Biomarkers are the answer.

But what is
the question?

Mauro F Rebelo I once saw a movie where the “best of the best” US
Is Adjunct Professor of Environmental Biophysics at Navy pilots went to a special school to become even
the Carlos Chagas Filho Biophysics Institute of the better. It was a kind of “graduate school” for pilots. In
Rio de Janeiro Federal University.
[email protected] the initial lecture, the commander explained that pilots
were becoming dependent on technology and
Mailing address
forgetting how to pilot. They were losing their piloting
Universidade Federal do Rio de Janeiro, Instituto de skills. The same is happening with science graduate
Biofísica Carlos Chagas Filho, Centro de Ciências
students (and many times also their advisors)
da Saúde, Bloco G, Ilha do Fundão, 21941-902, Rio
de Janeiro, Brasil throughout science. They can get really sophisticated
data from high-tech equipment, but do not really know
how to translate data into information and information
into knowledge. They are quite good at getting the
answers, but seemingly have lost the ability to ask the
questions. The resulting data are often uninteresting,
redundant, or simply useless.
Biomarkers are the answer ANO I VOL 1 NUM 01

In our field of environmental-health biology, this the mean and standard deviation, which do not apply
can be even a harder problem, because there are in most cases in environmental science! I have worked
many fewer standard practices than in human-health with sentinel species for 15 years and haven’t found
biology. For example, if a researcher from a tropical one yet that shows a normal distribution of
country wants to test the effect of a drug in humans, contaminant accumulation in its tissues. Beeby
starting from mice as a surrogate species, he will use (2001), in a very interesting article on sentinels,
the same mice as a researcher in higher latitudes. showed that normal distributions are simply not to be
However, if the same researcher wants to test the assumed! So why do people keep on presenting mean
effect of a pollutant in his environment, it will be an concentrations with standard deviations? And why do
entirely different story. Surrogate species are not the journals accept this? When it comes to experimental
same, and are certainly not standardized. Some will design, the problem gets worse. Anxious to cover all
say fish are better, others will say mollusks are, and no aspects of a given problem (let’s say “how a chemical
one will agree. Ludwig et al. (1993) showed in their affects the physiology of a given species”), in the hope
very interesting article about natural-resources to publish faster and in a more prestigious journal,
exploitation and conservation that environmental researchers are jumping to evaluate the effects of as
problems are both technically and politically complex. many treatments on as many variables as they can.
If we want to nurture a new generation of The inevitable outcome is that they cannot use as
environmental scientists with critical-thinking skills and many replicates as are necessary to determine, or at
the ability to make decisions, we need to encourage least to accurately express, the uncertainty or the
our students to consider some of these questions: degree of variability of the biological variables. The

results are often meaningless significant correlations.
Ioannidis (2005) showed that the insistence on
1 – The “Use my species” plague claiming “truth” based on statistical significance and to
Worse than the lack of surrogate species is the establish “cause” based on statistical correlation has
competition between scientific groups to establish a led to the astonishing conclusion that most published
“preferred” one. It would be a good exercise for a new scientific results are false. It is imperative that we
student coming to your laboratory: find as many teach our students to reduce uncertainty about our
articles as you can that begin or end with a suggestion scientific object (the species or the biological variable)
of a new surrogate species, based on a few toxicity BEFORE we start to test for variables and treatments.
tests or biomarker analyses. It is as if the one who will
find the “ultimate” surrogate species will gain fame and 3 – The “publish or perish” paradigm
fortune. They will not, but during the attempt, they are This is another reason why it can be contrary to the
spending significant amounts of money to conclude… best practices in science: I can’t help speculating that
less than they could. Understanding the limitations of most of the time, careless experimental design results
any given species as a surrogate species is more from the rush to publish. Environmental science, given
important to protect the environment than to the complexity of higher levels of biological
demonstrate their qualities. There will never be the organization – such as the ecosystem – simply
“one” surrogate species for all environments, because requires more planning and more time to execute and
they are simply too diverse to be compared in that publish than do studies on lower levels of organization
way. We should encourage students to stop looking for – such as the cell. But how to address the difficulties in
the ultimate surrogate and use available ones to the publishing system? My guess is that we could do
provide answers about toxicity mechanisms that can that by getting back to asking good, meaningful,
be replicated in different species relevant questions! For instance, how many articles
have you read where the authors are pretty much the
same, as well as the laboratories involved, and the
2 – The “lack of experimental design” articles would also be much the same if not for a
syndrome change in the chemical, the biomarker, or the species
Environmental-science students and researchers examined? Perhaps even worse are proposals to redo
(including reviewers) often don’t really know statistics. measurements using new instruments or markers.
Surely not enough, and most of the time no more than This kind of approach might be necessary, but does it

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ANO I VOL 1 NUM 01 O admirável mundo das células-tronco

really advance the science? It seems that we often and leave the task of converting the data into
teach the students only how to push the necessary information and then knowledge to their advisors. As a
buttons to get the results, without allowing time for result, we have an entire generation of students who
discussion and little room for reasoning as to whether think it is not necessary to read, to actually study. Let’s
this is necessary. be fair and share this fault/blame with modern society.
We live in a world saturated with information and there
4 – The “The answer is biomarkers” is simply no space in our brains to store everything
obsession that we might want or need. But we are facing a
Defined as the use of biochemical or molecular complete lack of interest in the literature, the history of
processes that can respond to an external stimulus, science, or the philosophy behind its methods. Why
helping to predict or prevent damage at higher waste time reading the book when we can merely read
organizational levels, biomarkers were the response of the abstract? Or even worse: “let’s wait for the movie
the environmental research community to the to come out”. Too bad “Avatar” is not acceptable as a
“molecularization” of science. literature reference. Things, or ways of thinking, that
Please do not misunderstand me; I do believe that students should have learned years ago – by simply
the ‘omics’ have a lot to contribute to science. A better reading the classics – could do so much for them to
understanding of the molecular processes occurring at understand their field and how it got where it is today.
the beginning of the sequence where events are still Not reading, students are often disappointed when
reversible is far more likely to help us to prevent they discover that their “breakthrough conclusion” has
environmental damage. actually been described and discussed (and
However, reduced machinery does not have to sometimes refuted) in a series of articles and books
mean reductionist questions. Biomarkers are a great published some 30 years ago. Moreover, most of the
approach, but “Is that enough”? Well, we can already time these older papers are on the shelves of their
say that one biomarker is not enough. We need a set, own lab! And of course, since they don’t read, they can
and a group of “core” biomarkers is well established barely write. The average papers and theses written
(Viarengo et al., 2007). However, there is still a kind by graduate students are a disaster – superficial,
of “gold rush” to find a new or ultimate biomarker. vague, and grammatically and orthographically
Every enzyme, protein, gene, reaction, metabolic irritating. Graduate school should do more for students
pathway, or behavior is a candidate to be the new them simply punish them for a terrible thesis. We have
savior of our environment. The reason might not be as to go back and teach our students how to ask a good
obvious as the consequence: despite a few local question and how to put that in good writing. We have
initiatives, in the quest for the “one” biomarker, we are to turn on their desire to reason.
forgetting to research the actual variability in the For me, the beauty of science also stems from its
biomarker and in the chain of events that leads from egalitarian nature: it accepts anyone regardless of
the damage at the initial level of organization to the social status, gender, race, or beliefs. However, it is
ultimate adverse effect on the organism or ecosystem. not a democracy, and science will not, and must not,
We are so excited to use our new mass spectrometer make exceptions for anyone. We professors are ready
or Affymetrix chip that we are leaving behind the to commit to every demanding and laborious
basics of toxicokinetics and toxicodynamics. Again, to requirement of science. It is imperative that we
understand the limitations of each of the established convince our students that it is “cool” to be a scientist,
“core” biomarkers to help to use them in ways that because this is the only way that we will live up to
they can provide useful information, should be more society’s expectations of scientists. If we don’t
important than to propose a new one in every article. It succeed in doing that while they are students, by the
is knowledge of the limitations, rather than the time they finish their PhD, it will have no more
qualities, that helps us make better use of the tools meaning than a title.
that we have available.
We live in times of great concern for the
5 – The “Don’t think! That is my job” environment. Poverty and hunger put as much
blindness pressure on the environment as the exploitation of any
Students are often encouraged to produce results natural resource demanded by developed societies to

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Biomarkers are the answer ANO I VOL 1 NUM 01

keep up their standards of living. The challenges we

face are enormous, and the choices we will eventually Acknowledgments
have to make will be very difficult. We need people The author is grateful to Dr. Francesco Dondero,
who truly understand the limits of our knowledge of our Dr. José Monserrat and Dr. Milton Morares for their
environment to help shape the solutions to these criticism during the elaboration of this manuscript.
problems. We need to prepare scientists who are able
to ask the right questions and then answer them, References
especially in regard to the environment. Instead of Beeby A. 2001. What do sentinels stand for? Environmental Pollution,
preparing scientists who only can make more precise 112, 285–298

and more accurate measurements (as Lord Kelvin said Ioannidis JPA. 2005. Why Most Published Research Findings Are False.
PLoS Medicine 2(8): e124
more than a hundred years ago), which could be
Ludwig D, Hilborn R, Waters C. 1993. Uncertainty, Resource Exploitation,
meaningless in a few years, we should prepare and Conservation: Lessons from History. Science 260, 17
scientists who are able to make careful and reliable Viarengo A, Lowe D, Bolognesi C, Fabbri F, Koehler A. 2007. The use of
interpretations based on precise measurements with biomarkers in biomonitoring: A 2-tier approach assessing the level of
pollutant-induced stress syndrome in sentinel organisms. Comparative
all the uncertainty that may exist, and convey these
Biochemistry and Physiology, Part C 146: 281–300.
interpretations to decision-makers in ways that are
clear and understandable. Graduate courses all over
the world should emphasize the reading and writing
ability of their students, their statistical and logical
skills, and their philosophical background, because
actually society is doing a great job teaching them
technology.
There is no other way of doing our job: easy
answers and magical predictions are for astrologists.