can only reabsorb a maximum of
about 4.5 liters per day. The only place the rest of the water can go is out
of the body.
Diarrhea—watery, profuse, and often painless—begins abruptly,
twelve to twenty-four hours after infection. As this vomiting and
defecation draw water out of the body, the patient’s skin becomes cold
and withered, the face becomes drawn, blood pressure falls, and the pulse
becomes faint. Death comes from dehydration after the patient has
plunged into shock and coma. In children, the symptoms of dehydration
are stark and even quicker: thirst, sunken eyes, dry tongue, shriveled
fingertips, and weakness. Pinch the skin on the top of the hands, and it
remains malformed for minutes. Children are more vulnerable to
dehydration because they exchange more than half their extracellular
( 95 )
David Nalin
fluids in their gut every day. Adults, in contrast, exchange only one-
seventh of their fluids. With cholera, the case fatality rate for children
under the age of five can run above 70 percent.
For centuries, every scientist knew that cholera victims could not
rehydrate their bodies by drinking water. Nor could they drink saltwater,
even though scientists knew that salt played a crucial role in the body’s
ability to move water around by way of osmosis. The key to the mystery
of how the body absorbs water in the gut proved to be sugar. Sugar was
slow to be recognized as crucial because it plays no role in osmosis,
which was the mechanism by which scientists thought the body absorbs
water. Although even today, scientists do not completely understand all
the details, during the 1960s, they began unraveling the intricacies of how
water is absorbed in the gut. Specialized proteins in cell membranes bind
to and transport sodium and glucose (sugar) across cell membranes
simultaneously—one glucose molecule for every two sodium ions—and
cannot be transported without the other. Hundreds of water molecules are
bound to each of these glucose molecules, and this is how water is
absorbed. For water to be absorbed in the gut, all three components—
water, salt, and sugar—are absolutely essential.
As Nalin says, “You receive patients who are about to die, in fact, not
infrequently are technically just dead, with no detectable pulse or blood
pressure, but with heart and brain still on the edge of irreversible fatality,
and within minutes, using standard intravenous fluids matching the ionic
composition of their losses, often with added glucose to ward off
hypoglycemia, they come back to life. Terminal patients typically
received the equivalent of 10 percent of their body weight in intravenous
therapy to correct shock, and then they continued to receive intravenous
fluids. Tetracycline, or other appropriate antibiotic capsules, were also
given to shorten the duration of diarrhea to about thirty-two hours on
average.
( 96 )
A Mantra of Failure
As the cholera epidemic rolled on into November and then December,
Nalin and his associates worked out of the Memorial Christian Hospital
at Malumghat.
The center was following up on Hirschhorn’s research on a digestible
formula, but this time using a new idea. During epidemics, there was
often a shortage of IV solution because cholera victims need gallons upon
gallons of it, all of which require sterile, distilled water. The idea was that
a drinkable solution might function as a supplement to the more quickly
wean cholera victims from I.V.s. It would save the IV solutions that could
be used for other patients.
Nalin spent hours poring over and analyzing the data from the failed
experiment, thinking about one patient after another. As he thought about
each patient’s failure, their results echoed through his head:
underhydration, overhydration, underhydration, overhydration. He
looked outside the tent as the results began to sound like a mantra of
failure—underhydration, overhydration, underhydration, overhydration.
Across the tent, he recognized the father of a convalescing infant. He
was wearing a sarong-like lungi with a white prayer cap on the top of his
head, and he was incongruously feeding his child with a baby bottle. It
was the old versus the new—the past versus the future. Killed by cholera,
healed of cholera.
“Then, suddenly, it hit me,” Nalin said. “Oral therapy had to work; it
was the methodology that was the problem. Fluid losses had to be replaced
with oral solution volumes that matched or slightly exceeded the volume
of losses. I remember a chill going up my spine when I realized this,
together with the overwhelming sense of how important this would be to
the countless patients who were continuing to be at the risk of death in
remote, resource-poor affected areas around the globe.
Immediately, Nalin jotted down a concept outline for a new protocol.
Nalin’s brain surged with ideas of how to turn his idea into reality. He
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David Nalin
conferred with Richard Cash, who immediately agreed to collaborate.

These two young doctors, with only three months immersion in this most
foreign of cultures and three months familiarity with this disease, were
ready to perform groundbreaking science. They were too young to fear
failure.
Net Gut Balance

Excited, Nalin and Cash returned to Dacca. They conferred with
Kendrick, who approved a new trial, Kendrick being the acting director
of The Cholera Research Lab. It would have controlled so that a
comparison could be made between those receiving an oral solution and
those receiving only IV solution. Since the patients would be deathly ill,
the researchers would use an excess of caution. The trial would take place
in the Cholera Research Laboratory Hospital, and the researchers would
use a specific gravity plasma test for patients receiving the liquid drink to
inform the doctors if dehydration was accelerating. In addition, either
Nalin or Cash would always be on call, twenty-four hours a day. There
had been centuries of failure in keeping cholera patients normally
hydrated with a drink. Would they be the first to succeed?
When the cholera season arrived in Dacca, in April of 1968, the
researchers chose twenty-nine of the sickest patients at the hospital. All
were in shock, as evidenced by having no pulse and either very low or
undetectable blood pressure. They were treated with IV solution until
their blood pressure became normal and then placed into one of three
groups:
• Ten were put into a control group that received normal IV treatment.
• Ten were given oral solution by plastic orogastric tube threaded
down their throat into their stomachs.
• Nine were given an oral solution to drink.
The oral solution consisted of 4.2 grams sodium chloride, .5 grams
potassium chloride, 4 grams bicarbonate of soda (baking soda), and 20
grams of glucose mixed in one liter of water, which was heated to 110
( 98 )
degrees Fahrenheit to aid absorption. The patients in the two oral solution
groups started off receiving 750 milliliters of solution (about three cups)
every hour if they weighed more than 55 pounds. If they weighed less,
they received 500 milliliters. Nalin’s breakthrough was that patients
should be rehydrated at the rate of their loss of fluid as measured by their
output of diarrhea and vomit. Too little rehydration solution resulted in
dehydration, whereas too much resulted in the fluid overload that could
lead to congestive heart failure. They called the difference between what
a patient drank and expelled “net gut balance.”
Nalin wanted scientific proof. He aggressively put everyone on
notice that the plan to maintain test patients with oral solution alone
would continue. To ensure the experiment remained valid, Nalin and
Cash decided to alternate twelve-hour waking shifts.
The results of the trial were spectacular, as Nalin and Cash later
reported in their first research paper: “Patients who drank the oral solution
tolerated it remarkably well. All twenty-nine recovered from massive
diarrhea after about two days. Eventually, all recovered completely. The
patients receiving oral therapy, by tube or by drinking a solution, primarily
only received IV solution to correct the initial shock and needed 80
percent less IV fluid compared to the controls not receiving the oral
solution.
Nalin and Cash quickly wrote up the results and published them just
four months later in The Lancet with the title Oral Maintenance Therapy
for Cholera in Adults.
The paper concluded: “Our findings indicate that an oral solution
containing glucose and electrolytes can eliminate the need for over three-
quarters of the intravenous-fluid requirements in the therapy of acute
cholera in adults. The ingredients of the oral solution are cheap and
widely available in virtually all areas affected by cholera. The solution
need not be sterile, and it can be made of any suitable drinking water.
Ingredients could be pre-weighed and stockpiled for use in cholera
epidemics.
( 99 )
David Nalin
“The drastic reduction in the need for intravenous fluids which

results from the use of an oral therapeutic solution should make it possible
for cholera treatment centers with limited supplies of intravenous fluids
to reduce the mortality from cholera to a level previously not possible in
the absence of abundant intravenous fluids. Mild cases of cholera (without
shock) may be treated with oral solution alone.”
Now the acronym becomes obvious. ORT stands for oral rehydration
therapy—a drink that cures the major symptom of diarrhea—dehydration.
Phillips’ Dark Secret

After they had written up The Lancet paper, Nalin and Cash began
planning further studies. The Cholera Research Laboratory had a field
hospital at Matlab. There were always patients who showed up with
diarrhea not caused by cholera. Nalin was optimistic that a drinkable
solution could rehydrate those patients as well. In addition, they could
test if adding the amino acid glycine to the solution would improve the
outcome, following up on prior research done by physiologists showing
that adding glycine to glucose increased intestinal sodium absorption.
Phillips was in the U.S., so Nalin and Cash sent their plans to John
Seal, the National Institute of Health administrator overseeing the Dacca
lab. In a letter they suspected that Phillips had influenced, Seal criticized
the ideas behind the new trial and suggested it be delayed and reviewed
by the Technical and Clinical Research Committees. Nalin and Cash
were dumbfounded. Their last trial had been such a success. They were
not moving too fast; they were planning to take the necessary baby steps
that medical advances require. Plenty of safeguards were built in the
experiments to ensure the patients’ safety. Plus, there was likely to be a
shortage of IV supplies during the next epidemic, so their trial might save
lives that otherwise would be lost. What could be the problem? Even the
staff had expressed unbridled enthusiasm for their study. So why was
Phillips so intractable?
Even though Phillips had just the previous year won a Lasker
( 100 )
Award—the most prestigious American medical award—for his work on

cholera, he was not a happy man. At times he showed signs of alcoholism
and depression. When pressed, Phillips retorted that he did not want his
clinical researchers to work on practical field problems. What Nalin and
Cash did not know was the secret Phillips had told Hirschhorn. Phillips
was doing his exploratory research in the Philippines in 1962. Phillips, a
Navy captain, ran the Navy’s medical research unit in Taipei, Taiwan. He
had been working with cholera treatment for fifteen years and had reduced
his patients’ mortality rate to below 1 percent using the latest IV
electrolyte protocol. When his exploratory work had shown that water/
electrolyte/glucose solution could be absorbed, he thought he had found
a magic bullet that would stop cholera diarrhea. He had formed his
hypothesis that the sodium pump in the intestine was poisoned by cholera
and that his “cholera cock-tail” undid the damage and stopped diarrhea.
He set up a larger experiment that would administer the oral solution at
the same time patients received an IV solution. Of the thirty patients in
the trial, five died. Devastated, he dropped most of his research on cholera
treatment and began a slow descent into guilt. Worse yet, he did not
publish the results concerning death.
Phillips did not want another trial, even with Nalin’s improved
protocol. If they went ahead with the study on their own, the repercussions
could be dire. Technically, they were Public Health Service officers
under the realm of the military, which meant they could face court-
martial. Yet, if they did nothing, no lives would have saved, and no
scientific advance would occur. The scientific community would not
believe their discovery based on a trial with only nineteen patients. Only
a large-scale trial would move their advance forward.
They turned to Henry Mosley, head of epidemiology at the lab, for
advice. Mosley technically worked for the Centers for Disease Control
(CDC), not the NIH. He came up with an elegant solution. “Simple,” he
said. “I’ll send you four CDC officers. You tell them what to do. You
won’t be doing the test and violating orders.” Mosley contacted Alex
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David Nalin
Langmuir of the Epidemiological Intelligence Service. Langmuir

recognized the revolutionary nature of the discovery and agreed to the
ruse.
ORT: Born at Matlab Bazaar

In October 1968, cholera hit Matlab, as it did every fall. Nalin, Cash,
and others from the cholera center traveled there by speedboat. Nalin
remembers Matlab Bazaar as a very primitive outpost: “There were a
single-story brick and cement building of several rooms for the hospital,
on a slip of land which had been picked because of its history as the
center of annual cholera outbreaks. The hospital was run by one doctor,
the late Mizanur Rahman, who had trained his helpers and nurses to treat
the patients and run the place. We, the visiting investigator Young Turks,
were housed on a floating barge inherited by the hospital. Ambulance
boats would come in and go out over the day, ferrying cholera patients to
and from the hospital.”
Nalin was by now conversant in Bengali and had designed a
questionnaire to interview patients to obtain their medical histories. He
says, “The hospital environment was a bit hectic, especially when
epidemics were at full blast with hundreds of patients admitted, many in
shock, every day. There was a scale at the entrance where patients could
be quickly weighed (held by an attendant if they couldn’t stand, then
deducting his weight from the total). In an instant, an IV drip started,
infusing over an hour or two the equivalent of 10 percent of the patient’s
body weight to bring back a pulse and blood pressure and correct shock.”
Once the IV started, patients were tested for cholera and then given
from 750 to 1500 ml per hour of oral rehydration solution to drink for the
first four hours. After that, the amount to drink was adjusted to the amount
they expelled from their bodies. When a patient came into a positive net
gut balance, which meant more fluids were taken in than expelled, he or
she was removed from the IV solution. If the patient then went into the
negative ‘net gut balance,’ he or she was returned to the IV solution.
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The protocol worked quickly. When this showed to work beyond any
doubt, they administered the drinking solution to five severely ill patients
without first administering an IV. The blood pressure of even these
gravely-ill patients get returned to normal, and they never required
treatment by IV infusion. When Nalin and Cash wrote the paper describing
the trial, their conclusions were revolutionary: Medical and paramedical
personnel were easily trained in the preparation and the use of oral
solutions. Oral therapy practically eliminated the need for intravenous
fluids in patients with mild cholera. It seems possible that if patients with
severe cholera were treated from the time of the onset, they might be
maintained on oral therapy alone. The public health implications of oral
therapy are obvious; it is inexpensive, simple, and effective. Its widespread
use should reduce mortality due to cholera, even in remote districts where
little or no intravenous fluid is available.”
Further Discoveries
In biology, a big breakthrough experiment often inspires numerous
additional investigations. In fact, later studies demonstrated that infants
as young as one-month-old could be given an ORT. The addition of
glycine was also a success, substantially reducing both the duration and
volume of diarrhea in cholera patients. This discovery set the stage for
numerous other studies refining and improving the solution. Nalin and
Cash also demonstrated that cholera patients could be fed food along with
the oral solution, not long after the shock was corrected, overturning the
long tradition of starving patients for several days. In fact, nourishment
can help a patient fight off the cause of diarrhea.
Most significantly, and surprisingly, to many doctors, Nalin and
Cash demonstrated that ORT is “as effective in the non-cholera diarrhea
patients as in cholera patients.” The importance of this finding was
monumental. Cholera accounts for at most 10 percent of the cases of
diarrhea sickness in the world. Diarrhea is also a major symptom of
dysentery, caused by bacteria or amoebas; traveler’s diarrhea, usually
caused by E. coli strains; and norovirus, which contaminates food and
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David Nalin
water. ORT has proven to be the main line of defense against dehydration
from diarrhea, no matter the cause. In fact, in 1972, Hirschhorn concluded
that IV use in the treatment of diarrhea was “old-fashioned” and said that
ORT was clearly the superior treatment.
In the words of Nobel Laureate Prof Joshua Lederberg, “De’s clinical
observations led him to the bold thought that dehydration was a sufficient
cause of pathology of cholera, that the cholera toxin can kill ‘merely’ by
stimulating the secretion of water into the bowel.”. Thus, ORT for
replenishing the massive fluid loss in cholera patients has saved
innumerable lives, should be considered as a direct outcome of De’s
discovery of cholera toxin.
Sambunath De’s findings on exotoxins set the stage for modern
views of diseases caused by toxin-producing bacteria, helped in the
purification of cholera and heat-labile (L.T.) enterotoxin produced by
Vibrio cholerae and E. coli, respectively, and to the development of series
of cholera and enterotoxigenic E. coli (ETEC strains) vaccines.
An Eye-Opening, Life-Changing Experience A Pinch of Salt

with a Fistful of Gur
“To save the life of a person with diarrhea is probably the cheapest
health intervention you can think of,” said David Sack, a past executive
director of the International Centre for Diarrhea Disease Research in
Bangladesh. Indeed, ORT packets could be produced for eight cents
apiece.
But this knowledge had to be conveyed to people in many parts of
the world who had few educational resources and little access to the
media. To spur the educational effort, Nalin traveled the globe as a
consultant for the WHO, starting national ORT programs in Costa Rica,
Jamaica, Jordan, and Pakistan. The remarkable thing about ORT is that it
does not have to be administered by the medical community—anyone
can use it, provided he or she has the necessary knowledge.
In 1971, less than 1 percent of children in the developing world had
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access to ORT. By 1980, access had increased to 30 percent, and by 1990

it was at 60 percent. Today, total production exceeds 800 million packets
a year.
Nalin’s regimen completely changed how doctors treat diarrhea.
Now doctors recommend drinking fluids as soon as diarrhea begins. They
also realize that prolonged fasting can impair the function of the intestines,
so they encourage solid food nourishment as well. And if diarrhea persists
to the point of dehydration—usually first evident by lack of urine—ORT
is the first line of treatment. Once the body can maintain hydration and
nourishment, the immune system will fight off most causes of diarrhea in
a few days, and the patient’s health will return.
The annual number of child deaths around the world attributable to
diarrhea fell from over 4.5 million a year in 1980 to about 1.5 million
today. In a 2007 article, the British Journal of Medicine estimated that
ORT saved the lives of more than 50 million people. ORT, of course,
only affects the outcome of diarrhea, not the cause. The number of
diarrhea cases has not dropped precipitously. Since ORT only treats the
symptoms, prevention is the best method of avoiding diarrhea altogether.
Clean water, better sanitation, breastfeeding, vitamin A supplementation
to aid the immune system, and rotavirus vaccination are important
preventative measures necessary to lessen the incidence of this virtually
ubiquitous human infirmity.
In 1993, post offices in Bangladesh began stamping an odd phrase on
envelopes. After the Bangladesh War of Independence in 1971, Abed
Fazle Hasan, who had been an accountant working for Shell Oil in
Chittagong, wanted to rebuild his country. He formed a private foundation,
the Bangladesh Rural Advancement Committee (BRAC), and quickly
realized the promise of ORT. There was no industry producing packets
of solution at the time, so Hasan, working in his kitchen, formulated oral
rehydration solutions, and then tested them in laboratories. He found that
the proper home mix for ORT was three pinches of salt and two-finger
scoops of sugar.
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David Nalin
BRAC, with Cash as its major consultant, promoted this recipe by

sending women trainers into rural Bangladesh. They taught ORT to 13
million illiterate mothers and to countless children in classrooms that
BRAC set up. It became such a culturally popular program that led to the
aforementioned stamp:
Mix with much care,
Good water, a liter,
A pinch of salt with a fistful of Gur,
Remove the menace for good
ORT acted as a catalyst for Abed Fazle Hasan’s efforts to transform
his society, his goal being to empower those in poverty. BRAC has since
promoted gender empowerment of women, micro-loans to lift people out
of poverty, and education. Now his model is being implemented
internationally.
In the U.S., ORT Never Gets Past Gatorade

Even people of science do not always practice science. Most of the
U.S. medical establishments still use I.V.s to treat dehydration from
diarrhea. ORT is an example of a less technological solution being
superior to a more complex solution.
In the South, in the 1960s, football players were falling from heat
exhaustion like flies on DDT. The University of Florida assistant coach
Dewayne Douglas, himself a past player who had experienced heavy
sweating and no urine output during games, asked physicians at the
college to develop a drink for the football team. They discovered the
water-salt-sugar coupling research and formulated a solution for the
players to drink. The rest is history. That year, the moribund Florida
Gators football team began using Gatorade and finished 7–4, winning
many games in the second half when fatigue takes its heaviest toll on
players. It was their first winning season in more than a decade. Soon,
every team was using Gatorade, which was simply a scientifically
formulated oral-rehydration therapy.
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While Gatorade works based on the same physiological mechanisms

as ORT, it is not a substitute for ORT in diarrhea cases. Gatorade is
formulated for healthy athletes, chiefly to replace sweat loss, and not for
sick children or adults who have diarrhea, which requires a different
solution. In order to make it easier for busy Americans to take, Abbot
Laboratories created a ready-mix ORT drink for diarrhea, available in a
bottle, called Pedialyte. Only in America does taking medicine have to be
fun. To encourage its use, Abbot began producing Pedialyte Freezer Pops
in numerous flavors.
Life Is a Candle
Back at his house, sitting in the shadow of the giant smiling Buddha,
it is obvious that Nalin has retained his childhood collecting proclivity.
Among other things, he has collected two highly prestigious awards. Abe
and Irene Pollin, best known as the owners of the Washington Wizards
professional basketball team, offer an esteemed medical award every
year. Nalin, along with three other scientists, instrumental in the
development of ORT—Norbert Hirschhorn, Dilip Mahalanabis, and
Nathaniel Pierce—received the 2002 Pollin Prize for Pediatric Research.
In 2006, Nalin, Mahalanabis, and Richard Cash received the Prince
Mahidol Award in Thailand for their life-saving advance.
He has also begun giving today’s students the same opportunity to
have first-hand exposure to health-care practices around the world in the
hope that they will learn some of the same lessons that Nalin himself
learned in Guyana and Bangladesh. In 2006, he pledged $200,000 to
establish the David R. Nalin 1965 Endowed Fund for International
Research. It is to be used to send two students abroad each year for non-
sectarian medical research. Nalin said, “The exposure to Guyana whetted
my appetite for international research. It changed my life. I hope this gift
will change the lives of others.”
Some people collect Buddha quotes like David Nalin collects art;
many could be placed alongside his life. Here’s one: “Thousands of
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David Nalin
candles can be lighted from a single candle, and the life of the candle will
not be shortened. Happiness never decreases by being shared.”
But here is perhaps a more compelling quotation relating to the story
of ORT: “There are only two mistakes one can make along the road to
truth: not starting, and not going all the way.”
Robert Phillips began the search for a magic bullet. David Nalin went
all the way.
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5
Norman Borlaug
(1914-2009)
A Green Revolution to Enhance Nutrition

A TALL, scrawny man in a checkered shirt, brown pants, and work

boots sat under a broiling Mexican sun, on a small folding camp stool
during an enormous field of ripening wheat. The dust from the fields and
nearby road coated his face, while a handkerchief wrapped around his
forehead failed to keep the sweat out of his eyes. In one large, weather-
browned hand, he held a pair of needle-nosed tweezers. The other hand
gently encircled a delicate head of wheat,
a tiny fleck of white or yellow hinting at
the grain that would eventually emerge.
With meticulous precision, his hands as
steady as a surgeon’s, he used the
tweezers to probe the barely formed
flower and pluck out each tiny stamen
(the male part of the plant), being careful
not to disturb the plant’s ovary (female
part of the plant). Then he slid a small
glassine envelope over the wheat head,
folding over the top and fastening it with
a paper clip. In five days, he would return Norman Borlaug in a Toluca, Mexico wheat
field. To produce 1999’s cereal crop using
to this same plant, remove the paper clip, pre-green revolution methods would have
required an additional 3 million square
and slip in the stamen of another type of miles to be farmed – about the size of the
wheat in the hope that the two parts would contiguous United States.
Bettmann Standard RM Collection/ Bettman/
create a third, a new breed of wheat CORBIS.
Norman Borlaug
capable of feeding the world.

Finished with the first plant, he moved his camp stool over a bit and
started on the second. Then the third. Then the fourth. Day after day, from
sunrise to sunset, the man worked, never looking up, his muscles grew
tense with fatigue, his eyes red with grit. As night fell, he spread a
sleeping bag in the rudimentary field station and heated a can of beans on
an open fire for his dinner.
From those painstaking efforts would raise new varieties of wheat,
strains resistant to deadly fungal diseases, that would thrive in the varied
Mexican climates, in poor, overworked soils in India and Pakistan, and
in family plots throughout much of the world. From the work of this man,
a farm boy named Norman Borlaug would come a Green Revolution, one
that would feed the world for at least a little while and change forever
how we think about the division between nature and man.
The Early Years: Game Changer

Norman Borlaug was born in 1914 in the hamlet of Saude, Iowa, on
his grandparent’s farm. Borlaug learned early on the meaning of hard
work. From age seven, he was an active participant on the farm.
But Borlaug never thought much of it—he knew that all boys his age
in his county worked just as hard. Unlike most boys, however, Borlaug’s
family had greater ambitions for him than simply plowing fields. As soon
as the boy could understand, his grandfather Nels drilled one overriding
ambition into his grandson: “Get an education.” His grandfather had
received only three years of formal schooling but retained a deep longing
to learn. “You’re wiser to fill your head now if you want to fill your belly
later on,” he told his oldest grandchild.
Despite the tremendous financial struggle, the Borlaug family
scrimped together enough to allow Norman to finish high school. He
graduated in 1932, at a time when the country had no jobs to offer and his
family no money to pay for college.
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He learned of a scholarship to train a science teacher at the Iowa State

Teacher’s College in Cedar Falls, Iowa. But it wouldn’t become available
for another year. Borlaug spent that year cutting fence posts and hunting
and trapping animals for their meat and pelts. A week before he was due
to leave for Cedar Falls, George Champlin turned up at the Borlaug door
to whisk the former wrestler off to Minneapolis and the university’s
fledgling wrestling team. Here was Borlaug’s chance to attend a full
university rather than a two-year teacher’s college. This was his
opportunity to receive the rich higher education that he and his grandfather
had always dreamed of.
The True Face of Hunger

The high spirits Borlaug enjoyed during the drive to Minneapolis
were dashed during his first week in Minneapolis. Because of differences
in the high school education offered in Iowa and Minnesota, he and
Upton were required to take an entrance exam. Upton passed easily;
Borlaug failed. There was one option left: the university offered him a
place at its “General College,” which some snide students called the
“college for dumbbells.” Borlaug could take a broad sweep of subjects
and, at the end of two years, receive a degree. It wasn’t what he’d hoped
and dreamed of, but he had no other choice. Despite his anger and shame
at having flunked the exam, he agreed to enter.
By the end of the first semester, he convinced the administrators to
let him out of the general college and into the College of Agriculture to
major in forestry.
Two incidents marked Borlaug during his first year at Minnesota
University. One occurred soon after he arrived in the metropolis of
Minneapolis when he went to visit the university’s agricultural campus
on the outskirts of St. Paul, the city. Walking back into town, he happened
upon a factory riot: the bad feelings were instigated when managers
slashed worker’s wages in half and then were fueled when the workers
went on strike. The desperation he saw in the workers’ faces as they
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Norman Borlaug
fought against truncheons with their bare hands, fighting to feed their
families, stayed with him throughout his life and ignited in him a burning
desire to eradicate hunger.
The second incident affected him more directly. As a member of the
wrestling team, Borlaug often had to fast to lose weight so he could
compete in his weight class. One time he went four days without food and
with very little water, spending hours in a steam box to sweat away the
pounds. On his fifth day without a meal, frustrated when he discovered
he was still a pound overweight, the normally gentle Borlaug lashed out
at another wrestler and would have punched him in the face if his friends
hadn’t pulled him away. For the usually calm Borlaug, such an outburst
was, to say the least, uncharacteristic. As he told Margaret, his wife, that
night: “I think I’ve learned a primal rule of nature. You see, it wasn’t me
at all. It was primitive. I can’t explain how hungry I was. I was starving,
and I found out that a hungry man is worse than a hungry beast.”
Then, as he prepared to start his final year of college in 1937, the
economic tide seemed to turn. Borlaug was offered a permanent job with
the Forest Service as an assistant ranger in the Idaho National Forest once
he graduated.
But a few days before Christmas and his graduation, Borlaug received
a letter that changed everything. Due to budget cuts, his job no longer
existed. It would turn out to be the best thing that could have possibly
happened to him and millions of people around the world.
From Wrestler to Protégé

During his final undergraduate semester, Borlaug had had a strange
encounter with the head of the plant pathology department, E.C. Stakman,
one of the most respected scientists in the field. For years, Borlaug
thought the interaction was accidental. Yet Stakman, who had seen the
courage and tenacity Borlaug showed during a wrestling match, had
deliberately sought out the young man to test his intelligence. Stakman
walked into the forest pathology lab where Borlaug was examining wood
( 112 )
samples under a microscope and, without introducing himself, began

peppering the student with questions about the samples. This Ph.D. level
pop quiz, Borlaug later learned, was designed to test his ability to meet
challenges head-on. Borlaug passed with flying colors.
A few weeks later, Borlaug attended a lecture Stakman delivered on
his decades-long research into the challenges of rust diseases in wheat.
The parasitic fungi causing the disease—the bane of all farmers—were
capable of changing their genetic makeup in less than a year to attack
previously resistant crops, wiping out a season’s yield in days. “Rust
diseases are the relentless, voracious destroyers of man’s food,” Stakman
told his audience, “and we must fight them by all means open to science.”
Stakman didn’t stop there, however. He warned of another threat to the
world’s food supply—the man himself. Population growth would soon
outstrip food supply, he said, and the one thing that could reverse the
trend was science. This was known as the Malthusian theory.
Thomas Robert Malthus was a famous 18th-century British economist
known for the population growth philosophies outlined in his 1798 book
“an Essay on the Principals of Population.” Malthus theorized that
populations would continue expanding until growth is stopped or reversed
by disease, famine, war, or calamity. He stated that the human population
increases geometrically while food production increases arithmetically.
Even there, however, his message held foreboding: “Do not deceive
yourselves—ever—that the scientific approach is omnipotent. It will
make its mistakes, but it will take us further than has ever been possible
to eradicate the miseries of hunger and starvation from this earth.” If ever
a speech was designed to ignite and motivate, this was it. “One day, I
would like to go back and study under that man, if it is ever possible,”
Borlaug told Margaret that night. When the implications of the forestry
letter sank in, Margaret gave him his chance. Go to graduate school with
Stakman; she urged her husband.
Buoyed by her support, Borlaug walked into Stakman’s office the
next morning and told the man he wanted to spend a couple of months
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Norman Borlaug
doing graduate work in forest pathology. “No way,” Stakman told the
young man, “You don’t dip your toe into the world of graduate work—
you jump in. And forest pathology is self-limiting: Focus on all plant
pathology, and you can work with any species.”
Borlaug became a Stakman disciple. He received his master’s degree
in 1940 and went on to study for his Ph.D., also under Stakman. In late
1941, as Borlaug was completing his thesis, Stakman arranged for his
protégé’s first professional job. Upon graduation, Borlaug was to work
for the chemical company DuPont in Wilmington, Delaware, in its
biochemical laboratory group.
To Mexico
Borlaug had barely begun his professional life when the U.S. entered
World War II. Although he wanted to enlist after the attack on Pearl
Harbor, he was told his work at DuPont was considered “too valuable” to
the war effort. Borlaug spent the war years at DuPont. He and his
colleagues developed, among other products, camouflage paint, aerosols,
and chemicals to purify water. He also oversaw the mass production of a
new insecticide: DDT. Then the Rockefeller Foundation came calling. In
1940, the Rockefeller Foundation sent a delegation of agricultural
experts, including Stakman, to tour Mexico and report on what was
required to help the starving country develop a viable agricultural
program. Their recommendation was to create an agricultural research
infrastructure. It was the only way, the men reported, that Mexico would
ever be able to feed its own people without depending on the handouts of
richer countries like the United States. The foundation agreed to fund the
project and asked Stakman to pick the man to lead it. Stakman
recommended one of his former students, George Harrar. When Harrar
needed a plant pathologist for his team, Stakman recommended his
protégé, Norman Borlaug. Borlaug was intrigued. The idea of improving
the quality of life of a whole country was attractive. He drove from
Wilmington to Laredo, Texas, where he met up with Edwin Wellhausen,
the communications specialist on the project. From there, they made the
( 114 )
three-day, 800-mile journey through the dusty, hot, yet colorful landscape
to the agricultural school at Chapingo, twenty miles outside Mexico City.
There, Borlaug found a newly built adobe shed with a tarpaper roof
surrounded by 800 acres of weed-choked fields.
Radically Speeding Up Agricultural Time

The science of agriculture, unlike that of some other disciplines, has
few “ah-ha!” moments. There are almost no major moments of discovery,
no miraculous recoveries, no sudden breakthroughs. There are only the
slow, inexorable seasons, the centuries-old methods of preparing the soil,
planting the seed, and observing the traits of what grows.
When you’re trying to feed a nation, however, such a pace can be
tortuous, and so, out of his need for action and his own frustration,
Norman Borlaug sped ahead. In doing so, he forced the rest of agricultural
science to keep up. To find the right types of wheat that would flourish
throughout Mexico, he knew he would have to cross thousands of
varieties, searching for the plants whose mutations would provide
increased yield while also fighting off the fungi causing rust. If he did it
the old way, it could take decades of crossing the wheat, planting the new
varieties, and waiting to see what happened. But the desperate need he
saw in Mexico impelled him to find a way to speed up agricultural time.
The first of three great innovations Borlaug developed in Mexico
was shuttle breeding. Rather than planting a wheat crop, waiting for it to
grow, and harvesting it to see which varieties survived, he came up with
the idea of supercharging the process by growing two plantings in the
same year. The summer crop would grow in the poor, high-altitude,
bone-dry soil of the Chapingo region outside Mexico City, and a winter
crop would grow over 1,200 miles north in the irrigated sea-level Yaqui
Valley in Sonora. It has more fertile soil and better-growing conditions.
The differences in altitude and temperature meant the two areas had
different growing seasons, so Borlaug could not only grow two crops of
wheat in a year, but he could also see if the plants that grew well in one
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Norman Borlaug
region also worked in the other. He would harvest seeds in the summer
from Chapingo and plant them in the winter in Sonora, and vice versa.
This was radically different from how agricultural science was done at
the time. His colleagues thought he was nuts. Harrar didn’t want to
expend resources in two areas of the country.
The foundation team voted against the Sonora planting, Harrar testily
told Borlaug. “If this is a firm decision, I also make a firm decision. You
will have to find someone else to conform to your rules.” Borlaug told
him, “You’re laying down a policy that is wrong. And I can’t go along
with it. As of now, I resign. You’ll have it in writing first thing in the
morning.” The next morning Stakman convinced Borlaug to go on to
work. The second major innovation Borlaug brought to Mexico was
high-volume crossbreeding. At the time, plant breeders typically only
crossed a few plants each season, waiting until the plants were harvested
before choosing the best varieties to use for crossbreeding a few more
varieties the following year. With this method, it could take decades
before a viable new breed emerged.
Ever impatient, Borlaug took a different approach. Knowing he had
one chance in a thousand to hit upon a winning variety, he collected
thousands of wheat varieties from throughout the world and began
crossing them simultaneously, hoping to find those that were most
resistant to fungal diseases like rust and could best survive in the various
Mexican soils and climates. He also optimized multiline breeding,
backcrossing hybrids with a single parent, thus putting multiple disease-
fighting genes into a variety. Hence, the long hours spent under the
broiling Mexican sun hand-pollinating his wheat varieties. A colleague
later wrote of him during this time: “Work was not just a word to him; it
became a code of honor. If genius is ‘an infinite capacity for taking
pains,’ Borlaug had it.”
Most importantly, he never sought perfection, only something better.
“We don’t have time to wait for perfection,” he said, thinking of the
starving population. To Borlaug, 40 percent better and harvestable this
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year was better than 90 percent better in five years. By 1952, he had more
than 40,000 wheat varieties in his nurseries, and more than 6,000
individual crosses—all meticulously recorded. Combined with the
shuttle-breeding approach, his approach cut the time required to develop
new varieties in half. By 1956, Borlaug had developed forty new rust-
resistant strains of tall wheat. There was only one problem, and it was a
major one: when the farmers began using the large amounts of fertilizer
required to increase yields, the wheat grew even taller and began lodging,
which is a farmer’s way of saying that the wheat had a tendency to flop
over in wind and rain, potentially ruining the crop. So, Borlaug embarked
on his third major innovation. He crossed his rust-resistant varieties with
a new Japanese dwarf variety of wheat to create a shorter, stiffer variety
of wheat. The results were spectacular—the dwarf Mexican wheat
varieties doubled the country’s yield from about two tons per acre to just
over four tons per acre.
On to India and the Start of the Green Revolution

By the late 1950s, Borlaug’s wheat was so successful that Mexico
was self-sufficient in wheat production and had its own scientists to run
agricultural projects. It was time for Borlaug to move on, and he began
negotiating a job with a tropical fruit company to investigate banana
diseases. Meanwhile, the Rockefeller Foundation found a new crisis to
focus upon impending famine in Asia.
In the early 1960s, Asia was undergoing a population explosion, and
its farmers were not producing enough food to keep up. Experts began
predicting mass starvation. Some were calling for the United States to
pull out of India and let millions of people starve in a social engineering
attempt to reduce its population. It was amid this crisis that the foundation
deployed Borlaug and other scientists on a fact-finding mission to the
region. The misery, poverty, and hunger the delegation saw there left
many of them shaken, but Norman Borlaug was not a defeatist. He
attacked problems. In this case, he came up with a scheme he called the
Kick-Off Approach that would work on three sets of factors—technical,
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Norman Borlaug
psychological, and economic—to overhaul the agricultural systems. The

technical work began immediately. In 1963, the Rockefeller Foundation
created the International Maize and Wheat Improvement Center in
Mexico, known by its Spanish acronym CIMMYT. Trainees arrived in
Mexico from Afghanistan, Cyprus, Saudi Arabia, Libya, Pakistan, and
various other Middle Eastern countries, as well as from ten South
American countries, to learn every aspect of agricultural development.
Conspicuously absent was anyone from India, whose agricultural
policymakers were suspicious of the whole endeavor. Simultaneously,
Borlaug established nurseries in North Africa, the Middle East, South
Asia, and throughout Latin America to find the best possible wheat
varieties from the Mexican strains for use in these areas. Once the trainees
learned all they could live in Mexico, they returned to their native
countries to manage the nurseries and oversee the dissemination of the
best varieties.
Borlaug’s second tactic evolved from his understanding of farmers’
psychology. He knew that the massive famines in the Soviet Union in
1932 and China in 1958 had been partly the result of top-down government
policy. While he believed government policy was integral, he understood
that agricultural advances always begin within the minds of individual
farmers. “He started with the farmers, always the farmers,” explained
Richard Zeyen. In Pakistan, for instance, Borlaug planted native wheat in
plots next to the new wheat. “Any fool could see the difference,” says
Zeyen. “Then he had invited the farmers in, and they would get very
excited. But Borlaug would say about the new varieties, ‘This is like
gold. Don’t touch it!’ Of course, as soon as his back was turned, they
were taking the heads off the wheat and gathering the seed.” In this way,
Borlaug built demand for his new wheat from the ground up, encouraging
farmers to put grassroots pressure on bureaucrats to find ways to support
them. “Farmers are very intelligent people,” explains Zeyen. “They knew
that if they could get more yield on the same land with these new varieties
of plants, then they could have more money and a better family life.”
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Borlaug’s third approach required governments to change their

agricultural policies radically. Because his wheat required new methods
of farming, farmers needed access to a system of credit so they could
afford fertilizer and seed in advance of planting. The fertilizer was always
a fight. Borlaug’s wheat was bred to take up heavy applications of
fertilizer, and economists at the time did not realize that fertilizer was an
investment that would be repaid with much higher yields. Also, Borlaug
insisted that government money be available for drainage and irrigation
improvements, as well as equipment to plant and harvest the wheat. In
addition, farmers needed the government to create an infrastructure of
roads, bridges, and warehouses to get the wheat from the farms to market.
Finally, governments had to guarantee farmers fair prices for their future
crops in advance. This American showing up on their doorstep and telling
them how to run their agricultural policies was often met with great
suspicion by governmental officials.
Borlaug knew if he merely provided them with academic papers,
nothing would change. He had to find a way to impress upon officials that
the miracle seed was only the first step to a fruitful agricultural policy.
This was especially difficult in India, which had become independent
from Great Britain in 1947. In 1964, the country’s first prime minister
had died, and the fragile democracy was teetering between the Cold War
superpowers.
Since India never sent trainees to Mexico in those early years,
Borlaug and the Rockefeller Foundation began showing India how
agriculture reform was progressing in India’s bitter rival Pakistan. It was
in Pakistan that Leon Hesser, the author of Borlaug’s 2006 biography,
The Man Who Fed the World, first met his subject forty years earlier.
Hesser was working for the U.S. State Department and was charged with
increasing food production in Pakistan, an impossible task until Borlaug
showed up. As Zeyen appraised the situation, “Once a country like
Pakistan took off and started heading into self-sufficiency, India had no
choice but to participate.”
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Norman Borlaug
But when India finally expressed interest, it wanted all the results
without the necessary policy changes. Once again, Borlaug was forced to
use his wrestler’s tenacity. Borlaug had already impressed the Minister
of Agriculture, Dr. Shri C. Subramaniam, with his program. Unfortunately,
Subramaniam had been voted out of the government. As a man with a
deep concern for his countrymen, he arranged for Borlaug to meet the
man in India’s government who had the power to change agricultural
policy, Deputy Prime Minister Ashoka Mehta, the number two man in
India’s government.
Borlaug attacked every argument the minister made for slow change.
He insisted that India import more fertilizer and build fertilizer plants,
and he provided a list of international agencies that could lend the money
to finance these operations, but none of this was acceptable to Mr. Mehta.
But then Borlaug told Mehta of the farmers: If the new policies were
adopted, the farmers would dramatically increase production, and this
would stimulate the whole economy. Borlaug believed India could feed
its people. “As the meeting ended, I think we had re-established mutual
respect, if not mutual friendship,” Borlaug related.
Two weeks later, India’s newspapers were full of stories concerning
India’s new agricultural policy. The government had capitulated—
Borlaug had won—and the farmers could go to work. That year Pakistan
and India placed an order for 600 tons of Mexican wheat seed.
The seed made it to the subcontinent. Despite its slow start, the first
crop still produced yields 70 percent higher than India had been producing
on its own, and the next crop showed a 98 percent improvement.
India’s government finally moved boldly. It ordered 18,000 tons of
Mexican wheat seed, chartered two freighters, and had the largest seed
purchase in history shipped directly from Mexico across the Pacific to
India. The following year, Pakistan ordered 42,000 tons of seed. It was as
if they were in a race to succeed. By 1968, Pakistan was self-sufficient in
grain production. By 1974, India joined it. In the years that followed,
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caloric intake per person steadily rose as wheat production rose, and the
percentage of undernourished people in India declined from 39 percent
to 22 percent. China, watching its rival and neighbor, also changed its
agricultural policies and saw the proportion of undernourished people in
their country drop from 52 percent to 12 percent over the next three
decades. Perhaps just as impressive was that the increased production
came with no increase in the amount of land required to grow the crops.
Yields increased in India by 150 percent and in China by 300 percent.
India practiced double cropping, a system in which two crops a season
were planted, one watered by the natural monsoon, the other by the
artificial monsoon of irrigation.
In 1968, United States Agency for International Development
director William Gaud stated, “The rapid spread of modern wheat and
rice varieties throughout Asia and other developments in the field of
agriculture contain the makings of a new revolution—I call it a Green
Revolution—based on the application of science and technology.” It was
the first time the phrase was used, but it stuck because the effects were so
monumental. Thomas R. DeGregori, Professor of Economics at Houston
University, says, “At the core of the Green Revolution was a grain
revolution, with Borlaug’s wheat providing roughly 23 percent of the
world’s calories.” Borlaug was not alone in making these dramatic
agricultural advances, but it was his extensive plant breeding in Mexico
and his iron-willed drive to make government officials take action that
was the catalyst for much of the Green Revolution.
It Is Nutrition that Saves Lives

Borlaug’s revolution did save millions upon millions of lives.
The long-term death toll from food shortages stems much more from
undernourishment than outright starvation. From the late 1800s, it was
known that nutrition is important in warding off specific diseases such as
scurvy. But two decades ago, Nobel laureate Robert William Fogel,
among others, discovered that nutrition also had a dramatic effect on the
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Norman Borlaug
length of a person’s life. In other words, your mother telling you to eat
your veggies as a child actually has an effect on how long you live. In
fact, it has been found that average height has increased dramatically in
populations around the globe whenever nutrition has improved. For
example, the average Frenchman in 1775 was five feet, four inches tall,
and is now five feet, ten inches tall. Additional height is an indicator of
more robust organs that better stave off disease.
Recently, new experiments in epigenetics, a revolutionary field
involving DNA inheritance, have shown that poor nutrition can impact
one’s chromosomes such that effects can even be passed on to future
generations. Epigenetics involves the study not of the makeup of the
DNA molecule itself but of the chemicals and structures that affect how
the genes coded by DNA are expressed. These structures can be affected
in a long-term way by environmental influences such as diet. These are
examples of how nutrition affects an adult’s lifespan; the effects of
malnutrition on children are more severe. Estimates today are that half of
all children who die in the developing world do so because of malnutrition.
Measuring growth retardation or stunting is one-way scientists assess the
health of children. Stunting is a direct consequence of poor nutrition and
is strongly correlated with increased mortality. In 1980, just after the start
of the Green Revolution, 47 percent of all children in the developing
world were stunted. By the year 2000, this figure had dropped to 33
percent. The Green Revolution laid the cornerstone for adequate
nourishment by increasing the available calories and protein of the
developing world’s people. The impact of Norman Borlaug’s Green
Revolution on saving people’s lives has been profound and is still being
played out. Our estimates are that Norman Borlaug’s Green Revolution
saved over 245 million lives due to improved nutrition. The most
significant measurable change was the decline in the death rate of children
under the age of five. In addition, increased nutrition has allowed millions
of adults to live gracefully into old age.
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The Nobel Prize

It was October 20, 1970, and Norman Borlaug was doing what he
had done at this time of year for the past twenty-six years—standing in a
Mexican wheat plot dressed in mud-splattered clothes, boots, and a
baseball cap, choosing exceptional wheat varieties. Around 10 AM, he
heard the sound of a car bumping along the rutted road at the edge of the
Toluca station. When it stopped, and he saw his wife emerge, he became
frightened; something must have happened to one of their two children.
“What’s wrong?” he cried, dropping his wheat samples, and running
towards her.
“Nothing,” she laughed. “You’ve won the Nobel Peace Prize, that’s
all.”
At first, he refused to believe it. Borlaug insisted Margaret return to
their house; he still had a day’s work to accomplish.
What, you might ask, do wheat and bread have to do with peace?
Perhaps expecting that question, the Nobel Committee answered it when
it awarded Borlaug the 1970 Peace prize. The committee compared
Borlaug’s work “to the basic human right of freedom from starvation as
recognized by the Charter of the United Nations,” and declared that his
work had “helped to turn pessimism into optimism in the dramatic race
between population explosion and food production.”
For Borlaug, however, the prize was a complete surprise. “You have
to understand that Norman Borlaug has no ego,” Zeyen says. “He’s the
world’s greatest humanist. He cannot stand to see people suffer.” He is
one of six people to have won the Nobel Peace Prize, the U.S. Presidential
Medal of Freedom, and the Congressional Gold Medal. He was also
awarded the Padma Vibhushan, India’s second-highest civilian honor.
An Environmentalist
As Borlaug continued his efforts to expand agricultural success, he
found himself fighting off critics who began denouncing his methods,
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Norman Borlaug
particularly the large quantities of fertilizers and pesticides required to

achieve the high yields.
Recall that Borlaug worked alone in the wilderness in Idaho during
his college summers. “To this day,” Borlaug has said, “I enjoy nature, the
luxury of undisturbed wilderness, forests, mountains, lakes, rivers, and
deserts, and their wildlife. But I also know that the greatest danger to their
perpetuity is the pressure of human population.” In a paper he wrote in
2000, he said, “We all owe a debt of gratitude to the environmental
movement that has taken place over the past forty years. This movement
has led to legislation to improve air and water quality, protect wildlife,
control the disposal of toxic wastes, protect the soils, and reduce the loss
of biodiversity. It is ironic, therefore, that the platform of the anti-
biotechnology extremists, if it were to be adopted, would have grievous
consequences for both the environment and humanity. Borlaug points out
that to produce 1999’s world cereal crop using 1961 agricultural methods,
an additional 2 billion acres would have to be under cultivation—that’s 3
million square miles, about the size of the contiguous United States.
Instead, this land can be used for other purposes, such as wilderness
preserves. As Vaclav Smil of the University of Manitoba says, “Without
the 80 million tons of nitrogen consumed annually (from chemical
fertilizer), the world could sustain no more than four billion people, two
billion fewer than inhabiting the Earth today.”
This type of evidence suggests that Borlaug’s Green Revolution may
have saved more land for wilderness than any single environmental
organization.
Workaholism Redefined
The Nobel Peace Prize slowed Borlaug, not one whit. He continued
to be an agricultural ambassador up into his seventies, with his methods
becoming widely acclaimed, especially outside of the U.S. It was in the
1980s when Borlaug was semi-retired that a notorious Japanese
shipbuilding magnate was struck by images of starvation in sub-Saharan
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Africa. Ryoichi Sasakawa, chairman of the Japan Shipbuilding Industry

Foundation, had experienced about as broad a career as one can imagine.
His past included an association with the Japanese war machine and
questionable business practices, along with international industrial
success, and being a friend of Jimmy Carter, the first U.S. president to
visit sub-Saharan Africa while in office. In the 1980s, Sasakawa began
donating millions to the United Nations to help fight hunger in Africa.
But as the years passed, he felt that not only was his money not enough,
but that it might be going for weapons, not food. So, in 1985, he had his
assistant call Borlaug and ask, “Why has there been no Green Revolution
in sub-Saharan Africa?” The assistant asked Borlaug to bring his
revolution to the last starving continent.
For more than three decades, Norman Borlaug had expended a huge
amount of his time away from his wife and kids, traveling all over the
world. For decades he had physically labored hours on end in the fields,
putting wear on his body matching any laborer. If anyone had earned the
reward of retiring, giving an occasional lecture, and bathing in the warm
social status of sitting on some policy boards, it was Norman Borlaug. He
knew little about Africa. Caught off guard, he told the assistant, “I’m too
old to start learning now.” The next day, Borlaug received a phone call
from Sasakawa himself. The billionaire told him, “I am 13 years older
than you are, Dr. Borlaug. We should have started sooner and didn’t, so
let’s start tomorrow!”
Borlaug had never been one to turn away from a challenge to help
people. And so, at age 72, he was called back into the battle to combat
hunger. He organized a meeting of experts in Geneva, Switzerland, to
evaluate the issue. Three conclusions emerged. First, the food crisis in
Africa was the direct result of the political anarchy that had ruled much
of the continent for decades. Second, as Borlaug asserted, “Lack of
infrastructure is killing Africa.” He explained that the United States had
13,000 miles of paved road for every million people, while Ethiopia had
forty-one miles for every million people. How could there exist efficient
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Norman Borlaug
markets with no way to transport the food? And finally, because wheat
could only be grown in some parts of Africa, Africa would require
additional food crops bred for better yields.
Jimmy Carter and Bill Foege, head of the newly formed Carter
Foundation, attended the Geneva Conference. There, Sasakawa turned
his persuasive powers on the former president, and in late 1985 Global
2000, Inc. was created to address the starving continent. Carter and
Sasakawa were co-chairmen, and Borlaug headed the agricultural
initiative. Africa became Borlaug’s new India.
The organization selected Ghana as its first country of focus in 1987,
instituting the classic Borlaug-inspired agricultural initiatives. By 1991,
Ghana was producing all its own food and a few years later actually
began exporting food to other countries. One secret to the country’s
success was a new form of corn: Quality Protein Maize (QPM), a grain
that is so nutritionally complete it could be used to wean infants off breast
milk. Unfortunately, the Ghana experiment has not been reproduced
throughout Africa. The main challenges remain a lack of infrastructure
and warring governments, which turn millions of citizens into refugees
and make agricultural production impossible.
Borlaug Today
Borlaug has remained on the world stage, preaching against
complacency. As he warned in his Nobel speech: “The Green Revolution
has won a temporary success in man’s war against hunger and deprivation;
it has given man a breathing space. If fully implemented, the revolution
can provide sufficient food for sustenance during the next three decades.
But the frightening power of human reproduction must be curbed;
otherwise, the success of the Green Revolution will be ephemeral only.”
When Borlaug was born, the world’s population stood at about 1.7
billion. When he won the Nobel Prize, it was at 3.7 billion. Today it
stands at 7 billion, with an average growth rate of 1.1 percent per year.
The population bomb did indeed explode during his lifetime. Borlaug
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asserts, “I am confident that the Earth can provide food for as many as ten
billion people—six times the number who lived when I was born—if, and
this is a big if, the world’s societies support a steady stream of both
conventional and biotechnology research, and political policymakers
stay attuned to the needs of rural development.”
Norman Borlaug, 94 years old when this chapter was written,
continues to try. For more than 85 years, he has been working to grow
food, first as a farm boy, next as an agricultural scientist, then as a world
agricultural diplomat, and finally, when he was 72 years old, in Africa.
Despite his age, the man seems never to rest. “He’s driven,” says Hesser.
“He obviously doesn’t need the money; he spends hardly anything at all.
But it’s just that he wants to accomplish something significant while he’s
still here.”
Food Security and environmental protection have been the major
challenge for the 21st century. The use of too much nitrogenous fertilizer
has created bigger environmental issues than carbon dioxide Pollution.
Coupled with the use of pesticides and weedicides, depletion of
micronutrients going down in the soil and water table going down has led
to Impact analysis of green revolution on the health of the human being.
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6
John Enders
(1897—1985)
The Father of Modern Vaccines

VACCINATION BEGAN in the late 1700s when Edward Jenner

inoculated a young boy against the smallpox virus, using a scab from
someone infected with the much milder but related cowpox virus. To
honor Jenner, Louis Pasteur later
termed all such immunizing medicines
as vaccines (“Vacca” is Latin for
cow), and the name stuck. While the
diseases caused by viruses were those
for which the need for vaccines was
greatest, there were no cures for any
of them, and, at best, doctors could
treat the symptoms.
Then everything changed thanks
to research led by a man you have
probably never heard of. His John Enders in his office (1955).
Enders didn’t receive his Ph.D. until
laboratory pioneered the techniques
he was 33 years old. He was 50
that quickly led to dozens of vaccines. when he started the viral research
Of all the common human diseases, that would revolutionize vaccines.
measles is the most contagious. Prior At that time, only three childhood
vaccines existed. Now there are
to the development of a vaccine in fifteen.
1963, getting measles was a childhood Verner Reed/ Time & Life Pictures Collection/
Getty Images.
rite of passage. Measles is a disease
John Enders
that is now gone. Thanks to the long and hard work of many scientists and
the money spent on it are for producing the vaccine.
A Member of the Lost Generation

John Enders was born on February 10, 1897, into a family of high-
achievers. His father was president of Hartford National Bank, left the
family a fortune of 19 Million dollars when he passed away. Thus, John
Enders became financially independent, which may help to account for
his rather atypical path to a career in biomedical research. A frequent
family visitor during Enders’ childhood was better known by his
pseudonym Mark Twain. The young Enders always admired Twain’s
immaculate white suits whenever he visited the Enders home. So, perhaps
enders’ early exposure to eminent writers among his father’s clients
planted the seed for his interest in literature. In school, the young Enders
had trouble with math and physics. At age 17, he was already concerned
about accomplishing something in life.
He matriculated to Yale University but interrupted his education to
enlist in the Naval Reserve to serve in World War I. After graduating
from Yale, Enders set out to uphold the family tradition of business. He
was brokering real estate. After four fruitless years in business, Enders
searched for something to interest him and, finding nothing, decided to
go back to school. Choosing Harvard this time, he received a master’s
degree in English, then decided to pursue a doctorate in philology, the
study of language as used in literature.
While lost in purpose, Enders’ life was not miserable. He lived with
some medical students in Mrs. Patch’s comfortable boarding house.
There he met an animated Australian, Hugh Ward, whose daily description
of his doctoral work in microbiology piqued Enders’ interest. Enders
wrote I became increasingly fascinated by the subject—which manifestly
gave him so much pleasure. Ward also introduced him to Hans Zinsser,
a charismatic professor
Together, Ward and Zinsser transformed Enders’ life, convincing
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him that his intellect was better suited to science than philology. So, in
1927, at the age of 30, considered late even in his day, Enders made a
180-degree turn in his studies. He entered the doctoral program in
bacteriology at Harvard. That same year he married Sarah Frances
Bennett.
It was rare to earn a doctorate under Zinsser, a demanding taskmaster,
but Enders earned him in 1930, with a thesis on anaphylactic shock
caused by carbohydrates extracted from tubercular bacteria. He became
an instructor and worked in the Harvard labs. As a teacher, he was noted
for his personal magnetism in small-group and one-on-one settings.
Perhaps because he had found his intellectual home in Zinsser’s lab,
Enders showed little of the academic ambition typical of Ph. Ds in their
30s. It was five years before he became even an assistant professor and
another seven years before he became an associate professor. It would be
thirteen years before he could employ a personal technician. Research, as
opposed to advancing his career, was his main interest. When, in 1937,
Harvard’s experimental kittens came down with feline distemper, Enders
and a young epidemiologist, William Hammon, began a careful study of
the disease. They found it was caused by a virus and worked on developing
a vaccine. This and other studies turned Enders’ interest toward viruses,
where he made his first major breakthrough— “the development of
serologic techniques for the detection of antibodies to the mumps virus.”
Viruses
Viruses are very different from bacteria, the other type of agent that
causes most diseases. They are so tiny that they were not even seen until
the advent of the electron microscope in the 1930s when Enders was
beginning his research. Made up of genetic material—either DNA or
RNA strands—and encapsulated in a protective protein shell, viruses
thrive in bacteria, fungi, plant, and animal cells, co-opting the cells’
genetic machinery to acquire energy to reproduce. When they parasitically
infect our bodies, they cause diseases such as the common cold, flu,
hepatitis, herpes, HIV, SARS, and Ebola, just to name a few.
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John Enders
Viruses’ exceedingly small in size, making them devilishly difficult

to study. At the time that Enders began to take an interest in them, most
viruses could only be grown in vivo (Latin for “in the living”), which
meant in living animals. Animal experiments are expensive, slow, and
awkward. They often require the sacrificing of live animals
What scientists needed were techniques for studying viruses in vitro
(in test tubes), which presented several challenges. First, a given virus
will only grow in certain cells from certain animals. Second, the cells
must be healthy when infected with a virus. Third, the cells must remain
healthy, which means they must be provided with nutritious food. Fourth,
the cells must remain uncontaminated. Finally, if a virus can be induced
to multiply, it often kills the very cells into which it has been cultured,
releasing viruses into the liquid remnants. The only way to maintain
those viruses is to transfer them to new tissue culture, called a subculture.
In the 1940s, growing viruses in test tubes in sufficient quantity to
experiment with was a major barrier to virology research.
The Iron Lung

The early 1940s greatly upset Enders’ idyllic lab life. In September
of 1940, Hans Zinsser died, not only costing Enders his cherished mentor
but also burdening him with the lab’s bureaucratic administrative duties,
which were not his forte. Then World War II began, resulting in most of
the young doctoral candidates leaving for military service. Tragedy
struck again in 1943, when Enders’ wife Sarah suddenly died from acute
myocarditis, an inflammation of the heart. The forties were particularly
tragic for another reason—polio epidemics. And it was out of polio
research that the techniques leading to the development of the measles
vaccine emerged.
When polio struck, terror followed, and if you had children, the panic
was completely understandable. Unlike anything parents face now, polio
came like clockwork when the weather warmed and left with the first
chill. Every few years, however, it struck with particular viciousness. In
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1916, New York City tallied 9,300 cases, with 2,200 children dying. Half
the survivors were paralyzed.
A decade later, scientists developed a respirator, technically known
as a “negative pressure ventilator,” that kept alive children who could not
breathe because of paralysis of the diaphragm. Invented at Harvard in the
late 1920s, when the pressure in the drum fell below the level of the
pressure in the lungs, the lungs expanded and sucked in the air; when the
pressure was greater outside the lungs, the lungs were squeezed to exhale.
Hospital wards were filled with them. Polio struck the wrong person in
1921, the future President Franklin Delano Roosevelt. FDR was grown
when he was diagnosed, and because he was from a wealthy family, they
turned many resources towards finding a cure, eventually founding the
National Foundation for Infantile Paralysis.
Almost every authority on the disease in America eventually either
worked directly for the foundation or was funded by it. Its budget dwarfed
that of the National Institutes of Health, which had only recently been
chartered with a tiny budget.
A Poor Polio Paradigm

Prior to the National Foundation for Infantile Paralysis, the
Rockefeller Institute for Medical Research funded most medical research.
Founded in 1901 by John D. Rockefeller, the Rockefeller Institute
produced impressive research, decades later financing most of Howard
Florey’s work on penicillin and Norman Borlaug’s Green Revolution.
Researchers under Simon Flexner made several mistaken conclusions
concerning polio. One led to a misconception that, propagated by Flexner,
held back polio research for over a decade. Flexner’s researchers proved
that polio was neurotropic, meaning it multiplied in nerve tissue, which
Flexner concluded as meaning polio multiplied only in nerve tissue.
Indeed, in the years prior to World War II, some researchers attempted,
unsuccessfully, to make a vaccine from the small amount of virus that
could be obtained from monkey spinal cords. It became clear that vaccine
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John Enders
creation would require a way to dramatically multiply the poliovirus,

which had proven very difficult to accomplish in nerve cells.
The Gentleman Scholar from Connecticut Gets His Own

Lab
After the war, Enders was asked to establish a research laboratory on
infectious diseases at Boston Children’s Hospital, which was located just
across the street from Harvard Medical School and had various ties to
Harvard. In 1940, Enders had worked with Thomas Weller, a young
medical student, on an experiment that had revolutionary implications.
By using a roller tube apparatus, they had kept the cowpox virus (vaccinia)
growing for nine weeks in a test tube. The hospital allocated four rooms
on the second floor of the Carnegie Building. First, it needed a thorough
cleaning. Then, two rooms were turned into labs; one room was the glass
washroom, and the final room was Enders’ office. On the wall, Enders
hung pictures of Edward Jenner and Louis Pasteur, and would later add
pictures of researchers who worked in the lab, each with a story Enders
loved to tell. Animals were kept a block away in another building. Enders
and Weller furnished the lab with the standard equipment, such as an
autoclave to sterilize equipment and chemical hoods to work under, along
with some more novel items. Embryonated hens’ eggs had recently been
introduced as media in which to grow viruses, so they purchased an egg
incubator and visualizing lights to shine into the eggs. Turning the eggs
was a daily chore, including weekends. Early in 1948, they added
Weller’s college roommate Frederick Robbins to the team. Robbins and
Wellers were both brilliant doctors but very different in personality.
Robbins was relaxed and reflective. Weller was dynamic and animated.
Enders never seemed in a hurry in his life, and by the time they had
the lab up and running, he was 50 years old, slightly stoop-shouldered,
and tweedy. His first priority was looking at new findings, so he made the
rounds to all the experiments, moving slowly, often with a pipe in his
mouth. Enders had already worked with viruses such as herpes simplex,
influenza, measles, and mumps and wanted the new lab to expand such
( 134 )
research. There were numerous experiments going on at any one time.
Almost Without Conscious Effort

Weller was full of ideas and set about trying to isolate the varicella
virus, the cause of chickenpox and shingles, using embryonated hens’
eggs. The experiment failed. Early in 1948, he decided to construct an
experiment that might work in a way similar to their 1940 experiment,
still trying to isolate the varicella virus. Enders suggested he try it with
the mumps virus instead.
Weller’s idea was to start with the Maitland technique, whereby
tissue is placed in a flask along with a nutrient solution, then inoculated
with a virus. He inoculated chicken eggs’ amniotic membranes (the fluid
sac that surrounds and protects the embryo) with the mumps virus and
placed it in a flask with a nutrient mixture of balanced salt solution and
ox serum ultrafiltrate. Weller’s idea was to modify this technique by
leaving the tissue in the flask and replacing the nutrient fluid every four
days. This allowed the tissue to remain alive for a longer period of time,
giving the virus more time to grow in each cell. The experiment worked.
The tissue did not quickly die, and the virus continued to multiply and
grow. Enders suggested they do the same experiment using an influenza
virus.
The Growth of Poliovirus in a Flask

Next, Weller prepared to use this technique to try to isolate the
chickenpox virus, as he had originally intended. He inoculated four of
them with cultures of throat washings from a child who had chickenpox.
Another four flasks were not inoculated and were to act as controls.
There were three strains of poliovirus known at that time. The
primary human pathogen was the Brunhilde polio strain, which had
previously only been grown in humans and monkeys. The Leon strain
was very rare, but significantly a third strain, the Lansing strain, had been
found to grow in mice. The lab had cultures of it, and Weller put it in the
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John Enders
four remaining flasks. Four days later, Weller changed the nutrient fluid
in all twelve flasks and changed it again on April 7, whereupon he took
samples to test for growth of the chickenpox virus. He was disappointed:
There was no evidence that the chickenpox virus was growing in the
flasks. He also took fluids of the cultures he had inoculated with poliovirus
and injected them into the brains of five mice. On April 14, one mouse
became paralyzed and died and, as the days passed, three more mice died.
Never before had there been evidence that poliovirus could be grown
in non-nerve cells. Enders now focused the lab’s efforts on the poliovirus.
Enders had Robbins repeat the experiment, using the intestinal tissue
obtained from an autopsy of an infant who had been born prematurely
and had died. This experiment, too, was successful.
Enders and his colleagues knew well they were dealing with a
dangerous pathogen, and they had already developed safety procedures
for handling viral specimens. Further experiments showed they could
grow the other two known types of polio, the Brunhilde and Leon strain,
in the same manner. Over the next year, Enders and his colleagues
demonstrated that the virus would grow in human embryonic tissues
from the intestine, liver, kidney, adrenal, brain, heart, spleen, and lung.
The Flexner polio paradigm was completely overturned.
Cytopathic Effect
Enders’ work with the mumps virus had shown that fluids infected
with the virus visibly affected red blood cells, which could be observed
under a microscope. This provided an important lab test that could be
used to tell if the fluid was really infected by the mumps virus.
One day, peering into the microscope, Enders saw a poliovirus-
infected cell explode. “Cytopathogenicity,” he exclaimed, inventing a
word. He and his team could observe the pathological effect of the
poliovirus on the cultured tissue cells sixteen to thirty-two days after
being inoculated.
( 136 )
Next, they implemented a chemical marker identifying the growth of

the virus in infected tissue by adding phenol red, a dye. The poliovirus
affected the cells’ metabolism, such that the cells produced less acid than
those not infected. In uninfected control cells, the dye changed color to
yellow as the cells acidified. In infected cells, it remained red. Thus, they
had a ready test for the presence of polio in human tissues. The researchers
also discovered a positive correlation between the acidity of the cultures
inoculated with poliovirus and the amount of time since the inoculation.
The team shortened its ability to recognize the virus to eight days using
another technique and found a way to develop a test tube test to determine
the type of poliovirus and their respective antibodies in human or animal
blood serum. These techniques would all become common testing
techniques in virology,
The Roller Tube Apparatus

Roller tube tissue cultures had been perfected by George Gey in
1933, and Enders had been one of the first to use them with viruses.
Rather than growing animal tissue in flasks, researchers, using roller
tubes, plant tissue cells in plasma clots on the sides of test tubes. Viruses
can then be inoculated into this tissue. The goal is to more accurately
mimic conditions inside the human body, where tissue is exposed to an
active environment of nutrients and waste product removal, rather than
the static environment of a motionless test tube or flask.
A big advantage of using the roller tube technique comes when
viewing the cultures under a microscope. When they used the roller
tubes, they found that the virus grew more rapidly and to higher titers
(concentration) than in the suspended cultures in the flasks. This cut the
time necessary to observe the growing virus to four days.
Leaving Monkeys at Play by Adding Antibiotics

Until that point, scientists who had wanted to isolate and type
poliovirus cultures could only do so by injecting the virus directly into
the brains of living monkeys, letting the virus infect the brain tissue,
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John Enders
killing the monkeys, and testing samples for the virus. In the end, more
than 100,000 monkeys were sacrificed; however, Enders and his team
found a way to spare future monkeys by successfully isolating poliovirus
from the monkeys’ feces. Robbins performed much of this research,
adding penicillin and streptomycin—two newly discovered antibiotics—
to kill off bacteria.
When Robbins found something exceptional, he wrote the results in
his laboratory notebook in red ink. The red ink flowed. Experiments
demonstrated that many children carry lots of viruses similar to polio,
often with no symptoms. Within two years, the team had isolated and
typed thirteen strains of poliovirus. They also discovered the first of a
whole group of viruses that became known as ECHO viruses (enteric
cytopathic human orphan viruses), cousins to polio.
During this time, the Enders team were writing papers and giving
frequent presentations of their findings, so many researchers would visit.
The Holy Grail—Attenuation

Weller continued to work on propagating the poliovirus. He grew the
Lansing virus through twenty-three passages (a passage occurring
whenever he changed the tissues in which the virus was growing), over
331 days. As the number of passages increased, the virus’s virulence
decreased well over 100,000-fold.
The weakening of a virus through serial passage was a method
developed by Louis Pasteur in the 1870s, arising from his work with
chicken cholera, anthrax, and rabies. Serial passage exploits evolution
through the principle of natural selection. Likewise, a virus that is
devastating to humans can be passed serially through various nonhuman
tissues and end up vastly weakened—known in virology as attenuation—
yet retain enough of its original protein coat signature that the antibodies
a human immune system produces to fight the attenuated virus in the
vaccine will also fight the original virus. In less understated words, —a
vaccine was possible!
( 138 )
A Revolution in Molecular Virology

In the 1870s, Robert Koch invented bacteriology by trying to grow
bacteria using potato slices but soon moved on to gelatin broths. These
worked well at cold temperatures, but not at hot ones. Others suggested
using a type of Japanese seaweed called agar-agar, which could be made
into a wax-like medium. Richard Petri added the dish. Using a petri dish
and agar and adding a sugar-rich substance as a nutrient, bacteriologists
found they could grow, identify, and study all sorts of bacteria. Thus,
microbiology was born.
Enders and his colleagues sparked a comparable revolution with the
development of their tissue culture techniques. Viruses had been grown
in tissue cultures prior to Enders, but only sporadically and with difficulty.
As a result, most researchers used live animals as the medium in which
to grow viruses. Enders’ team devised methods that provided virologists
with the ability to grow a limitless supply of virus in numerous tissues.
Moreover, their methods drastically shortened the time required for
experiments, allowing for the testing of virtually endless ideas. Soon
their methods were used in laboratories all over the world, leading to
numerous major discoveries.
By 1961, fifty-eight more human viral pathogens had been cultured,
plus another 300 viruses that infect animals. Finally, Enders’ team
demonstrated all the techniques which led to a cascade of vaccines for a
plethora of viral diseases.
Romance in the Lab

The lab began as a group of diverse researchers but grew, literally,
into a family. Shortly after Robbins joined the lab, he fell in love with
Alice Northrop, and soon they married. Enders followed suit, marrying
Carolyn Keane in 1951. Summers often found the Enders at their
waterfront house in Connecticut, where John liked to go powerboating on
Long Island Sound, often fishing for striped bass.
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John Enders
Salk and Sabin

A vaccine is a preventative medicine that jump-starts the immune
system into producing antibodies to attack a specific disease, usually
before the immunized person contracts the disease itself.
In the 1940s, there were vaccines for three childhood diseases—
diphtheria, tetanus, and whooping cough (pertussis)—all caused by
bacteria. For diphtheria and tetanus, researchers discovered how to make
toxoid vaccines, which are based on purified and deactivated forms of the
disease-causing toxins these bacteria produce. Whooping cough was a
killed vaccine: the bacteria that caused it was killed but retained the
protein coat signature that allows our immune system to identify them.
Before Enders, the only preventative viral vaccine was for yellow fever.
Using the serial passage technique, researchers had grown the virus over
and over again in different tissues until it had evolved into a much weaker
pathogen. Each of these types of vaccines was shown to trigger a
protective immune reaction in humans.
In 1952, Salk developed a vaccine that contained chemically killed
viruses from all three types of polio. In what was then the largest public
medical experiment in history, 200,000 children were injected with the
Salk vaccine, and the vaccine proved almost 80 percent effective at
preventing infection with polio. The Salk vaccine was licensed for use in
1955, and within the next decade, immunization made polio epidemics a
thing of the past in most of the developed world.
In 1957, Albert Sabin developed a vaccine of weakened, or attenuated,
virus, which he insisted was safer and more effective than the Salk killed
vaccine, and which could be taken orally in delicious sugar cubes. It was
Sabin’s live vaccine that became the standard vaccine used in the United
States in 1961. Endorsed by the WHO, it eventually was used throughout
most of the world.
The Nobel Prize

With the work on polio finished, Robbins left in 1952 for a position
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as Professor of Pediatrics at Western Reserve University in Cleveland,

and in 1954 Weller made the short move back to Harvard to become head
of the Tropical Public Health Department. His virology work later
isolated the viruses that cause chickenpox and rubella, among others.
In the fall of 1954, Enders, Weller, and Robbins were notified that
they had received the Nobel Prize in Physiology or Medicine “for their
discovery of the ability of poliomyelitis to grow in cultures of various
types of tissues.” While Salk and Sabin received most of the public
recognition for developing the polio vaccines, it is noteworthy whom the
Nobel Foundation chose to honor. Two years later, Harvard granted
Enders a full professorship, after his twenty-six years of productive
research. Meanwhile, he had already begun applying the new tissue
culture techniques to another virus.
Measles—Astonishingly Communicable
Measles has been with us for thousands of years and was described
by Persian doctor Rhazes around 900 A.D. as “the safer form of smallpox.”
It was not until the 1600s that the two diseases were recognized as
distinct, and efforts to inoculate against measles—began in the next
century, albeit without success. Measles usually strikes in waves of two
to four years and is astonishingly communicable—even the slightest
contact will pass it on. It remains incurable to this day, although secondary
infections can be treated with antibiotics. Measles starts with a high
fever, a runny nose, a cough, and a sore throat. After five days, a blotchy
red rash develops. One measles patient in every six develops pneumonia
or a serious ear infection. One in every thousand gets measles encephalitis,
an inflammation of the brain that can cause paralysis, mental retardation,
and even death. Measles kills more children than any other acute
infectious illness.
The WHO estimates that when Enders began his work, 106 million
people got measles each year, and more than 6 million, mostly children,
died.
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John Enders
An Assault on Measles
Measles had been a particularly difficult virus to work with because
there was no good animal host on which to experiment. When Enders
began researching measles in 1953, Asian monkeys were the only
nonhuman species that had been found to be susceptible to the virus.
Enders’ new tissue culture techniques did not do away with all animal
experimentation; monkeys were still needed to test vaccines upon.
Without a test animal, and with the tissue culture technique still being
relatively new, little progress had been made with the measles virus.
Six scientists in Enders’ lab played significant roles for varying
lengths of time in the assault on measles: Samuel Katz, Thomas Peebles,
Kevin McCarthy, Anna Mitus, Milan Milovanovic, and Ann Holloway.
Isolating and Growing the Virus

Enders sent Tom Peebles, a pediatric resident, to draw blood and
collect throat swabs from kids in Boston who had measles. Using roller
tube techniques, the team began trying to isolate and grow viruses from
their samples. They continued to grow the viruses in serial passages
through these media. From four to ten days after they were inoculated,
the tissues began to show the abnormal, cytopathic changes that indicated
a virus had taken over the cells.
Later, combined human sera from twelve people who had been
afflicted with measles to the tissues to see if antibodies in their sera would
inhibit the cytopathic process. It did. As early as 1954, tissue culture
techniques were producing great results.
The Monkey Riddle

The next step for Enders and his colleagues was to inoculate monkeys
with the virus they had grown after one, two, and twenty-three serial
tissue passages. Just as previous researchers had found, the results varied:
Some monkeys showed symptoms, and others did not. To try to solve this
riddle, they examined their next set of experimental monkeys before
( 142 )
running any trials on them and found that twenty-two of twenty-four

monkeys from three different laboratories already had complement-
fixing measles antibodies in their blood. The researchers next examined
thirty-one monkeys just caught in the wild from Malaya and the
Philippines—none had measles antibodies. They didn’t know how the
laboratory monkeys had become contaminated with measles antibodies,
but that did explain the variable results. It also allowed monkeys to be
used as reliable test animals once the contaminated ones were weeded
out.
Growing the Virus in Chick Cells

At the same time, the lab was trying to grow the virus in tissues other
than humans, such as pigs, cattle, or chick cells. In order to make a
vaccine, it was important to find a non-primate tissue in which to grow
the virus. Month after month, these attempts proved unsuccessful, so time
after time, Enders and his team left the lab without making progress.
Two years passed as they continued to experiment after experiment,
serial passage after serial passage, mincing more beef for more tissue
cultures. There is no definite recipe for growing a virus in foreign tissue
or for developing a vaccine.
Finally, in the team’s third year of working with measles, they
observed an interesting phenomenon. After passaging what they called
the Edmonston strain twenty-three times through human kidney cells,
then fourteen times through human amnion cells, they noticed that some
cells did not undergo the typical cytopathic change. Instead of enlarging
and blowing up when infected, some cells became star-shaped or spindle-
shaped. As the researchers continued to passage the virus, these cells
came to be the predominant manifestation of the virus.
They could continue to passage the virus many more times through
those cells and obtain the same cytopathic reaction as they had seen in
human amnion cells. They next tried growing measles in other chick
embryonic tissues, and that also worked. At long last, they had found a
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John Enders
growth medium that might yield a viable vaccine.
Attenuation
To attenuate the measles virus, Enders and his team needed to put it
through enough passages to weaken it so it would no longer infect humans
but not destroy so many that it would no longer produce enough viral
antigens to create an immune reaction. (The antigens are the protein coat
“signature” of the virus, and this is what allows the immune system to
recognize a particular virus and send antibodies after it.) In the end, the
lab developed two potential recipes. The best was from the Edmonston
strain. It was produced after an additional six passages through chick
embryos and fourteen passages in chick cell cultures.
Enders’ team now had to establish that their virus would work as a
vaccine in humans, so medical doctors began tests on small groups of
children. Between December of 1958 and March of 1960, they ran six
sets of tests on children. The vaccine gave the children a mild infection,
but nothing worse, and the tests did not make them contagious. More
importantly, it gave children immunity from full-fledged measles. They
published their results in eight papers in the New England Journal of
Medicine in July 1960. At a conference in New York, the eminent
virologist and bacteriologist Joseph Smadel said, “John, you’ve done it
again.” So, as he had done with polio, Enders made his attenuated strain
available to others to refine his work.
Here the vaccine developer Maurice Hilleman stepped in and applied
the resources of the pharmaceutical company Merck, Sharp, and Dohme
(now the giant corporation, Merck). Hilleman discovered that Enders’
strain had become contaminated with a chicken leukemia virus, and he
found a breeder in California who had developed a line of chickens that
were immune to the virus. Merck’s team passed Ender’s measles virus
twenty-four times through primary human kidney cells and twenty-eight
times through human amniotic cells. The end result of Hilleman’s labor,
after passing thirty-five quality control tests, was a commercial vaccine
licensed for use in 1963.
( 144 )
Eradication
Enders later wrote that his work on the measles vaccine was the most
personally satisfying and socially significant of his career. Over the
following decades, the measles vaccine spread all over the world. By
2006, the number of measles cases had fallen from 106 million in 1963
to 20 million, and the death rate from over 6 million to 345,000. Amy
Pearce calculates that the polio vaccine has saved more than 1 million
lives, and over 113 million lives have been saved by the measles vaccine.
The vaccine’s benefits have also extended to the fight against global
warming, as far fewer children get measles’ notorious fever, thereby
reducing humanity’s collective body heat by some 430 million degrees!
In 1988, the WHO, UNICEF, and Rotary International initiated a
worldwide polio eradication effort, trying to make it only the second
disease, after smallpox, to perish from the Earth as a result of humanity’s
efforts. Today, there are fewer than 2,000 cases a year, all in four countries
where polio is still endemic: Nigeria, India, Pakistan, and Afghanistan.
John Enders’ work has touched billions of lives around the world.
Within two decades of the publication of Enders’ tissue culture techniques,
vaccines for measles, mumps, rubella, and chickenpox became common.
What’s more, the polio publicity campaign, which used fear, celebrities,
and hype to galvanize public attention, played a hugely beneficial role in
convincing the public to vaccinate their children. There were and still are
religious, pseudoscience, and conspiracy groups that fight mandatory
vaccination. The beauty of vaccines is that children never know the
diseases against which they are vaccinated. They may also not know John
Enders, the father of modern vaccines, but his work has prevented so
many tears and suffering.
A Man of Letters and a Man of Science

When Enders retired, he could count many successful research
careers that began in his lab, and many were those who noted his personal
charm and unwavering curiosity in the workings of the world. Enders
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John Enders
received a host of honors from his peers and the public, including a
Lasker Award, Time magazine’s Man of the Year, and membership in the
National Academy of Sciences and the Royal Society of Britain. Not bad
for someone who didn’t even know what he wanted to do until he was in
his 30s and whose significant work only began at age 50.
On a September evening at their waterfront home in Connecticut in
1985, Enders was reading T.S. Eliot aloud to his wife, Carolyn. He
finished and went to bed, and then quietly died. He was 88. At his
memorial service, his friend, the bishop F. C. Laurence, said, “John
Enders never lost his sense of wonder at the great mystery that exists and
surrounds all of God’s creation.” His widow said that John briefly
revealed his heart when he told her, concerning how creation ran, “There
must be a mind behind it all.”
Vaccine research in the 21st century

SARS-Cov-2, which was reported in December 2019, has become a
pandemic brought the whole world to a standstill, and all hopes are on a
vaccine. More than 90 vaccines are being developed against SARS-
CoV-2 by research teams in companies and universities across the world.
Eight ways in which scientists hope to provide the vaccine. Researchers
are testing different technologies, some of which have not been used in a
licensed vaccine before. Vaccines are produced using a virus (inactivated
or weakened), viral vectors (Replicating or non-replicating), Nucleic acid
(DNA or RNA), and Protein-based (Protein subunit or virus-like particles.
Thanks to the classic work of Enders laboratory, growing the virus was
easy.
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7
Paul Müller
(1899-1965)
DDT and the Prevention of Malaria

THERE ARE over 3,000 species

of mosquitoes, 130 of which live in
North America, and they are wily
creatures. Flying at one-mile-per
hour, they sense exhaled carbon
dioxide or infrared radiation to home
in on warm-blooded animals like
you and me. Only the female bites—
because she needs the protein found
in blood to develop her eggs. She
can deposit dengue fever,
encephalitis, or yellow fever. The
Anopheles mosquito can inject you Paul Müller in 1948. Always
with a disease that dwarfs the others independent, Müller was known in the
in lethality. labs as a lone wolf, or, as his daughter
related, an Eigenbrotler, someone
You barely feel her proboscis “who makes his own bread.”
poking through your skin. Unaware Bettmann Standard RM Collection/ Bettman/
CORBIS.
of her sucking your blood, you move
your hand to brush the spot. She flies away, having consumed her weight
in your blood, but she leaves behind sinister microscopic one-celled
parasites. Within thirty minutes, the tiny parasites are infecting your
liver. During the next day or two, all you notice is an itchy red bump
Paul Müller
needing an occasional nuisance scratch. But two weeks later, your liver
cells burst open, releasing tens of thousands of daughter parasites. These
parasites then infect red blood cells, releasing eight to twenty-four
daughters with each cell burst. Unfortunately, your immune system has
trouble attacking the invaders because the parasites attach to red blood
cells with surface proteins of almost unlimited variation (each parasite
can have as many as sixty different attaching proteins). The parasites
cause red blood cells to bind to blood vessel linings and other red blood
cells. As they accumulate, they jam together stickily, blocking blood flow
in the body’s smallest vessels and limiting the local oxygen supply. Now
you have a fever, to be followed by sweats, headaches, and rigors. You
need medical attention quickly, for you have malaria, one of the greatest
scourges known to humankind.
Malaria’s history mirrors that of human civilization. It is thought to
have arisen in primates in Africa and evolved with humans, spreading
with them as they migrated around the world. Evidence of its characteristic
fevers appears in Chinese writings as far back as 2700 BC and in the
records of every major civilization since. Romans are responsible for the
disease’s modern name, calling it “mal-aria,” or bad air, from whence
they thought it originated. Malaria has killed numerous popes throughout
the centuries, prompting Pope Urban VIII to order in 1623 that a cure be
found.
Because the disease has infected a large portion of the human
population for thousands of years, forcing numerous genetic adaptations.
People from Africa and other endemic malarial areas have adapted by
developing specific physiological characteristics that provide some
protection against malaria. One is the sickle cell genetic trait. While the
mutation doesn’t protect against the initial infection, it does provide
about 60 percent protection against mortality, most of the benefit being
accrued to babies aged 2–16 months. Another evolutionary response to
malaria is the absence in some people of Duffy antigens, which are pairs
of proteins that reside on the outside of red blood cells. Lacking them
( 148 )
confers resistance to P. vivax, one of the four types of malaria, since that
species uses the Duffy antigens to invade blood cells. Until the early
1630s, these evolutionary responses were the only protection against
malaria for Europeans. Then a Jesuit priest carried some Peruvian bark
used by the Andean Indians to cure “shivering” back across the Atlantic
Ocean to Rome. The “Jesuit powder,” as it became known, was, of
course, the earliest form of quinine. Although quinine works well,
treatment must be obtained quickly. For strains of malaria that have
become resistant to it, there are now other drugs available, such as
artemisinin. However, only 60 percent of those suffering from malaria
today have access to affordable and appropriate treatment within 24
hours of the onset of symptoms. Army surgeon Ronald Ross while
working in India, discovered that the only way to catch malaria was
through the mosquito. Ross’s discovery of the vector allowed the first
concerted approach against the disease—eliminate the mosquito, and
you eliminate malaria. It was such an important discovery that in 1902
Ross became the first of four researchers to be awarded a Nobel Prize for
work associated with malaria.
Malaria thrives wherever the Anopheles mosquito lives, so it was
common in temperate climates all over the world, occurring even as far
north as the Russian town of Archangel on the Arctic Circle. Today, it is
endemic in parts of Mexico, Central and South America, the Middle East,
and all of South and Southeast Asia. The dreaded parasites the mosquitoes
carry belongs to protozoa, which are in the kingdom Protista.
As a parasite, malaria lives on or in another living organism, to the
detriment of its host. While it thrives in many animals, only four types
infect humans. If you are infected with any of three types, you will likely
survive, although the symptoms can reappear years later (the record is
thirty years; the parasite hides out in the liver during this time and can
reactivate). However, if you are infected with Plasmodium falciparum,
the most common species in Africa, your sickness may be severe or even
deadly. It is especially fatal to children and pregnant women. Each day in
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Paul Müller
sub-Saharan Africa, some 2,000 children perish from the disease’s

onslaught.
This recurring sickness erodes people’s productivity; it is estimated
to cost the African continent $12 billion a year in the lost gross domestic
product because of its debilitating symptoms. Today, malaria still infects
as many as 500 million people each year, killing more than a million.
Forty to 50 percent of the world’s population live in areas held hostage to
the Anopheles mosquito.
At the turn of the twentieth century, it was estimated that 10 percent
of all deaths around the globe were caused by malaria. Then along came
a man who completely changed that equation. He discovered a chemical
so portentous that in a 2005 essay, British politician Dick Taverne called
it “the single most effective agent ever developed for saving human
life.”
A Boy’s Fascination with Chemistry

Paul Hermann Müller, the eldest of four children, was born in Olten,
Switzerland, on January 12, 1899. His father was a railway clerk, and his
Lutheran mother ran the family with an iron hand. At first, a mediocre
student, Müller, suddenly awoke to the pleasures of experimentation
when he discovered science and chemistry.
Instead of studying, he spent hours locked in his home laboratory
working on his own experiments, with his father’s encouragement.
Despite constant lecturing from his mother and his school principal, the
frustrated Müller dropped out of school at 17 during World War I. He
found work at industrial chemical companies in Basel.
During this time, two events occurred that would influence the rest
of his life. The first was a severe war-exacerbated food shortage in
Switzerland. The second event was the Russian typhus epidemic, the
greatest such epidemic in history. It resulted from the chaos of the Russian
Revolution, coupled with a lack of any effective insecticide against the
( 150 )
common louse, which carried the infectious organism. Up to 30 million

people contracted the disease, and nearly 3 million died.
After two years in the “real world,” Müller had matured enough to
return to high school. In 1920, he entered the University of Basel. Under
the tutelage of chemistry professor Fichter, Müller became a hard-
working student, spending all his free time working in the labs both as a
student and a paid assistant. He majored in chemistry, with minors in
physics and botany. Professor Fichter proved to be both a mentor and a
friend. Müller had proven to be very adept at chemistry, and Fichter,
thinking practically, assigned him a Ph.D. thesis on a compound used to
manufacture dyes since that was what the nearby chemical companies
produced.
In 1925, Müller joined the chemical company J.R. Geigy (which
eventually became today’s drug giant Novartis). His initial work focused
on producing synthetic tanning materials. He then developed a seed
disinfectant that wasn’t based on mercury, which, though poisonous, was
at the time widely used in agricultural products. As the decade of the
twenties ended, Müller married. He and his wife, Friedel, eventually had
three children. Geigy wanted someone to work on developing new
insecticides. In those days, saving fabrics and raw materials from the
damaging effects of insects was of major economic import, and since the
company had already invented a compound that protected woolens from
moths, it now wanted to branch out into eliminating damage from other
insects. Other organic chemists felt insecticides were beneath them, but
Müller, whose interest in botany made the task compelling, volunteered.
In 1935 he began a deliberate search for new insecticides.
It was the perfect job for Müller. In her book Prometheus in the Lab,
Sharon Bertsch McGrayne writes that “as a scientist, Müller was doggedly
determined and methodical, his perception was acute, and his outward
reserve covered a passionate devotion to science.” There, Müller
alternated between reading science articles on pest control and breaking
away to indulge his hidden naturalist by taking his children on nature
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Paul Müller
walks, gardening, and photographing the wildflowers near the cottage.

Part of Müller’s reading focused on insecticides already in use. The
most common ones used in Europe and the United States were based on
the doubly toxic lead arsenate, whose residues could poison people long
after application. Müller was determined to find a safer substance.
The “Perfect” Insecticide

Müller shaped his own requirements for a successful synthetic
insecticide. As he recounted in his Nobel speech, “I considered what my
ideal insecticide should look like, and the properties it should possess. I
soon realized that a contact or ‘touch’ insecticide would possess very
much better prospects than an oral poison.” The properties of this ideal
insecticide should be as follows:
1. Great insect toxicity.
2. Rapid onset of toxic action.
3. Little or no mammalian or plant toxicity.
4. No irritant effect and no or only a faint odor (in any case, not an
unpleasant one).
5. The range of action should be as wide as possible and cover as
many Arthropods as possible.
6. Long, persistent action, i.e., good chemical stability.
7. Low price (= economic application).
Of the five known insecticide classes at the time, none met his
criteria. Müller knew that in order for a new pesticide to receive a patent
and succeed in the marketplace, it would have to not only be cheap and
effective but also have a unique property that none of the existing products
had.
Müller set about devising and testing various compounds. He was at
home in his lab, testing all the compounds himself, spraying them into a
big glass chamber, and putting insects—primarily Calliphora vomitoria,
( 152 )
otherwise known as the common housefly—into the chamber to see if

they lived. Müller had a hands-on experimental approach that he
maintained throughout his life. Sometimes new and valuable discoveries
may be made by small changes in methods of application, or again by the
correct observation of apparently unimportant side-effects.”
After a year of fruitless experiments on 100 compounds, Mueller
realized that “new substances do not always fulfill expectations; on the
contrary, they are often bad.”
After another year of testing, Müller recalled, “After the fruitless
testing of hundreds of various substances, I must admit that it was not
easy to discover a good contact insecticide. In the field of natural science,
only persistence and sustained hard work will produce results.”
Müller diligently pursued a new insecticide from 1935 to 1939. He
allowed insights drawn from previous investigations of his and others to
suggest new chemical combinations. He had begun with Geigy’s moth
repellant—a chlorinated hydrocarbon with one or more carbon-chlorine
bonds—because of its chemical stability. Finding a paper published in
1934 on a substance called diphenyl-trichloroethane inspired Müller to
investigate related substances, which have a trichloromethyl grouping
(carbon bonded to three chlorines).
Finally, in September of 1939, after four years of work and 349
failures, Müller placed his 350th compound—a diphenyl-trichloroethane
derivative—in the fly cage. For a short while, the flies buzzed around
normally, and Müller sighed at what appeared to be another failure. But,
looking at the cage after some time had elapsed, he was amazed to see
flies falling helplessly out of the air. Time after time Müller tested the
new substance, and always the flies died. Even more impressive was the
compound’s lasting power. As Müller recalled in his Nobel speech, “My
fly cage was so toxic after a short period that even after very thorough
cleaning of the cage, untreated flies, on touching the walls, fell to the
floor.”
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Paul Müller
Soon Müller confirmed that his insecticidal compound didn’t need to

be ingested but could kill insects that simply came into contact with it.
Thus, the tested compound met all of Müller’s requirements that he had
set out in the beginning except one – it did not kill quickly. But Müller,
the baker of his own bread, continued testing, finding that his compound
killed every insect he stuck in his glass cube in experiment after
experiment.
Endless Intricacies of Nature

Müller prepared his compound from chloral; the product was
dichloro-diphenyl-trichloroethane, which would become so well known
by its acronym, DDT. Müller went back to the literature and found that
he wasn’t the first to combine those three chemicals to create this new
chemical. The feat had been accomplished by an Austrian graduate
student back in the 1870s, but that young student, Othmar Zeidler, never
realized the compound’s devastating effect on insects, and so his mixture
was forgotten. The fact that Müller later made an identical discovery
independently from a predecessor is not uncommon in science. The
accumulation of knowledge over time generates a constant flow of new
ideas to scientists, so it is not surprising that more than one scientist can
have the same insight. However, Müller was not only looking for a new
chemical; he also was looking for a chemical that solved a specific
problem—unwanted insects.
Scientists later discovered that DDT kills insects by binding to
sodium ion channels in the insects’ nerve cells, or neurons. These ion
channels, which can open or close depending on the voltage difference
between the inside and outside of the cell, allow neurons to conduct
electrical signals. Normally, a discrete electrical signal travels the length
of the neuron and then moves along to other neurons via chemical
neurotransmitters, after which the neuron remains inactive for a certain
amount of time until it is excited by another electrical signal. This type of
controlled signal conduction is the basis of the nervous system, both in
insects and in other types of animals, including humans. When DDT
( 154 )
binds to an insect’s sodium channel, however, it forces the channel to

remain open, causing the neuron to continue firing and eventually leading
to paralysis and death of the insect. Fortunately for humans and other
mammals, the sodium channels in our brains evolved slightly differently
from those in insect brains, making them less susceptible to DDT. In
addition, DDT is more potent at the body temperature of a typical insect
than a human or mammalian body temperature. That said, it is worth
noting that DDT is very soluble in body lipids and has the potential to
affect several other systems in the body, so the fact that it does not
target our sodium channels doesn’t entirely let it off the toxicological
hook.
Müller knew nothing of ion channels while he was developing DDT,
or afterward; he just knew that some chemicals can kill insects while
leaving other animals apparently unharmed. Thus, DDT illustrates a very
common phenomenon in science, in which discovery is made long in
advance of a full understanding of the system to which it applies, and, in
fact, the discovery itself opens up the way to greater knowledge of the
endless intricacies of nature.
The higher-ups at Geigy proceeded to patent DDT as an insecticide,
then ran numerous experiments on different substances they could
combine it with to deliver it to crops, animals, and humans. Geigy ramped
up production and, by 1942, DDT was in wide use throughout Switzerland,
The Superior Insecticide of World War II

The story of how DDT reached the United States varies depending
on the source. What is known for sure is that in August of 1942, Geigy
sent 400 pounds of DDT to its U.S. offices. The U.S. Department of
Agriculture sent it down to its research station in Orlando, Florida.
The Orlando station was part of an effort that would eventually test
and classify more than 13,000 chemicals for insect toxicity. But countless
other scientists’ formulations were no match for Paul Müller’s creation.
One application of DDT killed lice for a month, which was four times
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Paul Müller
longer than previously available chemicals. More importantly, even a

few specks of DDT floating in the air and landing on a beaker were
enough to kill the mosquito larvae within. In a larger test, researchers
sprayed a duck pond with DDT on a windless day to compare the effects
on mosquito larvae in that pond with those in an untreated pond several
miles away. A week after the test, mosquito larvae in the untreated pond
died. They were killed by the DDT residue ducks carried from the treated
pond on their feathers and feet. To ensure the chemical was safe for
humans, volunteers slathered themselves with DDT and sat in vaults for
hours, inhaling the fumes with no ill effects. Quickly realizing the
potential of this new pesticide, the United States labeled it top secret,
subject to censorship. Clandestine production began in late 1942 in
dozens of factories.
The Allies first used the chemical to fight typhus in Italy. In January
1944, Army officials propelled a tiny puff of DDT powder down the
necks and into the clothes of 1.3 million Italian civilians. This “dusting”
protected them from typhus for weeks, for the first time in history averting
an anticipated typhus epidemic. And not only did the chemical kill lice
already present, but clothing treated with DDT became immune to them.
Any lice that happened onto DDT-treated fabric died, and as soon as their
eggs hatch, the larvae died, too. This effect lasted through several
washings. Eventually, DDT came to be considered the “wonder
insecticide of World War II.” Thanks to its use, the war was the first in
modern history in which fewer people died from disease than from the
war itself.
The Mosquito Men

In June of 1944, censorship of information on DDT was lifted, and
Time magazine ran an article about the chemical. After Ronald Ross’s
discovery that the mosquito was the vector for malaria, a worldwide
effort began to drain swamps, eliminate standing water, and kill as many
anopheles’ mosquitoes as possible. But as far as chemical protection
before DDT was concerned, the “mosquito men,” who called themselves
( 156 )
malariologists, had to make do with chrysanthemum-derived pyrethrum.

This only killed mosquitoes in the room when it was sprayed, and diesel
oil mixed with the toxic arsenic-based Paris Green mixture for bodies of
standing water. When DDT came on the market in the mid-1940s,
mosquito men had for the first time a vanquishing tool.
The most famous mosquito man was Fred Soper. After working to
eradicate yellow fever in South America, Soper proposed that with DDT,
it was possible to eradicate malaria completely. His focus was not on
killing every anopheles mosquito. Rather, Fred Soper supported
spraying the insides of houses in infected zones. After imbibing blood
from a human, mosquitoes will often land on a nearby wall to rest. There
the DDT would kill them. It takes three to four years for a human to clear
the parasite from his or her body completely, but once this time had
passed, even if mosquitoes were allowed to propagate again due to
decreased spraying, there would be no protozoan for them to ingest and
pass on.
This program began with some stunning successes. The first occurred
in 1946 in Sardinia, then the most malarial region of Italy. With financial
support from the Rockefeller Foundation, he hired 33,000 people to spray
more than 286 tons of DDT in 337,000 buildings. Along with
environmental approaches, such as draining swamps, he managed to
reduce the number of malaria cases on the island from 75,000 in 1946 to
nine in 1951. Such was the power of DDT.
A similar effort was made in the U.S. South. During the war, there
existed the Malaria Control in War Areas Agency. After the war, it was
turned into the Communicable Disease Center and oversaw the U.S.
National Malaria Eradication Program. Beginning on July 1, 1947, over
4,650,000 houses were sprayed in thirteen southern states. By 1951,
malaria was completely eradicated from the United States. The
Center eventually became the Centers for Disease Control (CDC),
one of the preeminent health organizations in the world. These types
of results led to the Global Malaria Eradication Program. The fledgling
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Paul Müller
World Health Organization led the effort, with the United States providing
$1.2 billion, half the funding. It was a grandiose plan, complicated by
economic, logistical, and cultural problems. The early successes were so
amazing that scientists predicted that the academic literature of
agricultural and medical entomology would have to be re-written. In
India, in 1953, when the eradication campaign began, there were 75
million malaria cases a year and 800,000 deaths. By 1966, there were
fewer than a million annual cases of malaria and zero deaths. A 1970
article in an Indian newspaper attributed the lengthened lifespan of
people in that country from 32 years in 1948 to 52 years in 1970 to
DDT.
In neighboring Sri Lanka (then known as Ceylon), DDT cut the
incidence of malaria from about 3 million cases in 1946 to 7,300 cases in
1956, and the death rate fell to zero. Dr. Arthur Brown led the effort in
parts of Southeast Asia and had the task of convincing the Buddhists to
support the effort.
DDT didn’t only work on mosquitoes, though. It worked on hundreds
of pests. Industry and public officials quickly came to the belief that if a
little DDT was good for humankind, then more had to be better. Soon it
was being sprayed on millions of acres of forest to stop spruce budworm
and on cotton fields by crop duster planes to control various pests. Rice
seeds were soaked in it, and apple orchards were sprayed; it worked on
the gypsy moth. An underreported story is DDT’s effectiveness on
sandflies. These tiny insects, no bigger than the period at the end of this
sentence, carry the parasitic protozoan, which causes black sickness, or
kala azur. It is usually a fatal disease that results in anemia, fevers, and
an enlarged spleen, liver, and lymph nodes. The disease is endemic in
most tropical and subtropical regions worldwide. Sandflies tend to reside
on the floor and walls of houses. But just one application of DDT kept a
home free of sandflies for a year. In fact, as long as spraying for malaria
was ongoing in India, black sickness disease disappeared.
Soper’s success and the World Health Organization’s far-reaching
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goals came at a time when people began to think science’s accomplishments

might be unlimited. Penicillin, the first antibiotic, had just been
discovered, and blood transfusions were coming into broad use. In 1948
Paul Müller won the Nobel Prize in Medicine, even though he was neither
a doctor nor a medical researcher, but rather a chemist. Such recognition
speaks volumes about the world’s perception of the benefits of DDT in
preventing human disease. “To few chemicals does man owe as great a
debt as to DDT,” the U.S. National Academy of Sciences concluded in
1970. Amy Pearce estimates that DDT saved more than 21 million lives
while it was widely used, and it surely prevented many times that number
of illnesses. In two decades, Paul Müller’s new insecticide had gained
international fame as a stupendous panacea of preventative medicine, but
this fame would soon turn to infamy as DDT became the primary target
of a burgeoning environmental movement, led by one marine biologist
turned anti-pesticide crusader.
The Ecology of Fear and the Birth of Environmentalism

In 1962, Paul Müller retired to work in a private laboratory he
established, trying to find a pesticide that plants could absorb through
their roots, rather than their leaves. Ironically, in that same year, Rachel
Carson’s book Silent Spring sprang. After being serialized in The New
Yorker, it was published as one of the first major environmental treatises.
The book was an indictment of the environmental devastation wrought
by DDT, tracking the way DDT entered the food chain and claiming it
caused cancer and other damage. Carson warned that DDT would silence
the birdsong and other natural sounds of our world forever. In this climate,
Silent Spring became one of the most influential books of the 20th
century.
The book centered upon the one negative attribute of DDT—its
ability to dissolve well in oil. This characteristic didn’t seem all that
important at first, but as Rachel Carson pointed out, it turns out to be
DDT’s Achilles heel. It allows the substance to build up in the fatty tissue
of animals, becoming more concentrated as it moves up the food chain.
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Paul Müller
This wasn’t completely surprising to Müller. After only a few years’ use
of his invention, the chemist in him could see the dangers. In his 1948
Nobel Prize lecture, he warned people to beware of humankind’s
ignorance: “Long years of patient, a detailed study has produced
explanations of the constitution of important vitamins, hormones, and
bacteriostatic substances such as Penicillin. Yet despite all these results,
we are still far removed from being able to predict with any degree of
reliability the physiological activity to be expected.”
Rachel Carson said that indiscriminate aerial spraying of DDT and
other chemicals was leading to disaster. Some of the facts backed her up.
The mass aerial spraying on forests and crops had a devastating effect.
Mosquitoes became resistant to its toxicity. If it had been used sparingly
and limited to the interior walls of homes, resistance would not have
occurred so rapidly. Still, it seemed that DDT influenced even resistant
mosquitoes’ behavior due to its “excito-repellent” effect, which causes
mosquitoes to fly away after just smelling the insecticide. And not all
insects developed resistance; sandflies, for example, never developed the
same resistance to DDT as mosquitoes.
Carson associated DDT with cancer. “The assertion that pesticides
were dangerous human carcinogens was a stroke of public relations
genius,” wrote Ronald Bailey in Reason Magazine in 2002.
Rachel Carson died of breast cancer in 1964, and a year later, Paul
Müller died of a stroke. Over the next decade, fueled by Rachel Carson’s
book, the environmental movement grew. In 1960, environmental groups
in the U.S. had barely 100,000 members. By the end of the decade, they
boasted over a million. When the first Earth Day was celebrated on April
22, 1970, more than 20 million Americans participated. Political change
quickly followed, with the passage of the Clean Air Act, Clean Water
Act, Endangered Species Act, and the creation of the Environmental
Protection Agency.
Then, in 1972, the U.S. Environment Protection Agency banned
DDT.
( 160 )
A Polarizing Life-or-Death Debate

Under Richard Nixon’s administration, the EPA banned DDT. The
EPA’s decision marked the first time the “precautionary principle,” a
principle that places the burden of proof of the safety of action on those
advocating for the action rather than against it, was used to justify a
comprehensive ban of a chemical. The same year the U.S. banned DDT,
Carson’s book was re-released with a new cover. Her publisher wrote:
“No single book did more to awaken and alarm the world than Rachel
Carson’s Silent Spring.” It makes no difference that some of the fears she
expressed ten years ago have proved groundless or that here and there,
she may have been wrong in detail. The U.S. ban brought swift action:
U.S. industry, DDT’s primary producer, ended production. Soon more
than thirty other countries banned the chemical, as well. In 1976, the
World Health Organization admitted its failure to eradicate malaria
worldwide and greatly scaled back its program. Economics, mosquito
resistance to DDT, organizational inflexibility, inadequate research, and
the demonizing of DDT were all blamed. Even though it was an awesome
success in temperate countries, helping to eliminate malaria in Europe
completely, the U.S., Japan, and Australia, DDT was still labeled a failure
by environmentalists.
Environmentalists wanted a worldwide ban. With malaria wiped out
of most of the wealthy nations, it was easy for them to gain political
support, ignoring the silent tears of people who were once again losing
loved ones to malaria. In the 1990s, a third of all hospital admissions in
Africa were for malaria (compared to virtually none in the U.S.). In the
1990s, the United Nations began trying to get the Stockholm Convention
on Persistent Organic Pollutants Treaty (POPs) passed. It laid out controls
over the production, import, export, disposal, and use of twelve persistent
organic pollutants, including DDT. Greenpeace, The Worldwide Fund
for Nature (WWF), and over 300 other environmental groups pressed
hard for a complete ban of DDT.
The environmentalists were certain they were saving the world, and
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Paul Müller
those in favor of using DDT were certain they were saving humanity. The
latter now had decades of proof of what the ban had wrought. In Sri
Lanka, the country’s malaria burden had shrunk from 2.8 million cases in
the 1940s to just seventeen in 1965. Five years after the country stopped
using DDT, the number of cases had risen to 500,000. In the 1980s,
Madagascar stopped using DDT and immediately had an epidemic of
malaria, with more than 100,000 dying. Michael Crichton, the author of
The Andromeda Strain and Jurassic Park, had one of his characters in the
novel State of Fear say that banning DDT was “arguably the greatest
tragedy of the twentieth century” and that the ban “killed more than
Hitler. The arguments led to research. But in a U.S. Uniformed Services
University study in Belize, huts treated with deltamethrin allowed in
thirty-two times as many mosquitoes as those treated with DDT, and of
those entering the DDT huts, most exited without biting. In fact, even
forty years after the publication of Silent Spring, many of Carson’s DDT
claims have still failed to materialize. Although it was found to cause
eggshell thinning in some bird species, DDT had no effect on others.
While no one disputes that DDT and its metabolite DDE persists in the
environment and in the fat of mammals and fish, there is no evidence of
any significant toxicity in humans, nor any strong link with cancer. Dr.
Donald Roberts, professor of tropical public health at the Uniformed
Services University, said, “You could eat a spoonful of it, and it wouldn’t
hurt you.” Amir Attaran, a lawyer, and human rights advocate, went
further, noting in an essay published in the British Medical Journal in
2000 that “not even one peer-reviewed, independently replicated study
linking exposure to DDT with any adverse health outcomes exists.” As
negotiations on the treaty proceeded, one of the most effective campaigns
came in 1999 from the Malarial Foundation International, an advocacy
group started by Dr. Mary R. Galinski. It produced a public letter signed
by more than 400 doctors from sixty-three countries advocating the
continued use of DDT.
Finally, in 2001, DDT supporters achieved a breakthrough. The
parties to the POPS treaty agreed to grant DDT a “health-related
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exemption” until cost-effective, environmentally friendly alternatives

could be found. The positive effects of the fight against malaria were
quickly apparent. These include South Africa, Mozambique, Zambia,
Madagascar, and Swaziland, who within two years of starting DDT
programs, slashed their malaria rates by 75 percent or more. In September
2006, nearly thirty years after phasing out the widespread use of DDT to
fight malaria, the World Health Organization reversed its stance. As the
director of the WHO’s malaria department said: “Of the dozen pesticides
WHO has approved as safe for house spraying, the most effective is
DDT.” Indoor spraying involves small amounts sprayed once or twice a
year at the cost of about $5 (most of that being for labor). No more is
needed because the chemical has such a long staying power. Even though
some mosquitoes have developed a resistance to it, they still are repelled
from DDT-sprayed environments. And when limited to indoor use, it
affects a few birds or other animals. “In South Africa, it prevented tens
of thousands of malaria cases and saved lots of lives.” Greenpeace
spokesperson Rick Hind agreed.
Steve Milloy, an adjunct scholar at the Cato Institute, thought the
environmentalists’ change of mind was belated: “It might be easy for
some to dismiss the past 43 years of eco-hysteria over DDT with a simple
‘never mind,’ except for the blood of millions of people dripping from the
hands of the WWF, Greenpeace, Rachel Carson, the Environmental
Defense Fund, and other junk science-fueled opponents of DDT.”
Humankind’s struggle against malaria, public hysteria, and
dogmatism is far from over, but the one clear champion in this story is the
scientific method. At each step along the way, evidence accumulated by
scientists has enhanced and refined our understanding of DDT and its
context in the environment and the society in which we live. Science
itself does not insist on seeing issues in black or white, and it can be used
to perform a nuanced risk-benefit analysis. Very few substances, even
medicines, have zero risks when used by humans on a large scale. Science
is based on evidence alone, not dogma, and when new evidence is
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Paul Müller
discovered that casts doubt on old theories, science will adapt.

When it was finally accepted that DDT need not be demonized, that
it could be used safely and beneficially in small amounts, indoors, away
from birds (the amount of DDT put on 1,000 acres of cotton during a
single growing season, for instance, can protect a whole country like
Guyana from malaria for a year when applied indoors), the evidence
overwhelmingly showed that DDT is the best insecticide currently
available to prevent malaria by killing or repelling the anopheles
mosquito. So today, DDT is back at work in some parts of the world,
saving lives, just as it did during the 1940s and 1950s. Paul Müller can
rest in peace because his life’s work is once again preventing tears.
( 164 )
8
Howard Florey
(1898-1968)
Penicillin: The Miracle of Antibiotics

SEVENTY YEARS ago, an immense

number of diseases were untreatable.
Doctors fumbled through their black
bags, tumbling among medicines based
on mercury or arsenic that they knew
were too toxic to be used in quantities
that would work. All they really had to
offer were vain words of comfort.
Children were used to losing playmates
to diphtheria, meningitis, rheumatic
fever, or scarlet fever. In 1924, President
Calvin Coolidge’s youngest son got a
In 1946 Howard Florey received
blister playing tennis. The 16-year-old’s
the Albert Gold Medal.
blister became infected, the infection J. A. Hampton/ Hulton Archive/ Getty
spread, and the resulting blood poisoning Images.
killed him. Even in the U.S., many

women giving birth developed childbed fever. Adults commonly died of
syphilis, sepsis, or pneumonia. These dangers disappeared quite suddenly
in 1942 with the advent of a new drug that would revolutionize medicine:
Penicillin, the first immensely strong antibiotic.
No one even knew antibiotics were needed until the middle of the
nineteenth century when Louis Pasteur proved that invisible organisms
Howard Florey
all around us are the cause of many diseases. In the decades that followed,
scientists realized that most of these “germs” fell into two broad
categories: bacteria and viruses. Viruses are so tiny that they remained
invisible until the advent of the electron microscope in the 1930s, but
bacteria could be observed under the optical microscope, which had been
invented centuries before but was only then being perfected. Scientists
have been studying them ever since. Bacteria are single-celled organisms
that exist nearly everywhere—forty miles up in the stratosphere and
miles below the ocean floor. Scientists at the University of Georgia have
estimated that the number of bacteria on the planet approaches five
million trillion trillion (that’s a five with thirty zeroes after it). Each
square centimeter of your skin carries about 100,000 bacteria, and most
of us carry around over 500 bacterial species that add about three pounds
to our body weight. In fact, there are about ten times as many bacterial
cells as there are human cells in our bodies. Many are indispensable to us,
ruminating in our gut to aid digestion.
While most bacteria are harmless, a few release toxins that attack our
bodies. Some of these rogue bacteria, such as those that cause bubonic
plague and cholera, are so infectious that they have been responsible for
some of history’s greatest epidemics.
Without a cure for bacterial infections, the medical field was very
different prior to 1942 than they are today. As the English doctor, Charles
Fletcher, said, “Every hospital had a septic ward, filled with patients with
chronic discharging abscesses, sinuses, septic joints and sometimes
meningitis chambers of horrors, seems the best way to describe those old
septic wards.” And there was little in the way of treatment; about half the
people who entered the wards exited on gurneys to the morgue.
A Great Fire Seemed to Burn within Him

It was into this era that Howard Florey was born. Florey’s father, a
bootmaker, emigrated from England to Australia in 1882 when his wife
came down with tuberculosis. Sunshine and fresh air were thought to be
( 166 )
the best treatment, so he moved his family to Adelaide, on Australia’s

south-central coast. Howard was born on September 24, 1898. He grew
to be handsome, an excellent athlete, competitive to a fault and spiced
with a fiery temper. In class, he won prizes in science competitions and
was most intrigued by chemistry, but the school’s headmaster insisted
that there was no future for a chemist in colonial Australia. Florey instead
went off to Adelaide University Medical School.
While working on the Adelaide Medical Students’ Society Review,
Florey asked Ethel Reed, one of the few women in the medical school, to
write an article on women in medicine, as an excuse to ask her to tea.
Upon graduation, Florey found the practice of medicine dramatically
different from his studies. Since doctors had few cures, they concealed
their ignorance by using big words and pompous phrases. He wrote, “I’m
now a ‘Doctor’ to the patients, and I have to cover my ignorance by
waving my arms and looking grave: the appalling thing of seeing young
people maimed or wiped out while one can do nothing.” In a short time,
he experienced the worst part of being a doctor.
He dreamed of alleviating that ignorance by performing research, but
to do so, he would have to leave Australia. He received a Rhodes
Scholarship to Oxford, among the most renowned universities in the
world. To get to England, he found work as a ship’s surgeon, which
proved to be a great month-long adventure. In England, Florey entered
Magdalen College, one of the most prestigious and class-conscious of
Oxford’s campuses. He won a major fellowship to Cambridge, marking
him as a rising star in British science.
In 1925, Florey won a Rockefeller grant to study in the U.S., where
he again impressed older scientists with his brilliance. He took as a
mentor Dr. Alfred Richards of the University of Pennsylvania, who
would become president of the National Academy of Sciences, and later
a valued ally.
In 1931, the chair of pathology at Sheffield University, 100 miles
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Howard Florey
northwest of Cambridge, became open, and Florey applied. It would take

more than an excellent academic record to head a laboratory, but Florey
was well suited to the task. His electors instructed him, “We don’t care
what you do as long as you make a mess in this laboratory; it’s been too
clean for a number of years.” Florey, who liked to perform one experiment
every day, including Sundays, enthusiastically complied. D. E. Harding,
a senior doctor at the university, said of him, “Florey was usually running
five or six lines of experiments, each with different collaborators, and he
published academic papers widely, building his reputation.”
Through these years, Florey and Ethel had two children. In 1935, the
chair of pathology at Oxford University came open. Getting appointed to
a prestigious endowed chair at Oxford was a matter of high politics.
Florey won by one vote.
The Need for Chemistry

Florey realized that at Oxford, he would need to let go of his rough
Australian temper in order to play the politics of academia, so he opted
not to shake things up immediately. Instead, he began gradually
transforming the school into his vision of what a research institute should
be.
By now, Florey had a strong belief that the study of disease would
“not go very well without a very big injection of chemistry into it” and
that in order to understand medicine truly, scientists needed to find the
specific active chemicals within the compound substances that nature
provided. He said, “I have never forgotten the remark made by Szent
Györgyi, a Nobel Prize winner, in 1929, who said that biochemical
methods were then sufficiently good to enable any naturally occurring
substance to be extracted, provided there was a quick test for it.” Florey
insisted that a chemist be on his research team.
A biochemist at Cambridge recommended that Florey hire Ernst
Chain. Chain spoke English with a pronounced German accent, looked
like a well-groomed Albert Einstein, was voluble and flamboyant, and
( 168 )
threw things when he lost his temper.

When Florey began a study of the metabolism of tumors, he and
Chain realized they needed someone who was proficient in micro-
dissection. Chain recommended Norman Heatley, who had just written
his doctoral thesis on the new field of measuring minute amounts of
individual elements in biological substances. Florey hired him to be
Chain’s assistant. In 1937 Florey asked Chain and Heatley to start
researching lysozyme. Alexander Fleming, a Scottish biologist, had
discovered lysozyme in people’s saliva and described it as an enzyme
that could kill some bacteria. Florey had been researching it off and on
since 1929. Interest in antibiosis, as the property of being able to kill
bacteria was called at the time, had risen when the Bayer Corporation’s
Gerhard Domagk reasoned that because some dyes attach permanently to
proteins in fibers of the cloth, they might also attach to proteins in
bacteria. Since dyes could be toxic, they might then kill the bacteria. In
1935, Domagk announced his group had made such a drug, which they
named Prontosil. Researchers at the Pasteur Institute in Paris found that
Prontosil’s active ingredient was sulfanilamide. Because they were the
first known drugs that had antibiotic characteristics, scientists became
very excited about what became known as sulfa drugs. Unfortunately,
they only treated a few diseases and could have harsh side effects.
Chain proved that lysozyme was indeed an enzyme, a protein that
accelerates and controls a chemical reaction, and he determined its
chemical structure; but Florey realized that they would not progress
beyond Fleming’s earlier conclusion that lysozyme’s antibacterial
properties were useless against bacteria that seriously harmed people. By
1938, as David Masters put it in a book based on interviews with Florey,
“Florey had concluded that the antibacterial substances offered almost a
virgin field for pure research.”
Fleming’s Serendipitous Discovery
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Howard Florey
Alexander Fleming was 47 years old in the summer of 1928 and had
just been named Professor of Bacteriology at St. Mary’s Medical School
in London. Fleming’s lab was a bit of a mess. He had been culturing
Staphylococcus aureus, a type of bacteria that causes numerous illnesses,
including food poisoning, and the many dirty dishes he had left in a basin
contained staph colonies. He was rummaging through the basin that
August day when he noticed something odd. A plate, its bottom filled
with staph, had been contaminated by a mold or fungus. What struck
Fleming was a halo-like clear area around the growth of yellow-green
mold. Something had killed off the bacteria.
Fleming put the dish down and went back on vacation. He wasn’t the
first to notice mold’s antibiotic characteristics, but observation alone had
produced little. When he returned, Fleming studied the mold for a while.
Another laboratory worker identified it as a Penicillium mold that likely
came from a family of common ground molds being studied in a lab
downstairs. Fleming showed that it was nontoxic in mice and using
human blood in test tubes, that it had a very short life—about a half-
hour—meaning that it was highly unstable. He found it hard to produce
insufficiently pure quantities to be useful even for testing, but he thought
it might have some antiseptic uses if applied to open wounds and that it
might be used in the laboratory to weed out unwanted bacteria in mixed
cultures. Whether Fleming thought that separating out and purifying the
active substance in the mold would call for someone with a greater
knowledge of chemistry than he had, or whether he thought it was simply
too unstable to be useful even if isolated, he published his findings and
then dropped the research. Penicillium remained nothing but a mold for
the next ten years. It would take three men to turn it into a lifesaver.
There Is No Question, We Will Have to Go for Penicillin

When Chain met with Florey to go over his scholarly reading, they
quickly agreed that their next research project should be a thorough
examination of bacterial antagonists (growth inhibitors). They eventually
chose three specific candidates for study: Bacillus subtilis (a species of
( 170 )
bacteria found in dirt that doesn’t cause disease but can promote healing),
Bacillus Pyocyaneus (now Pseudomonas pyocyanea—a bacterium that
turns pus blue and can inhibit the growth of other bacteria) and Penicillin.
But which to study first?
Penicillin’s potency against staphylococcus appealed to Florey.
“There is no question, we will have to go for penicillin,” Chain began
with the hypothesis that Penicillin was an enzyme. He would grow the
greenish-blue mold, wait for gold droplets of potent penicillin-containing
broth to form on the dry fronds, and then draw them off with a pipette.
They tested it on several bacteria, and a coworker remembered, “The
results were not impressive. It took ten days to produce enough of the
juice to run one experiment.” The impending war-affected Florey and his
coworkers in other ways as well. Florey wisely preempted the scattering
of his team by carving out a new war-related role for the laboratory—they
would work on blood transfusions, with Ethel heading a team of doctors
that gathered blood from donors. He turned to the Rockefeller Foundation,
writing, ‘Hitherto, the work on Penicillin has been carried out with very
crude preparations, and no attempt has been made to purify it. In our
opinion, the purification of Penicillin can be carried out easily and
rapidly. In view of the possible great importance of the above-mentioned
bactericidal agents, it is proposed to prepare these substances in a purified
form suitable for intravenous injections and to study their antiseptic
action in vivo.
Within three months, the Foundation granted Florey more than he
asked for £1,250 ($5,000) a year, guaranteed not just for the three years
he requested, but for five years. Florey had his funding and set to work,
breaking the problem of Penicillin down into five puzzles: What is the
best way to grow the most potent mold rapidly? Which bacteria does
Penicillin kill? How does it kill? What are the side effects on human
cells? And what is its chemical structure?
Florey had found that his lab was most productive if he did not have
committee meetings. Instead, each day he would make the rounds, talking
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Howard Florey
to each researcher. Only when there were problems would he gather a

few researchers to brainstorm. Florey had already set Heatley upon the
task of obtaining enough Penicillin to work with, and he proved absolutely
the right man for the job. Heatley needed to scale up the process
dramatically. Heatley grew it in anything shallow he could find, including
trays, dishes, flat bottles turned on their side, and sixteen hospital bedpans
borrowed from the infirmary. He added nitrates, sodium, salts, sugars,
phosphate, glycerol, oxygen, and carbon dioxide—anything he could
think of. None of these helped the mold grow. Around Christmas, 1939,
a visiting friend of Florey’s suggested adding brewer’s yeast, which cut
the fermentation time in half, although it did not increase the yield.
Over the next year, Heatley made improvement after improvement to
the lab’s brewing methods. He found that it was best to begin by sterilizing
the containers in an autoclave. Then he would incubate the penicillin
mold on a layer of Czapek-Dox liquid, a nutrient solution used to grow
fungi. In a few days, a yellowish gelatinous film formed on top of the
liquid, which became covered by green spores. Below it, the liquid turned
yellow from dissolved drops of penicillin-containing broth, which would
increase in quantity for ten days. Heatley found that if he drew off the
nutrient liquid and replaced it, the mold would continue to produce more
Penicillin. Heatley also worked on making the mold extract more potent.
First, he needed a reliable test that could compare its strength when he
harvested it at different stages of growth. He began his assays using a
technique of Florey’s that involved a Petri dish with holes cut in it. He
placed wax-like agar in the dish and colonized it with staph bacteria.
Penicillin derived from varying stages of growth was dropped into the
holes to see, which had the greatest effect on the bacteria. This wasn’t
precise enough, so Heatley designed a technique that replaced the holes
with porcelain tubes. This allowed for identical amounts of Penicillin to
be uniformly dropped into the bacterial colonies. After placing the
Penicillin into the tubes and allowing time to pass, he could measure the
size of the growth-free halo around each cylinder, which indicated how
much bacteria had been killed.
( 172 )
Meanwhile, Chain tested his initial hypothesis that Penicillin was an

enzyme by putting it through a cellophane filter. Penicillin went right
through it, proving it to be much too small to be an enzyme, and Chain
had to admit that his “beautiful working hypothesis dissolved into thin
air.” But rather than becoming discouraged, he became fascinated. “It
became very interesting to find out which structural features were
responsible for Penicillin’s instability. It was clear that we were dealing
with a chemically, very unusual substance.”
Chain tested Penicillin’s stability in solutions at varying pH levels
and found that it was stable only at the edges of acidity and alkalinity,
from pH5 to pH8 (pure water is neutral pH7, lower pHs are acidic, and
higher are alkaline). Since he knew his penicillin broths contained many
impurities, he tried conventional purification methods such as extracting
the active substance by dissolving it in various solvents. The idea was to
find a solvent in which Penicillin was more soluble than it was in the
moldy broth. Chain found that the weakly acidic Penicillin could be
extracted into ether, leaving the neutral impurities behind in the water
layer. But when Chain tried to remove the Penicillin from the ether, it
seemed to vanish.
Over time, Heatley mechanized and greatly improved the extraction
of Penicillin into the ether, building an apparatus to separate Penicillin
from its broth at a much faster rate. Once the penicillin-containing
solution deposited by the mold was filtered to remove bits of mold and
other contaminants, the liquid was jet-sprayed down a long tube, while a
stream of ether (later replaced by amyl acetate) flowed upwards past it in
the same tube, so that the two liquids had a large surface area of contact.
The Penicillin dissolved in ether and rose to the top, while much of the
rest of the original solution sank and was drawn off. But the problem of
how to remove the Penicillin from the ether remained.
In March of 1940, Florey held one of his informal brainstorming
meetings with Heatley and Chain to discuss their inability to extract
Penicillin from the ether. Hesitantly, because he thought it was so
( 173 )
Howard Florey
obvious, Heatley speculated that reversing Chain’s steps might work. If

the slightly acidic Penicillin would dissolve in ether, perhaps a slightly
alkaline solvent would pull it back out of the ether. Florey was intrigued,
but Chain immediately dismissed the idea.
Florey told Heatley to go for it. Heatley had found a way to stabilize
Penicillin. This allowed the researchers to create a “standard solution”
and define a “unit” (now sometimes called the “Florey unit” or “Oxford
unit” of Penicillin). To make a drug, the research team still needed to
precipitate Penicillin out of the water. Freeze drying had been developed
in 1935 in Sweden and had revolutionized the preservation of unstable
materials: The process involves first freezing the material and then using
drying techniques that remove water (now ice) by making it form a gas
without going through a liquid state, where chemical reactions are likely
to occur and affect the substance. This is usually done at low pressure to
promote evaporation, but you can observe it in your freezer, as well,
when frost forms on surfaces that were previously dry; this is water that
evaporated from other parts of your freezer and recondensed. Chain set
to work. “The result,” he later wrote, was “a very nice brown powder
which kept the activity of the medium undiminished, without any loss
whatsoever.”
After almost two years of work, the team had a real drug that could
be tested. Biological tests were Florey’s specialty.
They ran test after test on mice, rats, rabbits, and cats, injecting
Penicillin into their skin, their blood, their abdominal cavities, giving it
to them orally and through stomach tubes—all the typical tests drugs go
through. They found that Penicillin remained active when injected into
the blood but that it did not enter the bloodstream when delivered to the
stomach either orally or by a tube. Yet even an injection of Penicillin
never lasted long. Within an hour or two, it was gone from the bloodstream.
The team discovered that the mice were eliminating it in their urine, so
they learned to recycle it by collecting urine, extracting the Penicillin,
and then re-administering it.
( 174 )
They ran toxicity tests. One of the most fragile cells in the body is the
leucocyte, a white blood cell that engulfs foreign bodies as part of the
immune system. They tested Penicillin on leucocyte cells in test tubes
and were stunned to find it harmless.
They were surprised that it killed a diverse group of bacterial
pathogens, although at varying doses. What was the mechanism of its
power? Tests showed that Penicillin did not kill bacteria immediately on
contact, meaning it was not an antiseptic, and they knew it was not an
enzyme that dissolved them. Under a microscope, bacteria treated with
Penicillin became swollen and elongated, stopped dividing, and
eventually burst or died. Penicillin’s potency was all the more stunning
when it was discovered that if it was diluted to one part per million, it still
killed some types of bacteria, which meant it was twenty times more
effective than the latest sulfa drug.
It Looks Like a Miracle

Finally, Florey and his team were ready to end their preliminary tests
and perform a test on a living animal. At 11 AM on Saturday, May 25,
1940, Florey, and Kent injected eight white mice with a dose of virulent
streptococci known to kill mice. At noon, they gave two mice an injection
of 5 ml of Penicillin, and two others 10 ml. The other four were controls,
so they received none. That afternoon, Florey, Heatley, and Kent watched
the mice. At around 6 PM, Florey sent Kent home and then gave the first
two mice another dose. By 6:30, mice one, two, and three looked fine.
Mouse four looked so-so. The controls looked sick. The scientists went
home to eat. At 10 PM, Florey returned to give mice one and two other
injections. The mice acted about the same as at six o’clock. Heatley
returned around eleven and began marking down the times of death of the
four control mice. The last one died at 3:28 AM. The next day Florey,
Heatley, and Chain met to go over the results. The four mice that had
received Penicillin were still alive. Florey, ever known for his understated
manner, called Margaret Jennings. “It looks like a miracle,” he told her.
( 175 )
Howard Florey
On Monday, Florey and Jennings repeated the experiment using ten

mice. On Tuesday, they used sixteen mice, doubling the number of lethal
streptococci they gave each mouse and varying the doses of Penicillin. In
the months ahead, they treated mice infected with different diseases,
using fifty to seventy-five mice for each experiment. They learned that
for some pathogens, they had to keep Penicillin in the blood for long
periods of time, because Penicillin never lasted long in the blood. That
summer of 1940 was a foreboding time in England, as the nation prepared
for a German invasion. As a precaution, the lab drew up plans to save
Penicillin in the event of a German invasion. They would destroy all the
records, but Florey, Heatley, and some of the others smeared spores of
the penicillin mold into their clothes, where it could remain dormant for
years. If they escaped, they would wear the spores to safety.
The team’s clinical tests continued until they were confident that
Penicillin was a potent drug. They wrote up the results, and on August 24,
1940, the prestigious British medical journal The Lancet published a two-
page article titled “Penicillin as a chemotherapeutic agent.” Florey
expected a great deal of interest from other researchers and the
pharmaceutical industry, but in September, the bombing known as the
Blitz started, and the German air force struck London for fifty-seven
nights in a row.
The reaction to the publication was less than muted. Even when
Florey visited pharmaceutical companies and touted Penicillin’s benefits,
none were willing to make an investment in a radically new drug during
a time of uncertainty caused by the war. He noted that a human was 3,000
times the weight of a mouse, which meant that they would have to
produce at least 500 liters a week of the penicillin juice to test it on
humans. With Heatley, he set to work building a factory in the school.
They designed containers in the shape of bedpans and ordered 600 of
them from a ceramics factory. They hired six “penicillin girls” to help,
and production began on Christmas Eve, 1940.
Once in a Life
( 176 )
That January, Florey and his team were ready to test Penicillin on
humans. Consulting with Dr. Charles Fletcher, they realized that tests on
human subjects involved serious ethical issues since mice and humans do
not always react to drugs in the same way. They decided to first test
Penicillin on a consenting terminal cancer patient, who would not benefit
from the drug, but who, if harmed, would die shortly anyway. Elva Akers,
fully informed, agreed to be the guinea pig. She said Penicillin had a
curious musty taste, and several hours later, she developed chills and a
mild temperature, which the researchers took to be signs of impurities.
Over the next few weeks, the researchers worked at further purifying
Penicillin. Edward Abraham, another of Florey’s lab researchers, had
made an important contribution. Using chromatography—the technique
of isolating a substance by drawing a mixture through various layers that
act similar to filters—he separated the brown substance into bands of
powder, one of which was yellowish and 80 percent pure. It turned out
that the Penicillin the team had been using all this time was only 1 percent
pure. In the eighteen months, the team had been producing Penicillin.
They had produced a total of 4 million Florey units for all their experiments
and human trials. The ideal dose for a single patient, it would later be
learned, turns out to be 4 million units each day of treatment.
On February 12, 1941, they went to a septic ward where Dr. Charles
Fletcher was treating a patient who had been infected for five months
after scratching his face in his rose garden. The patient was Albert
Alexander. Heatley wrote in his diary that Alexander “was oozing pus
everywhere.” After eight doses of Penicillin, his infections were
dramatically reduced, his temperature was normal, and his appetite had
returned. Five days later, his swelling had almost disappeared. Regrettably,
Florey and his colleagues ran out of Penicillin, and Alexander relapsed
and died.
Clearly, Florey and his team didn’t have enough Penicillin to treat
adult patients with full-blown infections, so they decided to concentrate
treatment on children and localized infections. They watched a
( 177 )
Howard Florey
carbuncle—an abscess the width of a hand—melt away from a patient’s

back over days of treatment. As Fletcher bicycled patients’ urine back to
Florey’s lab to be recycled, he realized how privileged he was to be
taking part in such a monumental project. In Florey and Chain, he saw
“the intense joy of the scientist seeing that years of work had resulted in
an opportunity to save lives.” Later, when he asked Florey how it felt,
Florey said, “This is the sort of thing that only happens to you once in a
life.”
A Carpetbag Salesman Trying to Promote a Crazy Idea

Florey also faced the fact that the factory he and his colleagues had
cobbled together could never produce enough Penicillin to treat all the
people who needed it. Without the British pharmaceutical industry’s
help, Florey could only turn to one place—the United States. After
obtaining government approval, Florey chose Heatley, who knew how to
ferment Penicillin, to fly with him to New York. On June 27, 1941, they
boarded a plane for Portugal and then a final flight to New York.
The very day the scientists landed, they met with Dr. Alan Gregg,
head of the Rockefeller Foundation’s Medical Sciences Division, and
without notes, Florey told the story of the development of Penicillin and
its promise as a drug. Heatley remembered Florey’s talk: “In a startling
sort of way, it revealed the wide grasp of his scientific mind. Even though
I knew the subject well, he showed me new facts, and I realized suddenly
how great a man he was” Dr. Gregg was busy opening doors, and after a
flurry of meetings, the researchers met Dr. Percy Wells, the head of the
Bureau of Agricultural Chemistry and Engineering, a federal agency of
the Department of Agriculture. Florey and Heatley expressed to Wells
that great progress would have to be made in optimizing Penicillin’s
growth if they were ever going to produce enough of the drug to distribute
widely. Dr. Wells understood exactly what was needed and made
arrangements for work on the mold to begin immediately at the Bureau’s
laboratory in Peoria, Illinois, which was already working on fermentation
techniques for other uses. Florey and Heatley took their precious vials of
( 178 )
Penicillin by train to Peoria and decided that Heatley should stay so that
he could demonstrate all he knew about how to grow it. He settled into
work with the Bureau’s scientists for what would turn out to be a full
year.
After such a fast start, Florey felt optimistic. Month after month,
though, one pharmaceutical company after another balked at the
difficulties involved in making the drug. Not only would it require huge
rooms of vats to grow enough mold to produce Penicillin in great
quantities, but even if it were as successful a drug as Florey promised, the
companies were afraid other scientists would soon synthesize it, making
their investment in fermentation technology immediately obsolete.
Florey was left feeling like “a carpetbag salesman trying to promote a
crazy idea for some ulterior motive.”
However, Alfred Richards, the man with whom Florey had studied
in Philadelphia fifteen years earlier, was impressed when he heard
Florey’s presentation. “Florey is a scientist, and a scientist like that
doesn’t tell a lie,” he said. By this time, Richards was the vice president
of the University of Pennsylvania Medical School and chairman of the
Committee on Medical Research and Development, part of the growing
government military-scientific establishment. He started pulling strings,
letting companies know that the government wanted Penicillin produced.
Eventually, Merck, Charles Frosst, Squibb, and Pfizer agreed to produce
it.
While the companies began gearing up, the scientists back in Peoria
had quick success in using steep corn liquor instead of yeast in the
fermentation process. Corn wasn’t grown commercially in England, but
in Peoria, its derivative was the first choice for all fermentations, for it
was rich in nitrogen, which promotes the growth of molds and other
forms of life. The researchers realized that Penicillin was produced by
many different strains of the Penicillium mold, so they began looking for
ones that might produce a more potent extract. They had samples parceled
to them from all over the world but also sent a lab worker, Mary Hunt, to
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Howard Florey
local supermarkets to bring back moldy fruit and vegetables, which they
would then culture. One day “Moldy Mary,” as she was known, brought
back a cantaloupe infested with mold so powerful that it became the
source of most of the world’s Penicillin for years. Now there were two
penicillins, with the much more potent American version, Penicillin G,
differing molecularly from the British Penicillin F. With the resources the
major pharmaceutical companies brought to bear, many more incremental
improvements would be made over the next two years.
It Was a Revolution
Florey returned to England and kept his lab working to produce
Penicillin.
Later, Florey went to North Africa to oversee tests of Penicillin on
wounded soldiers. Most doctors were leery to give up their sulfa drugs,
but Penicillin’s effectiveness quickly dispelled their reluctance. U.S.
companies finally began producing enough Penicillin for its first mass
use, which was, oddly enough, to treat venereal diseases picked up by
soldiers and sailors in the whorehouses of the Philippines and North
Africa. One-shot completely cured a soldier if he had been infected by
syphilis for less than a year, and still does to this day. By D-day, June 6,
1944, there was enough Penicillin to treat all 40,000 men wounded in the
Normandy invasion. The first British soldier to be treated was James Hill.
By the time the war ended, U.S. companies were making enough
Penicillin treat a quarter of a million individuals a year.
Probably no other drug has ever had such a dramatic impact on
medicine. Lewis Thomas, one-time dean of Yale Medical School,
described the impact on his generation of doctors: “We could hardly
believe our eyes on seeing that bacteria could be killed off without at the
same time killing the patient. It was not just amazement. It was a
revolution.” The mortality of young people with bacterial pneumonia fell
from 66 percent to 6 percent.
Penicillin was magical like no other drug because it treated so many
( 180 )
diseases: syphilis, gonorrhea, childbed fever, septicemia, meningitis,

scarlet fever, gas gangrene, anthrax, tetanus, rheumatic fever, lobar
pneumonia, and diphtheria. Its strength and broad-spectrum gave a huge
dose of giddy optimism to the medical community. A post-war account
by well-known venereologist George Bankoff stated: “Soon young ladies
will be able to buy their lipsticks impregnated with Penicillin. They will
still have their lips made beautiful and inviting, but the danger of infection
that every kiss potentially can transmit will be removed.” It is an
interesting fact of human nature that we count deaths, but not lives saved.
Almost all of us have been dosed with Penicillin or its derivatives at one
time or another, sparing us pain and suffering, and in many cases, death.
Amy Pearce examined the best available data, looking at mortality rates
before Penicillin existed, and after it was available, and her estimate of
the number of lives penicillin has saved is staggering. Millions of children
have been saved from pneumonia, and millions of adults’ lives have been
saved from syphilis in the United States and Europe alone. Tens of
millions have been saved from meningitis and blood poisoning. There is
scant data from the third world, although Penicillin is widely used. But
counting only the developed world and these four diseases, the number
of lives saved is over 80 million.
Once Penicillin gained publicity, thousands of scientists began
studying it. In 1945, Dorothy Crowfoot Hodgkin of Oxford University
determined Penicillin’s structure using X-ray crystallography and went
on to win a Nobel Prize for her work on it and other substances, including
insulin. It was found that Penicillin works by binding to an enzyme that
many bacteria use to build their cell walls. Without this enzyme, the walls
of these bacterial cells weaken and collapse.
Penicillin itself has also undergone vast development since Florey’s
day. In order to slow down the rapid excretion of Penicillin from the
body, a search began for a molecule that would compete with Penicillin
in attaching to the organic acid transporters in the blood that were
ushering Penicillin so quickly from the body. It was found that
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Howard Florey
administering probenecid—a drug used to treat other ailments, including

gout—allowed Penicillin to last much longer in the body, all the while
killing bacteria. In 1957, John C. Sheehan of MIT synthesized Penicillin,
rendering unnecessary the fermentation process Heatley so labored over.
In the 1960s, the Beecham Research Laboratories in Surrey, England,
patented the synthesized penicillin derivatives ampicillin and amoxicillin,
which made good absorption of oral Penicillin possible in pill form. Fifty
years after the advent of Penicillin, amoxicillin was still the most
prescribed drug in the U.S.
The popularity of Penicillin also led to a broad search for other
natural substances with antibiotic properties. In 1944, Selman Waksman,
the man who coined the term antibiotic, discovered streptomycin, which
treated tuberculosis, long a scourge of humankind. Abraham and Heatley,
still working under Florey, went on to develop the cephalosporins, a class
of antibiotics that kill some penicillin-resistant bacteria. Today, more
than 10,000 substances with antibiotic properties are known, many of
which have been used to save millions of additional lives.
The Problem of Resistance

Four years after the mass-production of Penicillin began in 1943,
resistant strains of Staphylococcus aureus bacteria emerged. Staph a. is a
normally benign organism that many of us carry on our skin and in our
noses. It sometimes causes minor infections such as boils and urinary
tract infections, but it can also cause serious ones such as meningitis,
pneumonia, food poisoning, and toxic shock syndrome. It was this drug-
resistant staph that gave Muppets creator Jim Henson pneumonia, from
which he died.
Bacterial drug resistance occurs by evolution through mutation.
Individual bacteria with mutations that allow them to survive an antibiotic
thrive and replace those without resistance. For instance, some populations
of staph a. were observed in 1947, producing an enzyme that would break
apart the beta-lactam ring in Penicillin, which is the very structure that
( 182 )
gives Penicillin its antibiotic potency. Bacterial evolution can occur

rapidly. Bacteria (and many viruses) can reproduce as fast as every
twenty minutes: This equals three times an hour. and 525,600 times faster
than a human’s normal reproductive cycle of around twenty years. In
addition, an infection consists of many bacteria. When an antibiotic is
taken, it may kill billions of bacteria, but if only a few with mutations
survive, grow, and multiply, they will quickly repopulate, carrying with
them their resistant characteristic.
Soon a whole colony of bacteria can have its own life-saving gene,
which can be passed on to their progeny.
Scientists have worked diligently to develop new antibiotics to
replace those that become obsolete due to evolved resistance. But by the
late 1990s, half of all Staph a. bacteria was resistant to Penicillin,
methicillin, tetracycline, and erythromycin. Two million people in the
U.S. become infected in hospitals each year, according to the National
Institutes of Health. Seventy percent of the bacteria that cause these
infections are resistant to at least one antibiotic. Of those infected, 90,000
dies, an increase of 9 percent in the past ten years. Bacteria are as clever
at developing resistance to current antibiotics as scientists are at
developing new ones, and the battle against infection, begun in 1942 with
the development of Penicillin, is far from over.
The Fleming Myth

When news of Penicillin broke, the media turned their attention to
the discoverers. When reporters first showed up in Oxford, however,
Florey literally ran out the back door. He refused interviews, well aware
that there was still not enough Penicillin to treat all who needed it all over
the world. Alexander Fleming, in contrast, relished the spotlight and
granted an interview after interview. The press ignored the fact that
Penicillin had lain fallow for a decade before Florey’s team picked it up.
The reporters knew nothing of the years of chemical, engineering, and
clinical work that was necessary to turn a mold into the first antibiotic
( 183 )
Howard Florey
drug.
This lack of recognition culminated in a letter Florey received from
St. Mary’s Hospital. It started, “You may have heard of the discovery of
penicillin by Professor Fleming at St. Mary’s Hospital.” and invited him
to buy tickets for a charity show. Florey laughed. Florey to set the record
straight with the press, so he turned to Mellanby and Sir Henry Dale, the
President of the Royal Society. Both urged him to maintain a British stiff
upper lip and keep quiet. As he followed their directives, the press
concentrated on a willing Alexander Fleming. The Oxford team, whose
diligent work had actually created the drug, became a forgotten footnote
in the public story that became notorious as the Fleming Myth.
Florey’s team’s contribution was assumed to be minor, while Fleming
became one of the most famous men in Europe, traveling all over, posing
for pictures, and lecturing. In 1945, Howard Florey, Ernst Chain, and
Alexander Fleming received the Nobel Prize for Physiology and
Medicine. Fleming had discovered penicillium—the mold; Florey and
Chain and Heatley had discovered Penicillin—the drug. The Nobel
committee limits its awards to three people, and as a result, Norman
Heatley was overlooked in the committee’s decision. The omission of
Heatley was such an injustice that in 1990, to mark the 50-year anniversary
of Penicillin as a drug, Oxford University conferred upon the 78-year-old
Heatley its first honorary Doctor of Medicine in its 800-year history.
Working on Mucus
One day in the 1950s, a young student saw an older man in the
hallway at Oxford and asked a friend who he was. His friend replied, “At
breakfast a couple of days ago, I saw that chap sitting on his own. He let
me join him. I asked him what he was doing. He said he was working on
mucus.”
“My God,” the student replied. “How sad. Here’s a man probably in
his 60s, probably at the end of his career, studying mucus.”
( 184 )
Such were the accolades of the young. The man was Howard Florey,
leader of the team that created Penicillin, the most revolutionary drug of
all-time. His peers made him president of the Royal Society in 1960, the
highest honor in British science, and in 1963 he became president of
Queen’s College, one of the oldest of the colleges that make up the
University of Oxford. He worked until the day he died, February 21,
1968, at the age of 69.
Reflections
Howard Florey, along with E. B. Chain and Norman Heatly, converts
an accidental observation of Alexander Fleming from Promise to Potential
to Reality as the first antibiotic. What does it say about the Nobel Prize
being given to Alexander Fleming? Clearly, Fleming would not have
received the Nobel Prize had not a mold accidentally entered his
laboratory. This seems paradoxical since it was beyond his control. Is it
an example of moral luck in science and Technology? The Control
Principle says that people are not responsible for things beyond their
control (In this case, Fleming’s dessert!). Luck’s quintessential role in the
discovery of Penicillin by Fleming. Gwyn McFarlane’s provides a
masterly account.
1. Fleming inoculates a plate with staphylococci, and it happens to
become contaminated with a rare penicillin-producing strain of
mold.
2. He happens not to incubate this plate
3. He leaves it on his bench undisturbed while he is on a holiday
4. The weather during this period is at first cold and then warm
5. Fleming examines the plate, sees nothing interesting, and discards
it, but by chance, it escapes immersion in Lysol.
6. Pryce (one of Fleming’s former colleagues) happens to visit
Fleming’s room, and Fleming decides to show him some of the
many plates that had piled up on the bench.
( 185 )
Howard Florey
7. Fleming happens to pick the discarded penicillin plate out of the

tray of Lysol (in which it should have been immersed}’ and on a
second inspection sees something interesting.
Fleming himself, despite having used Penicillin successfully at least
since 1932, seemed to have lacked clear evidence for its therapeutic
potential. It remained up to the research team of Howard Florey, Ernst
Chain to screen various molds and discover a better higher-yielding strain
Penicillium chryosegeum yielding stream of Penicillin. Fleming’s skills,
his power of observation, and eager experimentalism, initially made him
aware of the mold in the petri dish, and it is those skills that induce praise
and admiration. More importantly, publishing his work in a journal an
{Unsung Hero} and was picked up by Howard Florey to relook at work
after 10 years of publication. Norman Heatley in Florey’s group scaled
up the process, and many feel he too should have been awarded Nobel
Prize. Unfortunately, the rule of 3 came into play.
( 186 )
9
Frederick Banting
(1891-1941)
Insulin: The First True Miracle Drug

LEONARD THOMPSON, age 14,

lay in the public charity ward of Toronto
General Hospital in Canada in the final
stages of consciousness before slipping
into a coma. He weighed just 65 pounds
on that day in January 1922, and he had,
at the most, just weeks to live.
In Washington, D.C., the 14-year-
old daughter of the Secretary of State
gazed at the hair covering her pillow.
Elizabeth Hughes weighed 44 pounds
and stood barely five feet tall, resembling
Charles Best and Frederick
a tiny skeleton more than a teenaged girl.
Banting on the roof of a
University of Toronto building
And in Rochester, NY, Jimmy with one of their dogs that had
Havens, 22, weighing 73 pounds, spent been given insulin (1921).
his day crying from pain, hunger, and Photo courtesy of the Thomas Fisher Rare
Book Library, University of Toronto.
despair. All suffered from a disease that,
in 1922, was a death sentence - diabetes. With no cure available, each
would die within a few months unless a miracle occurred.
Average Student and Poor Speller

Frederick Banting was born on November 14, 1891, on his family’s
Frederick Banting
farm in a small county in Ontario, Canada. He was the youngest of five

children in a family that prayed as hard as it worked. He was, at best, a
mediocre student, too afraid of getting the answer wrong to raise his
hand, too ashamed of his copybooks filled with spelling errors to show
them off.
Although few farm boys at that time managed to finish eighth grade,
let alone high school, Banting knew he wanted to attend university. He
loved the tales of adventure and hardship, of the worlds those writers
created so far away from the farm. Someday, he vowed, he would leave
the farm and find that world. The college offered a way to do that.
He barely passed his high school exams. Banting still managed to get
accepted into Toronto’s Victoria College in 1910. His goal—or, rather,
his father’s goal for him—was to become a minister. He was still a
terrible speller, an affliction that would haunt him throughout. He was
also famously stubborn, and the few beatings he received in his childhood,
at worst, developed into doggedness.
Since childhood, he had always had a fascination with medicine. As
a young boy, he had seen two construction workers fall off their
scaffolding and suffer severe injuries. Young Frederick ran for help and
then watched, mesmerized, as the doctor examined and treated the
stricken workers.
While it took a lot of talks, prayer, and convincing, his parents finally
agreed to help pay for his medical education. In the fall of 1912, Banting
enrolled in the University of Toronto’s five-year medical program.
Mustard Plasters and Fee Collections

Banting began his career during a time of great change in the medical
profession. Prior to the twentieth century, most practicing North American
doctors obtained their education through an apprenticeship program. If
they could afford it, they went off to Germany or Austria to train. As late
as the 1870s, most medical schools in Canada and the U.S. were without
laboratories.
( 188 )
By the 1890s, however, a new model of medical education had

emerged, one which encompassed hands-on laboratory work and
substantially more instruction in the basic and medical sciences during
the preclinical years. The average age of human beings was 25 before
1900. At the turn of the twentieth century, the enormous possibilities of
modern medicine were only beginning to become evident. Aspirin, the
first synthetic drug, came on the market in 1899. Millions of children died
before their 10th birthday of common infectious diseases like measles,
typhoid, and diphtheria (unfortunately, this is still true today in parts of
the developing world). Vaccines were rare, and in those days before
antibiotics, a simple infection could be a death warrant.
Small wonder patients often died from the treatment instead of the
disease.
Banting received training in all these approaches, as well as successful
doctor tips, such as when confronted with a syphilitic patient to “tell them
what your fees are and collect them first.” He also spent a great deal of
time in the operating rooms and soon developed a love of surgery. But it
wasn’t until his fourth year, while attending a lecture by the leading
diabetologist Frederick Allen, that he learned about diabetes and its only
treatment: starvation. He graduated with his medical degree on December
9, 1916. Canada was deeply involved in World War I, and like so many
of his classmates, he reported for military duty the following day. His
courage under fire later won him the Military Cross, with the official
citation noting that “his energy and pluck were of a very high order.”
In February 1919, he was back in Canada with his arm intact and
functioning despite injury by a shrapnel. He spent six months at a Toronto
military hospital helping set and mend the broken bones of soldiers
before receiving his formal discharge at the end of the summer of 1919.
Restless and not willing to marry without a source of income, he decided
to set up his own medical practice. He bought a large brick house for
$7,800 using part of the downstairs for his office. He waited for patients.
( 189 )
Frederick Banting
It took three weeks before he saw his first patient, and by the end of
his first month, he had earned a grand total of $4. After a couple of
months, he took a job teaching surgery and anatomy to medical students
at London, Ontario’s Western University. Going to the library, keeping
track of the latest developments in research was a routine. On October 31,
1920, he picked up the November issue of Surgery, Gynecology, and
Obstetrics, which had arrived the preceding day. He found himself
fascinated by the lead article, “The Relation of the Islets of Langerhans
to Diabetes with Special Reference to Cases of Pancreatic Lithiasis,”
written by Moses Barron. That one article set in motion a medical
revolution.
Sweet Urine and Death

Diabetes has likely been around as long as mankind. Diabetes stems
from the Greek word for “siphon,” or “pipe-like.” This refers to the
tremendous amount of urine that diabetics produce. In 1675, the British
physician Thomas Willis tasted the urine of several diabetics and found
it uniformly sweet. Today, we know the reason diabetics’ urine is so
sweet is that their bodies are unable to process glucose, the sugar molecule
that provides the energy that cells need to power every aspect of human
life.
Even in Banting’s time, doctors recognized that there were two types
of diabetes: a type they called “juvenile” or “childhood” diabetes, and
one called “adult” diabetes. The childhood version was deadly, striking
suddenly with symptoms of great thirst and urine output, tremendous
hunger, and frightening weight loss. Known today as type one diabetes,
it affects some 2 million people in Europe and North America and can
also strike adults. India currently records more than 50 million diabetic
patients. Insulin is the hormone that unlocks muscle and fat cells to let in
glucose. Hormones are your body’s chemical messengers. They travel in
your bloodstream to tissues or organs. Each tissue or organ has specific
receiving molecules known as receptors. When Insulin binds to receptors
on the cell membrane known as glucose carrier proteins, a chain of events
( 190 )
is set in motion that culminates in the cell synthesizing proteins that allow
glucose to cross the membrane. Without Insulin, these cells can’t get
access to glucose to make energy. Without energy, they can’t carry out
the functions vital for all animal life. The human body secretes and
circulates some 50 different hormones. A wide variety of these chemical
substances are produced by endocrine cells, most of which are glands.
The hormones then enter the blood system to circulate throughout the
body and activate target cells by binding to specific receptors for those
hormones. On binding, a secondary messenger is produced inside the
target cell, initiating a specific set of instructions for that cell to perform.
All hormones have a life which may be anywhere between minutes to
hours and should be destroyed by the body as they can do more damage
than good. Hormones also go through a cycle of creation followed by
destruction, and the cycle continues throughout the life of a human being
and other multicellular organisms.
The 100 percent mortality rate of type one diabetes defied hundreds
of years of efforts to find a way to arrest this dreadful disease. At first,
doctors prescribed great quantities of sugar to replace that lost in the urine
of diabetic patients, but this only hastened their deaths. In 1776, the
discovery of sugar in the blood of patients confirmed that diabetes was a
systemic disease. A few years later, the researcher Thomas Cawley
performed an autopsy on a patient who had died from diabetes and found
the pancreas shriveled up, the first intimation that the gland plays a role
in the disease. But it wasn’t until 1889, twenty years after the German
scientist’s Joseph von Merring and Oskar Minkowski first hypothesized
that something within the pancreas was responsible for the terrible sugar
disease.
German medical student Paul Langerhans found that the pancreas
contained two types of cells: the acini, which are clusters of cells that
secrete the pancreatic enzymes, and another type unconnected to the
acini. A few years later, the French researcher Laguesse bestowed the
name “islets of Langerhans” on those other cells—in honor of the man
( 191 )
Frederick Banting
who originally identified them. There are from one to three million of
these islet cells in the normal pancreas, constituting about 2 percent of its
mass. Over the next few years, more than 400 researchers set to work
trying to find that mysterious “something.”
On June 20, 1906, a German internist named Georg Ludwig Zuelzer
injected an extract of cow pancreas and adrenalin into a man in a diabetic
coma. The man came out of the coma feeling hungry, but he died twelve
days later when the extract ran out.
Years later, when pictures of World War II concentration camp
survivors circled the globe, doctors were reminded of those early diabetic
patients. The estimated lifespan for someone who developed type one
diabetes was a year to eighteen months without the ‘Allen diet,’ four or
five years with it. But the end was always the same—death.
Getting to Toronto
The article Banting read that October night didn’t have its desired
physiological effect; instead of falling asleep, he found himself wide
awake. The author wrote that while conducting an autopsy on a patient,
he had found a small stone obstructing the main pancreatic duct, through
which the strong pancreatic enzymes pass to the stomach to help digest
food. Find that substance, he wrote, and you might be able to cure
diabetes.
As later described in his obituary in Time magazine, Banting thought
the mysterious substance secreted by these islets must act as a spark plug,
providing the “juice” to help the body metabolize carbohydrates. He
wasn’t far off.
That next day, despite his sleepless night, Banting’s enthusiasm
remained at a fever pitch as he felt the excitement of the scientist who has
just seen a novel approach to a problem. While in Toronto for a wedding,
Banting called on Macleod, 44, the Scottish son of a minister. A small,
well-dressed man, he’d become an authority on carbohydrate metabolism
( 192 )
while at Western Reserve University in Cleveland, when he published a

monograph in 1913 called “Diabetes: It’s Pathological Physiology.” By
the time Banting came to see Macleod in November 1920, the professor’s
research focus had shifted to metabolism. He believed some part of the
brain-controlled glucose storage in the liver.
Macleod was skeptical of Banting’s idea. For his part, Banting was
shy and bumbling in his presentation.
At one point, historian Michael Bliss writes, Macleod began reading
some of the letters on his desk, a sometimes unconscious and common
gesture bound to offend the sensitive visitor to his office. When Banting
didn’t take the hint and leave, Macleod brusquely told him that it was
doubtful Banting would be successful. He assured Macleod he was
committed. But Macleod knew that what Banting wanted to do wasn’t
completely unique.
Banting returned to London, highly disappointed at being put off. He
wanted to close his practice and start the research immediately. But his
fiancée, Edith, told him to forget about diabetes and to settle down and
run his medical practice. Banting tried, but he could not stop thinking
about diabetes. It seemed to consume him. Regardless, he contacted
Professor Macleod again in January and once again in March, and this
time he put his thoughts into writing, a move that definitely improved his
standing with Macleod, who still put him off until the coming summer.
Impatient by nature, Banting became discouraged after the March
meeting. A few weeks later, a letter arrived with news that the Arctic
party had decided not to take a doctor. So, after giving final exams to his
students in London that spring, Banting took the train to Toronto on May
14 1921.
Dying Dogs and Isletin

When Banting arrived in Toronto, Macleod had left the country for
the summer but had ten dogs, a filthy laboratory on the top floor of the
( 193 )
Frederick Banting
university’s medical building, and a fourth-year student Charlie Best.

Macleod had chosen him and another student, Clark Noble, to help
Banting through the summer. The first order of business was scrubbing
down the filthy lab, which apparently hadn’t been cleaned in years.
Banting and Best washed the walls and floor on their hands and knees
until the lab was sparkling. Then they turned to the dogs.
The first dog, number 385, was a brown female spaniel. Spaniels are
often used in medical research because they’re small and relatively calm.
The plan was to anesthetize the dog, cut her open, pull out her pancreas,
tie off the pancreatic ducts, and close the incision, leaving the precious
islets of Langerhans and their mysterious substance isolated. Other dogs
would have their whole pancreas removed, giving them type one diabetes,
so they would be available to test the mysterious substance once it was
purified. Unfortunately, dog number 385 died the first day from an
anesthesia overdose. By the end of the second week, seven of the ten dogs
were dead. To continue their research Banting and Best took to buying
dogs on the streets of Toronto with their own money.
After seven weeks and fourteen dead dogs, and still, with no sign of
pancreatic atrophy, Banting and Best realized their mistake by trial and
error as they were not exposed to research methodology. They were
using catgut to tie off the pancreatic duct, and it loosened before any
damage could set in. Despite not having money to buy dogs for his study,
he wanted to give proof of concept of his hypothesis before McCleod
returned from his holiday. Banting sold his car and bought more dogs.
This time, he used surgical silk for the ligatures, and by July 30 he had
two atrophic pancreases. Banting and Best then made an extract from the
desiccated pancreases and injected 4 ccs into a small white terrier with a
blood sugar of 200 mg/dl (milligrams per deciliter). An hour later, the
terrier’s blood sugar had dropped 40 percent to 120 mg/dl. But despite
more injections, the sugar levels began to rise again within a couple of
hours. The next day, the dog died of diabetes. Another trial two days later
also failed. Two attempts, two dead dogs. They were running out of
diabetic dogs.
( 194 )
On August 3, Banting did a total pancreatectomy on a collie. The

following day, he and Best gave the collie some of the terrier’s remaining
extract. To their amazement and joy, the dog’s blood sugar dropped with
each injection. Banting and Best continued experimenting with injecting
extracts of liver and spleen and a boiled version of the pancreatic extract,
to no effect. Although the dog died on August 7 from a massive infection,
Banting could, at last, write Macleod about their progress: “I have to tell
you that
(1) the extract invariably causes a decrease in the percentage of blood
sugar and in the excretion of sugar in diabetic dogs.
(2) it is active at least for four days if kept cold.
(3) it is destroyed by boiling.
(4) extracts of spleen and liver at least, prepared under similar
conditions, have no such action.
(5) The clinical aspect of the animals is improved by the extract.”
Excited and energized by their progress, they worked round-the-
clock over the next two weeks, on more dogs and making more extract.
On August 19, Banting figured out a new way to deplete the pancreas of
external secretion by stimulating it with the hormone Secretin, which
caused the pancreas to release its enzymes until it was empty. They then
ground up the remaining pancreas, with its islets of Langerhans, to make
their extract.
Twelve hours after Banting and Best gave this new extract to a
diabetic collie so weak from its diabetes it could barely stand, the dog was
prancing around the lab. They’d done the impossible: created an extract
that reduced blood sugar! It didn’t have a name, and it would be another
40 years before anyone identified the chemical structure, but Banting and
Best had seen firsthand the life-giving benefits of Insulin, the hormone
secreted by the islets of Langerhans, the chemical needs to unlock cells
and allow in sugar, the energy of life.
( 195 )
Frederick Banting
In fat cells, Insulin converts glucose into triglycerides for storage. In

muscles (and the liver), it converts glucose into glycogen. Type one
diabetics don’t have this storage benefit, so their body runs out of fuel. In
contrast, about four hours after a meal, nondiabetics’ glycogen begins to
break down into glucose in the liver, providing fuel to the body. The body
can also break triglycerides down into glucose to use as fuel. Since
diabetics have no insulin, and their livers cannot store glucose as
glycogen, the bloodstream is consequently flooded with sugar after every
meal. The excess is filtered out by the kidneys and expelled in the urine.
In early September, Banting returned to London to sell his house and
settle his affairs. He and Edith were not getting along, and the dreams of
marriage had faded, so his focus was now 100 percent on Toronto.
Macleod returned from Scotland on September 21. Banting and Best
excitedly showed him the extract they had produced. But the senior
scientist, aware of the false hope that science often engenders, insisted
they repeat their experiments to prove that the extract, and not something
else, reduced blood sugar. They did and succeeded a second time, after
which Macleod agreed that they had found something. If it were ever
going to be produced as a life-saving drug, it had to be purified and
stabilized.
Banting and Best returned to the laboratory. Their work progressed
slowly through the fall until Macleod suggested they show that regular
injections of the extract could keep a dog alive over time. But getting
enough Insulin to provide long-term treatment was a problem. He learned
that the pancreases of newborn and fetal animals contained more islet
cells than other pancreatic cells since the animals didn’t need pancreatic
enzymes for digestion until they were born. He also knew from his time
on the farm that farmers sometimes bred cattle just before they were
killed to induce them to eat more, get fatter, and fetch a better price. Thus,
slaughterhouses often had cattle embryos available.
Banting and Best drove to the cattle yards in northwest Toronto and
( 196 )
secured permission to cut the pancreases from nine dead fetuses. From
these, they produced a new extract. On November 17, they injected dog
27, which had a blood sugar of 300 mg/dl. This new method of extracting
isletin meant Banting’s original hypothesis—that part of the pancreas
produces enzymes that destroy whatever the islets produce—was invalid.
But Banting didn’t mind discarding his original idea; what mattered was
that he and Best had found a better supply of isletin, one that didn’t kill
tail-wagging dogs. It turns out that Insulin in all animals is nearly identical
and so can be used across species.
The new extraction method marked the beginning of a new stage of
their work. He had in mind a young biochemist named Bert Collip.
Finally, MacLeod could tell by their progress that they needed more
resources, and Collip joined the team in mid-December 1921. A year
younger than Banting and brilliant at scientific research, Collip brought
to the team the technical knowledge of a chemist. He developed a method
to test the extracts on rabbits to evaluate purity and safety, one that would
be used for years. Collip also designed an experiment to show that the
liver of a diabetic dog receiving the injections of isletin began retaining
the stored form of glucose called glycogen, a key sign of normal glucose
metabolism.
Meanwhile, Banting and Best pursued their own experiments.
Without telling anyone, they injected each other with isletin. They waited.
There was no effect, proving that the extract was not toxic. In fact,
developing oral Insulin would prove a problem for more than eighty
years.
By Christmas, dog 33, now named Marjorie, was still alive, still
receiving regular isletin injections, and proving that the extract worked
over the long term. Macleod had seen enough. Best and another doctor
developed tests to determine if the body was actually breaking down and
using carbohydrates (a sign that the extract was working), and Collip
continued his work on purifying the extract. They now had a limitless
supply of their most important raw material.
( 197 )
Frederick Banting
Then came January 11, 1922, and the first human insulin trial on
14-year-old Leonard Thompson. After injecting the brown substance into
the boy, the house doctor, Edward Jeffrey, took a blood sample to the lab.
Within an hour, the boy’s blood sugar had dropped from 440mg/dl to
320mg/dl (normal is 100 when fasting). The small improvement was
short-lived and an abscess formed at the site of injection. The first human
clinical trial of this extract painstakingly created from a cow’s pancreas
had failed.
But no one was ready to give up. Collip returned to his lab and
worked tirelessly to find a way to improve the purity of the extract of the
bovine pancreas. On the evening of January 16, one of his methods finally
yielded results. The proper concentration of alcohol mixed with the
extract precipitated out the active ingredient.
On January 23, Leonard Thompson’s treatment resumed with the
purified extract. Within a day, his urine was nearly glucose-free. His
blood sugar dropped from a high of 520mg/dl to 120. “This was the first
time in medical history that a diabetic child had been restored to health.”
Thompson lived thirteen more years, finally dying of pneumonia
complicated by his diabetes. His pancreas is preserved at the University
of Toronto. But as the work to isolate the active ingredient and purifying
it continued, Banting found himself on the periphery of the action. First,
Macleod had renamed his discovery, then Collip refused to divulge to
him his method of purifying the extract, and finally, the Toronto hospital
refused to put him on its medical staff, so he was barred from treating
patients with the very elixir he had discovered! He stopped going to the
lab, and he spent his days sleeping and his nights smoking his pipe.
In May, Macleod decided their research was ready to be presented to
the scientific community. They wrote up their findings and were provided
a slot at the Association of American Physicians meeting in Washington,
D.C., to present their paper. Banting resented Macleod’s having taken
over the research, so he refused to attend. Only Macleod and Collip
traveled south. Called “The Effect Produced on Diabetes by Extracts of
( 198 )
Pancreas,” the talk marked the first time the word insulin was used in
public. It was also the first time the doctors in the audience had ever heard
of someone being brought back from the brink of death to actual health.
The doctors were stunned.
The Insulin Famine

By the time Macleod and Collip gave their talk, Toronto was in the
midst of an insulin famine. It seemed Collip had ‘lost’ the secret for
making the extract. The crisis prompted Best to pay a late-night call to
Banting, imploring him to work. Banting returned to the lab.
The few patients whose lives had been changed by the elixir now
began fading. To make matters worse, news of Macleod and Collip’s
presentation had spread like wildfire through the medical community.
From all over North America, parents flocked to Toronto, bringing their
sick and dying children.
Those with money offered to pay any price to cure their child.
Banting even turned down one man’s offer of one million dollars for the
patent. No amount of money could conjure up enough Insulin.
Finally, Best managed to produce the first batch of potent Insulin in
two months by adjusting the acidity of the mixture and using acetone to
extract the Insulin instead of high heat. He handed it to Banting, who used
some of it to treat his old medical school friend Joe Gilchrist, this time
injecting it directly into his bloodstream.
The Toronto group realized they could not produce enough Insulin
for the world, so it was time to turn to industry. The pharmaceutical
company Eli Lilly of Indianapolis had contacted the Toronto group back
in December when its research director, George Clowes, heard rumors of
the research. At the time, Macleod, “suspicious of a big American drug
company,” wasn’t interested in contracting out the research to America.
Now, however, the Toronto group realized the tremendous need to make
a large, dependable supply of the drug. The university agreed to give
( 199 )
Frederick Banting
Lilly a year of exclusivity to manufacture and sell the extract in the U.S.
It also took out a patent for Insulin in the name of Best and Collip.
Banting, who believed that patenting a discovery would go against
the Hippocratic Oath, refused to add his name.
More than 80 years later, diabetes treatments remain at the core of
Lilly’s products, contributing significantly to the company’s multi-
billion-dollar yearly sales.
Today, it is the global pharmaceutical company of Novo Nordisk.
Insulin still makes up more than half of its sales.
A “Truly Miraculous” Drug

Twenty-two-year-old Jimmy Havens received his first injection on
May 22, 1922, in Toronto, thereby becoming the first U.S. citizen to
receive Insulin. The U.S. Secretary of State’s daughter, Elizabeth Hughes,
received her first injection of Insulin with the thick, coarse needles of the
day on August 16, 1922. Fourteen years old at the time, she weighed 44
pounds and had the distinctive rounded belly of starvation. After five
weeks, she was eating anything she wanted, taking in 2,500 calories a
day, and had gained 10 pounds, with no sign of excess sugar in her urine.
Insulin was even able to bring diabetic patients out of comas, the first
being 15-year-old Elsie Needham, who lived another 22 years.
Steven Hume wrote in his book Frederick Banting: Healer, Hero,
Artist: ‘No single event in the history of medicine had changed the lives
of so many people, so suddenly.’ The discovery was tantamount to a stay
of execution for these children. Suddenly, thousands of young people
could actually be young again.
By 1945, childhood death from diabetes had become a rare
occurrence. Based on U.S. census data and prevalence and incidence
rates for type one diabetes, it can be estimated that over 136,000 children’s
lives were saved in the 1950s, resulting in close to 1.4 million American
children spared from death between 1922 and 2000. Insulin therapy has
( 200 )
saved well over 16 million lives worldwide to date and will continue to
save more for years to come.
A Treatment, Not a Cure

As Banting and his team quickly learned, Insulin was not a cure for
diabetes but a treatment for its symptoms. Within a few years of its
discovery, as the first childhood diabetics began living into adulthood,
doctors started seeing an increasing number of cases of blindness, heart
disease, kidney disease, and nerve damage in people with the disease.
To this day, insulin therapy requires that type one diabetics monitor
their blood sugar daily, usually by pricking their finger for a blood test.
Their goal is to maintain their blood sugar levels within a small range, not
too high, not too low. Blood sugar that is too high is known as
hyperglycemia and can result in great thirst, hunger, urination, and
blurred vision. If it is too low, the condition is called hypoglycemia and
can lead to confusion, unconsciousness, and coma. If their blood sugar
gets too low, they must eat sugar.
Today, about one in 500 children gets “childhood” type one diabetes
and must take Insulin to live—a total of about 30,000 American children
each year. Meanwhile, about one in ten adults will develop type two
diabetes. Type two diabetes is a very different disease. People at first still
make Insulin, but their bodies have difficulty using it. Later, they may
lose their ability to produce Insulin as well. It also carries the risk of
serious complications like nerve damage, blindness, stroke, and heart
disease. Sometimes a byproduct of obesity, its sheer frequency in most
Western countries today makes it a serious problem, one that threatens to
overwhelm health-care systems. The WHO estimates that over 150
million people have it worldwide.
Research on Insulin Has Never Stopped

In the mid-1950s, the British biologist Frederick Sanger identified
Insulin as a protein and revealed its chemical structure. This was possible
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Frederick Banting
courtesy of Eli Lilly, who gave 300 mg of pure Insulin free to Fred
Sanger. This work established how amino acids are linked in a Protein.
Technically, Insulin is a peptide as its molecular weight is below 10,000
Daltons. Peptides’ molecular mass of more than 10,000 Daltons are
called Proteins. In 1967, Dorothy Crowfoot Hodgkin determined the
molecule’s spatial shape using x-ray and demonstrated the importance of
Zinc ion for the activity of Insulin. The two each received the Nobel Prize
for their work.
Other researchers have found that the insulin molecule is remarkably
conserved from an evolutionary perspective. It is almost completely
identical in all animals, from fish to fowl to worms to mammals. In the
decades following its discovery, Insulin was obtained from cows, pigs,
and fish for the daily shots of diabetics.
Since it was very difficult to make animal-extracted Insulin absolutely
pure, people allergic to any of these animals could have an adverse
reaction to the impurities. They finally reached their goal in 1978 when
Herbert Boyer’s laboratory at the University of California at San
Francisco inserted a version of the human insulin gene into bacteria and
turned the bacteria into little insulin factories. The following year,
Genentech Corporation began producing synthetic Insulin, Humulin, the
first genetically engineered drug, using recombinant DNA technology.
Humulin launched the new industry of biotechnology. In 1982, the Food
and Drug Administration approved Humulin for the market, and today it
is the primary form of Insulin in use. A year after the introduction of
Humulin, the first insulin pump was introduced. About the size of a
pager, it was connected to the body via a catheter that had to be changed
every few days. In 2006, Exubera, an inhaled therapy, became the first
non-injected Insulin to be approved by the FDA.
A cure for diabetes is still being sought.
Other scientists are trying to use embryonic stem cells (which are
capable of differentiating into any type of cell) to grow new islet cells
identical to an individual’s own.
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The Nobel Prize

On October 26, 1923, the Nobel Prize in medicine was awarded to
Banting and Macleod. However, Banting became very upset that Best
was not included, swearing that he wouldn’t accept the award. Banting’s
friends and colleagues reminded him that he would be the first Canadian
to receive the prize, making it a major honor and achievement for both
him and his country. Banting grudgingly agreed with his friends that he
should not refuse the prize. One thing he could do, however, was split his
share of the $30,000 monetary prize with Best. Banting immediately
cabled Best, who was presenting an academic paper that night at Harvard
Medical School.
A few days later, Macleod, not to be outdone, announced he would
share his portion of the prize with Collip. However, the exclusion of
Charles Best remains, as one historian writes, “one of the worst mistakes
made by a Nobel committee.”
With adulation came academic envy, and many decried Banting’s
lack of credentials as a diabetes expert. But in the end, the secret to
science isn’t in the accreditation but in the results. Thousands of
scientists had studied diabetes for more than 100 years, trying to find the
secret to the “sugar disease,” yet it took a farm boy who was going broke
as a doctor and working in a broiling room that could barely be called a
laboratory to finally discover the world’s first truly life-saving drug.
Others argued that the specialists in the lab should have gotten more
Credit. Bert Collip himself put it best when he said in later years: “Credit
should be apportioned 80 percent to Banting, 10 percent to Best, and
5 percent each to Collip and J. J. R. Macleod.”
Banting was awarded a high administrative position at the University
of Toronto, his own research institute, a lifetime research grant from the
Canadian government, and knighthood in the British court. He married in
1924 and had a child, William, in 1928. Alarmed by the rise of Nazi
Germany, Banting spent the late 1930s involved in military research,
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Frederick Banting
including work that led to the development of the G-suit for the British
Royal Air Force. In March 1941, Banting was to fly to England for
military work, a precarious excursion in those days with the war going on
and aircraft being a still relatively new technology. The bomber on which
Banting was flying crashed in the wilds of Newfoundland. Banting
managed to dress the wounds of the pilot, Captain Joseph Mackey, but
then began lapsing into and out of consciousness. By the time the rescuers
arrived, Frederick Banting was dead. The purpose of Banting’s mission
is unknown to this day.
Frederick Banting was not a saint, nor perhaps a traditional scientist,
but it is rare for one to make history by following all the rules. Indeed,
those very traits that made some doubt Banting’s acclaim in science
might have been the keys to his success.
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10
Karl Landsteiner
(1868-1943)
The Superman Scientist:

Discoverer of Blood Groups
Over 1.3 Billion Lives Saved
“AS SOON as the blood

entered his veins, he felt the heat
along his arm and under his
armpits. His pulse rose, and soon
after, we observed a plentiful
sweat over all his face. His pulse
varied extremely at this instant.
He complained of great pains in
his kidneys that he was not well
in his stomach. He was ready to
choke unless given his liberty.
He was made to lie down and fell
asleep. He slept all night without Karl Landsteiner in his New York lab in
awakening until morning. When 1930. When Landsteiner discovered blood
he awakened, he made a great groups, his main job was as a pathologist.
He performed 3,639 autopsies over the
glass full of urine, of color as
ten years he held that job.
black. It looked as if it had been Bettmann Standard RM Collection/ Bettman/
mixed with the soot of CORBIS.
chimneys.”
Those were the words of the French doctor, Jean Denys, who had
transfused his patient, Antoine Mauroy, with calf’s blood in 1668.
Karl Landsteiner
Mauroy would later die, as would many who were transfused with human
blood before the era of modern medicine. Doctors were perplexed—
sometimes transfusions worked, but often the patient would excrete black
urine, followed by jaundice, kidney failure, and death. Autopsies would
show that these patients’ small arteries and capillaries were plugged with
red blood cells. Before the twentieth century and the work of a heroic
scientist now almost forgotten, the chance of a transfusion’s success was
no more predictable than a roll of dice.
Incremental Precociousness
In 1891 Austria, 23-year-old Karl Landsteiner looked like an
American cowboy. His father died when he was 6 years old. Raised by
his mother in a house full of books and music, he had no siblings. But
there is the chance as well that his solitude stemmed from a secret he held
inside—that he was alone in the world of thought, a genius.
At Vienna University, he took a wide range of courses. His future
colleague Philip Levine noted, “At 21 years of age, he had already known
that which had impressed me so much - that important discoveries will
emerge when one scientific discipline merges with another.”
When he graduated from medical school in 1891, he knew that
research, and not clinical practice, was the path he wanted to pursue, so
he sought out a famous scientist to study under. Landsteiner traveled
during the next five years to study under three of the most famous
chemists in Europe, including future Nobel Prize laureate Emil Fischer,
who was famous for his work on purines and sugar, and who would later
split proteins into amino acids.
Landsteiner practiced Thomas Edison’s formula that “genius is 1
percent inspiration and 99 percent perspiration.” Wherever he went,
his burning desire to learn made him a voracious reader of academic
articles and a voluntary partaker of courses that weren’t required. And he
could not be kept out of the laboratory; as soon as he arrived, he began
collaborating with his teachers on experiments that led to published
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papers.
After being thoroughly immersed in chemistry, Landsteiner studied
under a surgeon for a year, Later, returned to Vienna University to work
under the tutelage of bacteriologist Max von Gruber. Across the campus
at the university’s Institute of Pathological Anatomy resided Anton
Weichselbaum, a no-nonsense bacteriologist famous for discovering the
bacterial cause of meningitis. Landsteiner approached him to be an
unpaid assistant. He was accepted. In 1899, at the age of 31, Landsteiner
received his habilitation in pathological anatomy. The habilitation is a
degree above the doctorate that exists in many European countries and is
often required to become a full professor. Landsteiner never became a
full professor, but while pathology was what he was paid for, it was
research for which he had prepared himself.
Blood of Our Fathers

Blood has fascinated mankind for centuries. Romans were so
convinced that blood carried the vital essence of a person that gladiators
drank the blood of their slain opponents. We talk of the “blood of our
fathers,” “the nation’s blood,” “blood feuds,” and “lifeblood.” We
become “blood brothers” by smearing together cut thumbs. Christians
drink red wine or grape juice as a stand-in for the blood of Christ during
communion.
Hippocrates taught that all living matter contains four “humors”—
blood, phlegm, yellow bile, and black bile. Any illness stems from an
imbalance of those four elements. Over the next twenty-three centuries,
bloodletting—either with the aid of leeches or by simply opening a
vein—was often the preferred medical treatment, as it was thought to
realign the humors. Bleeding was also thought to be a way to rid the body
of its “evil” humors, since blood was thought to be the site of madness.
This barbaric approach was not fully abandoned until the 1920s,
when the composition and function of blood was finally deeply
analyzed. It was demonstrated through successful transfusions that
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Karl Landsteiner
adding blood could save a lot more lives than removing it.
The science of blood took its first tentative step in 1613, when
William Harvey demonstrated that blood circulates in the body, with the
heart as its pump. The Arab physician, Ibn al-Nafis, had actually
discovered this four hundred years earlier, but his writings never spread.
In the early 1800s, James Blundell, a British physician, and obstetrician
became famous when he proposed transfusing blood from person to
person. At the time, the only transfusions had been of animal blood,
which he argued against.
Blundell performed the first successful human-to-human blood
transfusion in 1829. A woman who was dying from childbirth hemorrhage
was transfused with the blood of Blundell’s assistant over three hours,
and Blundell was happy to report that “the patient expresses herself very
strongly on the benefits resulting from the injection of the blood. Her
observations are equivalent to this—that she felt as if life were infused
into her body.”
In 1849, C. H. F. Routh reviewed all the published transfusions to
date and reported. He concluded that air caught up in the blood was the
cause of transfusion reactions. Transfusion was not widely pursued
because the transfusion reaction was so terrible to watch. Most
doctors are aware of the paraphrase of the Hippocrates quote, “First,
do no harm,” refused to even experiment with the practice.
Avoiding the Line of Least Resistance

Germ theory dramatically changed medicine right at the time
Landsteiner was born in 1868. Prior to Louis Pasteur’s development of
the theory, most hypotheses presented throughout the centuries about the
disease could at best be called wild guesses. They were not anchored in
a foundation of basic knowledge of how the human body or the natural
world works, and moreover, they nearly always contained large
explanatory gaps between causes and effects. Such common beliefs as
spontaneous generation (that disease-causing organisms form from the
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decaying matter), miasma (that disease rides on bad air), or humoral

theory (that disease results from an imbalance of bodily humors) withered
away as germ theory allowed scientists to identify one specific microbial
agent as the cause of each infectious disease. Scientists learned to observe
a germ’s effect, such as the release of toxins; determine the means by
which the toxins cause illness; and thus, piece together a causal chain
ending in death.
A measure of the importance of a new scientific theory is to observe
how many new doors it opens to wide-eyed scientists. Joseph Lister
promulgated antiseptics. On a shelf sat the mouthwash, Listerene, named
after Lister. Louis Pasteur himself was puttering around, reasoning that
food could be decontaminated by heating it and killing the germs residing
in it (pasteurization).
But Landsteiner did not seek to become a microbiologist. Landsteiner
maintained his belief that chemistry was integral to medicine, and he
became intrigued by something more mysterious than germs.
By the 1890s, it was known that germs can kill humans by producing
toxins inside the body and that sometimes these toxins were destroyed in
the blood, rendering them harmless. Looking into a microscope, scientists
could also see bacteria themselves die in blood. What was in blood that
could destroy toxins and kill bacteria? These substances would eventually
be named “antibodies,” and their discovery opened the door to
immunology. What were these agents in the blood, so tiny that they could
not be seen, so powerful that they worked even when greatly diluted, so
specific that they could kill one and only one species in a batch of
bacteria? This was the area in which Landsteiner chose to spend his
research life.
I Selected the Simplest Experimental Arrangements

The Institute of Pathological Anatomy housed research in a wide
range of medical disciplines. Inside, in his white lab coat, his autopsies
completed for the day, Landsteiner would sit at a wooden table. Wooden
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Karl Landsteiner
six-pack racks of test tubes were lined up on the table, and a microscope
was at hand. Across the room were a centrifuge and containers of dyes.
Around Landsteiner were other scientists, some well-known, and myriad
assistants, all busy adding to the body of knowledge of the then only
decades-old science of medicine.
Early on, microbiologists saw that bacteria sometimes died and
dissolved when their cell membranes were broken, a phenomenon called
lysing (Necrosis). Another way cell death can occur is Apoptosis(Nuclear
DNA is destroyed). In 1896, the bacteriologist under whom Landsteiner
was studying, Max von Gruber, demonstrated that mixing cholera
bacteria with blood serum from a patient who had developed immunity
from cholera resulted in the clumping of bacteria. Clumping had been
observed before, but Gruber’s experiment was one of the first
demonstrations of an immune response to bacteria in the blood. Two
years later, another scientist mixed different animals’ blood and saw that
one animal’s red blood cells would clump when mixed with another
animal’s serum. The ability of blood serum to clump bacteria as well as
blood cells brought the phenomenon to the forefront of European science.
Agglutination, named from the Latin agglutinare— “to glue to”—became
of great interest, especially since, with blood cells, it could be viewed in
a test tube with the naked eye.
In 1900 he published a paper describing a multifaceted experiment
that tested the ability of different animals’ blood sera, including that of
humans’, to inhibit enzymes. In one part of the experiment, Landsteiner
observed agglutination of human red blood cells when mixed with both
animal and other human blood serum. From the experiment and from
reading others’ work, he would later write that he learned of an “important
general discovery in protein chemistry, namely, that proteins in
various animals and plants are different and are specific for each
species. The discovery of biochemical species specificity prompted
the question as to whether individuals within a species show similar,
though presumably slighter, differences.”
( 210 )
It was this discovery, along with his observation of agglutination,

that prompted Landsteiner to add a foreshadowing footnote to the paper:
“The sera of healthy individuals not only have an agglutinating effect
on animal red cells but also on human red cells from different
individuals. It remains to be decided whether this phenomenon is due
to individual differences or to the influence of injuries or bacterial
infection.”
Thinking on this into 1901, Landsteiner designed an experiment,
reasoning that “since no observations whatever had been made in this
direction, I selected the simplest experimental arrangements available
and the material which offered the best prospects. Accordingly, my
experiment consisted of causing the blood serum and erythrocytes
[red blood cells] of different human subjects to react with one
another.”
In hindsight, this might seem an obvious step, but at the time, all
human blood was thought to be uniform. If it were different, it would
also upset the paradigm that was forming about the newly discovered
immune system. Landsteiner eventually gathered blood from five
associates, most of the doctors in the lab, as well as himself. Then he set
up the straightforward experiment that could be run in any high school
laboratory, except that today it would require a phlebotomist to draw the
blood, and the students would have to wear hazmat suits to protect them
from potential HIV or hepatitis.
Each vial of human blood Landsteiner held was 55 percent serum
and 45 percent cells, of which red blood cells were the most numerous.
Red cells, which function for about 120 days before being replaced, have
the vital role of delivering oxygen to other cells throughout the body. The
liquid component, serum, is 90 percent water and was already known to
carry the agents that fight disease, which we now refer to as antibodies.
Landsteiner first centrifuged each individual’s blood at a soft-spin rate,
which separated the blood into three layers, with the denser red blood
cells at the bottom of the test tube, the white cells and platelets above
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Karl Landsteiner
them in what is today called the “buffy coat layer,” and the serum at the
top. He decanted the yellowish and clear serum layer into another test
tube, then isolated the red blood cells and washed them in a sterile saline
solution that removed about 99 percent of the serum proteins and
antibodies. After adding a saline solution to dilute them to about 5 percent
concentration, he let them sit.
Landsteiner affixed labels to the test tubes containing each
individual’s serum and red blood cells; he put the sera into one wooden
six-pack test-tube rack and the red blood cell test tubes into another. Into
a group of six empty test tubes, he placed a 0.6 percent saline solution.
Then, with a pipette, he drew up a little serum of the first person and
added it to a test-tube with the saline solution. He repeated the procedure
for each individual and then added a few drops of his own red blood cells
to all six test tubes. He waited. Nothing happened. He waited longer. The
process of agglutination can be seen with the naked eye, but there was no
agglutination to be seen.
He set up another six-pack of test tubes with saline solutions,
pipetting each individual’s serum into each solution. Then he dropped
Dr. Sturli’s red blood cells into each test tube. The first test-tube showed
no reaction (it was a mixture of Sturli’s own serum and blood cells, so
this was no surprise). But after a few minutes in the next test tube, the
blood cells began clumping together—agglutination was occurring.
Landsteiner’s eyes sparkled, but he did not draw any conclusions. To
confirm the agglutination, he pulled over his microscope and performed
a “hanging drop” test. Fastidiously, he placed a small drop of mineral oil
on each corner of a coverslip. In the center, he put a drop of the agglutinated
blood. Next, he took a microscope cavity slide, inverted it, and dropped
it onto the coverslip, gently pressing them together so that the mineral oil
spread out and formed a complete seal. Turning the slide over so that the
coverslip was on top, he was ready to inspect the drop, which was now
hanging freely.
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What Landsteiner saw was best described in the words of a scientist

from his era: “Under the microscope, the cells are close together and
cannot be separated by pressure on the coverslip, but they spread out
as if connected by threads. If the pressure is released, the cells move
together again.” It was agglutination. This was different from
precipitation, coagulation, or any other known phenomena.
He had definitely found something new and significant.
Make the Data Thick

Landsteiner had shown agglutination between different humans’
blood to be common, occurring almost 50 percent of the time. And as
Peyton Rous, a later associate of Landsteiner and Nobel laureate,
remembered, laboratory exactitude was Landsteiner’s signature
trait: “Whenever test mixtures were to be made, he would add the crucial
component to the tubes and read off the reactions, the assistant standing
by. This he did in greater part to assure himself that what took place
actually happened.” Experiments that revealed anything were done many
times over, and not until the data on a point under determination were, in
his term, ‘thick,’ would he publish.
Landsteiner performed a total of 144 cross matches on blood from
twenty-two healthy donors. Finally, he concluded that “the
experiments demonstrate that my data require no correction. All
twenty-two examined sera from healthy persons gave the reaction.”
Now he was certain that the observations were true, and the
phenomenon of agglutination between the blood of healthy humans
was real.
Well-Read
Today Landsteiner would be called a “data hog.” With his data set
confidently in hand, he proceeded to the second step of the Landsteiner
treatment: making certain he was aware of anything, and everything is
known about agglutination. Rous relates that Landsteiner “covered wide
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Karl Landsteiner
reaches in the scientific literature, scanned abstracts of articles for mental

relaxation.” With such a complete awareness of the current state of
knowledge, he well knew the hypotheses that others had proposed.
Clotting and agglutination are in some respects similar, so Landsteiner
obtained blood from two hemophiliacs, whose blood does not clot
normally, and used their sera. Their sera agglutinated with the blood of
some individuals but not others, just like with healthy donors, so that
ruled out a clotting factor.
Then Landsteiner turned to the prevalent hypothesis. Scientists knew
that blood that had been exposed to a particular disease thereafter carried
something that fought that disease. Agglutination could be a reaction to
that substance. But how could anyone ever find human blood that had
never been exposed to disease? The answer was deceptively easy and
available nearby. “To exclude the assumption that perhaps past
disease processes are of importance, I regarded investigations on the
blood of children and animals utilizable.” Recently born babies
would never have been sick, and you can imagine Landsteiner’s
enthusiasm as he walked into the lab with fetal placental blood. He
prepared the test tubes and mixed the blood cells of the mothers with the
sera of their babies—and met with a setback. No agglutination occurred,
ever. Landsteiner was forced back to the library. Going through the
literature, he found that another scientist had also failed to produce
agglutination with serum from infants, and thus Landsteiner concluded
that baby blood serum was not developed enough to cause
agglutination. Interestingly, and of course completely unknown to
Landsteiner, we are not born with these blood-related antibodies in our
serum. Instead, they’re formed when we’re about three months old. The
formation of blood cells is an intense area of research, also known as
Hematopoiesis. Hematopoietic Stem Cells is an active area of research,
and biotechnologies blockbuster drugs in the 1980’s such as erythropoietin,
G CSF, to name a few, have opened up a whole window of opportunities.
Landsteiner next mixed the babies’ red blood cells with the mothers’
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sera. This produced result is comparable to those in his other experiments:

Out of thirty cross matches, the babies’ red blood cells agglutinated ten
times.
Landsteiner reasoned that if it was an autoimmune response to
something red blood cells were released, then all the sera should react
with what was being released: “Moreover, my investigations show that
the different sera do not act identically with respect to agglutination. If
one believes, therefore, that they owe their agglutination ability to a kind
of auto immunization through resorption of cell constituents, then one
must again assume individual differences to obtain the different sera.”
Landsteiner did not claim this completely ruled out an autoimmune
response but thought it unlikely to be the cause.
Advancing by One Limited Hypothesis at a Time

Having ruled out the hypotheses offered by other scientists;
Landsteiner sought to propose his own explanation. Many of Landsteiner’s
associates were most surprised that such a brilliant man rarely formed
speculative hypotheses.
What Landsteiner saw was a completely new blood phenomenon that
contradicted the then-current paradigm of the immune system—that its
only purpose was to fight germs. Today, we think that the basic function
of the immune system is the production of antibodies, but in Landsteiner’s
day, antibodies were such a new and ill-defined concept that they didn’t
even have a name. In fact, the term antibody was only first used that same
year in another scientist’s paper. The word antigen, the other fundamental
component of the immune system, did not come into use until 1908.
Landsteiner seemed to have found something new. Some people’s
blood reacted with others’ blood, and some did not. His study of science
had taught Landsteiner that if a phenomenon is real, it should offer
predictions that can be tested. So, he searched through the 144
combinations from the twenty-two donors, looking for a predictable
pattern. It was a kind of mathematical problem, and here his genius was
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Karl Landsteiner
fruitful.
Landsteiner noted that if one excludes the fetal placental blood,
which did not produce agglutination, in most cases, the sera could be
divided into three groups: In several cases of - group A the serum reacted
on the corpuscles of another group B, but not on those of group A,
whereas the A corpuscles are again influenced in the same manner by
serum B. In the third group, C, the serum agglutinates the corpuscles of
A and B, while the C corpuscles are not affected by sera of A and B. In
ordinary speech, it can be said that in these cases, at least two different
kinds of agglutinins [antibodies] are present: some in A, others in B, and
both together in C.”
When he wrote up the experiment, he titled it “On Agglutination
Phenomena of Normal Human Blood.” He recognized the importance of
his discovery with the last sentence of his academic article: “Finally, it
must be mentioned that the reported observations allow us to explain
the variable results in therapeutic transfusions of human blood.”
On November 14, 1901, Karl Landsteiner had made one of the
fundamental medical discoveries of all time. Human blood, which
delivers nutrients, oxygen, and disease-fighting capacity to the human
body, is not all identical; it varies among individuals in a fundamental
way that allows it to be categorized into a small number of groups. Only
specific groups can be transfused. This discovery would manifest
humankind’s highest trait—sharing—the sharing of humankind’s most
valuable commodity, the blood.
Today’s Blood Group System

A common image used to visualize red blood cell surface antigens is
that they are like trees sticking out from the cell surface. Each red blood
cell contains millions of antigen trees, which can be either sugars or
proteins. If our immune system comes across an antigen, it isn’t familiar
with, and it produces an antibody to attack it. The antibody then destroys
the cell, sometimes by agglutinating it, often releasing the oxygen of the
( 216 )
cell in the process. This is very helpful when bacteria are in our blood,
but it is not so beneficial when antibodies go after a transfused blood cell.
The agglutination from such an attack is what leads to transfusion
reactions, which can occur when our serum’s antibodies attack the
transfused red blood cell antigens (the most severe reaction) or when the
transfused serum has antibodies that attack our own red blood cell
antigens (less severe due to the dilution of antibodies in the donor serum).
Landsteiner had found three of the four types of human blood—A,
B, and C. Because C contained no antigens, Landsteiner later renamed it
0 (zero), which was later changed to the letter “O” in the U.S., but remains
zero in much of the rest of the world. Adriano Sturli working with Alfred
Decastello, discovered the fourth blood group, A.B. A person with blood
type A.B. has both A and B antigens on the surface of his or her red blood
cells. Today, we know that each of us has blood that can be categorized
as being part of the ABO blood group. Each of our blood’s red cells has
either an A antigen on its surface, a B antigen, both, or neither.
Toward the end of his life, Landsteiner, along with former student
Alexander Wiener, discovered another important blood group, the Rh
(rhesus) group, so named because the researchers were working with red
blood cells taken from rhesus macaque monkeys. Wiener and Philip
Levine, another of Landsteiner’s former students, determined its
importance, which explained most of the rare blood transfusion reactions
that still occurred. In addition, they saved many babies from the
previously mysterious and potentially fatal condition erythroblastosis
fetalis, or Rh disease, which occurs when a Rh-negative mother carries a
Rh-positive baby and develops anti-Rh antibodies as a result of being
exposed to her baby’s Rh antigens. During subsequent pregnancies with
a Rh-positive baby, the mother’s antibodies can react with the baby’s red
blood cells in a potentially fatal way. The Rh group is the most polymorphic
of the blood groups known, with at least forty-five distinct antigens, of
which the D antigen is the most reactive to the immune system. As a
result of its critical importance, all people are now tested to categorize
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Karl Landsteiner
their red blood cells in both the ABO and RhD blood groups. The RhD
antigen is noted by adding a plus sign if it is present on a person’s red
blood cells or a minus sign if it is absent. About 85 percent of the U.S.
population has the RhD antigen. Thus, all people are classified into one
of these eight categories:
Landsteiner’s discovery of the ABO blood group opened the door to
the discovery of many other blood groups. The ABO and RhD blood
groups are only two of at least 26 blood groups now known (Landsteiner
also discovered the M.N. and P groups), and each group is distinguished
by antigens on red blood cells that are controlled by a single gene. Most
of the blood groups other than ABO and RhD don’t cause transfusion
reactions because blood serum rarely carries antibodies that will attack
these antigens. One of these antigens is the Duffy antigen discussed in the
Paul Müller chapter. A majority of people of African descent do not have
the Duffy antigen, as it is strongly selected against because it provides a
means of entry for a certain type of malaria into red blood cells. All
human blood serum contains antibodies, which are Y-shaped proteins
that the immune system creates to identify and destroy foreign objects
(sometimes latching onto them and sometimes calling forth other
processes to disrupt them). They are produced as a specific reaction to the
presence of these antigens, whether on a poliovirus, a strep bacterium, or
a red blood cell. It is not known what triggers most humans’ immune
systems to produce A or B antibodies since our bodies are not always
confronted with these antigens prior to a blood transfusion, but all humans
have A and B antibodies unless they have the A or B antigen on their red
blood cells.
The primary risk of blood transfusion reactions with the other twenty-
four blood groups occurs after a transfusion or pregnancy, which
sometimes causes the body to produce an antibody to the newly acquired
antigen, thereafter keeping it in reserve. When a second transfusion is
given or second pregnancy occurs, the antibodies come out to fight. Even
so, serious reactions to the other groups are extremely rare.
( 218 )
After 3,639 Autopsies, Marriage

Adriano Sturli, one of the doctors who donated blood for Landsteiner’s
blood group experiment, told an amusing story about Landsteiner:
“Towards the end of 1901, I was asked by Landsteiner, with whom I had
up to then only done some histological and bacteriological studies,
whether I would like to join him in some serological studies and
experiments [these would lead to the discovery of A.B., the fourth blood
group]. I agreed with alacrity, and thus had an opportunity of repeating
all his experiments to his explicit satisfaction. I should add that the final
studies started on the afternoon of December 31, 1901 and went on
without a break until 8:30 PM. The two of us were quite alone in the
Pathological Institute, now silent and deserted. These hours were a sort
of tragicomedy for me because I had naturally been itching for hours to
join my friends and see the New Year in style. However, Landsteiner was
gently but firmly insistent and kept me washing blood-corpuscles, mixing
sera, centrifuging, saturating charcoal-powder with dyes, etc., under his
supervision, with results that seemed to me amazing but to Landsteiner
were self-evident. Eventually, we took leave of one another, tired but still
good friends.”
One journalist, tallying up Landsteiner’s work hours, concluded that
over a fifty-year span, he spent 90 percent of his conscious life in
scientific pursuits.
In 1908, his work ethic paid off. Landsteiner took over the Department
of Pathology at the Imperial Wilhelmina Hospital in Vienna. Finally,
after performing 3,639 autopsies, he could leave the dead-house work to
an assistant. Now freed of the autopsies, there were many good days of
experiments at the institute. After a few years, he began dating Helene
Wlasto, and then, as World War I began, they married.
One of those students, John Jacobs, contrasted his work in
Landsteiner’s lab with his previous experience at Harvard University,
where he was largely left to his own devices. Jacobs particularly
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Karl Landsteiner
remembered the process of writing up their scientific discoveries: “Papers

were generally written at night on the dining-room table in Dr.
Landsteiner’s large, very simply furnished apartment. It would begin by
presenting a first draft, which, in the course of the evening, would be so
crisscrossed with corrections and suggestions that it would have to be
entirely rewritten. After three or four such sessions, made more pleasant
by snacks prepared by Mrs. Landsteiner and including foreign cheeses
and a little wine when work was over, the shape of a paper gradually
appeared. In writing papers, Dr. Landsteiner was never ready to put pen
to paper until he had definitely established a new fact. The paper was
then built about this fact, and its relationships discussed. The discussions
seemed to me to be unique. This was brought about by the fact that he
limited himself severely to pointing out the highly probable implications
and relationships of the facts observed, almost completely omitting
opinion and theory summaries were likewise worded with extreme
caution and conservation. A large element of his genius consisted in the
humility with which he would forgo the opportunity to draw broad
theoretical conclusions in the interest of maintaining a high degree of
accuracy and objective reality.”
Jacob wrote, “After I had been with him something over a year, one
day he put his hand on my shoulder and said, ‘John, you have a gift for
research,’ I felt that this was an honor that no degree, title, praise, or
honor has or could ever equal.”
346 Scientific Articles

If Pasteur opened doors to many rooms with his germ theory,
Landsteiner entered them and filled them with trophies. While still
researching blood groups, he quickly foresaw the usefulness of his
discovery for paternity tests and forensics. He knew from the ‘hanging
drop’ test that it took very little blood to cause an agglutination reaction,
so he tested a drop of blood he had spilled on a cloth. “The described
agglutination can also be produced with serum which has been dried and
then dissolved. I did this successfully with a solution from a drop of blood
( 220 )
which had been dried on linen and preserved for 14 days. This led to
another new conclusion: “Thus the reaction may possibly be suitable for
forensic purposes of identification in some cases, or, better, for the
detection of the nonidentity of blood specimens.”
When Landsteiner took up the study of syphilis, he made several key
discoveries, the most far-reaching being the application of a microscopic
technique known as darkfield illumination. Landsteiner furnished most
of the basic knowledge about polio. He proved that it was caused by one
specific agent and that the agent was a virus, not a bacterium. He
introduced a technique for preserving the virus in glycerin, developed a
blood test for it, and demonstrated how to transfer it to monkeys. Monkeys
would be the primary experimental animal for polio until John Enders’
work in the 1940s. Finally, Landsteiner demonstrated that the serum of
monkeys who had become ill with polio could inactivate the virus,
indicating that a vaccine was potentially possible.
He published 346 scientific articles, many of which significantly
advanced the field with which they dealt. Besides his blood group
research, he also provided some of the first evidence that allergic reactions
are, in fact, immune reactions.
Specificity
Paul Ehrlich was the most famous scientist in Europe in the early
1900s. He was not only a legitimately great scientist but also media
savvy, popular for formulating grand hypotheses that were intuitively
easy to understand. For instance, he popularized the notion that science
could produce a specific ‘magic bullet’ to fight any given disease. He
suggested that blood cells have side-chains—hypothetical structures that
grow out of the cells when stimulated by toxins. These side-chains are
shaped to grab toxins and then lock them away in their grasp. The most
popular implication of Ehrlich’s theory—that there is a perfect one-to-
one antigen-antibody fit that became known as the ‘lock and key’ fit—
still persists to some degree today, even though it is mostly incorrect.
( 221 )
Karl Landsteiner
Landsteiner, by contrast, was not one to put forth bold,

speculative hypotheses. Steadily, year after year, experiment by
experiment, he added to the basic body of knowledge about the immune
system. In 1909, one year after Ehrlich had received the Nobel Prize,
Landsteiner gave a report at the 16th International Medical Congress in
Budapest that cited his own and other investigators’ research and
concluded that antibody formation is not an “overproduction” of cell
structures, as Ehrlich had proposed. Through more than two decades of
work, Landsteiner demonstrated that the immune system is much more
recondite, labyrinthine, and complex than Ehrlich had thought.
To sum up his immunological discoveries, Landsteiner wrote a book,
which was read for decades thereafter by immunologists. He named it
‘The Specificity of Serological Reactions’ because he was seeking to
define how specific antibodies were in attacking pathogens or other
substances.
Let the Blood of the Healthy Person Leap, Hot and Vigorous,
into the Sick Man
It is interesting to compare the uptake time of Einstein’s theory of
special relativity and Landsteiner’s theory of blood groups. Both were
born in the early 1900s, and both took around fifteen years to become
widely accepted.
In the first years after Landsteiner’s blood group discovery, not much
happened. There existed one major practical hurdle—the fact that
blood clotted within minutes after it was withdrawn. In an effort to
jumpstart blood group testing, Landsteiner repeated in a scientific
publication that transfusion reactions likely stemmed from blood group
incompatibility, and eventually, Reuben Ottenberg carried out the first
blood group compatibility testing in 1907, at Mount Sinai Hospital in
New York City. He went on to observe that people with group O blood
could be universal donors (an understanding which has since been
revised). Up until 1913, only around fifty transfusions a year were carried
( 222 )
out in a typical New York City hospital. Then, in 1914, Dr. Richard
Lewisohn, also at Mount Sinai Hospital, discovered that adding
sodium citrate could prevent blood from clotting. Surgical transfusion
procedures could now be abandoned, and blood could instead be
drained into a container and then transfused in a measured amount.
The discovery came just in time. The modern warfare of WWI was
causing widespread injury and death, much of it from shock and blood
loss. With a safe, storable form of blood now available, an American
lieutenant serving as a surgeon on the Western Front took it upon himself
to build the first blood bank. Oswald Hope Robertson, using some of
the ideas of Peyton Rous (who has been quoted in this chapter),
collected blood from donors into clean glass bottles containing the
anticoagulant solution and transported them to battlefield hospitals.
Tens of thousands of transfusions were performed from 1914 to 1918,
and British medical history books declared blood transfusion “the most
important medical development of the war.”
Thereafter, transfusions became a normal hospital procedure.
The first civilian blood bank in the world was established in 1932
in Leningrad, Russia. Bernard Fantus, who coined the term “blood
bank,” established the first one in the U.S. at Cook County Hospital
in Chicago in 1937. Cities all over the world quickly built blood
banks. After World War II, the Red Cross started a nationwide collection
program that now supplies nearly 50 percent of the blood transfused in
the United States. In 1950, plastic bags were introduced and quickly
replaced glass bottles, making handling blood much easier and safer.
As soon as blood transfusions became common, other risks became
apparent. The biggest danger was that the transfusion of blood carried
with it a disease from the donor. In Landsteiner’s day, before the
advent of antibiotics, syphilis was a dreaded contagious disease. In
1906, August Wassermann became famous for developing the first
blood test for syphilis. Blood transfusion is now amazingly safe. Fatal
blood group reactions occur only about once in 250,000 transfusions.
( 223 )
Karl Landsteiner
About half of those are due to error, usually incorrect screening or blood
given to the wrong person. The risk of getting HIV from a transfusion
dropped dramatically in the 1990s after improved tests were developed
and implemented, to about one in two million.
The Greatest Life-Saving Medical Advance in History

Blood transfusions have turned out to be the greatest life-saving
medical advance in history. To tabulate the lives saved by transfusions,
Amy Pearce began counting only in 1955, when data began to be
documented well. She arrived at the astounding figure of 1 billion, 38
million lives saved. Transfusions are at the heart of critical care, saving
lives due to trauma such as occurs in automobile accidents. A blood unit
is an amount that most people give, which is about one pint. Other major
uses of blood are organ transplants (up to thirty units), severe burns (up
to twenty units), and heart surgery (up to six units). James Blundell, the
nineteenth-century obstetrician, would be happy as well. In the developing
world, where maternal hemorrhaging after childbirth is still common,
transfusions are vital to save new mothers’ lives. Blood can also be
transformed into at least twenty-five specific blood products used in
medicine. Platelets aid in the clotting process, gamma globulins
increase immune activity, and plasma (A.B. plasma is considered the
universal blood plasma) is used for trauma patients.
Donating blood is one of the most charitable and beneficial gifts a
man or woman can give another person. Almost 4 million Americans
receive gifts of blood each year. Americans donate approximately 12
million units of blood yearly, which are processed into 20 million blood
products. Worldwide, 80 million units are donated every year. Almost
half of the U.S. population has donated blood at some time, making it
impossible not to be optimistic about humankind’s compassion.
The Melancholy Genius

As World War I proceeded, Landsteiner’s career stalled. He was
never made a full professor in Vienna; He could not play the academic,
( 224 )
social game. When Austria-Hungary began losing the war, living

conditions in the empire rapidly deteriorated. Landsteiner bought a
goat to provide milk for his son, but a visiting scientist reported that
Landsteiner “looked as if he were starving.” Electricity became rare in
the city, and all the trees around Landsteiner’s house were cut for
firewood. One of his 1917 experiments involved thirty-three different
antigens, twenty-three sera, and 759 test reactions. This enormous project
was carried out with no heat in his lab. Experimental animals were
malnourished, dooming other experiments. At the end of the war,
conditions became even worse, so when Landsteiner arrived home one
evening to find the fence around his yard stolen for firewood, he resolved
to leave. A professor friend at Leiden University in the Netherlands,
Storm van Leeuwen, found Landsteiner a lab tech position at the
Catholic Hospital in The Hague in Holland.
So, in 1919, at the age of 51, having lost everything, Landsteiner
emigrated to Holland, where he did routine lab work, including, once
again, dead-house post mortems. He even had to take a part-time job.
Working in one small room that he shared with a nun, and that was also
the coffee break room, he continued his research unabated and
published twelve papers over the next two years. But van Leeuwen
realized that Landsteiner’s research was stifled, and so recommended
him to the Rockefeller Institute, which invited him to New York.
Landsteiner had always wanted his own research institute, and while not
promised quite this, for the first time in his life, at the age of 54, he was
offered a position that gave him the freedom to devote all of his time to
research.
With his family and a barrel of carcinogenic tar he used to induce
tumors in animals, Landsteiner arrived in New York in the spring of 1923
and found an apartment over a butcher shop on Madison Avenue. He
delighted at learning new words, and as he picked up English quickly, he
and his family resolved to stay and become citizens.
However, his longtime associate Constantin Levedati related, “For
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Karl Landsteiner
many years I had had no news of Landsteiner at all; but during a study-
tour of America in 1929, I ran him to earth in his laboratory. I found him
rather depressed and full of complaints about his work, especially about
the regulations that, apart from restricting his activities in certain fields,
bore no relation at all to the virtually unlimited scope of his own scientific
ambitions.”
It was most likely his inability to research polio that most
disturbed Landsteiner. Polio was the pet project of Simon Flexner,
who, as the head of the Rockefeller Institute, controlled who worked
on it. It is only speculation, but Flexner may have been afraid that
Landsteiner would overturn his own firmly held polio paradigm. Since
Landsteiner had discovered most of the fundamental knowledge about
polio, it is difficult to understand any motive other than envy that Flexner
could have had in forbidding Landsteiner to research it. Landsteiner told
Levaditi with a wry smile, “If I am asked to make do with only half a
microscope, I have to comply.”
As the Depression encroached into the 1930s, Landsteiner became
more and more discouraged about the state of civilization, as well.
Friedrich Schiff, whom Landsteiner called “the foremost German
research-worker in the field of blood-groups,” was forced to emigrate to
the U.S. in 1936 when, ironically, only two years before, Nazi storm
troopers had arrived at his laboratory wanting to have their blood-groups
identified. Landsteiner inquired about jobs for German professors and
also was known to have sent them money.
Not that Landsteiner was always dire. He still relished his lab, never
losing his wit while there. The young scientists in his charge often rushed
to conclusions. One day he said, “Is it not strange that I, who have so
little time left, should be teaching patience to you, who have your life
before you?”
In 1939, Landsteiner officially retired, but in a highly unusual
arrangement, was allowed to keep his lab. Working just as hard, he
( 226 )
produced another twenty-eight publication. But time was catching up

with him.
Levine related how one day, “with tears in his eyes,” Landsteiner
divulged that his wife had cancer and that he hoped to die before she did.
He turned to his lab for solace, studying cancer to try to help his wife, but
on June 24, 1943, he suffered a heart attack and died two days later. He
was 75 and had spent 51 years in the lab.
He contributed to the primary knowledge to four fields: serology,
virology, immunology, and allergy. Karl Landsteiner was one of the
last possessed of the tremendous intellect that could comprehend
and, better still, use practically all of the scientific knowledge of his
time.” Said his student, Dr. Michael Heidelberger.
Together, all of the events of his last years, as well as his reserved
attributes, brought him the nicknames like “the investigator with the
mournful eyes” and the “melancholy genius.”
His Was a Sad Pessimism, Never Bitter

It is fitting that Landsteiner’s discovery led to the most lives saved in
medical history. He was the consummate scientist, contributing primary
knowledge to four fields: serology, virology, immunology, and allergy.
Michael Heidelberger, a collaborator, said, “The time is past when one
man can know all of science. Karl Landsteiner was one of the last
possessed of the tremendous intellect that could comprehend and, better
still, use practically all of the scientific knowledge of his time.”
Landsteiner’s research had a lasting influence. In the 1970s, scientists
developed a flu vaccine known as Hib (for Haemophilus influenzae type
b). Hib was at the time one of the most lethal pathogens of early childhood
in the developed world. The vaccine worked fine for children over two,
but it did not work well for infants. Stymied, researchers searched through
historical references and discovered a technique developed by none
other than Karl Landsteiner. In the 1980s, using Landsteiner’s
articulation of hapten-carrier theory, Oswald Avery and W. F.
( 227 )
Karl Landsteiner
Goebel developed the first Hib conjugate vaccine. Introduced into

widespread use in 1990, it brought about a 99 percent decline of
invasive Hib disease. So, every parent whose child gets vaccinated is
receiving a small gift from Landsteiner’s far-reaching research.
Landsteiner was truly the superman scientist. What’s more, in
personality, he was essentially human: strong in intellect and sensitively
insecure in human relations, full of the excitement of discovery and the
despair at civilization’s frailty, sometimes all at the same time.
One evening in 1930, Philip Levine went to Landsteiner’s apartment.
He found the family placidly reading as usual. Levine was quite surprised,
considering the news of the day. “What news?” Landsteiner’s wife and
son asked. Their looks told the story. Karl had told neither Helene
nor Ernst what he had learned earlier that day—that he had been
awarded the Nobel Prize in Medicine. Beginning in 1923, fourteen
different nominators had put him up for the award for three different
discoveries: his polio research, his immune system work, and his
discovery of the blood groups. The committee finally granted him the
award for his blood group works Nobel in 1930.
Landsteiner feigned that he was uncertain it was true. But it was. And
true also was what this incident revealed of his personality. Peyton Rous,
who would earn his own Nobel Prize 37 years later for discovering
tumor-inducing viruses, and who had congratulated him that same day at
the lab, later wrote Landsteiner’s obituary. He said that “Karl was
peremptory by nature, but he was downcast, too self-questioning and
never sure in his human relations. His pessimism was sad, not bitter,
and never obtrusive; despite it, he cheered others in what they were
trying to do. But he was held in the grip of his temperament, and
gradually this tightened upon him: Only in his scientific life was he
serene and whole. Fortunately, he was sensitive, else he might have
been stern and demanding, and he had an eager yet hesitant desire
to be liked. Liking came to him, for he was simple, sincere, modest
and gentle, and witty as well in a shy way.”
( 228 )
Determining the Number of Lives Saved
by Amy R. Pearce, Ph.D.
An approximate answer to the right problem is worth a good deal more

than an exact answer to an approximate problem.
—John Tukey, Ph.D. and statistician
As this project’s statistician, my task was to tabulate figures that
were in all practicality impossible to pinpoint. Consequently, each
number represents a conservative estimate of lives saved for each of the
“lifesavers,” based on the best available data and a commonsense
approach.
Whenever possible, I employed a consistent and logical multistep
process. I used both aggregated and disaggregated world population
figures from the twentieth century and beyond to count the potential
beneficiaries from each discovery, and I established a timeline from the
discovery’s invention and first widespread use through 2008. I calculated
lives saved based on published data from the most reputable, corroborative,
and accessible evidence and resources (WHO, CDC, NIH, UNICEF, and
databases such as Medline, Lexus Nexus, and PubMed). Yet, on occasion,
these yielded insufficient data, and I then considered alternate sources
such as Internet websites and a variety of nonacademic literature.
Software programs such as Excel and SPSS were used for calculations
and graphics.
I found population data for countries with ready access to the then-
new cure, and also mortality and morbidity statistics for targeted illnesses
then determined a percentage of this population that would logically have
died without the intervention. For the most part, the information for the
developed World (North America, Western Europe, parts of South
America, Southeast Asia, and certain other countries) was the most
accessible and reliable, and so the majority of calculations were
extrapolated from these figures.
( 229 )
Statistics from the developing World were scarce, and if figures were
not available or could not be credibly inferred, they were not included in
extrapolated figures. Hence, while many lives-saved totals are
astoundingly high, I believe each result is wholly conservative and likely
underestimates the true number of beneficiaries. For more information
and source material please visit – www.scienceheroes.com)
(Based on these calcualtions we revised the numbers for 2020 –
Srinivasa K. Rao, Ph.D.).
( 230 )
Part II
Introduction to Bhatnagar awards
Dr Shanti Swarup Bhatnagar was the

Founder Director (and later first Director
General) of Council of Scientific &
Industrial Research (CSIR) who is
credited with establishing twelve national
laboratories in as many years. Dr
Bhatnagar played a significant role in
building of post independent S & T
infrastructure and in the formulation of
India’s S & T policies. Dr Bhatnagar
concurrently held number of important
position in the Government. He was the first Chairman of the University
Grants Commission (UGC). He was Secretary, Ministry of Education
and Educational Adviser of Government. He was the first Secretary to
Ministry of Natural Resource & Scientific Research and also Secretary of
Atomic Energy Commission. He played an instrument role in the
establishment of the National Research Development Corporation
(NRDC) of India. His research contribution in the areas of magneto
chemistry and physical chemistry of emulsion were widely recognized.
In 1936, Dr Bhatnagar was conferred with Order of British Empire
(OBE). He was Knighted in 1941and elected Fellow of Royal Society,
London in 1943. He was awarded the Padma Vibhushan in 1954 by the
President of India.
( 233 )
Eligibility
Any citizen of India engaged in research in any field of science and

technology up to the age of 45 years as reckoned on 31st December of the
year preceding the year of the Prize. Overseas citizen of India (OCI) and
Persons of Indian Origin (PIO) working in India are also eligible.
The Prize is bestowed on a person who, in the opinion of CSIR, has
made conspicuously important and outstanding contributions to human
knowledge and progress – fundamental and applied – in the particular
field of endeavour, which is his/her specialization.
The Prize is awarded on the basis of contributions made through
work done primarily in India during the five years preceding the year of
the Prize. (For this purpose ‘primarily’ will mean ‘for the most part’)
( 234 )
Preface
Shanti Swaroop Bhatnagar Awards in Biology & Medicine
Since the inception of these awards in 1960, a hundred scientists have

been awarded the Prize in Biology & Medicine until 2020. A lion’s share
of these awards went to scientists working in Research Institutes with a
very few instances of academicians from traditional universities receiving
the awards. The institute that stands top in bagging these awards is the
Indian Institute of science with twenty awards of which ten went to
scientists in the Molecular Biophysics Unit and the others to the
Biochemistry, Cell and Microbiology and Ecology department. The other
institutes that bred scientists who received the awards are the CCMB,
CDFD, Bose Institute, Jawahar Lal Nehru Centre for advanced Scientific
Research, Indian Institute of Immunology, Indian Institute of science
education and research, IARI and NCBS. Among the universities which
bred Bhatnagar awardees are the JNU, Madhurai Kamraj Univ, Banaras
Hindu University.
With respect to research in subject areas for which most of the awards
went most of the recent awards are in Molecular Biology with special
reference to DNA replication and repair, Cell biology, Signal transduction,
brain and neuronal functions. A significant number of awards were in the
field of protein structure and function, human pathogens with applications
in discovery of drug targets. Far fewer awards are in the field of plant
sciences – for developing wheat and sorghum hybrids, high yielding
semi-dwarf wheat varieties that led to green revolution in India, genomics
of legumes, pathogen resistant rice and plant pathogenic fungi.
All awardees without exception had research experience abroad, the
award-winning research being either a continuation of the topic of their
post-doctoral research or in conformation to the research mandate of the
institute they served. The contributions of very few awardees are available
either in the form of their interviews or TED talks. As it is the most
( 235 )
prestigious award in science awarded in India, it would be inspiring for
the younger generation of scientists if the research leading to the award
is described by the awardee just as the Nobel lectures given by Nobel
laureates.
Prof. Uma Devi Koduru

Visakhapatnam
2020.
( 236 )
Section 1 – Biological Sciences
Dr Shubhadeep Chatterjee (1975)
Award Year: 2020

Discipline: Biological Sciences
Specialization: Molecular Microbiology and Host-
Pathogen Interaction
Address: Laboratory of Plant-Microbe Interactions
(CDFD) Uppal
Hyderabad – 500039,TS
Telephone: 040-27216108
E-Mail: [email protected]
Identified a reversible, non-genetic process that Xanthomonas (a family of

economically important plant pathogenic bacteria) bacterial cells use to regulate
their population, through a basic social communication process known as quorum
sensing. The understanding of quorum sensing mechanism and coordination of
regulation of cellular functions in response to quorum sensing greatly helped in
understanding the complex lifestyles of pathogens and insights into microbial
evolution. These fundamental findings have implications in bacterial disease
management including those of medical importance.
Dr Vatsala Thirumalai (1975)
Award Year: 2020

Specialization: Neuroscience
Address: Neural Circuits and Development Laboratory
National Centre for Biological Sciences
Tata Institute of Fundamental Research Bellary Road
Bengaluru - 560065, Karnataka
Telephone: 040-27216108
Made fundamental discoveries that led to the understanding of the hierarchy,

mechanisms, and development of brain and spinal cord circuits that generate
movement – a very important function in animals using a very suitable model organism
- the zebrafish. The embryonic and larval stages of these fish are transparent, which
enables to directly observe the developing internal organs, including the brain. The
work led to the understanding of how single neurons operate along with large
neural networks to produce neural commands for movement. These findings
will help to work out therapies for impairment of movement resulting from
brain stroke or tumours.
Dr Soumen Basak (1974)
Award Year: 2019

Specialization: Cell Signaling, Immunology, Systems
Biology
Address: Systems Immunology Lab
National Institute of Immunology Aruna Asaf Ali Marg
New Delhi - 110067, Delhi
Telephone:
Investigated the NF-Kappa B molecular signalling system in cells that responds

to multiple signals and plays myriad roles in mammalian physiology and disease
including cancer. The cross talk between different signalling pathways in response
to different signals of NF-Kappa B system was studied in a murine model. This led to
mechanistic insights into the regulatory role of this cross talk in human immunity and
diseases. The discoveries have therapeutic importance. Targeting the proposed
crosstalk components in inflammatory diseases and in pathogenesis bears the
promise to reduce the devastating side effects that are often associated with
the treatment regimens that target signalling hub molecules.
Dr Kayarat Saikrishnan (1975)
Award Year: 2019

Specialization: Structural Biology
Address: Department of Biology
Indian Institute of Science Education and Research
Dr Homi bhabha Road Pashan
Pune - 411008, Maharashtra
Telephone: +91 20 2590 8047
Determined crystal structure of an NTP (Nucleotide tri phosphate) -dependent

restriction-modification (RM) enzyme of the Type ISP that is a major bacterial
defense system against invading foreign DNA, such as bacteriophage DNA. The
structure revealed a new mechanism of double-strand DNA-break formation
resulting from multiple nicks of the DNA strands.
Dr Ganesh Nagaraju (1973)
Award Year: 2018

Specialization: DNA Repair, Chromosome Instability,
Genetic Diseases and Cancer
Address: Department of Biochemistry Indian Institute of
Science, CV Raman Road
Bangalore - 560012, Karnataka
Telephone:
Unravelled the mechanistic basis of a family of five proteins called RAD51 paralogs
in repair of double stranded breaks in DNA through homologous recombination.
These proteins were found to transduce DNA damage signal to kinases that
promote DNA break repair and restore homeostasis of the genome.
Dr Thomas Pucadyil (1976)
Award Year: 2018

Specialization: Membrane Biochemistry and Vesicular
Transport
Address: Indian Institute of Science Education and
Research Pune, Dr. Homi Bhabha Road, Pashan
Telephone: +912025908204
Contributed to understanding of vesicular transport through reconstruction biology

(a paradigm of watch makers learning). Focussed on identifying protein machines
that help in active bending and fission of membranes to form vesicles and identifying
where and how they function in cells. The investigations shed light on how cells form
membrane bound compartments.
Dr Deepak Thankappan Nair (1973)
Award Year: 2017

Specialization: Structural Biology & Molecular Biology
Address: Regional Centre for Biotechnology

3rd Milestone Faridabad-Gurgaon Expressway
Faridabad - 121001, Haryana
Telephone: 0129 2848844
Provided new insights into the molecular mechanisms that determine the fidelity
of the replication process in bacteria and flaviviruses (single stranded RNA
viruses that cause yellow fever, dengue, Ebola and encephalitis etc.) mediated by
specialized DNA polymerases. His research demonstrated how GTP binding
to the viral RNA-dependent-RNA polymerase ensures accurate initiation of
replication of the viral genome.
Dr Sanjeev Das (1976)

Award Year: 2017
Specialization: Cancer Biology
Address: Molecular Oncology Laboratory

National Institute of Immunology, Aruna Asaf Ali Marg
Telephone: 011 2670 3702
For his studies on tumour suppressing genes and focus on various aspects of cancer
biology which is reported to have assisted in widening the understanding of the
functioning of P53, a tumour suppressing gene referred to as the ‘Guardian of the
Genome’ and sirtuins. a family of signalling proteins involved in metabolic regulation.
Dr Rishikesh Narayanan (1974)
Award Year: 2016

Address: Molecular Biophysics Unit Indian Institute of

Science, C V Raman Avenue
Telephone: +91-80-22933372
Research in the field of Cellular Neurobiology on experimental and theoretical

aspects of information processing in single neurons and their networks. His work
on the roles of dendritic ion channels and their plasticity in several aspects of
neural coding and homeostasis is of critical significance for the understanding
of neuronal physiology.
Dr Suvendra Nath Bhattacharyya (1975)
Award Year: 2016

Specialization: Molecular Cell Biology and Epigenetics
Address: Molecular and Human Genetics Division CSIR-

Indian Institute of Chemical Biology, 4, Raja S C Mullick Rd.
Kolkata - 700032, West Bengal
Telephone: 033-24995783
Contributed to the understanding of the mechanisms of mighty regulation by

the tiny regulator – miRNA (a non- coding micro RNA molecule) activities
in mammalian immune and cancer cells which have potential therapeutic
applications.
Dr Balasubramanian Gopal (1970)
Award Year: 2015

Specialization: Structural Biology, Molecular
Microbiology, Molecular Biophysics
Address: Molecular Biophysics Unit Indian Institute of
Science C V Raman Ave
Telephone: 080 22933219
Studied the mechanistic aspects of membrane associated proteins involved in

inter-cell communication, transcriptional regulation and mediate antimicrobial
resistance. Research led to the understanding of initiation and regulation of
transcription in the TB bacterium. This work has implications in the treatment of
TB and understanding the development of drug resistance.
Dr Rajeev Kumar Varshney (1973)
Award Year: 2015

Specialization: Genetics, Genomics and Molecular
Breeding (Crop Improvement)
Address: Centre of Excellence in Genomics International
rops Research Institute for the Semi-Arid Tropics,
Patancheru
Hyderabad - 502324, Telangana
Telephone: +040 30713305 E-Mail: [email protected]
Contributions to genomics and molecular breeding of major orphan tropical crops:

legumes (pigeon pea, chick pea) and oil seeds (peanut, sesame). Participated in the
genome sequencing of these crops. Identified through DNA marker technologies
gene loci/candidate genes for drought and pest tolerance in these key staple
crops suitable for the marginal environments of sub-Saharan Africa and India which
resulted in developing creating and delivering superior crop varieties tolerant to
biotic and abiotic stress to some of the world’s poorest farmers.
Dr Roop Mallik (1970)
Award Year: 2014

Specialization: Biophysics of Molecular Motors and
Intracellular Transport
Address: Department of Biological Sciences Tata
Institute of Fundamental Research Homi Bhabha Road
Mumbai - 400005, Mumbai
Telephone: 022 22782702
Contributed to the understanding of the mode of functioning of nanoscale

molecular motors that carry cellular material as cargo from one factory to the
other within the cell by walking in a step like manner on pre laid tracks. Investigated
how different motors with inclination to walk in different directions attached to the
same cargo and demonstrated that a cellular cargo reverses its direction due to
a physical tug-of-war between kinesin and dynein motors.
Dr Sathees Chukkurumbal Raghavan (1970)
Award Year: 2013

Specialization: DNA Repair, Cancer Biology, Genetics
Address: Department of Biochemistry Indian Institute of

Science
Telephone: 080 22932674
For investigations that led to understanding the mechanism of regulation of repair

of DNA double strand breaks, generation of chromosomal translocations and their
role in oncogenesis. Discovered a chemical compound SCR7 that blocks DNA
repair in cancer cells and impedes cancer cell growth and therefore has the
potential in cancer therapeutics.
Dr Shantanu Chowdhury (1968)
Award Year: 2012

Specialization: Genomics & Structural Biology
Address: CSIR-Institute of Genomics & Integrative

Biology, South Campus Mathura Road
Delhi - 110025, Delhi
Telephone: 011 29879487
A structural biologist Identified a novel mechanism of gene regulation mediated

by DNA secondary structures like G-quadruplex ( formed in sequences that are
rich in guanine that occur in the transcriptional regulatory regions of several genes)
and elucidated the process of gene transcription involving G-quadruplex.
Dr Suman Kumar Dhar (1968)
Award Year: 2012

Specialization: Molecular Biology, Biochemistry,
Parasitology, Bacteriology
Address: Special Centre for Molecular Medicine
Jawaharlal Nehru University
New Delhi - 110067, New Delhi
Telephone: 011 2674 2576
Dr Suman Kumar Dhar is awarded for furthering our understanding of DNA

replication and cell-cycle regulation in two human pathogens, Helicobacter pylori
and Plasmodium falciparum.
Dr Amit Prakash Sharma (1968)
Award Year: 2011

Specialization: Structural Biology, Malaria, Protein
Translation
Address: ICMR- National Institute Of Malaria Research
Sector-8, Dwarka
Telephone: 011 25307103/104
Sharma’s research is focused in the field of structural parasitology, and he has

carried out advanced research in malaria parasite biology. Sharma has made
seminal contributions leading to the delineation of principles governing structure
function relationships of key malaria parasite proteins. This work may also lead
to the design of inhibitors targeting critical stages of the parasite in the human
host.
Dr Rajan Sankaranarayanan (1968)
Award Year: 2011

Specialization: Structural Biology, Translation of
Genetic Code, Enzyme Mechanisms
Address: Structural Biology Laboratory
CSIR-Centre for Cellular & Molecular Biology Uppal Road
Hyderabad - 500007, Andhra Pradesh
Telephone: 040 27192832
Contributions in the area of structural biology of protein biosynthesis. Explored the

mechanistic basis and functional relevance of unique proofreading mechanisms
that are operational in the cell to maintain a high-fidelity during translation of
the genetic code that is essential for cell survival.
Dr Sanjeev Galande (1967)
Award Year: 2010

Specialization: Epigenetics, Molecular Cell Biology,
Gene regulation, Genomics and Proteonics
Address: Centre for Excellence in Epigenetics Indian
Institute of Science Education and Research, 900, NCL
Innovation Park Dr Homi Bhabha Road
Pune - 411008, MH Telephone: 020 25908060
Made outstanding contribution to the understanding of how dynamic changes

in higher-order chromatin architecture lead to spatio-temporal changes in
gene expression. Studied the role of global chromatin organizer and master
regulator gene SATB1 (Special AT-rich binding protein 1’) in the development and
differentiation of cells of the immune system. Found unequivocal evidence to
establish that SATB1 is a novel target of Wnt signalling that plays a critical role
in thymocyte development. T-lymphocyte development begins in the thymus.
Dr Shubha Tole (1967)
Award Year: 2010

Specialization: Developmental Biology, Neuroscience
Address: Department of Biological Sciences Tata

Institute of Fundamental Research, Dr Homi Bhabha
Road Colaba
Mumbai - 400005, MH Telephone: 022 22782878
Contributed to understanding of the genetic and epigenetic mechanisms that

control formation of highly specialised structures in the human brain using knock
out mice and transgenic approaches. Discovered a regulatory gene LhX2 that is
crucial for the proper development of hippocampus (that controls learning and
memory), cortex (responsible for higher brain functions like perception, language,
learning and memory) and amygdala which is the emotion centre of the brain.
Dr Amitabh Joshi (1965)
Award Year: 2009

Specialization: Population & Quantitative Genetics,
Evolutionary Genetics and Population Ecology
Address: Evolutionary & Organismal Biology Unit
Jawaharlal Nehru Centre for Advanced Scientific
Research
Telephone: 080 2308 2802 E-Mail: [email protected]
A passionate geneticist whose studies in evolutionary biology through studies of

Drosophila populations for over more than 600 generations captured the process
of evolution and differentiation of subspecies in the lab. Creatively applying
theoretical mathematical models and computer simulations to experimental
results at. ecology - evolution interphase explained how adaptation to crowding
in Drosophila influenced competitive ability and how developmental rates and
competitive ability are intertwined. Studied metapopulation dynamics and
explained how migration rate and local dynamics interact to effect global stability
and global dynamics in metapopulations.
Dr Bhaskar Saha (1964)
Award Year: 2009

Specialization: Immunology, Cell Signaling, Drug
Development, Leishmaniasis, Tumor Immunology
Address: National Centre for Cell Science
Ganeshkhind
Telephone: 020 25708139
Outstanding contributions in the fields of immunology and cell signalling. Analysed

TLR4, a membrane protein of toll like receptor family that recognize pathogen-
associated molecular patterns (PAMS). Activation of TLR4 leads to an intracellular
signalling pathway NF-κB and inflammatory cytokine production that is responsible
for triggering the innate immune system. Work on this led to the understanding of
the plasticity of the signalling system uncovering novel signalling connections
and helped in identifying potential drug targets for infections.
Dr Lingadahalli Subrahmanya Shashidhara (1963)
Award Year: 2008

Specialization: Developmental Biology, Evolution and
Genetics
Address: School of Biology Indian Institute of Science
Education and Research Pune, 900, NCL Innovation Bank
Dr Homi Bhabha Road
Pune - 411008, MH Telephone: 020 25908001
Developmental Biological studies on Drosophila led to an understanding of the

genetic basis of the differentiation of limbs. Elucidated the molecular pathways
that control growth. Developed a fly model for studying gene responsible for
colon cancer in humans which assisted in a wider understanding of the relation
between genes and diseases and in the development of cancer drug discovery
systems.
Dr Gajendra Pal Singh Raghava (1963)
Award Year: 2008

Specialization: Bioinformatics, Genome Annotation ans
Vaccine Design, Searching Drug Targets
Address: Indraprastha Institute of Information
Technology, Delhi, Okhla Industrial Estate, Phase III Near
Govind Puri Metro Station
Telephone: 011 26907444 E-Mail: [email protected]
Developed a method for prediction of secondary structure of proteins. Contribute

to development of methods of Computer aided vaccine (subunit type) and drug
design.
Dr Narayanaswamy Srinivasan (1962)
Award Year: 2007

Specialization: Computational Genomics, Structural
Biology
Address: Molecular Biophysics Unit
Indian Institute of Science
Telephone: 080 22932837
Dr Srinivasan has made outstanding contribution in the area of computational

genomics, protein structure analysis, modeling and computational studies on
proteins that are involved in cellular signal transduction pathways. His studies at
the whole genome level have helped to identify remotely similar proteins sharing
structural and functional features.
Dr Upinder Singh Bhalla (1963)
Award Year: 2007

Specialization: Systems Biology, Computational
Neuroscience and Systems Neurobiology
Address: National Centre for Biological Sciences
GKVK Campus Bellary Road
Bangalore - 560 065, Karnataka
Telephone: 080 2366 6130
Dr Bhalla has made outstanding contributions in computational and experimental

approaches to understanding neuronal and Synaptic signaling in memory and in
coding of olfactory information.
Dr Vinod Bhakuni (1962-2011)
Award Year: 2006

Specialization: Protein Folding , Molecular Biophysics
Address:
Telephone:
E-Mail:
Dr Bhakuni has made outstanding contribution to our understanding the role of

noncatalytic structural domains and ionic interactions in regulating the functional
activity of the catalytic domains in proteins
Dr Rajesh Sudhir Gokhale (1967)
Award Year: 2006

Specialization: Chemical Biology, Skin Biology,
Mycobacterium Tuberculosis, Immunometabolism
Address: National Institute of Immunology
Aruna Asaf Ali Marg Jawaharlal Nehru University
Telephone: 011 26703545
Dr Gokhale’s work has discovered a new family of long-chain fatty acyl-AMP ligases
(FAALs) and has also elegantly elucidated biochemical crosstalk between fatty
acid synthases and polyketide synthases, which produce diverse unusual lipids of
the complex cell wall of Mycobacterium tuberculosis. His studies have significantly
expanded our understanding of how pathogens evolve their gene products to
generate metabolic diversity.
Dr Shekhar Chintamani Mande (1962)
Award Year: 2005

Specialization: Protein Structure Function,
Macromolecular Crystallography
Address: Director General, CSIR and Secretary
DSIR Council of Scientific and Industrial Research,
Anusandhan Bhawan 2 Rafi Ahmed Kidwai Marg
Dr Mande has contributed very richly to the area of structural biology of proteins.
His studies have thrown light on the unrecognized function of chaperonin-10 of
Mycobacterium tuberculosis. His studies have provided unusual insights to the
mechanism of action of heat shock proteins and those involved in oxidative stress
from M. tuberculosis.
Dr Tapas Kumar Kundu (1962)
Award Year: 2005

Specialization: Molecular Biology, Regulation of Gene
Exp, Chemical Biology
Address: Molecular Biology & Genetics Unit
Jawaharlal Nehru Centre for Advanced Scientific
Research, Jakkur
Dr Kundu has done outstanding research in the area of chromatin transcription. He

has identified PC4 as a functional component of chromatin and as a unique activator
of P53. He has also established the role of acetylation in chromatin transcription
and histone chaperone activity, besides using this process for identifying new drug
candidates.
Dr Gopal Chandra Kundu (1959)
Award Year: 2004

Specialization: Regulation of Gene Expression,Signal
Transduction, Tumor Biology, Angiogenesis
Address: KIIT Deemed to be University
Institute of Eminence Patia
Bhubaneswar - 751024, Odisha
Telephone: 0674 2725466
Dr Kundu’s outstanding contributions have resulted in the molecular dissection of the

regulation of metastatic potential of melanoma and breast cancers by a chemokine
like, extra-cellular matrix protein - osteopontin. He has further demonstrated the
existence of a novel signaling pathway that involves protein tyrosine kinase in
regulating the motility of breast cancer cells.
Dr Ramesh Venkata Sonti (1960)
Award Year: 2004

Specialization: Microbe Plant Interactions, Plant
Genetics, Bacterial Genetics
Address: National Institute of Plant Genome Research
Aruna Asaf Ali Marg
New Delhi - 110 067, New Delhi
Telephone: 011 2674 2267
Dr Sonti has made outstanding contribution in the area of plant-pathogen

interactions. His work has led to the identification of novel virulence genes which
led to a better understanding of pathogenic function of these genes. This has also
provided insight into the different ways by which host plant specialization might
be achieved. His work on marker-assisted breeding has led to the incorporation of
disease resistance characteristics into the genetic background of the commercially
important Samba Mahsuri rice variety.
Dr Satyajit Mayor (1963)
Award Year: 2003

Specialization: Cell Biology, Biophysics and
Biochemistry
Address: National Centre for Biological Sciences
GKVK Campus Bellary Road
Telephone: 080 2366 6301
Dr Mayor has made outstanding contribution to the study of endocytosis in living

cells. His work has greatly advanced the understanding of the endocytic pathway
of lipid-anchored proteins. The concept of lipid rafts has emerged directly from
Dr Mayor’s work. His studies of endocytic processes have been based on the
development of novel fluorescence methodologies which permit visualization of
specialized domains in cell membranes. Dr Mayor’s work represents a significant
advance in the understanding of membrane-associated trafficking events in cells.
Dr Amitabha Mukhopadhyay (1959)
Award Year: 2002

Specialization: Cell Biology, Host-pathogens Interaction,
Drug Discovery
Aruna Asaf Ali Marg JNU Complex
Telephone: 011 2659 1106
Dr Amitabha Mukhopadhyay has made outstanding contribution to our

understanding of the molecular mechanisms of host-parasite interactions in respect
of two microbial pathogens, Salmonella and Leishmania. He has delineated the
processes by which the Salmonella bacterium avoids being killed in lysosomes of
the host macrophage. He has also discovered a new receptor system that mediates
hemoglobin endocytosis in Leishmania. His research investigations have given
important leads for the identification of new targets for therapeutic interventions in
human infectious diseases such as typhoid fever and kala azar.
Dr Raghavan Varadarajan (1960)
Award Year: 2002

Specialization: Protein Folding and Design

Telephone: 080 22932612
Dr Varadarajan has made outstanding contribution in the area of protein folding. He

has incisively explored the relationship between protein sequence, three-dimensional
structure and thermodynamic stability. His work has led to the development of new
methods for depth probing in protein structure and for predicting temperature
sensitive mutants from sequences. His work has provided experimental tests of
sequence-stability relationships. His work has also provided new insights into the
forces driving fragment complementation and the nature of disordered states in
proteins.
Dr Umesh Varshney (1957)
Award Year: 2001

Specialization: Molecular Biology, Protein Biosynthesis,
DNA Repair
Address: Department of Microbiology and Cell Biology
Telephone: 080 23600169
Dr Varshney has made outstanding research in unravelling unique mechanisms of

protein synthesis and DNA repair with particular reference to these fundamental
processes in Mycobacterium tuberculosis. These processes relate to the interaction
between ribosome recycling factor and chryation factor G, crucial for protein
synthesis. The uracil excision repair pathway is an important facet of the biology
of mycobacterium.
Dr Amitabha Chattopadhyay (1956)
Award Year: 2001

Specialization: Membrane biology, Molecular & Cellular
Neurobiology, Fluorescence Spectroscopy and Microscopy
Address: CSIR-Centre for Cellular & Molecular Biology
Uppal Road
Dr Chattopadhyay has made outstanding contribution to the study of the organization

and dynamics of ion channels in membranes. His incisive studies have clarified many
features of gramicidis channel function. He has developed widely used fluorescence
techniques for probing the structure of biological membranes using wavelength
selective excitation. He has extended biophysical characterization of membrane
proteins to the difficult problem of bovine hippocampal serotonin receptor. His work
has contributed many key insights into the understanding of biological membranes.
Dr Jayant Bhalchandra Udgaonkar (1960)
Award Year: 2000

Specialization: Physical Biochemistry, Protein Folding
Address: Indian Institute of Science Education and

Research, Homi Bhabha Road Pashan
Pune - 411 008, Maharashtra
Telephone: 020 2590 8000/8009
Dr Jayant Bhalchandra Udgaonkar has made outstanding contribution to the area of

protein folding. Using the model protein barstar, he has established that the earliest
event in folding is an initial hydrophobic collapse. His work has provided elegant and
incisive characterization of multiple unfolding intermediates and transition states of
folding and unfolding of proteins.
Dr Dinakar Mashnu Salunke (1955)
Award Year: 2000

Specialization: Structural Biology, Macromolecular
Crystallography, Immunology
Address: International Centre For Genetic Engineering
And Biotechnology, Aruna Asaf Ali Marg
Telephone: 011 26742317
Dr Dinakar Mashnu Salunke has made fundamental contribution to the area of

molecular recognition and mimicry using the immune system as a model. He has
demonstrated the structural as well as functional consequences of mimicry involving
a variety of chemically different molecules. He has also established structural biology
of certain molecular recognition events associated with endocrine regulation.
Dr Siddhartha Roy (1954)
Award Year: 1999

Specialization: Structural Biology, Protein Nucleic Acid
Interaction, NMR Spectroscopy
Address: Bose Institute
P1/12, CIT Rd, Kankurgachi
Telephone: 033 23559544
Dr Roy has made outstanding contribution to the study of gene expression using
the operator-repressor system of bacteriophage lambda (l). He has also contributed
to the understanding of macromolecular interactions that lead to high fidelity of
protein synthesis.
Dr Valakunja Nagaraja (1954)
Award Year: 1999

Specialization: Protein Nucleic Acid Interaction, Molecular
Biology of Mycobacteria, Regulation of Gene Expression
Address: Jawaharlal Nehru Centre for Advanced Scientific
Research, Near MGIRED, Rachenahalli Lake Road Jakkur
Bengaluru - 560064, Karnataka
Telephone: 080 2360 0668
Dr Nagaraja has made outstanding contributions in understanding the role

of modulation of DNA structure in gene expression and unique properties of
mycobacterium. His work on mycobacterial topoisomerases has laid the basis for
new drug discovery.
Dr Debi Prasad Sarkar (1958)
Award Year: 1998

Specialization: Biochemistry, Biotectnology, Molecular
Cell Biology, Virology, Immunology
Address: Department of Biochemistry University of
Delhi, South Campus, Benito Juarez MargSouth Campus,
Benito Juarez Marg
Dr Sarkar has made outstanding contribution in developing reconstituted sendai

viral envelops containing only the fusion protein for efficient gene delivery for
therapeutic application.
Dr Krishnaswamy Vijayraghavan (1954)
Award Year: 1998

Specialization: Developmental Biology, Genetics,
Neurogenetics
Address: Department of Biotechnology
721, 7th Floor, Block No. 2 CGO Complex, Lodi Road
Telephone: 011 24362950
Dr Vijayraghavan has made outstanding contribution to the understanding of the

role of homeotic genes in muscle development. His work on Drosophila flight muscle
has been extremely incisive and makes a major contribution to our understanding
of myogenesis.
Dr Kanury Venkata Subba Rao (1958)
Award Year: 1997

Specialization: Synthetic Peptides, Cell Signalling,
Biology of Tuberculosis Infection, System Biology
Address: Immunology Group International Centre for
Genetic Engineering & Biotechnology, Aruna Asaf Ali
Marg
New Delhi - 110067, Haryana
Dr Subba Rao has made outstanding contribution in the design of synthetic peptide
vaccines based on the regeneration of conformational epitopes and self association
of such peptides to give high immunogenicity in humans. He has also contributed
significantly to the understanding of the antigen-specific B cell selection and
amplification. He has also been involved in the development of HIV diagnostics.
Dr Jayaraman Gowrishankar (1956)
Award Year: 1997

Specialization: Microbial Genetics, Molecular Biology
Address: Centre for DNA Fingerprinting and

Diagnostics
Hyderabad - 500 039, Andhra Pradesh
Telephone: 040 2474 9388
Dr Gowrishankar has made significant contribution in elucidating the molecular

genetics of osmoregulation in Escherichia coli with important biotechnological
applications. This work has led to the development of a salt inducible expression
vector. Recently, he has developed an imaginative bacterial system to demonstrate
that mutations can arise in stationary state bacteria.
Dr Ghanshyam Swarup (1953)
Award Year: 1996

Specialization: Cell Biology, Molecular Biology, Signal
Transduction
Address: CSIR-Centre for Cellular and Molecular Biology
Uppal Road
Telephone: 040 27192616
Dr Swarup has made important contribution in the area of cell biology. Notably, he
has discovered a novel nuclear protein tyrosine phosphatase and shown that this
protein is a positive regulator of cell proliferation.
Dr Vishweshwaraiah Prakash (1951)
Award Year: 1996

Specialization: Physical Biochemistry, Biophysics of
Proteins, Food Chemistry, Nutrition, Food Biotechnology,
Food Science
Address: Innovation and Development JSS Technical
Institutions Campus JSS CMS
Mysore - 570006, Karnataka
Dr Prakash for his work encompassing structure-function relationship and structural

homology of seed proteins bearing on ligand binding, association-dissociation
and denaturation profiles of these proteins. His work has been fundamental to
understanding the behaviour of a number of seed proteins and enzymes in many
diverse solvents from the point of view of their stabilisation and destabilisation. The
above work has generated an in-depth knowledge and signifies deep understanding
of the structural biology of seed proteins from the biophysical angle.
Dr Kalappa Muniyappa (1952)
Award Year: 1995

Specialization: Molecular Genetics, Genetic
Recombination and Telomere Biology
Address: Department of Biochemistry
Telephone: 080 2360 0278
Dr Muniyappa has made outstanding contribution to the elucidation of the

molecular basis of homologous genetic recombination. In particular, he has used
RecA paradigm to understand the effects of chromatization of DNA on homologous
pairing and strand exchange which has opened up new vistas to discern this
complex phenomenon at the cellular context, which has implications for robust gene
targeting.
Dr Seyed Ehtesham Hasnain (1954)
Award Year: 1995

Specialization: Molecular Biology, Infection Biology
Address: Jamia Hamdard

Hamdard Nagar
Telephone: 011 26581481
Dr Hasnain has made pioneering contributions to understanding the fundamental

process involved in gene expression in the baculovirus system. His discovery of
an unusual host protein factor that binds to previously unknown DNA sequence
motifs of the baculovirus polyhedrin gene producer opens up a new horizon in the
regulation of transcription of very late viral genes.
Dr Ramakrishnan Nagaraj (1953)
Award Year: 1994

Specialization: Biophysics, Membrane, Biochemistry,
Protein Nanostructures.
Address: CSIR-Centre for Cellular & Molecular Biology
Uppal Raod
Telephone: 040 27192589
Dr Nagaraj has made contribution towards delineating structure-activity

relationships for membrane targeting signal peptides and peptide antibiotics. His
work has successfully established the separation of hemolytic and antibacterial
properties in synthetic analogs of bacterial toxins leading to possibilities in rational
design of antibiotic peptides. Dr Nagaraj has made contribution towards delineating
structure-activity relationships for membrane targeting signal peptides and peptide
antibiotics. His work has successfully established the separation of hemolytic
and antibacterial properties in synthetic analogs of bacterial toxins leading to
possibilities in rational design of antibiotic peptides.
Dr Alok Bhattacharya (1951)
Award Year: 1994

Specialization: Parasitology, Genomics, Bioinformatics
Address: School of Life Sciences

Jawaharlal Nehru University
Telephone: 011 2670 4516
Dr Bhattacharya has done pioneering work on the identification and characterization

of lipophosphoglycan and its modulation by bacterial flora, and a novel species-
specific calcium binding protein and its gene, in Entamoeba histolytica. Identification
of these molecules has opened up avenues to understand pathogenesis at the
molecular level.
Dr Mathur Ramabhadrashastry Narasimha Murthy (1950)
Award Year: 1993

Specialization: Macromolecular Crystallography,
Structural Biology, X-Ray Diffraction
Telephone: 080 23372981
Dr Murthy and his group have worked out the three-dimensional structure of
Sesbania mosaic virus at 2.9 Å resolution by X-ray diffraction technique. His
contributions have sharpened the understanding of how the complex molecular
assemblies are put together in viruses.
Dr Raghavendra Gadagkar (1953)
Award Year: 1993

Specialization: Insect Sociobiology, Animal Behavior
Ecology, Evolution
Address: Centre for Ecological Sciences
Telephone: 080 2360 1429
Dr Gadagkar has discovered the phenomena of behavioural caste differentiation and

pre-imaginal caste bias in eusocial insects. He has demonstrated that differential
larval nutrition is a major determinant of social differentiation.
Dr Kuppamuthu Dharmalingam (1949)
Award Year: 1992

Specialization: Molecular Genetics, Genetic Engineering
and Biotechnology
Address: MKU Madurai
Aravind Medical Research Foundation 1, Anna Nagar
Madurai - 625020, Tamil Nadu
Telephone: 0452 4356550
Dr Dharmalingam was the first to discover the induction of mutagenic DNA repair
during restriction of nonglucosylated T4 DNA in Escherichia coli. He also discovered
in this system the alleviation of restriction by SOS functions. He has characterized
the rglA (mcrA) and rglB (mcrB) components of the rgl (mcr) restriction system.
Dr Dipankar Chatterji (1951)
Award Year: 1992

Specialization: Biophysical chemistry, Molecular biology,
Biomolecular Spectroscopy
Telephone: 080 23600137
Dr Chatterji has studied the mechanism by which RNA polymerase of Escherichia

coli gets switched from the initiation to elongation mode and also mapped the active
site geometry of the enzyme. He has shown that the sigma subunit is released from
RNA polymerase after it has transcribed a short transcript of 3-7 nucleotides.
Dr Virendra Nath Pandey (1947)
Award Year: 1991

Specialization: Molecular Virologist, Enzymologist , Protein
Biochemist
Address: Department of Biochemistry and Molecular
Biology International Center for Public Health, 225 Warren
Street Room E450B
Newark - 7103, New Jersey
Dr Pandey has demonstrated the presence of a DNA recombinase enzyme complex

associated with the thymic nuclear matrix of young rats. The complex specifically
occurs in prelymphocytes and is presumably involved in the rearrangement and
recombination of genes for the generation of immunodiversity in vertebrates.
Dr Srinivas Kishanrao Saidapur (1947)
Award Year: 1991

Specialization: Biology of Reproduction, Comparative
Endocrinology, Herpetology & Animal Behvior
Address:
Telephone:
Dr Saidapur has contributed to comparative endocrinology of amphibians. He

has elucidated the diverse patterns of reproductive processes and their control
mechanisms in tropical anurans.
Dr Samir Kumar Brahmachari (1952)
Award Year: 1990

Specialization: Structural Biology, Biophysical
Chemistry, Molecular Biology
Address: CSIR-Institute of Genomics & Integrative
Biology, Mathura Road
New Delhi - 110 025, New Delhi
Telephone: 011 29879304
Dr Brahamchari has made contribution in regard to functional interactions of DNA.

His work has helped to elucidate the sequence dependence of the conformation
of Z-DNA. He and his associates have shown that the action of certain restriction
endonucleases is sensitive to local conformational alterations and the Z-conformation
blocks the action of Escherichia coli DNA polymerase-1.
Dr Manju Ray (1947)
Award Year: 1989

Specialization: Tumor Biochemistry, Bioenergetics,
Enzymology, Metabolic regulation, Nano-Biotechnology
Address: Department of Biophysics Bose Institute
Centenary Building P-1/12 C I T Scheme VII M
Telephone:
Dr Ray has firmly placed methylglyoxal, a biochemical enigma for a long time, as
an integral component of carbohydrate and intermediary metabolism by isolation,
purification and characterization of a series of enzymes involved in its anabolism
and catabolism.
Dr Subhash Chandra Lakhotia (1945)
Award Year: 1989

Specialization: Genetics, Cell Biology, Developmental
Biology
Address: Department of Zoology
Banaras Hindu University
Varanasi - 221005, Uttar Pradesh
Telephone: 0542 2368145
Dr Lakhotia has made outstanding contributions to the fields of cytogenetics and

cell biology. His work has shed important light on chromosome organization and
replication in Drosophila and heat shock response at the 93D locus of Drosophila
melanogaster.
Dr Bhabatarak Bhattacharyya (1944)
Award Year: 1988

Specialization: Structural Biology, Biochemistry,
Molecular Spectroscopy
Address: Department of Biochemistry Bose Institute
Acharya J C Bose Centenary Building P- 1/12 CIT
Scheme VII M
Telephone: 033 24223812
Dr Manchanahalli Rangaswamy Satyanarayana Rao (1948)
Award Year: 1988

Specialization: Molecular Genetics, Biochemistry,
Cancer Genomics
Address: Jawaharlal Nehru Centre for Advanced
Scientific Research, Jakkur
Telephone: 080 22082754
Prof. Rao has made vital contribution towards our understanding of the molecular
mechanism of meiosis during spermatogenesis. He has identified several testis-
specific proteins which may be involved in modulating the chromatin structure.
Dr Sudhir Kumar Sopory (1948)
Award Year: 1987

Specialization: Molecular Plant Physiology, Plant Tissue
Culture, Transformation
Address: International Centre For Genetic Engineering
And Biotechnology, Aruna Asaf Ali Marg Jawaharlal Nehru
University
Telephone: E-Mail: [email protected]
Dr Sopory has done important work in the field of physiology of plant growth and
development. His researches have led to a better understanding of the mode of
action of phytochrome, and the possible involvement of calcium as a second
messenger in higher plant cells.
Dr Avadhesha Surolia (1947)
Award Year: 1987

Specialization: Protein Chemistry, Protein Folding,
Function and Design for Therapeutics
Address:
Telephone:
Dr Surolia has made important contribution to our understanding of the biological

activities of lectins. He has elucidated the steps involved in the recognition of
carbohydrates by lectins, by studying the molecular forces, thermodynamics and
specificities involved in the interaction. His findings have enhanced our understanding
of carbohydrate-mediated recognition processes in biological systems.
Dr Madhav Dhananjaya Gadgil (1942)
Award Year: 1986

Specialization: Ecology, Ecological History,
Environmental Management
Address:
Telephone:
Dr Gadgil has made significant contributions to ecology, population biology and the
theory of evolution of social behaviours.
Dr Chhitar Mal Gupta (1944)
Award Year: 1985

Specialization: Molecular Cell Biology, Biochemistry,
Bioorganic Chemistry, Biophysics
Address: Institute of Bioinformatics & Applied
Biotechnology
Room No. GF 18, Biotech Park Electronic city
Dr Gupta has made significant work aimed at gaining understanding of the basis of
phospholipid asymmetry in biological membranes.
Dr Mamannamana Vijayan (1941)
Award Year: 1985

Specialization: Structural Biology, X-Ray
Crystallography
Indian Institute of Science, Karnataka
Telephone: 080 23600765
Dr Vijayan has done significant crystallographic studies on proteins and complexes

of amino acids and other small molecules.
Dr Thavamani Jegajothivel Pandian (1939)
Award Year: 1984

Specialization: Genetics and Energetics, Aquaculture
Address:
Telephone:
Dr Pandian has done significant work in the fields of bioenergetics and animal
ecology and has developed a prediction model for transformation of food energy
into growth and metabolism.
Dr Kalpathy Ramaier Katchap Easwaran (1939)
Award Year: 1984

Specialization: Molecular Biophysics, Structural Biology,
Membrane Biophysics
Telephone: 080 40943455
Dr Easwaran has made important contribution in respect of conformational,

mechanistic and kinetic aspects of transmembrane ion transport mediated by carrier
ionophores which have led to a possible model at molecular level for transmembrane
cation transport.
Dr Govindarajan Padmanaban (1938)
Award Year: 1983

Specialization: Eukaryotic Gene Expression
Address: Department of Biochemistry

Telephone: 080 23601492
Dr Padmanaban has to his credit significant work on haemoprotein biosynthesis. His

work has helped in gaining understanding of the regulation of the biosynthesis of
cytochrome P-450 and cytochrome oxidase. His work is of importance in elucidating
the molecular basis of drug metabolism.
Dr Sunil Kumar Podder (1939)
Award Year: 1982

Specialization: Biophysical Studies on Ligand,
Macromolecule Interraction of Biological Interest
Address:
Telephone:
Dr Podder has made notable contribution on the chemical specificity of the

recognition process in biological systems. He has demonstrated that specificity
can be expressed quantitatively in terms of free energy of association of amino
acids of proteins with nucleic acid bases. He has also studied protein-carbohydrate
interaction in a model membrane system.
Dr Ramamirtha Jayaraman (1937)
Award Year: 1982

Specialization: Microbial Biology, Molecular Genetics
Address:
Telephone:
Dr Jayaraman has done significant work on the genetics of bacteria in relation

to control of transcription. His studies have provided direct genetic evidence for
the participation of accessory factors in transcription. His contributions include
interactions of these factors with RNA polymerase.
Dr Sushil Kumar (1940)
Award Year: 1981

Specialization: Genetics, Food Crops, Medical and
Aromatic Plants
Address:
Telephone:
Dr Sushil Kumar has made significant contribution in the broad area of gene
expression in Escherichia coli and its phage lambda. His principal contributions
involve the demonstration that the dispensable cAMP-receptor protein complex
determines adaptation in bacteria by controlling the structure of cell wall. His recent
contribution on mutants of Rhizobium having high nitrogen fixing ability has far-
reaching implications in agriculture.
Dr Prafullachandra Vishnu Sane (1937)
Award Year: 1981

Specialization: Plant Biochemistry, Photosynthesis,
Plant Biotechnology
Address:
Telephone:
Dr Sane has done significant work in the area of structure and function of the
cellular organelle chloroplast involved in photosynthesis. This has been achieved by
proposing the most likely locations of certain important enzymes in the thylakoid
system. His suggestion of the role of proton translocating proteins in the chloroplast
membranes has wide significance in proton movement across the membrane. His
studies on light emission from photosynthetic membranes have contributed to the
understanding of energy storage during electron transport.
Dr Jamuna Sharan Singh (1941)
Award Year: 1980

Specialization: Plant Ecology, Ecosystems, Ecology
Physio
Address: Department of Botany
Banaras Hindu University
Varanasi - 221005, Uttar Pradesh
Telephone: 0542 2368399
Dr Singh has done pioneering work in the field of ecology with reference to grassland
ecosystems, enunciating new concepts on trophic biomass relations, eco-physiology,
energy flow, diversity and mathematical modelling of tropical grasslands. His
contributions have added substantially to knowledge on the structure and function
of grassland ecosystems in general and tropical grasslands in particular, which have
important implications in their management.
Dr Asis Datta (1944)
Award Year: 1980

Specialization: Molecular Biology, Genetic engineering
& Biotechnology, Biochemistry
Address:
Telephone:
Prof. Datta has done significant work in the field of molecular biology. His work on
gene regulation in yeast using an inducible N-acetylglucosamine catabolic pathway
is a notable contribution and has advanced knowledge on the mechanism of gene
expression in eukaryotes.
Dr Maroli Krishnayya Chandrashekaran (1937)
Award Year: 1979

Specialization: Chronobiology Field Ethology, Animal
Behaviour,Neurophysiology and Human Circadian Rhythms
Address:
Telephone:
E-Mail:
Dr Chandrashekaran has done significant work on biological rhythms in plants and

animals. His work on the circadian rhythms of tropical mammals, especially the bats
which exchange ultrasonic sound information in the cave environment, has led to an
understanding of the existence of social synchronization of these rhythms. Another
notable contribution of Prof. Chandrashekaran is elucidation of ‘eclosion clock’ in
the fruit-fly Drosophila.
Dr Amar Nath Bhaduri (1935)
Award Year: 1979

Specialization: Enzymology, Parasite Biochemistry,
Parasitology
Address:
Telephone:
E-Mail:
Dr Bhaduri has made significant contributions to the study of the enzyme UDP
glucose 4-epimerase. He has thrown new light on the regulatory properties of
enzymes catalyzing freely reversible reactions. His work has led to a deeper
understanding of the molecular mechanism of allostericity. It constitutes a notable
contribution to our understanding of enzymology.
Dr Viswanathan Sasisekharan (1933)
Award Year: 1978

Specialization: Biomolecular structure, Chemical
Physics, Quantum chemistry
Address: Department of Chemical Engineering
Massachusettes Institute of Technology
Cambridge - 2139, MA
Telephone: +1 781 5384045
Dr Sasisekharan has done significant work on the conformation of biopolymers,

specially polynucleotides and polypeptides. He has developed incisive methods
for arriving at optimal conformations of macromolecules. These methods have led
him to suggest an alternative model for the Watson-Crick double helical structure
of DNA. This model permits separation of polynucleotides without uncoiling and
provides a novel solution to an unsolved paradox in biology.
Dr Trichnopoly Chelvaraj Anand Kumar (1936)
Award Year: 1977

Specialization: Reproductive Biology, Fertility Regulation,
Neuroendocrinology, Primate Biology, Electron Microscopy
Address:
Telephone:
E-Mail:
Dr Anand Kumar has to his credit major contribution in the area of neuro-
endocrinology of primate reproduction. He has demonstrated the presence of
gonadal hormones in the cerebro-spinal fluid (csf) and their transport to the brain.
His work on fertility regulation, especially the administration of contraceptive
steroids through the nasal route which results in their preferential transfer into the
csf, is of distinct advantage in developing newer approaches to contraception.
Dr Kishan Singh (1931)
Award Year: 1976

Specialization: Plant Pathology, Phytonematology, Plant
Protection in Sugarcane
Address:
Telephone:
E-Mail:
Dr Singh has to his credit major contribution in sugarcane pathology and has
organized under his leadership active teams of applied research in the field of
sugarcane cultivation. His work in crop pathology covers a wide canvas, including
viruses, mycoplasmas, fungi and nematodes. Of special significance are his
contributions on epidemiology and control of sugarcane diseases, association of
mycoplasma with grassy shoot disease and its control by hot air therapy.
Dr Guru Prakash Dutta (1933)
Award Year: 1976

Specialization: Protozoology Cell Biology, Malaria,
Amoebiosis, Leishmaniasis, Immunology, Drug Research
Address:
Telephone:
Dr Dutta’s work has been aimed at getting an understanding of the functional

morphology of the various components of the protozoa. He has developed new
techniques for their culture. He has also elucidated the metabolic and growth
responses of several micro-organisms, including Entamoeba histolytica, to various
physico-chemical factors. Dr Dutta’s main field of activity has been experimental
protozoology.
Dr Archana Sharma (1932)
Award Year: 1975

Specialization: Genetics Chromosomes, Genetic
Toxicology
Address:
Telephone:
E-Mail:
Dr (Mrs) Sharma has done significant work on chromosomes of plant and human
systems, with special reference to differentiation and mechanisms of evolution. New
techniques developed by her for studies on chromosomes have had a significant
impact in the field of plant and human genetics.
Dr Obaid Siddiqi (1932)
Award Year: 1975

Specialization: Genetics Neurobiology
Address:
Telephone:
E-Mail:
Dr Siddiqi has done significant work in molecular biology with special reference to
transfer and recombination of DNA in micro-organisms and genetic regulation of
protein synthesis. His studies have helped in clarifying the relationship between
DNA replication and recombination.
Dr John Barnabas (1929)
Award Year: 1974

Specialization: Molecular Evolution
Address:
Telephone:
E-Mail:
Dr Barnabas has made important contributions in the field of evolutionary genetics

through his studies on the sequences of amino acids in hemoglobin of mammals.
His work has contributed to having a deeper understanding of evolution. Prof.
Barnabas has developed methods which make it possible to use molecular structure
to measure evolutionary distance as well as rates of evolutionary change. His work
is marked by experimental ingenuity and incisiveness.
Dr Bhyravabhotla Radhakrishna Murty (1928)
Award Year: 1973

Specialization: Biometry Genetics, Radiation Genetics
Address:
Telephone:
E-Mail:
Dr Murty, an outstanding biometrical geneticist, has developed a new school of

thought utilizing multivariate analysis for assessment of genetical divergence
of crops with different breeding systems. His basic approach on the selection of
developmental traits in both self- and cross-pollinated crops has helped considerably
in the improvement of grain quality, disease resistance and productivity of
agricultural crops.
Dr Sardul Singh Guraya (1930)
Award Year: 1973

Specialization: Reproductive Physiology Cell and
Development Biology
Address:
Telephone:
E-Mail:
Dr Guraya’s main contributions have been in the fields of cell biology and
reproduction. Dr Guraya’s work on histology and ultra-structure of the mammalian
ovary has thrown light on folliculogenesis and steroidogenesis. His research on
follicular atresia has enabled gaining understanding of the buiding up of interstitial
tissue and the latter’s part in hormone formation.
Dr Birendra Bijoy Biswas (1928)
Award Year: 1972

Specialization: Nucleic Acid Matabolism, Plant
Biochemistry and Genetic Engineering
Address:
Telephone:
Dr Biswas has done significant work on regulation of RNA and protein synthesis in
the cell, particularly plant cell. He has contributed to understanding the metabolic
cycle involving glucose-6-P and myoinositol phosphates during the formation and
germination of seeds. His studies have opened up new vistas in the transcription
process in higher organisms as well as in the regulation of some of the enzyme
functions in relation to biosynthesis of inositol phosphates.
Dr Satish Chandra Maheshwari (1933)
Award Year: 1972

Specialization: Plant physiology, Biochemistry, Plant
Molecular biology and Botany
Address: School of Life Sciences
Jaipur National University, Jagatpura
Jaipur - 302025, Rajasthan
Telephone: 0141 2573377
Dr Maheshwari has made significant contribution in plant and cell physiology,

particularly in the physiology and biochemistry of growth and differentiation in
plants. His researches have led to isolation of cytokinins and gaining understanding
of their role in flowering. Dr Maheshwari and his group have recently discovered
the technique of raising haploid plants by anther culture. Development of haploids
by anther and pollen culture technique makes possible the establishment of
homozygous lines in plants and opens the area of biochemical genetics of higher
plants.
Dr Narayana Balakrishnan Nair (1927)
Award Year: 1971

Specialization: Fisheries Ecology, Marine Conservation,
Management of Aquatic Resources.
Address:
Telephone:
E-Mail:
Dr Balakrishnan Nair has carried out extensive researches on marine fouling

organisms. During the past five years, he has made outstanding contribution to our
knowledge on the wood-boring molluscs, particularly the mechanism of boring of
timber by them.
Dr Madhu Sudan Kanungo (1927)
Award Year: 1971

Specialization: Biochemistry, Molecular Biology
Address:
Telephone:
E-Mail:
Dr Kanungo has to his credit certain new approaches to the study of the changes
in some key enzymes of the brain, heart, muscle and liver of the rat in relation to
ageing processes. He has been able to identify the changes in the qualitative nature
of enzymes, their modulation by various regulators, and induction and repression of
their syntheses by hormones as the function of age.
Dr Tathamangam Ananthanarayanan Venkitasubramanian (1924)
Award Year: 1968

Specialization: Biochemistry of Tubercle Bacilli
Address:
Telephone:
E-Mail:
Dr Venkitasubramanian has done pioneering systematic investigations in India

on the lipid metabolism of different strains of Tubercle bacilli. His researches on
experimental tuberculosis have added significantly to knowledge on the biochemical
pathology of the disease. These investigations help in early diagnosis of tuberculosis
and in evolving effective chemotherapeutic agents. Studies carried out by him on
cheap and commonly available plant proteins have useful implications in tackling
the problem of protein malnutrition. He has developed several new and simple
laboratory techniques for the analysis of biologically important compounds.
Dr Arun Kumar Sharma (1924)
Award Year: 1967

Specialization: Cytogenetics, Cytochemistry, Cell
biology
Address:
Telephone:
Dr Sharma has built up an active school of research on cytogenetics and

cytochemistry. He and his colleagues have developed a number of new techniques
for the study of detailed chromosome structure of plants. A new concept of
speciation in plants reproducing through sexual means has been developed and
established by his group. He was able to induce division in adult nuclei through the
application of chemicals and this has importance in cell rejuvenescence.
Dr Neelamraju Ganga Prasada Rao (1927)
Award Year: 1966

Specialization: Plant Bbreeding and Genetics
Address:
Telephone:
E-Mail:
Dr Rao has made important contribution in the field of sorghum breeding, leading
to the release of the first commercial sorghum hybrids, CSH-1 and CSH-2 in India.
Subsequently, a high yielding variety, Swarna, that equalled the commercial hybrid
CSH-1 in yield levels, was developed and released for general cultivation. The
performance of the first hybrids, following their release, demonstrated that the
average yields of this rain-fed crop could be stabilized at 2000-2500 kg/hectare
as against the national average of only 400-500 kg/hectare. Maximum yields of
the order of 7000 kg/hectare were recorded under optimum conditions. These
hybrids also performed well in several African, South East Asian and Latin American
countries. The advent of the hybrids has given rise to an organized hybrid sorghum
seed industry in both public and private sectors.
Dr Hari Krishan Jain (1930)
Award Year: 1966

Specialization: Cytogenetics and Plant Breeding
Address:
Telephone:
Dr Jain has made extensive contribution in the field of genetic recombination, including its
mechanism and regulation, more particularly its control at interchromosome level. A new
hypothesis on such a control has been developed and considerable experimental evidence
has been obtained in support of it. Dr Jain’s work on tomato and later on Drosophila has
provided what is regarded as perhaps the first convincing evidence in support of the
phenomenon of mutagen specificity. Manipulation of mutation rates and spectrum has been
one of the main objectives of contemporary mutation research. Dr Jain’s work has been an
important contribution in this direction. His other studies relate to the synthesis of RNA
in plant cells, more particularly the demonstration of hyperactive nature of the nucleolus-
organizing in this synthesis.
Dr Chirayathumadom Venkatachalier Subramanian (1924)
Award Year: 1965

Specialization: Mycology, Plant Pathology Evolution
Address:
Telephone:
Dr Subramanian has made significant contributions on taxonomy of Fungi

imperfecti. His systematic exploration of the hyphomycete flora of India led to the
discovery of many new and interesting genera. He has proposed a new system of
classification of Hyphomycetes based on conidium ontogeny. His studies on and
original interpretations of conidium ontogeny based on cell-wall relationships have
led to the formulation of a terminology based on new concepts. Dr Subramanian is
well known for his work on soil mycology and soil-borne plant diseases, and for his
contributions to knowledge on the systematics, distribution and ecological behaviour
of soil Fusaria, and on the nutritional physiology, mainly nitrogen utilization of plant
pathogenic species of Fusarium and Drechslera.
Dr Dilbagh Singh Athwal (1928)
Award Year: 1964

Specialization: Genetics & Plant Breeding
Address:
Telephone:
E-Mail:
Dr Athwal has made important contribution to knowledge on genetics of rust

resistance in wheat. His contribution relate to the genetics and breeding of pearl
millet, gram, wheat and tobacco, the most outstanding being the development of the
first commercial hybrid in bajra. Hybrid Bajra No. 1 developed by him has demonstrated
its potential to give nearly double the yield obtained from the traditional variety and
heralds a new era in the cultivation of this important foodgrain. The cytoplasmic
male sterile lines and a large number of genetic stocks developed by him will make a
significant contribution in future research on bajra breeding and genetics.
Dr Jagannath Ganguly (1921)
Award Year: 1963

Specialization: Lipids Biochemistry
Address:
Telephone:
E-Mail:
Dr Ganguly is internationally known for his work on the metabolism of vitamin A,

biosynthesis of fatty acids and intestinal absorption of lipids.
Dr Bimal Kumar Bachhawat (1925)
Award Year: 1962

Specialization: Biochemistry, Neurochemistry,
Liposomes Immunology
Address:
Telephone:
E-Mail:
Dr Bachhawat has contributed to knowledge on the metabolism of

mucopolysaccharides, gangliosides and cerebrosulphatides, especially in relation to
brain function.
Dr Monkombu Sambasivan Swaminathan (1925)
Award Year: 1961

Specialization: Genetics, Cytogenetics Plant Breeding
Address: MS Swaminathan Research Foundation

3rd Cross Street, Taramani Institutional Area
Chennai - 600113, Tamil Nadu
Telephone: 044 22542790
Dr Swaminathan has set up a well-known school of research in the field of radiation
genetics and mutation research at the Institute. His original contributions (1948-58)
include elucidation of the origin of potato, dwarf coconut and bread wheat, nuclear
cytology of yeasts, classification and genetics of polyploid plants, monosomic analysis in
wheat, elucidation of the role of infection in heredity, relationship between chromosome
associations and seed fertility in autopolyploids and standardization of techniques for
overcoming interspecific incompatibility barriers. His later contributions (1959-64)
relate to experimental manipulation of genes in a purposeful direction. This work has
involved the introduction, selection and hybridization of a wide range of dwarf material
by wheat containing the Norin dwarfing genes from Mexico and the use of a wide array
of mutagens, both physical (X-rays, gamma-rays, fast and thermal neutrons, and beta
particles) and chemical (alkylating agents and free radicals).
Dr Toppur Seethapathy Sadasivan (1913)
Award Year: 1960

Specialization: Physiological Plant Pathology, Soil
Microbiology
Address:
Telephone:
E-Mail:
Dr Sadasivan is well known for his work in mycology and plant pathology. His work
on fungal wilts has attracted wide attention. His research work has considerable
bearing on such fundamental concepts as production of toxins and antibiotics in soil
and in the rhizosphere of plants and the changes in the physiology of the host. His
recent studies concern the occurrence of blast disease of rice and its relationship
with night temperatures. This has explained the hitherto unsolved problems of the
causes of breakdown of resistance in rice to blast.
Section 2 – Medical Sciences
Dr Bushra Ateeq (1976)
Award Year: 2020

Discipline: Medical Sciences
Specialization: Cancer Biology and Molecular Oncology
Address: Department of Biological Sciences &

Bioengineering, Indian Institute of Technology Kanpur
Kanpur - 208016, Uttar Pradesh
Telephone:
Established the oncogenic role of Serine Protease Inhibitor Kazal Type-1 (SPINK1)
in colorectal cancer and unraveled its role in metabolic regulation. Her work has
highlighted how Androgen Deprivation Therapy aggravates prostate cancer instead
of curing. Her current research is focused on unraveling the molecular mechanisms
underlying Distal-less homeobox (DLX) gene family mediated prostate cancer,
which is expected to help in developing novel therapeutic strategies for a particular
subtype of prostate cancer.
Dr Ritesh Agarwal (1975)
Award Year: 2020

Specialization: Allergic Pronchopulmonary Aspergillosis
Address: Department of Pulmonary Medicine Postgraduate

Institute of Medical Education and Research, Sector 12
Chandigarh - 160012, Punjab
Telephone:
Dr Ritesh Agarwal has made outstanding contributions in the field of Allergic

Broncho Pulmonary Aspergillosis (ABPA). His research showed that lower doses of
glucocorticoids are sufficient. Through well conducted randomized controlled trials,
he also showed that Azole Monotherapy is useful in treatment of ABPA.
Dr Dhiraj Kumar (1978)
Award Year: 2019

Specialization: Immunology, Cell Biology
Address: Cellular Immunology Group, International

Centre For Genetic Engineering And Biotechnology,
New Delhi - 110067, Delhi Telephone: +91-11-26741358
The major focus of his lab is to understand the innate defense mechanisms in
response to pathogenic infections like Mycobacterium tuberculosis (Mtb) or HIV.
His group has established an exciting concept of selectivity in autophagy (a cellular
homeostatic mechanism), showing uncoupling between the homeostatic arm and
anti-mycobacterial arm of autophagy within the cell. His group has also developed
analytical tools to understand the complex nature of transcriptional reprogramming
in the macrophages in response to Mtb infections using next-generation RNA-seq
approach.
Dr Mohammad Javed Ali (1977)
Award Year: 2019

Specialization: Dacryology
Address: Govindram Seksaria Institute of Dacryology

L.V. Prasad Eye Institute, Road No 2 Banjara Hills
Telephone: +91-040-68102020
The Shanti Swarup Bhatnagar Prize for the year 2019 in Medical Sciences has been
awarded to Dr Mohammed Javed Ali of L V Prasad Eye Institute, Hyderabad, for his
SEMINAL contribution to the field of DACRYOLOGY, the science of tear ducts. He
has described new diseases entities related to the lacrimal glands, their pathology,
novel diagnostics and treatments.
Dr Ganesan Venkatasubramanian (1975)
Award Year: 2018

Specialization: Psychiatry
Address: Department of Psychiatry, National Institute of

Mental Health and Neurosciences, Hosur Road
Telephone: 08026995256
He has made significant contributions in the fields of Clinical cognitive neuroscience

and Psychopharmacology and has extensively worked in the area of evolutionary
biology of human brain with respect to psychiatric disorders and exceptional
skills. His contributions in the pathogenesis of Schizophrenia and its management
including the development of indigenous machine-learning algorithm “EMPaSchiz”
that learns, from a training set of schizophrenia patients and healthy individuals are
well recognized.
Dr Amit Dutt (1973)
Award Year: 2017

Specialization: Cancer Genomics: interpretation, charac-
terization, and translation of genomic discoveries to clinics
Address: Tata Memorial Centre
Sector 22 Kharghar
Navi Mumbai - 410210, Maharashtra
Telephone: 022 2740 5050
His group has made significant contributions in the genetics of FGF receptor family
in lung cancer, including the identification of novel mutations in Indian patients.
They have developed a computational pipeline, HPV detector to detect the presence
of HPV DNA sequences in human clinical cancer samples and detect the presence
of non-typhoidal Salmonella in gallbladder cancer. His group recently developed
“TMC-SNPdb” - the first Indian germline SNPd.
Dr Deepak Gaur (1972)
Award Year: 2017

Specialization: Malaria Parasite Biology and Vaccine
Development
Address: School of Biotechnology, Jawaharlal Nehru
University, New Mehrauli Road Munirka
Telephone: 011 2673 8892
His group discovered a multiprotein adhesion complex on Plasmodium falciparum,

the malaria causing parasite that helps the parasite to invade red blood cells. This
discovery has the potential in the development of a vaccine against the parasite by
developing antibodies which blocks the antigen that assists the parasite to penetrate
red blood cells of the host. His current research foci include the development of a
nano-formulation of the drug for anti-malaria therapy.
Dr Niyaz Ahmed A S (1971)
Award Year: 2016

Specialization: Medical Microbiology and Infectious
Diseases
Address: Department of Biotechnology and Bioinformatics,
School of Life Sciences, South Campus University of
Hyderabad, Prof. C R Rao Road, Gachibowli
Hyderabad - 500 046, AP Telephone: 040 6679 4585
Ahmed has made impactful contributions in the functional epidemiology of chronic

pathogens like enteropathogenic bacteria and mycobacterium tuberculosis by
combining genome inspired epidemiology and decipherment of bacterial virulence
mechanisms. His group has also developed a widely used multi-locus sequence
typing scheme for species level identification of pathogenic Leptospira with a
potential to replace the highly ambiguous serotyping method that currently is used
for Leptospiral strain identification.
Dr Vidita Ashok Vaidya (1970)
Award Year: 2015

Address: Department of Biological Sciences, Tata Institute

of Fundamental Research, 1, Homi Bhabha Road, Colaba
Mumbai - 400005, Maharashtra
Telephone: 022-22782608
Dr Vaidya has made outstanding contributions in identifying specific norepinephine and thyroid
hormone receptors as targets for rapid-action antidepressants. She has also demonstrated the
role of serotonin2A receptors and histone deacetylase4 in anxiety and depression. The primary
focus of her research is to study the neuro-circuits that regulate emotion and the influence of
life experiences, and antidepressants. Discovered that serotonin (a neurotransmitter) boosts
energy production in brain cells by increasing the number of mitochondria and helps them
execute cellular functions, including deal with stress and survive better. This new knowledge
can potentially be used to develop anti-stress drugs in the future. She also investigates how
changes in brain circuits form the basis of psychiatric disorders like depression and how early
life experiences contribute to persistent alterations in behavior.
Dr Anurag Agrawal (1972)
Award Year: 2014

Specialization: Lung Diseases, Mitochondrial
Dysfunction, Asthma, Intelligent Systems.
Address: CSIR -Institute of Genomics and Integrative
Biology, Mall Road
Delhi - 110007, Delhi
Telephone: 011 2766 7298
Dr Agrawal has made outstanding contributions in establishing a functional

link amongst obesity, mitochondrial dysfunction and asthma, elucidating the
mechanism of stem cells donating new mitochondria to dysfunctional human lung
cells. His area of research encompasses lung diseases, asthma and functional issues
related to mitochondria and his work has established a functional link between the
three diseases, elucidating how stem cells donated mitochondrial cells to human
dysfunctional lung cells to restore function.
Dr Pushkar Sharma (1969)
Award Year: 2013

Specialization: Malaria, Signaling, Apoptosis

Aruna Asaf Ali Marg
Telephone: 011 26703791
Dr. Pushkar Sharma has demonstrated signaling and trafficking pathways in malaria
parasite (Plasmodium falciparum), envisaged to be useful in the design of novel
strategies to develop effective antimalarials. His group has also unraveled signaling
pathways involving cyclin D1 in Cell cycle Related Neuronal Apoptosis (CRNA; a
form of programmed cell death) involved in neurodegeneration, which is expected
to facilitate the management of neurodegenerative disorders.
Dr Sandip Basu (1971)
Award Year: 2012

Specialization: Nuclear Medicine
Address: Nuclear Medicine Centre, Bhabha Atomic

Research Centre, Tata Memorial Hospital Annexe Jerbai
Wadia Road, Parel
Dr Sandip Basu has made outstanding contribution in the field of nuclear medicine
by innovation in integrating functional radionuclide imaging and therapy for
individualized management of patients and for expanding the applicability of
position emission tomography. His group has carried out extensive clinical work
in developing novel approaches of using Positron emission tomography (PET) for
diagnostics and also developed innovative approaches in Targeted Radionuclide
Therapy in Cancer. These efforts have resulted in the optimizing personalized
treatment of cancer by individualizing the management strategy.
Dr Kithiganahalli Narayanaswamy Balaji (1966)
Award Year: 2011

Specialization: Pathogenic Mycobacteria (Mycobacterium
tuberculosis, M. bovis, M. bovis BCG), Infectious diseases, I
Address: Department of Microbiology and Cell Biology
Telephone: 080 2293 3223
Made contribution for characterization of fundamental principles of plasticity

associated with signaling transduction mechanism in immune cells utilizing
mycobacteria as a model and demonstrated the cross talk between Notch Signaling
and nitric oxide.
Dr Mitali Mukerji (1967)
Award Year: 2010

Specialization: Genomics, Human Molecular Genetics,
Ayurgenomics
Address: Genomics and Molecular Medicine, Institute
of Genomics and Integrative Biology, Sukhdev Vihar
Mathura Road
Delhi - 110 025, Delhi
Dr Mitali Mukerji has made outstanding contribution to genomics, particularly in

deciphering the genome underpinnings of some important neurological disorders.
She has also provided leadership and important insights into the genomic diversity
of the people of India, with profound implications on disease-association studies.
Dr Santosh Gajanan Honavar (1965)
Award Year: 2009

Specialization: Tumours of the ocular surface, Eyelid and
orbit, Retinoblastoma, Ptosis and Pediatric lacrimal disorders
Address: Ophthalmic and Facial Plastic Surgery, Orbit
and Ocular Oncology Centre for Sight Superspeciality Eye
Hospital, Road No 2 Banjara Hills
Hyderabad - 500034, Hyderabad
Dr Honavar has made seminal contribution to the management of advanced retinoblastoma

with dramatically improved patient survival, eye salvage, and visual recovery. His work on high-
dose chemotherapy and periocular chemotherapy for advanced intraocular retinoblastoma,
adjuvant therapy to minimize the risk of metastasis in patients with high-risk features, and
multimodal management of orbital retinoblastoma have been recognized worldwide. His
research work on retinoblastoma, tumors of the ocular surface, and orbit has made a very
significant impact on the diagnosis and management of retinoblastoma and its outcome. He
also established the comprehensive Ocular Oncology Service at the LV Prasad Eye Institute,
Hyderabad; the first of its kind in the country
Dr Ravinder Goswami (1963)
Award Year: 2008

Specialization: Autoimmune Endocrine Disorders, Sporadic
Idiopathic Hypoparathyroidism and Metabolic Bone
Address: Department of Endocrinolgy & Metabolism
All India Institute of Medical Sciences, Ansari Nagar
Telephone: 011 26594272
Dr Ravinder Goswami is recognized for his significant contribution in the field of clinical
endocrinology with particular reference to lypocalcemic disorders. His research work has
documented the prevalence, significance and causes of vitamin D deficiency in apparently
healthy individuals for the first time in India. His work on sporadic idiopathic hypoparathyroidism
has provided valuable information on the etiopathogenesis and clinical feature of this disorder
prevalent in India. He has made immense contribution on in understanding the clinical
implications of vitamin D deficiency including etiopathogenesis and gravity of the disorder
across the population and his work was the first of its kind in India. His work on diseases
such as hypocalcemia and idiopathic hypoparathyroidism is universally well recognized. His
research has revealed that vitamin D deficiency among Indian population is linked to the dark
skin which prevents the formation of vitamin D by blocking ultra violet rays as well as inhibition
of over-expression of calcitriol receptor gene, resulting in inadequate bio-adaptation. He is
a prominent advisor of exposure to sunlight as a remedial measure for treating vitamin D
deficiency and against treating the nutritional deficiency through supplements.
Dr Pundi Narasimhan Rangarajan (1963)
Award Year: 2007

Specialization: Eukaryotic Gene Expression, Infectious
Diseases
Address: DNA vaccine development.
Department of Biochemistry, Indian Institute of Science
Telephone: 080 23601492
Dr Rangarajan has made outstanding contribution towards understanding gene expression

changes induced by neurotropic viruses as well as DNA vaccine development. His research
focused on unraveling the mechanism of transcriptional regulation of alcohol oxidase (AOX)
gene has identified Mxr1p response elements (MXREs) which binds with a key transcription
factor called Mxr1p and activates transcription, besides the identification of additional
transcription factors Rop1p and Trm1p in regulating AOXI expression. His group also
unraveled the moon-lighting function(s) of methionine synthase, a crucial enzyme involved
in the biosynthesis of methionine in the nucleus of P. pastoris. They also identified a novel
post-transcriptional regulator Rtg1p, which functions as a nuclear transcription factor in
Saccharomyces cerevisiae but acts as a cytosolic regulator in P. pastoris.
Dr Virender Singh Sangwan (1964)
Award Year: 2006

Specialization: Biology Surgery
Address: Dr Shroff Charity Eye Hospital

Daryaganj
New Delhi - 110 002, Delhi
Telephone:
Dr. Sangwan has made outstanding contribution to the application of limbal stem
cell biology to restore vision to victims of corneal injury. He is an established leader
in Limbal Stem Cell research, Ocular Surface and Uveitis. He is a pioneer in using
small explants of the cornea to treat limbal stem cell deficiency (LSCD) that could
provide a solution for surgeons who did not have access to the technique of cultured
limbal epithelial stem cells.
Dr Javed Naim Agrewala (1961)
Award Year: 2005

Specialization: Immunology, Tuberculosis
Address: Centre for Biomedical Engineering

Indian Institute of Technology Ropar
Rupnagar - 140 001, Punjab
Telephone:
Dr Agrewala has made significant contribution in understanding the bi-directional regulation of Th1
and Th2 cells. He has developed a novel and unique vaccination strategy for inducing protective
immunity in Mycobacterium tuberclosis (Mtb) infection. His research work has established that …
can be effectively exploited to develop immunotherapy either using humanized antibodies against
CD80 or CD86 or CD28 fusogenic proteins for the treatment of refractory lymphomas (a type of
cancer) and intracellular pathogens. His research has also helped in designing immunotherapies
that can reinvigorate T-cell potency to protect patients from TB. They also established the
potential role of 16 kDa antigen of Mtb in latency, its expression, regulation, and implication in host
immune response, highlighting the scope of employing 16 kDa in early diagnosis, development
of vaccine and as a potential drug target. His group has recently engineered a multi-epitope-
based DNA vaccine (C6) based on studies using immunodominant CD4 and CD8 T cell epitopes
of Mycobacterium tuberculosis expressed during latent, acute, and chronic stages of infection.
Dr Chetan Eknath Chitnis (1961)
Award Year: 2004

Specialization: Molecular Parasitology, Malaria
Vaccines, Molecular and Cell Biology
Address: Malaria Parasite Biology and Vaccine
Institut Pasteur, 28, Rue Du Dr Roux
Paris - 75 015, FRANCE
Telephone: +33-1 4438 9428
Dr. Chitnis has made outstanding contribution in the area of the biology of malarial
infection. His work has provided a considerable understanding on the receptor-
ligand interactions that mediate the host cell invasion process and cytoadherance
by malarial parasites which can facilitate the development of intervention strategies
to inhibit red cell invasion and block blood stage parasite growth. He has applied
this knowledge to develop novel vaccine concepts for Plasmodium vivax and
Plasmodium falciparum malaria. Currently, his group is developing recombinant
vaccines based on functional receptor-binding domains of parasite proteins that
mediate critical interactions with host receptors to facilitate invasion.
Dr Chinmoy Sankar Dey (1961)
Award Year: 2003

Specialization: Cell Biology, Molecular Biology, Insulin
Signalling, Diabetes, Drug Resistance in Lieshmania
Address: School of Biological Sciences
Indian Institute of Technology Delhi, Hauz Khas
Telephone: 011 2659 7523
Dr Dey has made a seminal contribution by developing a novel in vitro model of

insulin resistance. His discovery has potential in molecular target-based screening
of new anti-diabetic drugs.
Dr Anil Kumar Mandal (1958)
Award Year: 2003

Specialization: Paediatric Glaucoma
Address: Jasti V Ramanamma Children’s Eye Care

Centre, LV Prasad Eye Institute
Telephone: 040 30612345
Dr. Mandal has developed an alternative and innovative mode of surgical treatment
for paediatric glaucoma and has contributed to a molecular genetic analysis of
primary congenital glaucoma. He has developed an integrated approach for treating
glaucoma comprising the choice of appropriate surgical method, preservation of
residual vision, genetic analysis and genetic counseling. His research work has
resulted in widening the understanding of glaucoma at large and particularly the
developmental and pediatric glaucoma.
Dr Sunil Pradhan (1957)
Award Year: 2002

Specialization: Neurology, Neuromuscular Diseases
Address: Department of Neurology. Sanjay Gandhi

Postgraduate Institute of Medical Science, Raebareli Road
Lucknow - 226014, Uttar Pradesh
Telephone: 0522 249 5006
Dr Sunil Pradhan has made outstanding contribution in the field of clinical neurology,
described some new signs, elaborated the pathogenic mechanism of a number of
neurological syndromes, utilizing the most recent technologies.
Dr Birendra Nath Mallick (1956)
Award Year: 2001

Specialization: Neurobiology, Physiology, Sleep-
Wakefulness
Address: School of Life Sciences, Jawaharlal Nehru
University, New Mehrauli Road
Telephone: 011 26704522
Dr Mallick has made significant contributions in the area of neural mechanisms of

sleep and his work on the generation and regulation of REM sleep which combines
electrophysiological and biochemical studies has received wide acclaim both
nationally and internationally. His research work has established that the increased
production of noradrenaline activates neuronal Na+/K+-ATPase, triggering REM
sleep-loss and resultant brain excitability. He work has also shown that loss and/ or
disturbance of REM sleep is associated with several somatic, psychic, developmental,
and other disorders.
Dr Shahid Jameel (1957)
Award Year: 2000

Specialization: Molecular Virology, Molecular Biology
Address: The Welcome Trust, DBT India Alliance

1110 DLF Tower B Jasola
Telephone: 011 4100 8402
Dr Jameel has carried out pioneering research related to the molecular bass
of hepatitis E virus (HEV) and human immunodeficiency virus (HIV) infections.
He has made novel contributions in identifying the routes of transmission and
molecular characterization of HEV and Indian variants of HIV. His work has helped
in increasing our understanding of the structural and functional biology of HEV
and HIV which has contributed to the development of better modes of diagnosis
and immunoprophylaxis. His group is also credited with the identification of HIV-1
subtype C as the most prevalent form of HIV infection in India, which is useful in the
management of the infection.
Dr Chintalagiri Mohan Rao (1954)
Award Year: 1999

Specialization: Biomedical science, Molecular Biology,
Biophysics
Address: CSIR-Centre for Cellular and Molecular Biology
Uppal Road
Telephone: 040 27195631
Dr Mohan Rao’s major research contribution has been in the area of protein folding
with special reference to lens protein and cataract formation. He has unraveled the
details of the molecular chaperone-like activity of a-crystalline, a protein present in
the lens, heart, brain and kidney. He has shown that this activity can be enhanced
several fold, which has a potential to prevent or delay cataract and other protein-
aggregation-related complications.
Dr Gopinath Balakrish Nair (1954)
Award Year: 1998

Specialization: Medical Molecular Microbiology, Molecular
Epidemiology, Diarrhoeal Diseases
Address: Microbiome Laboratory, Rajiv Gandhi Centre for
Biotechnology, Melarannoor Road Poojapura, Thycaud
Thiruvananthapuram - 695014, Kerala
Telephone: 0471 2529400
Dr Nair has done outstanding work for characterizing a novel toxin in Vibrio cholerae
and identifying and characterizing a new serogroup 0139 causing a cholera pandemic.
Dr Satish Kumar Gupta (1953)
Award Year: 1997

Specialization: Immunology, Reproductive Biology,
Reproductive Immunology
Address: Reproductive Cell Biology Lab, National Institute
of Immunology, Aruna Asaf Ali Marg JNU Complex
Telephone: 011 26741249
Dr Gupta has contributed to the development of indigenous diagnostic reagents

of medical importance and has done outstanding work on the possible use of zona
pellucida proteins in designing immunocontraceptive measures.
Dr Vijay Kumar (1954)
Award Year: 1997

Specialization: Molecular Biology and Hepatitis
Address: Department of Molecular and Cellular Medicine,

Institute of Liver and Biliary Sciences, D-1, Vasant Kunj
Telephone: 011 46300000
Dr Kumar has contributed to basic understanding of the transactivator domain

of the X protein of the hepatitis B virus. He has been instrumental in technically
assembling the multiepitope protein gene for hepatitis B virus. These have led to
significant understanding of the basic immunology and biology of hepatitis B virus.
Dr Vijayalakshmi Ravindranath (1953)
Award Year: 1996

Specialization: NeuroScience, Toxicology,
Pharmacology
Address: Centre for Neuroscience
Telephone: 080 22933433
Dr Ravindranath is known for her pioneering work on the xenobiotic metabolizing

capability of the brain, with special reference to environmental toxins and
psychoactive drugs.
Dr Shiv Kumar Sarin (1952)
Award Year: 1996

Specialization: Medicine, Gastroenterology, Hepatology
Address: Institute of Liver and Biliary Sciences

D-1, Vasant Kunj
Telephone: 011 4630 0000
Dr Sarin has done original extensive work, clinical and experimental, in the field of
liver diseases, especially portal hypertension.
Dr Anil Kumar Tyagi (1951)
Award Year: 1995

Specialization: Biochemistry, Molecular Biology,
Microbiology
Address: Guru Gobind Singh Indraprastha University
Sector 16C, Dwarka, New Delhi
Telephone: 011 2530 2104
Dr Tyagi has made outstanding contributions towards characterization of

mycobacterial transcriptional signals and developing several vectors for studying
molecular genetics and gene expression. In addition, his work on the identification
of a new gene from M. tuberculosis and its association with pathogenesis of the
disease is of great importance.
Dr Subrat Kumar Panda (1954)
Award Year: 1995

Specialization: Viral Hepatitis, Molecular Virology,
Pathology
Address: Department of Pathology
All India Institute of Medical Sciences
Telephone:
Dr Panda has made outstanding contribution in the field of viral hepatitis. In

particular, he has demonstrated the transmission of Hepatitis E virus in Rhesus
monkeys and its association with severe liver disease and protracted viremia.
Dr Yagya Dutta Sharma (1951)
Award Year: 1994

Specialization: Molecular Biology of Malaria, Protein
Chemistry
Address: Department of Biotechnology, All India
Institute of Medical Sciences, Ansari Nagar
Telephone: 011 26594609
Dr Sharma has made outstanding contribution to molecular biology of malaria. He

has constructed a genomic library of a noncultivable parasite - P. vivax - which is
an important pathogen for India. He has isolated and characterized immunologically
relevant recombinant antigens of P. vivax and P. falciparum which are important
for the understanding of host-parasite interaction and for the development of
immunotherapeutic reagents.
Dr Krishna Balaji Sainis (1949)
Award Year: 1994

Specialization: Cellular Immunology
Address: Bhabha Atomic Research Centre

Trombay
Telephone: 022 25593781
Dr Sainis has made outstanding contribution to immunobiology. He has studied the

role of subsets of T cells and their receptors in influencing immune response to DNA
in lupus nephritis and mycobacterial antigens.
Dr Gaya Prasad Pal (1950)
Award Year: 1993

Specialization: Spine Clinical Anatomy
Address: Department of Anatomy

MGM Medical College
Indore - 452 001, Madhya Pradesh
Telephone:
Dr Pal has made original contribution in the field of biomechanics and load
transmission of human spine. He has shown that besides vertebral bodies and
intervertebral discs, the vertebral arches and their zygapophyseal joints also play
an important role in weight transmission. Dr Pal’s studies on the biomechanics of the
thoracic skeleton have helped to understand the mechanism of idiopathic scoliosis.
Dr Undurti Narasimha Das (1950)
Award Year: 1992

Specialization: Internal Medicine, Clinical Immunology
Address: Bio-Science Research Centre

Gayatri Vidya Parishad College of Engineering
Visakhapatnam - 530048, Andhra Pradesh
Telephone: 0891 273 9507
Dr Das has shown that cis-unsaturated fatty acids are tumoricidal in vitro. He has
demonstrated that gamma linolenic acid arrests human gliomas. This observation
has possible clinical applications.
Dr Narinder Kumar Mehra (1949)
Award Year: 1992

Specialization: Histocompatibility and Immunogenetics,
Transplant Immunogenetics
Address: All India Institute of Medical Sciences
Telephone: 011 26549170
Dr Mehra has made significant contribution in the subject of ‘histocompatibility and

immunogenetics’ and has identified the role of HLA-linked genes in the important
diseases of India. He has shown that susceptibility to leprosy and tuberculosis is
associated with a subtype of HLA-DR2 carried on a unique class II haplotype. He
has further Shown that Indian patients show a pattern of DR and DQ association in
rheumatoid arthritis and insulin dependent diabetes mellitus quite distinct from that
of the Western Caucasian patients.
Dr Shashi Wadhwa (1948)
Award Year: 1991

Specialization: Human Anatomy, Neuroanatomy,
Developmental Neurobiology
Address:
Telephone:
Dr Wadhwa has made outstanding contribution in the area of human development

neurobiology. Her work is responsible for a description of the chronology of
proliferation, migration, synaptogenesis and organisation of neurons as well as of
the neurotransmitter profiles of GABA and substance P in the lateral geniculate
body in the visual pathway.
Dr Maharaj Krishan Bhan (1947)
Award Year: 1990

Specialization: Pediatrics Gastroenterology, Infectious
Diseases & Nutrition
Address:
Telephone:
E-Mail:
Dr Bhan’s main areas of activity have been aetiology, pathophysiology and treatment
of persistent intestinal injury in children. His work has led to the identification of the
aggregative Escherichia coli as a major causative organism of diarrhoeal disease
in India. He has developed starch-based oral rehydration solutions for control of
diarrhoea.
Dr Shyam Swarup Agarwal (1941)
Award Year: 1986

Specialization: Internal Medicine, Genetics, Immunology
Address:
Telephone:
E-Mail:
Dr Agarwal has to his credit significant contribution in the field of genetics and
molecular biology.
Dr Pradeep Seth (1943)
Award Year: 1986

Specialization: Virology, Vaccinology
Address: Seth Research Foundation

H8/3 First Floor DLF Phase I
Gurugram - 122002, Haryana
Dr Seth has done notable work aimed at gaining an understanding of the role of
herpes simplex virus infection in etiopathogenesis of cancer of uterine cervix which
is the dominant cancer in Indian women.
Dr Dilip Kumar Ganguly (1940)
Award Year: 1985

Specialization: Neurophysiology, Human Movement
Disorders, Neuropharmacology
Address:
Telephone:
Dr Ganguly has to his credit the significant demonstration of direct involvement of

spinal and peripheral motor control mechanisms in the genesis of certain clinical
features of Parkinsonism.
Dr Jagdish Narain Sinha (1939)
Award Year: 1984

Specialization: Neuropharmacology
Address: Department of Pharmacology & Therapeutics

Uttar Pradesh Dental College Research Centre Sector I,
Dr Akhilesh Das Nagar, Faizabad Road
Lucknow -, Uttar Pradesh
Telephone: E-Mail:
Dr Sinha has done important work on the delineation of the neurochemical

modulation of medullary baroreceptor reflex by studying the nature and function of
the receptors and the primary pathways involved.
Dr Brahm Shanker Srivastava (1943)
Award Year: 1984

Specialization: Medical Microbiology, Biotechnology,
Molecular Biology
Address: Nextec Life Sciences Pvt Ltd
Lucknow, Uttar Pradesh
Dr Srivastava has done important work in the field of microbial genetics using
strains of Vibrio cholerae. He developed bacterial mutants using genetic techniques
and got plasmid-induced loss of virulence and characterised antigens for adherence.
The strains thus obtained have potential for use in vaccine development.
Dr Indira Nath (1938)
Award Year: 1983

Specialization: Immunology, Pathology, Infectious
Diseases, Leprosy
Address:
Telephone:
Dr Nath has studied the immunological mechanisms involved in various types

of leprosy and contributed to basic understanding of the cellular mechanisms
regulating natural immunity in human form of the disease. Development of a
new in vitro radiometric assay using macrophages has provided a rapid method
for screening anti-leprosy drugs, drug resistance and immunologically- mediated
microbiocidal activity.
Dr Umesh Chandra Chaturvedi (1939)
Award Year: 1981

Specialization: Virology, Immunology, Medical
Microbiology
Address:
Telephone:
Dr Chaturvedi has made original contribution to our knowledge of the immune

response to Dengue virus infection. Starting with the epidemic of Dengue fever in
Kanpur, Dr Chaturvedi extended his studies in the animal model and worked out the
precise mechanism of immune-suppression mediated by factors induced by Dengue
virus, thus opening up a new field of investigation using other virus models. These
studies are valuable for obtaining a better understanding of Dengue Haemorrhagic
Fever and Shock Syndrome prevalent in several parts of South-East Asia.
Dr Turaga Desiraju (1935)
Award Year: 1980

Specialization: Neurophysiology, Neuroscience,
Psychobiology
Address:
Telephone:
E-Mail:
Dr Desirajus work on the intricate and complex neurophysiological activities of

the cerebral cortex related to the states of sleep and waking has led to further
understanding of the principles of organisation of the highly evolved areas of the
cerebral cortex. The experimental techniques employed by him have enabled a
better understanding of the mechanisms of transmission of neuronal signals for
conscious behavior.
Dr Perdur Radhakantha Adiga (1935)
Award Year: 1980

Specialization: Endocrine Biochemistry, Reproductive
biology
Address:
Telephone:
E-Mail:
Dr Adiga has done significant work on the purification of carrier proteins for the
water-soluble vitamins, thiamin and riboflavin Their induction under hormonal
influence has been demonstrated. Evidence has been presented for the role of
these proteins in transport of vitamins to the foetus and the possibility of pregnancy
termination through antibodies in rodents.
Dr Nuggehalli Raghuveer Moudgal (1931)
Award Year: 1976

Specialization: Biochemical Endocrinology,
Reproductive Biology
Address:
Telephone:
E-Mail:
Dr Moudgals work on the elucidation of gonadotropin action using immunological

methods has been of a pioneering nature. The unfolding of LH binding to LH
receptors in the target cell and the biochemical reactions elicited is of significance
in exploring the molecular mechanism of action of the hormone concerned. He has
conducted systematic studies on follicular maturation and the role of FSH and
LH in this. The extensive work done by Prof. Moudgals school on reproductive
endocrinology based on his findings in experimental animals has provided a possible
approach for devising fertility control processes by passive immunization technique.
Dr Ajit Kumar Maiti (1928)
Award Year: 1971

Specialization: Applied and Clinical Neurophysiology,
Electroencephalography
Address:
Telephone:
E-Mail:
Dr Maiti has done pioneering work aimed at understanding the autonomic and
viscero-vegetative functions of spinal cord physiology. He has organised and co-
ordinated research in neuro-physiology, electrophysiology, histochemistry, with
reference to the role of spinal cord in blood pressure and carbohydrate metabolism
regulations.
Dr Om Dutt Gulati (1927)
Award Year: 1971

Specialization: Autonomic Pharmacology
Address:
Telephone:
E-Mail:
Dr Gulati has made notable contribution in the field of Autonomic Pharmacology. His
work on adrenergic mechanisms is widely acclaimed.
Dr Janak Raj Talwar (1931)
Award Year: 1970

Specialization: Cardiothoracic, Vascular surgery
Address:
Telephone:
E-Mail:
Dr Talwar has done extensive work on the experimental production of various types
of cold injury and on evaluation of the efficacy of various drugs and physiologically
active substances in the management of cold injuries. His work has led to some
practical ameliorative measures for the prevention and treatment of cold injury.
Dr Ranjit Roy Chaudhury (1930)
Award Year: 1969

Specialization: Rational use of Medicines, Clinical
Pharmacology Plants
Address:
Telephone:
E-Mail:
Dr Chaudhury has made a significant contribution by demonstrating that interference

in the release of histamine from most of the cells may be one of the modes of action
of the intra-uterine contraceptive devices
Dr Subramanian Kalyanaraman (1934)
Award Year: 1969

Specialization: Neurosurgery
Address: Anuradha Clinic

2 (New No 7) Central Street Kilpauk Garden Colony
Chennai - 600010, Tamil Nadu
Telephone: 044 26442667
Dr. Kalyanaraman was able to establish the position occupied by the pyramidal
tract in the internal capsule and has successfully used stereotaxic surgery in the
treatment of Parkinsonism. He was also successful in producing bilateral stereotaxic
lesions and in demonstrating that these mirror lesions are not harmful.
Dr Uttamchand Khimchand Sheth (1920)
Award Year: 1968

Specialization: Clinical Pharmacology
Address:
Telephone:
E-Mail:
Dr Sheth has made notable contribution in the field of clinical pharmacology. He is

also deeply interested in undergraduate education in pharmacology.
Dr Sarashi Ranjan Mukherjee (1919)
Award Year: 1968

Specialization: Neurobiology, Nuclear Medicine
Address:
Telephone:
E-Mail:
Dr Mukherjee has to his credit studies on homeostasis of blood pressure, hypothermia,

iodine metabolism and thyroid gland functions, Marsiline, epilepsy, Brahmi, healing
of fractures, and Prasarani.
Dr Mandayam Jeersannidhi Thirumalachar (1914)
Award Year: 1967

Specialization: Mycology, Microbiology,
Chemotherapeutic Control
Address:
Telephone:
E-Mail:
Dr Thirumalachar has done considerable work in the fields of medical mycology

and plant disease control. Studies carried out under his guidance have led to the
discovery of a new antiparasitic antibiotic, antiamoebin, which is being used by the
Armed Forces for deworming military dogs.When fed with animal feed, it increases
the yield of milk in cows, and enhances egg production in poultry. In the field of
antibiotics, he has developed the antifungal antibiotics Hamycin, Dermostatin,
Aureofungin, MYc-4 and Tetraenenin.
Dr Ajit Kumar Basu (1912)
Award Year: 1967

Specialization: Open Heart Surgery
Address:
Telephone:
E-Mail:
Dr Basu has made significant contribution to the understanding of the problem

of liver disease through a multidisciplinary approach. He has done notable work
on non-cirrhotic portal hypertension. He has also played an important role in the
development of surgical science as also post-graduate education in surgery, in India.
Dr Jyoti Bhusan Chatterjea (1919)
Award Year: 1966

Specialization: Nutritional Anaemias,
Haemoglobinopathies
Address:
Telephone:
E-Mail:
Dr Chatterjea elucidated the aetiopathogenetic aspects of the common disorders

of the human red cells, unfolding the spectrum of hereditary disorders of human
haemoglobin as prevailing in India. His discovery of haemoglobin-E in Bengalis
and comprehensive studies on haemoglobin-E thalassaemia disease from clinical,
haematological, biochemical, biophysical and genetical points of view have provided
new information and greatly enriched the relevant areas of contemporary medical
sciences.
Dr Rustam Jai Vakil (1911)
Award Year: 1966

Specialization: Cardiology
Address:
Telephone:
E-Mail:
Dr Vakil has made notable contribution to the discovery of the uses of Rauvolfia
serpentina.
Dr Vulimiri Ramalingaswami (1921)
Award Year: 1965

Specialization: Pathology, Nutrition, Medical Education
& Research
Address:
Telephone:
E-Mail:
Dr Ramalingaswami is well known for his work on protein malnutrition in India. He

was one of the first investigators who discovered and described the syndrome
of Kwashiorkor or protein malnutrition in the young growing Indian children and
reproduced it successfully in experimental animals.
Dr Nirmal Kumar Dutta (1913)
Award Year: 1965

Specialization: Microbiology, Experimental Medicine
Address:
Telephone:
E-Mail:
Dr Dutta introduced a new and highly effective laboratory model for the study of
human cholera in animals, namely, the use of infant rabbits for the replication of
human cholera. This has enabled laboratories throughout the world to undertake
studies of cholera even though cholera is not prevalent in their countries. His
discovery that Cholera vibrios produces a toxin which causes intense diarrhoea
in the animal, is a major breakthrough in cholera research since Koch isolated the
vibrio. He has developed a method for evaluating cholera vaccines and antisera, and
has discovered a remedy against choleric diarrhoea.
Dr Bal Krishan Anand (1917)
Award Year: 1963

Specialization: Physiology, Neurophysiology, Neuro
Endocrinology
Address:
Telephone:
E-Mail:
Dr Anand has made significant contribution in the field of physiology, especially

neurophysiology. One of his main interests has been the study of nervous regulatory
mechanisms for various internal activities of the body which enable it to maintain
homeostatic conditions. He has been instrumental in the discovery of ‘feeding
centre’ in the hypothalamus. He has elucidated various nervous mechanisms
regulating food intake.
Dr Sibte Hassan Zaidi (1918)
Award Year: 1963

Specialization: Toxicology, Pathology
Address:
Telephone:
E-Mail:
The work of Dr Zaidi on experimental silicosis has shown that in spite of the same
chemical nature, the various forms of free silica differ in their fibrogenic action and
that the optimum particle size of silica dust to cause maximum damage to the lung
is in 1-2 m diameter range. Dr Zaidi experimentally established the pathogenesis
and etiology of progressive massive fibrosis of the coal workers, lungs. He has
established that the combined action of Tubercle bacilli and coal-mine dust
produces an extensive pulmonary disease.
Dr Ram Behari Arora (1917)
Award Year: 1961

Specialization: Cardiovascular Pharmacology,
Therapeutics Clinical Cardiology
Address:
Telephone:
E-Mail:
Dr Arora has been conducting and guiding research in various fields of biological and
medical sciences, with special reference to cardiovascular pharmacotherapeutics.
He has a large number of research publications to his credit.

Scientists Greater Than Einstein

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Scientists Greater Than Einstein

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What are the four revolutions in modern science according to the passage?

What are the four revolutions in modern science according to the passage?

What is the goal of Indian students and scientists according to the passage?

What is the goal of Indian students and scientists according to the passage?

Scientists

These remarkable stories of human achievement on a truly grand scale

—Dr. Jeff Wicker M.D.

This engaging book is a fascinating read chronicling the genesis of

—Dr. Susan R. Campbell, Ph.D.

Printed in the United States of America.

eBOOK Rs. 100

In spite of great advancements in stopping viruses, more

—Srinivasa K. Rao,Ph.D. & Team (eBook 2020)

Despite strides made by many scientists, millions of people

—Srinivasa K. Rao Ph.D.

Dedicated to the memory of Gertrude Elion and George

—Billy Woodward (2009)

IT WAS a delight conversing with Al Sommer, Akira Endo, Bill

Foreword by Dr. B. Sesikeran ........................................................ 1

Outstanding Scientific Discoveries ................................................ 2

Real Life-Savers ............................................................................. 5

About Authors ................................................................................ 7

1. Al Sommer—Over 9 Million Lives Saved

2. Akira Endo—Over 10 Million Lives Saved

3. Bill Foege—Over 169 Million Lives Saved

4. David Nalin—Over 71 Million Lives Saved

5. Norman Borlaug—Over 320 Million Lives Saved

6. John Enders—Over 143 Million Lives Saved

7. Paul Müller—Over 22 Million Lives Saved

9. Frederick Banting—Over 18 Million Lives Saved

10. Karl Landsteiner—Over 1.3 Billion Lives Saved

Determining the Number of Lives Saved ................................... 229

Introduction to Bhatnagar awards winners ................................. 233

We all know of Albert Einstein, who is a benchmark of extraordinary

Reading this book “Scientists Greater Than Einstein: The Biggest

— Rama Haritha Pusarla, Ph.D.

Inter-dependence is the core message of creation. On earth, it cannot

— T.A. Venkateswaran, Former Regional Manager,

Billy Woodward is a University of

In 2004, after two years of having gout, a drug - allopurinol -

Modern Medicine is New

The Eye Doctor Who

ALFRED SOMMER was

had come to Indonesia to spend three years investigating nutritional

the “Vitamin Hypothesis.” He called them Vitamins, linking the word

Following in Forrest Gump’s Path

all-male college in upstate New York. He chose it because a friend was

vaccine trials, then engaged with new rubella (measles) vaccine.

dependent on outside food relief for survival. It was the biggest

Compulsively Driven to Collect Data

Challenges of measurement of Malnutrition

have was so much greater than I could on a one-to-one patient-physician

circumference is a standard measurement.

Chance Favors the Prepared Mind

While there, Sommer’s favorite saying of Louis Pasteur’s—”Chance

What’s So Important About Vitamin A Anyway?

Night blindness is one of the first symptoms of a condition formally

over the cornea of the eye—hence the correlation between vitamin A

effective. We, therefore, attended several treatment sessions, which were

The Studies of Children’s Eyes