DNA Technology in Forensic

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DNA Technology in Forensic Science
DNA Technology in
Forensic Science
Committee on DNA Technology in Forensic Science

Board on Biology
Commission on Life Sciences
National Research Council
NATIONAL ACADEMY PRESS

Washington, D.C. 1992
Copyright National Academy of Sciences. All rights reserved.
ii
National Academy Press 2101 Constitution Avenue., N.W. Washington, DC 20418

NOTICE: The project that is the subject of this report was approved by the Governing Board of the
National Research Council, whose members are drawn from the councils of the National Academy
of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of
the committee responsible for the report were chosen for their special competences and with regard
for appropriate balance.
This report has been reviewed by a group other than the authors according to procedures approved
by a Report Review Committee consisting of members of the National Academy of Sciences, the
National Academy of Engineering, and the Institute of Medicine.
This Board on Biology study was supported by the Federal Bureau of Investigation, the National
Institutes of Health National Center for Human Genome Research, the National Institute of Justice,
the National Science Foundation, the Alfred P. Sloan Foundation, and the State Justice Institute.
Library of Congress Cataloging-in-Publication Data
National Research Council (U.S.). Committee on DNA Technology in Forensic Science. DNA tech-
nology in forensic science / Committee on DNA Technology in Forensic Science, Board on Biol-
ogy, Commission on Life Sciences, National Research Council.
p. cm.
Includes bibliographical references and index.
ISBN 0-309-04587-8
1. Forensic genetics—Congresses. 2. DNA fingerprinting— Congresses. I. Title.
[DNLM: 1. DNA analysis. 2. Forensic Medicine methods. W 786 N277d]
RA1057.5N37 1992
614'.1—dc20
DNLM/DLC
for Library of Congress 92-16341
CIP
This book is printed with soy ink on acid-free recycled stock.
Copyright 1992 by the National Academy of Sciences.
Printed in the United States of America
First Printing, July 1992
Second Printing, January 1993
Third Printing, May 1997

iii
COMMITTEE ON DNA TECHNOLOGY IN FORENSIC

SCIENCE
VICTOR A. McKUSICK, Chairman, The Johns Hopkins Hospital, Baltimore,

Maryland
PAUL B. FERRARA, Division of Forensic Sciences, Department of General
Services, Richmond, Virginia
HAIG H. KAZAZIAN, The Johns Hopkins Hospital, Baltimore, Maryland
MARY-CLAIRE KING, University of California, Berkeley, California
ERIC S. LANDER, Whitehead Institute for Biomedical Research, Cambridge,
Massachusetts
HENRY C. LEE, Connecticut State Police, Meriden, Connecticut
RICHARD O. LEMPERT, University of Michigan Law School, Ann Arbor,
Michigan
RUTH MACKLIN, Albert Einstein College of Medicine, Bronx, New York
THOMAS G. MARR, Cold Spring Harbor Laboratory, Cold Spring Harbor, New
York
PHILIP R. REILLY, Shriver Center for Mental Retardation, Waltham,
Massachusetts
GEORGE F. SENSABAUGH, Jr., University of California, Berkeley, California
JACK B. WEINSTEIN, U.S. District Court, New York, Brooklyn, New York
Former Members
C. THOMAS CASKEY (Resigned December 21, 1991), Baylor College of
Medicine, Houston, Texas
MICHAEL W. HUNKAPILLER (Resigned August 17, 1990), Applied
Biosystems Inc., Foster City, California
National Research Council Staff

OSKAR R. ZABORSKY, Study Director; Director, Board on Biology
NORMAN GROSSBLATT, Editor
MARIETTA E. TOAL, Administrative Secretary
MARY KAY PORTER, Senior Secretary

iv
BOARD ON BIOLOGY
HAROLD E. VARMUS, Chairman, University of California, San Francisco,

California
ANANDA M. CHAKRABARTY, University of Illinois Medical Center,
Chicago, Illinois
MICHAEL T. CLEGG, University of California, Riverside, California
RICHARD E. DICKERSON, University of California, Los Angeles, California
RICHARD E. LENSKI, University of Michigan, East Lansing, Michigan
BARBARA J. MAZUR, E. I. du Pont de Nemours & Company, Wilmington,
Delaware
HAROLD J. MOROWITZ, George Mason University, Fairfax, Virginia
DANIEL E. MORSE, University of California, Santa Barbara, California
PHILIP NEEDLEMAN, Monsanto Company, St. Louis, Missouri
MARY LOU PARDUE, Massachusetts Institute of Technology, Cambridge,
Massachusetts
DAVID D. SABATINI, New York University, New York, New York
MICHAEL E. SOULÉ, University of California, Santa Cruz, California
MALCOLM S. STEINBERG, Princeton University, Princeton, New Jersey
DAVID B. WAKE, University of California, Berkeley, California
DANIEL I. C. WANG, Massachusetts Institute of Technology, Cambridge,
Massachusetts
BRUCE M. ALBERTS, ex officio, University of California, San Francisco,
California

COMMISSION ON LIFE SCIENCES
BRUCE M. ALBERTS, Chairman, University of California, San Francisco,

California
BRUCE N. AMES, University of California, Berkeley, California
J. MICHAEL BISHOP, University of California Medical Center, San
Francisco, California
MICHAEL T. CLEGG, University of California, Riverside, California
GLENN A. CROSBY, Washington State University, Pullman, Washington
LEROY E. HOOD, California Institute of Technology, Pasadena, California
DONALD F. HORNIG, Harvard School of Public Health, Boston, Massachusetts
MARIAN E. KOSHLAND, University of California, Berkeley, California
RICHARD E. LENSKI, University of Michigan, East Lansing, Michigan
STEVEN P. PAKES, University of Texas, Dallas, Texas
EMIL A. PFITZER, Hoffmann-La Roche, Inc., Nutley, New Jersey
THOMAS D. POLLARD, The Johns Hopkins Medical School, Baltimore,
Maryland
JOSEPH E. RALL, National Institutes of Health, Bethesda, Maryland
RICHARD D. REMINGTON, University of Iowa, Iowa City, Iowa
PAUL G. RISSER, University of New Mexico, Albuquerque, New Mexico
HAROLD M. SCHMECK, JR., Armonk, New York
RICHARD B. SETLOW, Brookhaven National Laboratory, Upton, New York
CARLA J. SHATZ, University of California, Berkeley, California
TORSTEN N. WIESEL, Rockefeller University, New York, New York
National Research Council Staff

JOHN E. BURRIS, Executive Director

vi
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National Research Council.
www.national-academies.org
Acknowledgement and Disclaimer:
This report was supported with joint funding from the National Institute of
Justice, the Federal Bureau of Investigation, and the State Justice Institute,
under award # 89-IJ-CX-0055 from the National Institute of Justice
Programs, U.S. Department of Justice. Points of view in these doc ument are
those of the authors and do not necessarily represent the official position of
the U.S. Department of Justice.

PREFACE vii
Preface
In recent years, advances in the techniques for mapping and sequencing the
human genome have contributed to progress in both basic biology and medicine.
The applications of these techniques have not been restricted to biology and
medicine, however, but have also entered forensic science. Today, methods
developed in basic molecular biology laboratories can potentially be used in
forensic science laboratories in a matter of months.
On the basis of its study of the mapping and sequencing of the human
genome (reported in 1988), the Board on Biology and several federal agencies
recognized the potential of DNA typing technology for forensic science. In
particular, the Federal Bureau of Investigation, the preeminent organization in the
United States for the development and application of forensic techniques, initiated
an effort to develop and evaluate DNA typing in forensic applications in the
mid-1980s. The first case work was performed in December 1988. Several
private-sector laboratories entered the field early, and state government crime
laboratories also began to offer services in DNA typing. However, as DNA typing
entered the courtrooms of this country, questions appeared about its reliability
and methodological standards and about the interpretation of population
statistics.
By the summer of 1989, a crescendo of questions concerning DNA typing
had been raised in connection with some well-publicized criminal cases, and calls
for an examination of the issues by the National Research Council of the
National Academy of Sciences came from the scientific and legal communities.
As a response, this study was initiated in January 1990.
Because of the broad ramifications of forensic DNA typing, a number

PREFACE viii
of federal agencies and one private foundation provided financial support for this
study: the Federal Bureau of Investigation, the National Institutes of Health
National Center for Human Genome Research, the National Institute of Justice,
the National Science Foundation, the State Justice Institute, and the Alfred P.
Sloan Foundation.
Many persons offered assistance to the committee and staff during this
complex study. In particular, the following deserve recognition and praise for
their efforts: John Hicks, Federal Bureau of Investigation; Elke Jordan and Eric
Juengst, National Institutes of Health National Center for Human Genome
Research; James K. Stewart, Charles B. DeWitt, Bernard V. Auchter, and Richard
Laymon, National Institute of Justice; John C. Wooley, National Science
Foundation; David I. Tevelin, State Justice Institute; and Michael S. Teitelbaum,
Alfred P. Sloan Foundation.
I also thank the many experts who offered their advice to the committee
during its briefings and open meetings. The names of those who offered
testimony are given in the appendix. Additionally, I want to thank the many who
wrote to me or to the National Research Council and provided valuable data and
suggestions to the committee; much was gained from their input. We also
acknowledge the efforts of Robert Kushen, Columbia Law School, in assisting
Judge Weinstein. I also thank Della Malone, my secretary, for her help
throughout. The committee thanks the reviewers of our report for many valuable
comments and suggestions. Although the reviewers are anonymous to us, I
personally want to thank them for their constructive comments and suggestions.
The staff of the Board on Biology deserve special praise for their efforts
during the many months of intense activity. Oskar R. Zaborsky, Study Director
and Director of the Board on Biology, deserves recognition for his administrative
and technical contributions and for handling many complex matters. Marietta
Toal, Administrative Secretary, served the committee well in logistics and the
preparation of the report. The committee also thanks Mary Kay Porter for her
assistance. Norman Grossblatt edited the report.
Last but not least, I thank my colleagues on the committee who served so
well and unselfishly to address key issues from the perspective of their special
expertise and to prepare this report in a timely fashion.
DNA typing for personal identification is a powerful tool for criminal
investigation and justice. At the same time, the technical aspects of DNA typing
are vulnerable to error, and the interpretation of results requires appreciation of
the principles of population genetics. These considerations and concerns arising
out of the felon DNA databanks and the privacy of DNA information made it
imperative to develop guidelines and safeguards for the most effective and
socially beneficial use of this powerful tool. We hope that our efforts will
enhance understanding of the issues and serve to

PREFACE ix
bring together people of good will from science, technology, law, and ethics. We
hope that our report will serve well the sponsors and the general public.
Victor A. McKusick
Chairman
Committee on DNA Technology in Forensic Science

A STATEMENT BY THE COMMITTEE ON DNA TECHNOLOGY IN FORENSIC SCIENCE x
A Statement by the Committee on DNA

Technology in Forensic Science
On April 14, 1992, The New York Times printed an article on this report.
That article seriously misrepresented the findings of the committee; in an article
on April 15, the Times corrected the misrepresentation. To avoid any potential
confusion engendered by the April 14 article, the committee provides the
following clarifying statement:
We recommend that the use of DNA analysis for forensic purposes,
including the resolution of both criminal and civil cases, be continued while
improvements and changes suggested in this report are being made. There is no
need for a general moratorium on the use of the results of DNA typing either in
investigation or in the courts.
We regard the accreditation and proficiency testing of DNA typing
laboratories as essential to the scientific accuracy, reliability, and acceptability of
DNA typing evidence in the future. Laboratories involved in forensic DNA
typing should move quickly to establish quality-assurance programs. After a
sufficient time for implementation of quality-assurance programs has passed,
courts should view quality control as necessary for general acceptance.
The Committee

CONTENTS xi
Contents
SUMMARY 1
1 INTRODUCTION 27
Background 27
Genetic Basis of DNA Typing 32
Technological Basis of DNA Typing 36
Population Genetics Relevant to the Interpretation of DNA Typing 44
Characteristics of an Optimal Forensic DNA Typing System 48
References 49
2 DNA TYPING: TECHNICAL CONSIDERATIONS 51

Essentials of a Forensic DNA Typing Procedure 52
Technical Issues in RFLP Analysis 56
Technical Issues in PCR-Based Methods 63
National Committee on Forensic DNA Typing 70
Summary of Recommendations 72
References 73
3 DNA TYPING: STATISTICAL BASIS FOR INTERPRETATION 74

Estimating the Population Frequency of a DNA Pattern 75
Determining Allele Frequencies in a Population Databank 85
Implications of Genetic Correlations among Relatives 86
Implications of Increased Power of DNA Typing Compared with 88
Conventional Serology

CONTENTS xii
Laboratory Error Rates 88

Toward a Firm Foundation for Statistical Interpretation 89
References 95
4 ENSURING HIGH STANDARDS 97

Defining the Principles of Quality Assurance 98
Potential Methods for Ensuring Quality 99
Quality Assurance in Related Fields 101
Initial Efforts Toward Establishing Standards in Forensic DNA 102
Typing
A Regulatory Program for DNA Typing 104
References 109
5 FORENSIC DNA DATABANKS AND PRIVACY OF INFORMA- 111

TION
Comparison of DNA Profiles and Latent Fingerprints 111
Confidentiality and Security 113
Methodological Standardization 116
Cost Versus Benefit 117
Whose Samples Should Be Included? 118
Sample Storage 122
Information To Be Included and Maintained in a Databank 122
Rules on Accessibility 123
Statistical Interpretation of Databank Matches 124
Status of Databank Development 124
Model Cooperative Information Resource 126
References 129
6 USE OF DNA INFORMATION IN THE LEGAL SYSTEM 131

Admissibility 132
DNA Databanks on Convicted Felons: Legal Aspects 142
Assessing the Admissibility of Evidence Based on Results of Fur- 143
ther Advances in DNA Technology
Suggestions For Use of DNA Evidence 145
DNA Evidence and the Various Parties in the Legal System 146
Testing Laboratories 148
Protective Orders 148
Availability and Cost of Experts 148
References 150

CONTENTS xiii
7 DNA TYPING AND SOCIETY 152

Economic Aspects 153
Ethical Aspects 154
Abuse and Misuse of DNA Information 158
Expectations 160
Accountability and Public Scrutiny 162
International Exchange 162
References 163
ORGANIZATIONAL ABBREVIATIONS 165
GLOSSARY 167
BIOGRAPHICAL INFORMATION ON COMMITTEE MEMBERS 173
PARTICIPANTS 179
INDEX 179

SUMMARY 1
Summary
Characterization, or ''typing," of deoxyribonucleic acid (DNA) for purposes

of criminal investigation can be thought of as an extension of the forensic typing
of blood that has been common for more than 50 years; it is actually an extension
from the typing of proteins that are coded for by DNA to the typing of DNA
itself. Genetically determined variation in proteins is the basis of blood groups,
tissue types, and serum protein types. Developments in molecular genetics have
made it possible to study the person-to-person differences in parts of DNA that
are not involved in coding for proteins, and it is primarily these differences that
are used in forensic applications of DNA typing to personal identification. DNA
typing can be a powerful adjunct to forensic science. The method was first used in
casework in 1985 in the United Kingdom and first used in the United States by
commercial laboratories in late 1986 and by the Federal Bureau of Investigation
(FBI) in 1988.
DNA typing has great potential benefits for criminal and civil justice;
however, because of the possibilities for its misuse or abuse, important questions
have been raised about reliability, validity, and confidentiality. By the summer of
1989, the scientific, legal, and forensic communities were calling for an
examination of the issues by the National Research Council of the National
Academy of Sciences. As a response, the Committee on DNA Technology in
Forensic Science was formed; its first meeting was held in January 1990. The
committee was to address the general applicability and appropriateness of the use
of DNA technology in forensic science, the need to develop standards for data
collection and analysis, aspects of the

SUMMARY 2
technology, management of DNA typing data, and legal, societal, and ethical
issues surrounding DNA typing. The techniques of DNA typing are fruits of the
revolution in molecular biology that is yielding an explosion of information
about human genetics. The highly personal and sensitive information that can be
generated by DNA typing requires strict confidentiality and careful attention to
the security of data.
DNA, the active substance of the genes, carries the coded messages of
heredity in every living thing: animals, plants, bacteria, and other
microorganisms. In humans, the code-carrying DNA occurs in all cells that have a
nucleus, including white blood cells, sperm, cells surrounding hair roots, and
cells in saliva. These would be the cells of greatest interest in forensic studies.
Human genes are carried in 23 pairs of chromosomes, long threadlike or
rodlike structures that are a person's archive of heredity. Those 23 pairs, the total
genetic makeup of a person, are referred to as the human "diploid genome." The
chemistry of DNA embodies the universal code in which the messages of heredity
are transmitted. The genetic code itself is spelled out in strings of nucleotides of
four types, commonly represented by the letters A, C, G, and T (standing for the
bases adenine, cytosine, guanine, and thymine), which in various combinations of
three nucleotides spell out the
FIGURE 1 Diagram of the double-helical structure of DNA in a chromosome.

The line shown in the chromosome is expanded to show the DNA structure.

SUMMARY 3
codes for the amino acids that constitute the building blocks of proteins. A gene,
the basic unit of heredity, is a sequence of about 1,000 to over 2 million
nucleotides. The human genome, the total genetic makeup of a person, is
estimated to contain 50,000-100,000 genes.
The total number of nucleotides in a set of 23 chromosomes—one from each
pair, the "haploid genome"—is about 3 billion. Much of the DNA, the part that
separates genes from one another, is noncoding. Variation in the genes, the
coding parts, are usually reflected in variations in the proteins that they encode,
which can be recognized as "normal variation" in blood type or in the presence of
such diseases as cystic fibrosis and phenylketonuria; but variations in the
noncoding parts of DNA have been most useful for DNA typing.
Except for identical twins, the DNA of a person is for practical purposes
unique. That is because one chromosome of each pair comes from the father and
one from the mother; which chromosome of a given pair of a parent's
chromosomes that parent contributes to the child is independent of which
chromosome of another pair that parent gives to that child. Thus, the different
combinations of chromosomes that one parent can give to one child is 223, and the
number of different combinations of paired chromosomes a child can receive from
both parents is 246.
The substitution of even one nucleotide in the sequence of DNA is a
variation that can be detected. For example, a variation in DNA consisting of the
substitution of one nucleotide for another (such as the substitution of a C for a T)
can often be recognized by a change in the points at which certain biological
catalysts called "restriction enzymes" cut the DNA. Such an enzyme cuts DNA
whenever it encounters a specific sequence of nucleotides that is peculiar to the
enzyme. For example, the enzyme HaeI cuts DNA wherever it encounters the
sequence AGGCCA. A restriction enzyme will cut a sample of DNA into
fragments whose lengths depend on the location of the cutting sites recognized by
the enzyme. Assemblies of fragments of different lengths are called "restriction
fragment length polymorphisms" (RFLPs), and RFLPs constitute one of the most
important tools for analyzing and identifying samples of DNA.
An important technique used in such analyses is the "Southern blot,"
developed by Edwin Southern in 1975. A sample of DNA is cut with a restriction
enzyme, and the fragments are separated from one another by electrophoresis
(i.e., they are separated by an electrical field). The fragments of particular interest
are then identified with a labeled probe, a short segment of single-stranded DNA
containing a radioactive atom, which hybridizes (fuses) to the fragments of
interest because its DNA sequence is complementary to those of the fragments (A
pairing with T, C pairing with G). Each electrophoretic band represents a separate
fragment of DNA, and a given person will have no more than two fragments
derived from a partic

SUMMARY 4
ular place in his or her DNA—one representing each of the genes that are present
on the two chromosomes of a given pair. The forms of a given gene are referred
to as alleles. A person who received the same allele from the mother and the
father is said to be "homozygous" for that allele; a person who received different
alleles from the mother and the father is said to be "heterozygous." Many RFLP
systems are based on change in a single nucleotide. They are said to be
"diallelic," because there are only two common alternative forms. And there are
only three genotypes: two kinds of homozygous genotypes and a heterozygous
genotype. Another form of RFLP is generated by the presence of variable number
tandem repeats (VNTRs). VNTRs are sequences, sometimes as small as two
different nucleotides (such as C and A), that are repeated in the DNA. When such a
structure is subjected to cutting with restriction enzymes, fragments of varied
length are obtained.
It was variation of the VNTR type to which Alex Jeffreys in the United
Kingdom first applied the designation "DNA fingerprinting." He used probes that
recognized not one locus, but multiple loci, and "DNA fingerprinting" has come
to refer particularly to multilocus, multiallele systems. A locus is a specific site of a
gene on a chromosome. In the United States, in particular, single-locus probes are
preferred, because their results are easier to interpret. "DNA typing" is the
preferred term, because "DNA fingerprinting'' is associated with multilocus
systems. Discriminating power for personal identification is achieved by using
several—usually at least four—single-locus, multiallelic systems.
The entire procedure for analyzing DNA with the RFLP method is
diagrammed in Figure 2.
After the bands (alleles) are visualized, those in the evidence sample and the
suspect sample are compared. If the bands match in the two samples, for all three
or four enzyme-probe combinations, the question is: What is the probability that
such a match would have occurred between the suspect and a person drawn at
random from the same population as the suspect?
Answering that question requires calculation of the frequency in the
population of each of the gene variants (alleles) that have been found, and the
calculation requires a databank where one can find the frequency of each allele in
the population. On the basis of some assumptions, so-called Hardy-Weinberg
ratios can be calculated. For a two-allele system, the ratios are indicated by the
expressions p2 and q2 for the frequency of the two homozygotes and 2pq for
heterozygotes, p and q being the frequencies of the two alleles and p + q being
equal to 1. Suppose that a person is heterozygous at a locus where the frequencies
of the two alleles in the population are 0.3 and 0.7. The frequency of that
heterozygous genotype in the population would be 2 × 0.3 × 0.7 = 0.42. Suppose,
further, that at three

SUMMARY 5
other loci the person being typed has genotypes with population frequencies of
0.01, 0.32, and 0.02. The frequency of the combined genotype in the population
is 0.42 × 0.01 × 0.32 × 0.02 or 0.000027, or approximately 1 in 37,000.
FIGURE 2 Schematic representation of Southern blotting of single-locus,

multiallelic VNTR. In example shown here, DNA from four persons is tested.
All have different patterns. Three are heterozygous and one homozygous, for a
total of seven different alleles. From L. T. Kirby, "DNA Fingerprinting: An
Introduction," Stockton Press, New York, 1990. Copyright © 1990 by Stockton
Press. Reprinted with permission of W.H. Freeman and Company.
That example illustrates what is called the product rule, or multiplication

rule. Its use assumes that the alleles at a given locus are inherited independently
of each other. It also assumes that there are no subpopulations in which a
particular allele at one locus would have a preferential probability of being
associated with a particular allele at a second locus.
Techniques for analyzing DNA are changing rapidly. One key technique
introduced in the last few years is the polymerase chain reaction (PCR), which
allows a million or more copies of a short region of DNA to be easily made. For
DNA typing, one amplifies (copies) a genetically informative sequence, usually
100-2,000 nucleotides long, and detects the genotype in the amplified product.
Because many copies are made, DNA

SUMMARY 6
typing can rely on methods of detection that do not use radioactive substances.
Furthermore, the technique of PCR amplification permits the use of very small
samples of tissue or body fluids—theoretically even a single nucleated cell.
The PCR process (Figure 3) is simple; indeed, it is analogous to the process
by which cells replicate their DNA. It can be used in conjunction with various
methods for detecting person-to-person differences in DNA.
It must be emphasized that new methods and technology for demonstrating
individuality in each person's DNA are being developed. The present methods
explained here will probably be superseded by others that are more efficient,
error-free, automatable, and cost-effective. Care should be taken to ensure that
DNA typing techniques used for forensic purposes do not become "locked in"
prematurely, lest society and the criminal justice system be unable to benefit fully
from advances in science and technology.
TECHNICAL CONSIDERATIONS
The forensic use of DNA typing is an outgrowth of its medical diagnostic
use—analysis of disease-causing genes based on comparison of a patient's DNA
with that of family members to study inheritance patterns of genes or comparison
with reference standards to detect mutations. To understand the challenges
involved in such technology transfer, it is instructive to compare forensic DNA
typing with DNA diagnostics.
DNA diagnostics usually involves clean tissue samples from known
sources. Its procedures can usually be repeated to resolve ambiguities. It involves
comparison of discrete alternatives (e.g., which of two alleles did a child inherit
from a parent?) and thus includes built-in consistency checks against artifacts. It
requires no knowledge of the distribution of patterns in the general population.
Forensic DNA typing often involves samples that are degraded,
contaminated, or from multiple unknown sources. Its procedures sometimes
cannot be repeated, because there is too little sample. It often involves matching
of samples from a wide range of alternatives in the population and thus lacks
built-in consistency checks. Except in cases where the DNA evidence excludes a
suspect, assessing the significance of a result requires statistical analysis of
population frequencies.
Each method of DNA typing has its own advantages and limitations, and
each is at a different state of technical development. However, the use of each
method involves three steps:
1. Laboratory analysis of samples to determine their genetic-marker

types at multiple sites of potential variation.
2. Comparison of the genetic-marker types of the samples to determine

SUMMARY 7
FIGURE 3
Polymerase chain reaction (PCR). Courtesy, Perkin-Elmer Cetus Instruments.

SUMMARY 8
whether the types match and thus whether the samples could have
come from the same source.
3. If the types match, statistical analysis of the population frequencies
of the types to determine the probability that a match would have
been observed by chance in a comparison of samples from different
persons.
Before any particular DNA typing method is used for forensic purposes,
precise and scientifically reliable procedures for performing all three steps must
be established. It is meaningless to speak of the reliability of DNA typing in
general—i.e., without specifying a particular method.
Despite the challenges of forensic DNA typing, it is possible to develop
reliable forensic DNA typing systems, provided that adequate scientific care is
taken to define and characterize the methods.
Recommendations
• Any new DNA typing method (or a substantial variation of an existing

method) must be rigorously characterized in both research and forensic
settings, to determine the circumstances under which it will yield
reliable results.
• DNA analysis in forensic science should be governed by the highest
standards of scientific rigor, including the following requirements:
— Each DNA typing procedure must be completely described in a detailed,

written laboratory protocol.
— Each DNA typing procedure requires objective and quantitative rules
for identifying the pattern of a sample.
— Each DNA typing procedure requires a precise and objective matching
rule for declaring whether two samples match.
— Potential artifacts should be identified by empirical testing, and
scientific controls should be designed to serve as internal checks to test
for the occurrence of artifacts.
— The limits of each DNA typing procedure should be understood,
especially when the DNA sample is small, is a mixture of DNA from
multiple sources, or is contaminated with interfering substances.
— Empirical characterization of a DNA typing procedure must be
published in appropriate scientific journals.
— Before a new DNA typing procedure can be used, it must have not only a
solid scientific foundation, but also a solid base of experience.
• The committee strongly recommends the establishment of a National

Committee on Forensic DNA Typing (NCFDT) under the auspices of an

SUMMARY 9
appropriate government agency or agencies to provide expert advice

primarily on scientific and technical issues concerning forensic DNA
typing.
• Novel forms of variation in the genome that have the potential for
increased power of discrimination between persons are being
discovered. Furthermore, new ways to demonstrate variations in the
genome are being developed. The current techniques are likely to be
superseded by others that provide unambiguous individual identification
and have such advantages as automatability and economy. Each new
method should be evaluated by the NCFDT for use in the forensic
setting, applying appropriate criteria to ensure that society derives
maximal benefit from DNA typing technology.
STATISTICAL BASIS FOR INTERPRETATION

Because any two human genomes differ at about 3 million sites, no two
persons (barring identical twins) have the same DNA sequence. Unique
identification with DNA typing is therefore possible, in principle, provided that
enough sites of variation are examined. However, the DNA typing systems used
today examine only a few sites of variation and have only limited resolution for
measuring the variability at each site. There is a chance that two persons have
DNA patterns (i.e., genetic types) that match at the small number of sites
examined. Nevertheless, even with today's technology, which uses 3-5 loci, a
match between two DNA patterns can be considered strong evidence that the two
samples came from the same source. Interpreting a DNA typing analysis requires a
valid scientific method for estimating the probability that a random person by
chance matches the forensic sample at the sites of DNA variation examined. To
say that two patterns match, without providing any scientifically valid estimate
(or, at least, an upper bound) of the frequency with which such matches might
occur by chance, is meaningless. The committee recommends approaches for
making sound estimates that are independent of the race or ethnic group of the
subject.
A standard way to estimate frequency is to count occurrences in a random
sample of the appropriate population and then use classical statistical formulas to
place upper and lower confidence limits on the estimate. (Because forensic
science should avoid placing undue weight on incriminating evidence, an upper
confidence limit of the frequency should be used in court.) If a particular DNA
pattern occurred in 1 of 100 samples, the estimated frequency would be 1%, with
an upper confidence limit of 4.7%. If the pattern occurred in 0 of 100 samples,
the estimated frequency would be 0%, with an upper confidence limit of 3%.
(The upper bound cited is the traditional 95% confidence limit, whose use implies
that the true value has only a 5% chance of exceeding the upper bound.) Such
estimates produced

SUMMARY 10
by straightforward counting have the virtue that they do not depend on

theoretical assumptions, but simply on the samples having been randomly drawn
from the appropriate population. However, such estimates do not take advantage
of the full potential of the genetic approach.
In contrast, population frequencies often quoted for DNA typing analyses
are based not on actual counting, but on theoretical models based on the
principles of population genetics. Each matching allele is assumed to provide
statistically independent evidence, and the frequencies of the individual alleles
are multiplied together to calculate a frequency of the complete DNA pattern.
Although a databank might contain only 500 people, multiplying the frequencies
of enough separate events might result in an estimated frequency of their all
occurring in a given person of 1 in a billion. Of course, the scientific validity of
the multiplication rule depends on whether the events (i.e., the matches at each
allele) are actually statistically independent.
Because it is impossible or impractical to draw a large enough population to
test directly calculated frequencies of any particular DNA profile much below 1
in 1,000, there is not a sufficient body of empirical data on which to base a claim
that such frequency calculations are reliable or valid. The assumption of
independence must be strictly scrutinized and estimation procedures appropriately
adjusted if possible. (The rarity of all the genotypes represented in the databank
can be demonstrated by pairwise comparisons, however. Thus, in a recently
reported analysis of the FBI databank, no exactly matching pairs were found in
five-locus DNA profiles, and the closest match was a single three-locus match
among 7.6 million pairwise comparisons.)
The multiplication rule has been routinely applied to blood-group
frequencies in the forensic setting. However, that situation is substantially
different. Because conventional genetic markers are only modestly polymorphic
(with the exception of human leukocyte antigen, HLA, which usually cannot be
typed in forensic specimens), the multilocus genotype frequencies are often about
1 in 100. Such estimates have been tested by simple empirical counting. Pairwise
comparisons of allele frequencies have not revealed any correlation across loci.
Hence, the multiplication rule does not appear to lead to the risk of extrapolating
beyond the available data for conventional markers. But highly polymorphic DNA
markers exceed the informative power of protein markers and so multiplication
of their estimated frequencies leads to estimates that are far less than the
reciprocal of the size of the databanks, i.e., 1/N, N being the number of entries in
the databank.
The multiplication rule is based on the assumption that the population does
not contain subpopulations with distinct allele frequencies—that each person's
alleles constitute statistically independent random selections from

SUMMARY 11
a common gene pool. Under that assumption, the procedure for calculating the
population frequency of a genotype is straightforward:
• Count the frequency of alleles. For each allele in the genotype, examine a
random sample of the population and count the proportion of matching
alleles—that is, alleles that would be declared to match according to the
rule that is used for declaring matches in a forensic context.
• Calculate the frequency of the genotype at each locus. The frequency of a
homozygous genotype a1/a1 is calculated to be pa12, where pa1denotes
the frequency of allele a1. The frequency of a heterozygous genotype
a1/a2 is calculated to be 2pa1pa2, where pa1 and pa2 denote the
frequencies of alleles a1 and a2. In both cases, the genotype frequency is
calculated by multiplying the two allele frequencies, on the assumption
that there is no statistical correlation between the allele inherited from
one's father and the allele inherited from one's mother. When there is no
correlation between the two parental alleles, the locus is said to be in
Hardy-Weinberg equilibrium.
• Calculate the frequency of the complete multilocus genotype by
multiplying the genotype frequencies at all the loci. As in the previous
step, this calculation assumes that there is no correlation between the
genotypes at the individual loci; the absence of such correlation is called
linkage equilibrium. Suppose, for example, that a person has genotype
a1/a2, b1/b2, c1/c1. If a random sample of the appropriate population
shows that the frequencies of alleles a1, a2, b1, b2, and c1 are
approximately 0.1, 0.2, 0.3, 0.1, and 0.2, respectively, then the
population frequency of the genotype would be estimated to be [2(0.1)
(0.2)][2(0.3)(0.1)][(0.2)(0.2)] = 0.000096, or about 1 in 10,417.
The validity of the multiplication rule depends on the assumption of absence

of population substructure. Population substructure violates the assumption of
statistical independence of alleles. In a population that contains groups each with
different allele frequencies, the presence of one allele in a person's genotype can
alter the statistical expectation of the other alleles in the genotype. For example, a
person who has one allele that is common among Italians is more likely to be of
Italian descent and is thus more likely to carry additional alleles that are common
among Italians. The true genotype frequency is thus higher than would be
predicted by applying the multiplication rule using the average frequency in the
entire population.
To illustrate the problem with a hypothetical example, suppose that a
particular allele at a VNTR locus has a 1% frequency in the general population,
but a 20% frequency in a specific subgroup. The frequency of homozygotes for
the allele would be calculated to be 1 in 10,000 according to the allele frequency
determined by sampling the general population, but would actually be 1 in 25 for
the subgroup. That is a hypothetical and

SUMMARY 12
extreme example, but illustrates the potential effect of demography on gene

frequency estimation.
The key question underlying the use of the multiplication rule—i.e., whether
actual populations have significant substructure for the loci used for forensic
typing—has provoked considerable debate among population geneticists. Some
have expressed serious concern about the possibility of significant substructure.
They maintain that census categories—such as North American Caucasians,
blacks, Hispanics, Asians, and Native Americans—are not homogeneous groups,
but rather that each group is an admixture of subgroups with somewhat different
allele frequencies. Allele frequencies have not yet been homogenized, because
people tend to mate within their subgroups.
Those population geneticists also point out that, for any particular genetic
marker, the actual degree of subpopulation differentiation cannot be predicted in
advance, but must be determined empirically. Furthermore, they doubt that the
presence of substructure can be detected by the application of statistical tests to
data from large mixed populations. Population differentiation must be assessed
through direct studies of allele frequencies in ethnic groups.
Other population geneticists, while recognizing the possibility or likelihood
of population substructure, conclude that the evidence to date suggests only a
minimal effect on estimates of genotype frequencies. Recent empirical studies
concerning VNTR loci detected no deviation from independence within or across
loci. Moreover, as pointed out earlier, pairwise comparisons of all five-locus DNA
profiles in the FBI database showed no exact matches; the closest match was a
single three-locus match among 7.6 million pairwise comparisons. Those studies
are interpreted as indicating that multiplication of gene frequencies across loci
does not lead to major inaccuracies in the calculation of genotype frequency—at
least not for the specific polymorphic loci examined.
Although mindful of those opposing views, the committee has chosen to
assume for the sake of discussion that population substructure may exist and to
provide a method for estimating population frequencies in a manner that would
adequately account for it. Our decision is based on four considerations:
1. It is possible to provide conservative estimates of population

frequency, without giving up the inherent power of DNA typing.
2. It is appropriate to prefer somewhat conservative numbers for
forensic DNA typing, especially because the statistical power lost in
this way can often be recovered through typing of additional loci,
where required.
3. It is important to have a general approach that is applicable to any
loci used for forensic typing. Recent empirical studies pertain only to
the population genetics of the VNTR loci in current use. However,
we expect

SUMMARY 13
forensic DNA typing to undergo much change over the next decade—
including the introduction of different types of DNA
polymorphisms, some of which might have different properties from
the standpoint of population genetics.
4. It is desirable to provide a method for calculating population
frequencies that is independent of the ethnic group of the subject.
The committee is aware of the need to account for possible population

substructure, and it recommends the use of the ceiling principle. The
multiplication rule will yield conservative estimates even for a substructured
population, provided that the allele frequencies used in the calculation exceed the
allele frequencies in any of the population subgroups. The ceiling principle
involves two steps: (1) for each allele at each locus, determine a ceiling frequency
that is an upper bound of the allele frequency that is independent of the ethnic
background of a subject; and (2) to calculate a genotype frequency, apply the
multiplication rule according to the ceiling allele frequencies.
To determine ceiling frequencies, the committee strongly recommends the
following approach: (1) Draw random samples of 100 persons from each of 15-20
populations that represent groups relatively homogeneous genetically. (2) Take as
the ceiling frequency the largest frequency in any of those populations or 5%,
whichever is larger.
Use of the ceiling principle yields the same frequency of a given genotype,
regardless of the suspect's ethnic background, because the reported frequency
represents a maximum for any possible ethnic heritage. Accordingly, the ethnic
background of the individual suspect should be ignored in estimating the
likelihood of a random match. The calculation is fair to suspects, because the
estimated probabilities are likely to be conservative in their incriminating power.
Some legal commentators have pointed out that frequencies should be based
on the population of possible perpetrators, rather than on the population to which a
particular suspect belongs. Although that argument is formally correct,
practicalities often preclude use of that approach. Furthermore, the ceiling
principle eliminates the need for investigating the perpetrator population, because
it yields an upper bound to the frequency that would be obtained by that
approach.
Although the ceiling principle is a conservative approach, we feel that it is
appropriate. DNA typing is unique, in that the forensic analyst has an essentially
unlimited ability to adduce additional evidence: whatever power is sacrificed by
requiring conservative estimates can be regained by examining additional loci.
(Although there might be some cases in which the DNA sample is insufficient to
permit typing additional loci with RFLPs, this limitation is likely to disappear
with the eventual use of PCR.)
That no evidence of population substructure is demonstrable with the

SUMMARY 14
markers tested so far cannot be taken to mean that such does not exist for other
markers. Preservation of population DNA samples in the form of immortalized
cell lines will ensure that DNA is available for determining population
frequencies of any DNA pattern as new and better techniques become available,
without the necessity of collecting fresh samples. It will also provide samples for
standardization of methods across laboratories.
Because of the similarity in DNA patterns between relatives, databanks of
DNA of convicted criminals have the ability to point not just to individuals but to
entire families—including relatives who have committed no crime. Clearly, this
raises serious issues of privacy and fairness. It is inappropriate, for reasons of
privacy, to search databanks of DNA from convicted criminals in such a fashion.
Such uses should be prevented both by limitations of the software for searching
and by statutory guarantees of privacy.
The genetic correlation among relatives means that the probability that a
forensic sample will match a relative of the person who left it is considerably
greater than the probability that it will match a random person.
Especially for a technology with high discriminatory power, such as DNA
typing, laboratory error rates must be continually estimated in blind proficiency
testing and must be disclosed to juries.
Recommendations
• As a basis for the interpretation of the statistical significance of DNA

typing results, the committee recommends that blood samples be
obtained from 100 randomly selected persons in each of 15-20 relatively
homogeneous populations; that the DNA in lymphocytes from these
blood samples be used to determine the frequencies of alleles currently
tested in forensic applications; and that the lymphocytes be
''immortalized" and preserved as a reference standard for determination
of allele frequencies in tests applied in different laboratories or
developed in the future. The collection of samples and their study should
be overseen by a National Committee on Forensic DNA Typing.
• The ceiling principle should be used in applying the multiplication rule
for estimating the frequency of particular DNA profiles. For each allele
in a person's DNA pattern, the highest allele frequency found in any of
the 15-20 populations or 5% (whichever is larger) should be used.
• In the interval (which should be short) while the reference blood samples
are being collected, the significance of the findings of multilocus DNA
typing should be presented in two ways: (1) If no match is found with
any sample in a total databank of N persons (as will usually be the case),
that should be stated, thus indicating the rarity of a random match. (2) In
applying the multiplication rule, the 95% upper confidence limit of the
frequency of each allele should be calculated for separate U.S. "racial"

SUMMARY 15
groups and the highest of these values or 10% (whichever is the larger)
should be used. Data on at least three major "races" (e.g., Caucasians,
blacks. Hispanics, Asians, and Native Americans) should be analyzed.
• Any population databank used to support DNA typing should be openly
available for scientific inspection by parties to a legal case and by the
scientific community.
• Laboratory error rates should be measured with appropriate proficiency
tests and should play a role in the interpretation of results of forensic
DNA typing.
STANDARDS
Critics and supporters of the forensic uses of DNA typing agree that there is a
lack of standardization of practices and a lack of uniformly accepted methods for
quality assurance. The deficiencies are due largely to the rapid emergence of DNA
typing and its introduction in the United States through the private sector.
As the technology developed in the United States, private laboratories using
widely differing methods (single-locus RFLP, multilocus RFLP, and PCR) began
to offer their services to law-enforcement agencies. During the same period, the
FBI was developing its own RFLP method, with a different restriction enzyme
and different single-locus probes. The FBI's method has become the one most
widely used in public forensic-science laboratories. Each method has its own
advantages and disadvantages, databanks, molecular-weight markers, match
criteria, and reporting methods.
Regardless of the causes, practices in DNA typing vary, and so do the
educational backgrounds, training, and experience of the scientists and
technicians who perform the tests, the internal and external proficiency testing
conducted, the interpretation of results, and approaches to quality assurance.
It is not uncommon for an emerging technology to go without regulation
until its importance and applicability are established. Indeed, the development of
DNA typing technology has occurred without regulation of laboratories and their
practices, public or private. The committee recognizes that standardization of
practices in forensic laboratories in general is more problematic than in other
laboratory settings; stated succinctly, forensic scientists have little or no control
over the nature, condition, form, or amount of sample with which they must
work. But it is now clear that DNA typing methods are a most powerful adjunct
to forensic science for personal identification and have immense benefit to the
public—so powerful, so complex, and so important that some degree of
standardization of laboratory procedures is necessary to assure the courts of
high-quality results. DNA typing is capable, in principle, of an extremely low
inherent rate of false results, so the risk of error will come from poor laboratory

SUMMARY 16
practice or poor sample handling and labeling; and, because DNA typing is
technical, a jury requires the assurance of laboratory competence in test results.
At issue, then, is how to achieve standardization of DNA typing laboratories
in such a manner as to assure the courts and the public that results of DNA typing
by a given laboratory are reliable, reproducible, and accurate.
Quality assurance can best be described as a documented system of activities
or processes for the effective monitoring and verification of the quality of a work
product (in this case, laboratory results). A comprehensive quality-assurance
program must include elements that address education, training, and certification
of personnel; specification and calibration of equipment and reagents;
documentation and validation of analytical methods; use of appropriate standards
and controls; sample handling procedures; proficiency testing; data interpretation
and reporting; internal and external audits of all the above; and corrective actions
to address deficiencies and weight their importance for laboratory competence.
Recommendations
Although standardization of forensic practice is difficult because of the
nature of the samples, DNA typing is such a powerful and complex technology
that some degree of standardization is necessary to ensure high standards.
• Each forensic-science laboratory engaged in DNA typing must have a

formal, detailed quality-assurance and quality-control program to
monitor work, on both an individual and a laboratory-wide basis.
• The Technical Working Group on DNA Analysis and Methods
(TWGDAM) guidelines for a quality-assurance program for DNA RFLP
analysis are an excellent starting point for a quality-assurance program,
which should be supplemented by the additional technical
recommendations of this committee.
• The TWGDAM group should continue to function, playing a role
complementary to that of the National Committee on Forensic DNA
Typing (NCFDT). To increase its effectiveness, TWGDAM should
include additional technical experts from outside the forensic community
who are not closely tied to any forensic laboratory.
• Quality-assurance programs in individual laboratories alone are
insufficient to ensure high standards. External mechanisms are needed,
to ensure adherence to the practices of quality assurance. Potential
mechanisms include individual certification, laboratory accreditation,
and state or federal regulation.
• One of the best guarantees of high quality is the presence of an active

SUMMARY 17
professional-organization committee that is able to enforce standards.

Although professional societies in forensic science have historically not
played an active role, the American Society of Crime Laboratory
Directors (ASCLD) and the American Society of Crime Laboratory
Directors-Laboratory Accreditation Board (ASCLD-LAB) recently have
shown substantial interest in enforcing quality by expanding the
ASCLD-LAB accreditation program to include mandatory proficiency
testing. ASCLD-LAB must demonstrate that it will actively discharge
this role.
• Because private professional organizations lack the regulatory authority
to require accreditation, further means are needed to ensure compliance
with appropriate standards.
• Courts should require that laboratories providing DNA typing evidence
have proper accreditation for each DNA typing method used. Any
laboratory that is not formally accredited and that provides evidence to
the courts—e.g., a nonforensic laboratory repeating the analysis of a
forensic laboratory—should be expected to demonstrate that it is
operating at the same level of standards as accredited laboratories.
• Establishing mandatory accreditation should be a responsibility of the
Department of Health and Human Services (DHHS), in consultation with
the Department of Justice (DOJ). DHHS is the appropriate agency,
because it has extensive experience in the regulation of clinical
laboratories through programs under the Clinical Laboratory
Improvement Act and has extensive expertise in molecular genetics
through the National Institutes of Health. DOJ must be involved,
because the task is important for law enforcement.
• The National Institute of Justice (NIJ) does not appear to receive
adequate funds to support proper education, training, and research in the
field of forensic DNA typing. The level of funding should be re-
evaluated and increased appropriately.
DATABANKS AND PRIVACY OF INFORMATION

DNA typing in the criminal-justice system has so far been used primarily for
direct comparison of DNA profiles of evidence samples with profiles of samples
from suspects. However, that application constitutes only the tip of the iceberg of
potential law-enforcement applications. If DNA profiles of samples from a
population were stored in computer databanks (databases), DNA typing could be
applied in crimes without suspects. Investigators could compare DNA profiles of
biological evidence samples with profiles in a databank to search for suspects.
In many respects, the situation is analogous to that of latent finger-prints.
Originally, latent fingerprints were used for comparing crime-scene evidence with
suspects. With the development of the Automated Fingerprint Identification
Systems (AFIS) in the last decade, the investigative use

SUMMARY 18
of fingerprints has dramatically expanded. Forensic scientists can enter an

unidentified latent-fingerprint pattern into an automated system and within
minutes compare it with millions of person's patterns contained in a computer
file. In its short history, automated fingerprint analysis has been credited with
solving tens of thousands of crimes.
The computer technology required for an automated fingerprint
identification system is sophisticated and complex. Fingerprints are complicated
geometric patterns, and the computer must store, recognize, and search for
complex and variable patterns of ridges and minutiae in the millions of prints on
file. Several commercially available but expensive computer systems are in use
around the world. In contrast, the computer technology required for DNA
databanks is relatively simple. Because DNA profiles can be reduced to a list of
genetic types (hence, a list of numbers), DNA profile repositories can use
relatively simple and inexpensive software and hardware. Consequently,
computer requirements should not pose a serious problem in the development of
DNA profile databanks.
Confidentiality and security of DNA-related information are especially
important and difficult issues, because we are in the midst of two extraordinary
technological revolutions that show no signs of abating: in molecular biology,
which is yielding an explosion of information about human genetics, and in
computer technology, which is moving toward national and international
networks connecting growing information resources.
Even simple information about identity requires confidentiality. Just as
fingerprint files can be misused, DNA profile information could be misused to
search and correlate criminal-record databanks or medical-record databanks.
Computer storage of information increases the possibilities for misuse. For
example, addresses, telephone numbers, social security numbers, credit ratings,
range of incomes, demographic categories, and information on hobbies are
currently available for many of our citizens in various distributed computerized
data sources. Such data can be obtained directly through access to specific
sources, such as credit-rating services, or through statistical disclosure, which
refers to the ability of a user to derive an estimate of a desired statistic or feature
from a databank or a collection of databanks. Disclosure can be achieved through
one query or a series of queries to one or more databanks. With DNA
information, queries might be directed at obtaining numerical estimates of values
or at deducing the state of an attribute of an individual through a series of
Boolean (yes-no) queries to multiple distributed databanks.
Several private laboratories already offer a DNA-banking service (sample
storage in freezers) to physicians, genetic counselors, and, in some cases, anyone
who pays for the service. Typically, such information as name, address, birth
date, diagnosis, family history, physician's name and address, and genetic
counselor's name and address is stored with samples.

SUMMARY 19
That information is useful for local, independent bookkeeping and record

management. But it is also ripe for statistical or correlative disclosure. Just the
existence in a databank of a sample from a person, independent of any DNA-
related information, may be prejudicial to the person. In some laboratories, the
donor cannot legally prevent outsiders' access to the samples, but can request its
withdrawal. A request for withdrawal might take a month or more to process. In
most cases, only physicians with signed permission of the donor have access to
samples, but typically no safeguards are taken to verify individual requests
independently. That is not to say that the laboratories intend to violate donors'
rights; they are simply offering a service for which there is a recognized market
and attempting to provide services as well as they can.
Recommendations
• In the future, if pilot studies confirm its value, a national DNA profile
databank should be created that contains information on felons convicted
of particular violent crimes. Among crimes with high rates of
recidivism, the case is strongest for rape, because perpetrators typically
leave biological evidence (semen) that could allow them to be
identified. Rape is the crime for which the databank will be of primary
use. The case is somewhat weaker for violent offenders who are most
likely to commit homicide as a recidivist offense, because killers leave
biological evidence only in a minority of cases.
• The databank should also contain DNA profiles of unidentified persons
made from biological samples found at crime scenes. These would be
samples known to be of human origin, but not matched with any known
persons.
• Databanks containing DNA profiles of members of the general
population (as exist for ordinary fingerprints for identification purposes)
are not appropriate, for reasons of both privacy and economics.
• DNA profile databanks should be accessible only to legally authorized
persons and should be stored in a secure information resource.
• Legal policy concerning access and use of both DNA samples and DNA
databank information should be established before widespread
proliferation of samples and information repositories. Interim protection
and sanctions against misuse and abuse of information derived from
DNA typing should be established immediately. Policies should
explicitly define authorized uses and should provide for criminal
penalties for abuses.
• Although the committee endorses the concept of a limited national DNA
profile databank, it doubts that existing RFLP-based technology
provides an appropriate wise long-term foundation for such a databank.
We expect current methods to be replaced soon with techniques that are
sim

SUMMARY 20
pler, easier to automate, and less expensive—but incompatible with

existing DNA profiles. Accordingly, the committee does not recommend
establishing a comprehensive DNA profile databank yet.
• For the short term, we recommend the establishment of pilot projects
that involve prototype databanks based on RFLP technology and
consisting primarily of profiles of violent sex offenders. Such pilot
projects could be worthwhile for identifying problems and issues in the
creation of databanks. However, in the intermediate term, more efficient
methods will replace the current one, and the forensic community should
not allow itself to become locked into an outdated method.
• State and federal laboratories, which have a long tradition and much
experience in the management of other types of basic evidence, should
be given primary responsibility, authority, and additional resources to
handle forensic DNA testing and all the associated sample-handling and
data-handling requirements.
• Private-sector firms should not be discouraged from continuing to
prepare and analyze DNA samples for specific cases or for databank
samples, but they must be held accountable for misuse and abuse to the
same extent as government-funded laboratories and government
authorities.
DNA INFORMATION IN THE LEGAL SYSTEM

To produce biological evidence that is admissible in court in criminal cases,
forensic investigators must be well trained in the collection and handling of
biological samples for DNA analysis. They should take care to minimize the risk
of contamination and ensure that possible sources of DNA are well preserved and
properly identified. As in any forensic work, they must attend to the essentials of
preserving specimens, labeling, and the chain of custody and must observe
constitutional and statutory requirements that regulate the collection and handling
of samples. The Fourth Amendment provides much of the legal framework for
the gathering of DNA samples from suspects or private places, and court orders
are sometimes needed in this connection.
In civil (noncriminal) cases—such as paternity, custody, and proof-of-death
cases—the standards for admissibility must also be high, because DNA evidence
might be dispositive. The relevant federal rules (Rules 403 and 702-706) and
most state rules of evidence do not distinguish between civil and criminal cases in
determining the admissibility of scientific data. In a civil case, however, if the
results of a DNA analysis are not conclusive, it will usually be possible to obtain
new samples for study.
The advent of DNA typing technology raises two key issues for judges:
determining admissibility and explaining to jurors the appropriate standards for
weighing evidence. A host of subsidiary questions with respect to how

SUMMARY 21
expert evidence should be handled before and during a trial to ensure prompt and
effective adjudication apply to all evidence and all experts.
In the United States, there are two main tests for admissibility of scientific
information through experts. One is the Frye test, enunciated in Frye v. United
States. The other is a "helpfulness" standard found in the Federal Rules of
Evidence and many of its state counterparts. In addition, several states have
recently enacted laws that essentially mandate the admission of DNA typing
evidence.
The test for the admissibility of novel scientific evidence enunciated in Frye
v. United States is still probably the most frequently invoked test in American
case law. A majority of states profess adherence to the Frye rule, although a
growing minority have adopted variations on the helpfulness standard suggested
by the Federal Rules of Evidence.
Frye predicates the admissibility of novel scientific evidence on its general
acceptance in a particular scientific field: "While courts will go a long way in
admitting expert testimony deduced from a well-recognized scientific principle or
discovery, the thing from which the deduction is made must be sufficiently
established to have gained general acceptance in the particular field in which it
belongs." Thus, admissibility depends on the quality of the science underlying the
evidence, as determined by scientists themselves. Theoretically, the court's role in
this preliminary determination is narrow: it should conduct a hearing to determine
whether the scientific theory underlying the evidence is generally accepted in the
relevant scientific community and whether the specific techniques used are
reliable for their intended purpose.
In practice, the court is much more involved. The court must determine the
scientific fields from which experts should be drawn. Complexities arise with
DNA typing, because the full typing process rests on theories and findings that
pertain to various scientific fields. For example, the underlying theory of
detecting polymorphisms is accepted by human geneticists and molecular
biologists, but population geneticists and other statisticians might differ as to the
appropriate method for determining the population frequency of a genotype in the
general population or in a particular geographic, ethnic, or other group. The
courts often let experts on a process, such as DNA typing, testify to the various
scientific theories and assumptions on which the process rests, even though the
experts' knowledge of some of the underlying theories is likely to be at best that
of a generalist, rather than a specialist.
The Frye test sometimes prevents scientific evidence from being presented
to a jury unless it has sufficient history to be accepted by some subspecialty of
science. Under Frye, potentially helpful evidence may be excluded until
consensus has developed. By 1991, DNA evidence had been considered in
hundreds of Frye hearings involving felony prosecutions in

SUMMARY 22
more than 40 states. The overwhelming majority of trial courts ruled that such
evidence was admissible, but there have been some important exceptions.
In determining admissibility according to the helpfulness standard under the
Federal Rules of Evidence, without specifically repudiating the Frye rule, a court
can adopt a more flexible approach. Rule 702 states that, "if scientific, technical
or other specialized knowledge will assist the trier of fact to understand the
evidence or to determine a fact in issue, a witness qualified as an expert by
knowledge, skill, experience, training, or education, may testify thereto in the
form of an opinion or otherwise."
Rule 702 should be read with Rule 403, which requires the court to
determine the admissibility of evidence by balancing its probative force against
its potential for misapplication by the jury. In determining admissibility, the court
should consider the soundness and reliability of the process or technique used in
generating evidence; the possibility that admitting the evidence would
overwhelm, confuse, or mislead the jury; and the proffered connection between
the scientific research or test result to be presented and particular disputed factual
issues in the case.
The federal rule, as interpreted by some courts, encompasses Fryeby making
general acceptance of scientific principles by experts a factor, and in some cases a
decisive factor, in determining probative force. A court can also consider the
qualifications of experts testifying about the new scientific principle, the use to
which the technique based on the principle has been put, the technique's potential
for error, the existence of specialized literature discussing the technique, and its
novelty.
With the helpfulness approach, the court should also consider factors that
might prejudice the jury. One of the most serious concerns about scientific
evidence, novel or not, is that it possesses an aura of infallibility that could
overwhelm a jury's critical faculties. The likelihood that the jury would abdicate
its role as critical fact-finder is believed by some to be greater if the science
underlying an expert's conclusion is beyond its intellectual grasp. The jury might
feel compelled to accept or reject a conclusion absolutely or to ignore evidence
altogether. However, some experience indicates that jurors tend not to be
overwhelmed by scientific proof and that they prefer experiential data based on
traditional forms of evidence. Moreover, the presence of opposing experts might
prevent a jury from being unduly impressed with one expert or the other.
Conversely, the absence of an opposing expert might cause a jury to give too
much weight to expert testimony, on the grounds that, if the science were truly
controversial, it would have heard the opposing view. Nevertheless, if the
scientific evidence is valid, the solution to those possible problems is not to
exclude the evidence, but to ensure through instructions and testimony that the
jury is equipped to consider rationally whatever evidence is presented.

SUMMARY 23
In determining admissibility with the helpfulness approach, the court should

consider a number of factors in addition to reliability. First is the significance of
the issue to which the evidence is directed. If the issue is tangential to the case,
the court should be more reluctant to allow a time-consuming presentation of
scientific evidence that might itself confuse the jury. Second, the availability and
sufficiency of other evidence might make expert testimony about DNA
superfluous. And third, the court should be mindful of the need to instruct and
advise the jury so as to eliminate the risk of prejudice.
Recommendations
• Courts should take judicial notice of three scientific underpinnings of

DNA typing:
— The study of DNA polymorphisms can, in principle, provide a reliable

method for comparing samples.
— Each person's DNA is unique (except that of identical twins), although
the actual discriminatory power of any particular DNA test will depend
on the sites of DNA variation examined.
— The current laboratory procedure for detecting DNA variation
(specifically, single-locus probes analyzed on Southern blots without
evidence of band shifting) is fundamentally sound, although the validity
of any particular implementation of the basic procedure will depend on
proper characterization of the reproducibility of the system (e.g.,
measurement variation) and inclusion of all necessary scientific
controls.
• The adequacy of the method used to acquire and analyze samples in a

given case bears on the admissibility of the evidence and should, unless
stipulated by opposing parties, be adjudicated case by case. In this
adjudication, the accreditation and certification status of the laboratory
performing the analysis should be taken into account.
• Because of the potential power of DNA evidence, authorities should
make funds available to pay for expert witnesses, and the appropriate
parties must be informed of the use of DNA evidence as soon as
possible.
• DNA samples (and evidence likely to contain DNA) should be preserved
whenever that is possible.
• All data and laboratory records generated by analysis of DNA samples
should be made freely available to all parties. Such access is essential
for evaluating the analysis.
• Protective orders should be used only to protect the privacy of
individuals.

SUMMARY 24
DNA TYPING AND SOCIETY

The introduction of any new technology is likely to raise concerns about its
impact on society. Financial costs, potential harm to the interests of individuals,
and threats to liberty or privacy are only a few of the worries typically voiced
when a new technology is on the horizon. DNA typing technology has the
potential for uncovering and revealing a great deal of information that most
people consider to be intensely private. Examples might be the presence of genes
involved in known genetic disorders or genes that have been linked to a
heightened risk of particular major diseases in some populations.
Although DNA technology involves new scientific techniques for
identifying or excluding people, the techniques are extensions and analogues of
techniques long used in forensic science, such as serological and fingerprint
examinations. Ethical questions can be raised about other aspects of this new
technology, but the committee does not see it as violating a fundamental ethical
principle.
A new practice or technology can be subjected to further ethical analysis by
using two leading ethical perspectives. The first examines the action or practice in
terms of the rights of people who are affected; the second explores the potential
positive and negative consequences (nonmonetary costs and benefits) of the
action or practice, in an attempt to determine whether the potential good
consequences outweigh the bad.
Two main questions can be asked about moral rights: Does the use of DNA
technology give rise to any new rights not already recognized? Does the use of
DNA technology enhance, endanger, or diminish the rights of anyone who
becomes involved in legal proceedings? In answer to the first question, it is hard
to think of any new rights not already recognized that come into play with the
introduction of DNA technology into forensic science. The answer to the second
question requires a specification of the classes of people whose rights might be
affected and what those rights might be.
Concerns about intrusions into privacy and breaches of confidentiality
regarding the use of DNA technology in such enterprises as gene mapping are
frequently voiced, and they are legitimate ethical worries. The concerns are
pertinent to the role of DNA technology in forensic science, as well as to its
widespread use for other purposes and in other social contexts. A potential
problem related to the confidentiality of any information obtained is the
safeguarding of the information and the prevention of its unauthorized release or
dissemination; that can also be classified under the heading of abuse and misuse,
as well as seen as a violation of individual rights in the forensic context.
Another factor to be weighed in a consequentialist ethical analysis is

SUMMARY 25
whose interests are to count and whether some people's interests should be given
greater weight than others'. For example, there are the interests of the accused, the
interests of victims of crime or their families in apprehending and convicting
perpetrators, and the interests of society. Whether the interests of society in
seeing that justice is done should count as much as the interests of the accused or
the victim is open to question.
A major issue is the preservation of confidentiality of information obtained
with DNA technology in the forensic context. When databanks are established in
such a way that state and federal law-enforcement authorities can gain access to
DNA profiles, not only of persons convicted of violent crimes but of others as
well, there is a serious potential for abuse of confidential information. The
victims of many crimes in urban areas are relatives or neighbors of the
perpetrators, and these victims might themselves be former or future perpetrators.
There is greater likelihood that DNA information on minority-group members,
such as blacks and Hispanics, will be stored or accessed. However, it is important
to note that use of the ceiling principle removes the necessity to categorize
criminals (or defendants in general) by ethnic group for the purposes of DNA
testing and storage of information in databanks.
The introduction of a powerful new technology is likely to set up
expectations that might be unwarranted or unrealistic in practice. Various
expectations regarding DNA typing technology are likely to be raised in the
minds of jurors and others in the forensic setting. For example, public perception
of the accuracy and efficacy of DNA typing might well put pressure on
prosecutors to obtain DNA evidence whenever appropriate samples are available.
As the use of the technology becomes widely publicized, juries will come to
expect it, just as they now expect fingerprint evidence.
Two aspects of DNA typing technology contribute to the likelihood of its
raising inappropriate expectations in the minds of jurors. The first is a jury's
perception of an extraordinarily high probability of enabling a definitive
identification of a criminal suspect; the second is the scientific complexity of the
technology, which results in laypersons' inadequate understanding of its
capabilities and failings. Taken together, those two aspects can lead to a jury's
ignoring other forensic evidence that it should be considering.
As large felon databanks are created, the forensic community could well
place more reliance on DNA evidence, and a possible consequence is the
underplaying of other forensic evidence. Unwarranted expectations about the
power of DNA technology might result in the neglect of relevant evidence.
The need for international cooperation in law enforcement calls for
appropriate scientific and technical exchange among nations. As in other areas of
science and technology, dissemination of information about DNA

SUMMARY 26
typing and training programs for personnel likely to use the technology should be
encouraged. It is desirable that all nations that will collaborate in law-
enforcement activities have similar standards and practices, so efforts should be
furthered to exchange scientific knowledge and expertise regarding DNA
technology in forensic science.
Recommendations
• In the forensic context as in the medical setting, DNA information is

personal, and a person's privacy and need for confidentiality should be
respected. The release of DNA information on a criminal population
without the subjects' permission for purposes other than law
enforcement should be considered a misuse of the information, and legal
sanctions should be established to deter the unauthorized dissemination
or procurement of DNA information that was obtained for forensic
purposes.
• Prosecutors and defense counsel should not oversell DNA evidence.
Presentations that suggest to a judge or jury that DNA typing is infallible
are rarely justified and should be avoided.
• Mechanisms should be established to ensure accountability of
laboratories and personnel involved in DNA typing and to make
appropriate public scrutiny possible.
• Organizations that conduct accreditation or regulation of DNA
technology for forensic purposes should not be subject to the influence
of private companies, public laboratories, or other organizations actually
engaged in laboratory work.
• Private laboratories used for testing should not be permitted to withhold
information from defendants on the grounds that trade secrets are
involved.
• The same standards and peer-review processes used to evaluate advances
in biomedical science and technology should be used to evaluate
forensic DNA methods and techniques.
• Efforts at international cooperation should be furthered, in order to
ensure uniform international standards and the fullest possible exchange
of scientific knowledge and technical expertise.

INTRODUCTION 27
1
Introduction
BACKGROUND
Characterization, or ''typing," of blood, semen, and other body fluids has
been used for forensic purposes for more than 50 years.1 It began with blood
groups, such as those of the ABO system, and later was extended to serum
proteins and red-cell enzymes and in some forensic applications, particularly
paternity testing, to human leukocyte antigens (HLA), which are associated with
tissue types. The genetically determined person-to-person variation revealed by
such typing was used mainly to include or exclude suspects, that is, to determine
whether a person showed a combination of genetically determined characteristics
consistent with having been the source of an evidence sample in a criminal case
or having been the father of a child in a paternity case. Except when HLA testing
was used, the chance that a randomly chosen person would be excluded by the
tests was about 98%; that left a 2% chance that the test would "include" an
innocent person.
In the last decade, methods have become available for deoxyribonucleic acid
(DNA) typing, that is, for showing distinguishing differences in the genetic
material itself. Advances in DNA technology in the 1970s paved the way for the
detection of variation (polymorphism) in specific DNA sequences and shifted the
study of human variation from the protein products of DNA to DNA itself. By
analyzing a sufficient number of regions of DNA that show much person-to-
person variability, one can reduce the probability of a chance match (inclusion)
of two persons to an extremely low

INTRODUCTION 28
level. Indeed, the probability can, in principle, be made so low that DNA typing
becomes not simply a method for exclusion or inclusion, but a means of absolute
identification.
The potential applicability of DNA typing to forensic samples was
demonstrated during the mid-1980s by laboratories in the United Kingdom,
United States, and Canada. Their work established that DNA was present in
forensic samples in sufficient quantity for testing (see Table 1.1) and that it
survived in a state that allowed it to be typed. In the publications in 1985 by
Jeffreys and colleagues,2,3 the term ''DNA fingerprint" carried the connotation of
absolute identification. The mass-media coverage that accompanied the
publications fixed in the general public's minds the idea that DNA typing could
be used for absolute identification. Thus, the traditional forensic paradigm of
genetic testing as a tool for exclusion was in a linguistic stroke changed to a
paradigm of identification. (See Box 1 for a contrasting of dermatoglyphic
fingerprints with "DNA fingerprints.")
Forensic DNA typing, first used in casework in 1985 in the United
Kingdom, was initiated in the United States in late 1986 by commercial
laboratories and in 1988 by the Federal Bureau of Investigation (FBI) and is now
being used by dozens of state and local crime laboratories. Because of its great
potential benefits for criminal and civil justice, but also because of the
possibilities for its misuse or abuse, forensic DNA typing has been subjected to
special scrutiny. Important questions have been asked about reliability, validity,
and confidentiality:4-6
TABLE 1.1 DNA Content of Biological Samples
Type of Sample Amount of DNAa
Blood 20,000-40,000 ng/ml
stain 1 cm2 in area ca. 200 ng
stain 1 mm2 in area ca. 2 ng
Semen 150,000-300,000 ng/ml
postcoital vaginal swab 0-3,000 ng
Hair:
plucked 1-750 ng/hair
shed 1-12 ng/hair
Saliva 1,000-10,000 ng/ml
Urine 1-20 ng/ml
a The amount of DNA is given in nanograms (ng); 1 ng = one-billionth of a gram (10-9 g).

INTRODUCTION 29
FINGERPRINTS IN PERSONAL
IDENTIFICATION:DIFFERENCES BETWEEN DNA TYPING
AND DERMATOGLYPHICS
Because of the central role of dermatoglyphic fingerprints in human
identification, arising out of the personal uniqueness of the patterns, it is
useful to compare and contrast traditional fingerprints with "DNA
fingerprints".
Fingerprints were described as an individualizing characteristic as early
as 1892. The use of fingerprints in forensic science (and in relation to
chromosonal abnormalities, such as Down syndrome, and other clinical
disorders) was developed empirically without reference to the specific
genetic basis of patterns. Ridge count is a polygenetic or multifactoral trait.
The close correlation for ridge counts with that expected for an almost
exclusively genetic trait, when "identical" and fratenal twins and other
relatives are compared, supports polygenetic inheritance.
In the forensic application, minutiae in the fingerprint patterns, not ridge
counts, are used for personal identification. The minutiae result from random
nongenetic events during embryonic development of the fingerpads. As a
consequence, the patterns even of "identical" twins are distinguishable.
Indeed, it appears that the fingerprint pattern of each human being is
unique.
The distinction between two types of fingerprints is illustrated by prints
from "identical" twins shown here. The dermatoglyphic fingerprints shown in
figure B-a (Twin A) and figure B-B (Twin B) are distinguished by the
patterns of loops and whorls.
Twin A Twin B
Finger Right Hand
Thumb (1) Whorl Whorl
2 Whorl Central pocket Whorl
3 Ulnar loop Whorl
4 Whorl Whorl
5 Ulnar loop Whorl
Finger Left Hand
Thumb (1) Whorl Whorl
2 Whorl Ulnar loop
3 Ulnar loop Ulnar loop
4 Whorl Ulnar loop
5 Ulnar loop Ulnar loop
However, typing of DNA from the blood of these twins in three
laboratories showed a match for all tests. One laboratory, testing for
variation in four chromosones, estimated the population frequency of

INTRODUCTION 30
FIGURES B-a and B-b Fingerprints of identical twins are distinguishable.

INTRODUCTION 31
the particular DNA patterns to be 1 in about 700,000. A second

laboratory used four other probes and estimated the chance of a random
match as 1 in 1.8 million. For illustrative purposes, the patterns obtained
with a "cocktail" of four signal-locus probes are shown in figure B-c. Twin A
gave sample B, twin B gave sample E, and samples A, C, and D were from
unrelated males of the same ethnic group. All five samples were submitted
and tested in a blind manner. The other lanes show controls. (Courtesy of
Robin W. Cotton and Matthew John McCoy, Cellmark Diagnostics.)
The uniqueness of the "DNA fingerprint" is based on genetic variation,
whereas that of the dermatoglyphic fingerprint is based largely on
nongenetic variation.
FIGURE B-c DNA types of identical twins are indistinguishable. Samples in

lines A-E are from different white males; samples B and E are from identical
twins.

INTRODUCTION 32
• Criticisms were raised concerning the reliability of the technical

methods, including the criteria for identifying DNA patterns and
declaring matches, as well as quality control.
• Questions were raised about the validity of estimates of probability of
random inclusion that were being presented in courts. Were the
individual components of a specific DNA pattern statistically
independent, so that it was proper to multiply their frequencies together
in calculating the chance of a match? What population databanks were
appropriate?
• Because DNA can be used to derive medical and other personal
information, questions of confidentiality and privacy have assumed
greater importance in DNA typing than in the use of non-DNA tests.
By the summer of 1989, because of questions concerning DNA typing raised

in connection with some well-publicized criminal cases, the scientific and legal
communities had called for an examination of the issues by the National Research
Council of the National Academy of Sciences.5,7,8 As a response, the Committee
on DNA Technology in Forensic Science was formed, and its first meeting was
held in January 1990. The committee was to address the general applicability and
appropriateness of the use of DNA technology in forensic science, the need for
standards in data collection and analysis, the need for advances in technology,
management of DNA typing data, and legal, societal, and ethical issues
surrounding DNA typing.
GENETIC BASIS OF DNA TYPING

Genetics is the science of biological variation. The fundamental basis of
genetics and the essence of Mendel's discovery in 1865 is that inheritance is
particulate and that the inherited factors (genes) that determine visible traits exist
in pairs of alleles (i.e., alternative forms of a gene at a given site)—one on a
chromosome inherited from the father and one on a chromosome from the
mother. Chromosomes that contain genes are threadlike or rodlike structures in
the cell nucleus. An organism's particular combination of alleles is referred to as
the organism's genotype; the collection of traits resulting therefrom is referred to
as the organism's phenotype. Most markers (i.e., identifiable physical locations on
a chromosome) used in forensic DNA typing are not parts of expressed genes
(i.e., genes that code for products like proteins); they are in noncoding portions of
DNA. Hence, they are not associated with a phenotype.
A trait that differs among individuals is referred to as a polymorphism.9In
DNA typing, that term is used interchangeably with "variation." The variations in
blood groups, serum protein types, and HLA tissue types used for forensic testing
in the pre-DNA era were polymorphisms in the protein product; these proteins
contain variations that reflect variations in DNA. But DNA technology makes it
possible to study the variations directly.

INTRODUCTION 33
STRUCTURE AND FUNCTION OF DNA

A human has 22 pairs of nonsex chromosomes (autosomes) and two sex
chromosomes—two X chromosomes in a female or an X chromosome and a Y
chromosome in a male. Each autosome or X or Y chromosome is composed of a
long DNA molecule constructed as a double helix (Figure 1-1). Each component
strand of the double helix is a chain of nucleotides of four types designated by the
names of the bases adenine (A), cytosine (C), guanine (G), and thymine (T). The
nucleotides bond, A to T and C to G, between the two strands of the helix like the
rungs of a ladder or, better, the steps in a spiral staircase. A pair of
complementary nucleotides (or bases)—A-T, G-C, T-A, or C-G—is called a
basepair (bp). DNA replication, which takes place in association with cell
division, involves the separation of the two strands of the double helix and the
synthesis of a new strand of nucleotides complementary to each strand.
Genes are segments of the DNA molecule. They constitute the blueprint for
the structure of proteins of various types that are responsible for the makeup and
function of cells and the body as a whole. A human has 50,000-100,000 genes,
each occurring in every nucleated body cell. Chromosome 1, the largest, might,
for example, have about 5,000 genes spaced at intervals along the DNA molecule
that it consists of.
FIGURE 1-1 Diagram of the double-helical structure of DNA in a chromosome.

The line shown in the chromosome is expanded to show the DNA structure.

INTRODUCTION 34
Individual Variation in DNA

DNA technology has revealed variations in the genome, the total genetic
makeup of the members of a species: single-nucleotide differences, deletions, and
insertions. In noncoding regions of DNA, which are less constrained by forces of
selection, it is estimated that at least one nucleotide per 300-1,000, on the
average, varies between two people.10 The nucleotide difference might change the
recognition site for a particular site-specific endonuclease (restriction enzyme) so
as to keep the DNA from being cut at that site by that enzyme. For example, in
Figure 1-2 note that a single nucleotide change from C to T has eliminated a
restriction enzyme cutting site. In addition, some regions of DNA contain
repetitive units, multiple identical strings of nucleotides arranged in tandem. In
VNTRs (variable
FIGURE 1-2 Basis of restriction fragment length polymorphism (RFLP).

Diagram indicates heterozygosity at a "restriction site": chromosome on left has
sequence CCGG that is recognized and cut by specific restriction enzyme,
whereas chromosome on right has one-nucleotide difference that results in
sequence CTGG, which is not recognized and cut by enzyme.

INTRODUCTION 35
number tandem repeats), the number of repetitions of a sequence can vary from
person to person. VNTRs are a leading form of variation used currently in
forensic DNA typing. The repeating unit can be as small as a dinucleotide—e.g.,
the (TG)n polymorphism—or as large as 30, or even more, nucleotides. Tandem
repeats are not limited to noncoding segments of DNA, although they are found
less frequently in coding segments.
The two main types of variation—single-nucleotide differences and VNTRs
—are both potentially recognizable by change in the lengths of fragments that
result when DNA is cut with a restriction enzyme. Variation in the lengths of
fragments can result from a change in the cluster of four, five, or six nucleotides
that is the specific cutting site of the particular restriction enzyme (Figure 1-2).
Or the variation can result, not from a change in the cutting site of the enzyme,
but from the existence of different numbers of tandem repeats between two
cutting sites. Figure 1-3 diagrams the major characteristics of the two forms of
variation and their use in DNA typing.
FIGURE 1-3 Two types of RFLPs. Structure of alleles in chromosome is

diagrammed at top: arrows indicate sites of cutting by enzyme; lengths of
fragments demonstrated by probe (short line above) are given. Electrophoretic
patterns are diagrammed below. A. Diallelic RFLP system resulting from single
nucleotide change as diagrammed in Figure 1-2. Electrophoretic patterns are
those of three genotypes: homozygotes for either allele 1 or allele 2 and 1/2
heterozygote. B. Multiallelic VNTR system. With three alleles as diagrammed,
there are six possible genotypes as demonstrated by electrophoresis.

INTRODUCTION 36
As shown in Figures 1-2 and 1-3A, variation at the cutting site of a

restriction enzyme can result in two alternative forms (alleles): the enzyme cuts
or it does not. That is called a diallelic system; three genotypes are possible. If a
person received the same allele at a particular site (locus) from both parents, the
genotype (or person) is said to be homozygous for that allele; if different alleles
were inherited from the two parents, the person is heterozygous at that locus.
(Some use the term locus, rather than site. Others reserve locus for use in relation
to expressed genes.)
As also shown in Figure 1-3B, when the variation is in the number of tandem
repeats, there can be many alleles, of which a given person can have only two.
That is called a multiallelic, or hypervariable, system. The number of genotypes
possible is the sum of the positive integers from 1 to the number of alleles; e.g., in a
three-allele system, as shown in Fig. 1-3B, there are expected to be 6 genotypes
(1 + 2 + 3). The number of genotypes is also given by the formula n(n + 1)/2,
where n is the number of alleles.
Inheritance of variation in the noncoding segments of DNA follows the same
rules that Mendel inferred for expressed genes. A given individual inherits one of
the father's two alleles and one of the mother's two alleles. When two variable
sites, each on a different chromosome, are examined, the inheritance at one site is
independent of that at the other; i.e., which paternal allele is inherited at site 1
bears no relation to which paternal allele is inherited at site 2. When the two sites
are on the same chromosome, they might also be transmitted independently, if
they are sufficiently far apart. When they are very close on the same
chromosome, the phenomenon of linkage disequilibrium can result—a deviation
from independent inheritance in which particular alleles at the two sites tend to be
transmitted together.
TECHNOLOGICAL BASIS OF DNA TYPING

Forensic DNA typing usually consists of comparing "evidence DNA" i.e.,
DNA extracted from material—most often semen—left at a crime scene with
"suspect DNA" (i.e., DNA extracted from the blood of a suspect). The tools of
DNA typing include restriction enzymes, electrophoresis, probes, and the
polymerase chain reaction.11,12,13
Restriction Fragment Length Polymorphisms

In the RFLP approach shown in Figure 1-4, DNA is subjected to controlled
fragmentation with restriction enzymes that cut double-stranded DNA at
sequence-specific positions. The long DNA molecules are thereby reduced to a
reproducible set of short pieces called restriction fragments (RFs), which are
usually several hundred to several thousand basepairs long. Many hundreds of
thousands of fragments are produced by digestion of human

INTRODUCTION 37
DNA with a single restriction enzyme; each fragment has a distinct sequence and
length. For analysis of RFs to demonstrate RFLPs, the fragments are separated
electrophoretically on the basis of size. Electrophoresis, typically performed on
agarose or acrylamide gels, results in large fragments at one end and small
fragments at the other; the small fragments migrate farthest in the electric field.
The fragments are then denatured (i.e., rendered single-stranded), neutralized, and
transferred from the gel to a nylon membrane, to which they are fixed; this
facilitates detection of specific RFLPs and VNTRs.
FIGURE 1-4 Schematic representation of Southern blotting of single-locus,

multi-allelic VNTR. In example shown here, DNA from four persons is tested.
All have different patterns. Three are heterozygous and one homozygous, for a
total of seven different alleles. From L. T. Kirby, "DNA Fingerprinting: An
Introduction," Stockton Press. New York, 1990. Copyright © 1990 by Stockton
Press. Reprinted with permission of W.H. Freeman and Company.
RFLPs that are defined by specific sequences are detected by hybridization

with a probe, a short segment of single-stranded DNA tagged with a group such
as radioactive phosphorus, that is used to detect a particular complementary DNA
sequence. The nylon membrane is placed in a bath that contains the probe, and
the probe hybridizes to the target denatured RF. Nonspecifically bound probe is
washed off. Hybridization probes have

INTRODUCTION 38
conventionally been labeled with radioactive isotopes, but attention is

increasingly being given to nonisotopic labeling. When isotopically labeled
probes are used, the pattern of probe binding is visualized with autoradiography
(see examples in Box 1-A and Figure 1-5).
The complete process—DNA digestion, electrophoresis, membrane transfer,
and hybridization—was developed by Edwin Southern in 1975;14 in its present
modified form, it is still usually referred to as Southern blotting. These
procedures are routinely used in molecular biology, biochemistry, genetics, and
clinical DNA diagnosis; there is no difference in their forensic application.
Differences among individuals are expressed as differences in the lengths of
RFs.15 RFLPs can result from several kinds of differences at the level of the
genome:
• Mutations that alter the base sequence at a restriction-enzyme

recognition, or cleavage, site can result in a loss of the cutting site or the
generation of a cutting site that was not present before. Insertion or
deletion of nucleotides between two cleavage sites also changes RF
lengths. Variation of these sorts is generally associated with a small
number of alleles. For example, the loss or gain of a particular cleavage
site might be responsible for only two alleles.
• Some regions of DNA contain multiple segments of short-sequence
repeats. Consequently, there is a class of RFs that differ in the number
of repeated segments present. Some VNTR polymorphisms have a small
number of alleles, and the patterns of RFs that represent each of the
alleles at a given locus can be readily distinguished. But highly
polymorphic VNTR loci have 50-100 alleles or even more. In that
situation, the distribution of RF size is essentially continuous; alleles
with RFs close in size might not be resolvable with electrophoresis, and
the limit of resolution must be defined operationally. Because of the
extensive variability, the VNTR class of RFLPs has proved the most
informative in distinguishing among persons.
RFLP analysis with single-locus probes is usually designed to result in a

simple pattern of one or two RFLP bands, depending on whether the

INTRODUCTION 39
FIGURE 1-5 One of several autoradiographs generated during course of

investigation of actual rape-murder case. Law enforcement officials submitted
blood samples from victim and suspect and vaginal swabs from victim. DNA
was isolated from stains found on vaginal swabs, digested with restriction
enzyme PstI, and hybridized to probes at genetic loci D2S44, D17S79, D14S13,
and D18S27 and monomorphic locus DXZ-1. Known samples are represented in
lanes labeled ''victim (known)" and "suspect (known)." Lanes labeled "male
fraction" and "female fraction" represent DNA resulting from differential lyses
of vaginal swabs. "Sensitivity control" lane and "K562 cell line" lane contain 50
ng and 1 g, respectively, of DNA from immortalized cell line. "Combination
market" lane contains "cocktail" of molecular-weight marker and adenovirus (to
monitor migration during electrophoresis).

INTRODUCTION 40
person is homozygous or heterozygous, respectively. The range of variation

shown in the patterns from different persons depends on how many different
alleles exist at the particular target locus, e.g., how many different tandem repeats
are in the population as a whole (see Figure 1-3B).
An alternative to the use of a single-locus probe is the use of a multilocus
probe that hybridizes to many different VNTR sites in the genome. The resulting
patterns in a single person contain many bands of varied intensity; the patterns
have been compared with barcodes. The approach was developed by Jeffreys and
colleagues.2,3,16,17 Because of the complexity of the patterns, interpretation can be
difficult. Consequently, the use of multiple single-locus probes is favored.
Polymerase Chain Reaction for Amplifying DNA

Use of the polymerase chain reaction (PCR) allows a million or more copies
of a short region of DNA to be made. It is a method of DNA amplification. For
DNA typing, one amplifies a genetically informative sequence, usually 100-2,000
bp long, and detects the genotype in the amplified product. Because many copies
are made, genetic typing can rely on nonisotopic methods. With PCR
amplification, very small samples of tissue or body fluids—theoretically even a
single nucleated cell—can be used to study DNA.18,19
The PCR process (Figure 1-6) is simple; indeed, it is analogous to the
process by which cells replicate their DNA.20,21,22,23 Two short oligonucleotides
are hybridized to the opposite strands of a target DNA segment in positions
flanking the sequence region to be amplified; the two oligonucleotides are
oriented so that their 3' ends point toward each other. (The ends of a DNA
segment are referred to as 5' and 3'; synthesis of new chains proceeds from the 3'
end.) The two oligonucleotides serve as primers for an enzyme-mediated
replication of the target sequence. The PCR amplification process itself consists
of a three-step cycle:
1. The double-stranded template DNA is dissociated into single strands

by incubation at high temperature, typically 94°C.
2. The temperature is lowered to allow the oligonucleotide primers to
bind to their complementary sequences in the DNA that is to be
amplified.
3. A DNA polymerase extends the primers from each of the two
primer-binding sites across the region between them, with the target
sequence as template.
Because the extension products of one primer bind the other primer in
successive cycles, there is in principle a doubling of the target sequence in each
cycle. However, the efficiency of amplification is not 100%, and the yield from a
30-cycle amplification is generally about 106-107 copies of the

INTRODUCTION 41
FIGURE 1-6 Polymerase chain reaction (PCR). Courtesy, Perkin-Elmer Cetus

Instruments.

INTRODUCTION 42
target sequence. The primers become physically incorporated into the

amplification products.
Both the amplification and the genetic typing can be completed in a day. The
efficiency can be improved by amplifying several different products in the same
reaction mix; this is termed multiplex amplification.
Several methods have been coupled with PCR for the detection of genetic
variation in the amplified DNA; some are listed in Table 1.2. Detection of
variation in DNA with PCR-amplified material is fundamentally no different from
detection with unamplified samples. The difference is technical: the availability
of the larger quantity of pure material produced with PCR affords more options
for means of detection.
The use of allele-specific oligonucleotide (ASO) probes is the most
generalized approach to the detection of alleles that differ in sequence.33The
sequence-specific probe is usually a short oligonucleotide, 15-30 nucleotides
long, with a sequence exactly matching the sequence of the target allele. The ASO
probe is mixed with dissociated strands of PCR reaction product under such
conditions that the ASO and the PCR product strands hybridize if there is perfect
sequence complementarity, but do not if there are mismatches in sequence.
The usual format for the use of ASO probes is to spot dissociated PCR
product strands onto a nitrocellulose or nylon membrane and probe the membrane
with labeled ASO. That is analogous to Southern blotting; because the samples
are spotted as a "dot" on the membrane, the method is referred to as "dot
blotting" (Figure 1-7). An alternative method uses an array of ASO probes
immobilized on a test strip.34 The test strip is immersed in a solution of labeled
PCR product; the PCR product hybridizes only to its complementary probe. This
procedure has been called ''reverse dot blotting" or "blot dotting." A commercial
kit based on the reverse dot blot principle has been released (Cetus Corporation).
TABLE 1.2 Some PCR-Based Systems for the Detection of Genetic Variation
Sequence-based detection systems
Allele-specific oligonucleotide (ASO)24
Allele-specific priming of PCR25,26,27
Oligonucleotide-ligation assay (OLA)28
Restriction-site-specific cleavage (Amp-FLPs)29
Denaturing-gradient gel electrophoresis30
Chemical cleavage of mismatched heteroduplexes31
Length-variation systems
Simple insertions and deletions
VNTR polymorphisms32
Analysis of nucleotide sequences

INTRODUCTION 43
FIGURE 1-7 Diagrammatic representation of dot-blot procedure. PCR-amplified

target DNA is immobilized on nylon membrane, and biotinylated probe
hybridizes to the target if there is no nucleotide mismatch. Avidin-horseradish
peroxidase (HPR) conjugate that binds to biotinylated probe is added. HPR
converts colorless substrate to colored product. From L. T. Kirby, "DNA
Fingerprinting: An Introduction," Stockton Press, New York, 1990. Copyright ©
by Stockton Press. Reprinted with permission of W.H. Freeman and Company.
Amplification of DNA regions that contain inserts or deletions yields

products of different size, which are readily detected with electrophoresis. It has
proved possible to amplify some of the discrete alleles that make up VNTR
polymorphisms;19 these typing systems combine convenience with the potential
for good discrimination. A number of PCR-VNTR typing systems are in
development, and it is anticipated that they will come into greater use over the
next few years.35 Indeed, the whole technology of DNA typing can be expected to
evolve continually in the next decade. A recent description of PCR-based
"digital" DNA typing by Jeffreys is but one example of what might come.36 In his
method, PCR is used to amplify tandem repeats in a portion of DNA. These
repeats are then analyzed for the presence of nucleotide polymorphism and
assigned numerically (digits 1,2.3, etc.). Thus, by analyzing the repeats (50 or
more repeats can easily be analyzed), one is able to assign a specific digital code
to each sample (e.g., 1122113111221112…) and unambiguously distinguish one
sample from another. The method is simple, avoids match criteria, and requires
no side-by-side comparison of DNA samples. The Jeffreys "digital" DNA typing
method is still in the research stage, but, if perfected and adapted for foren

INTRODUCTION 44
sic samples, it might be possible to achieve absolute identification of persons by

analysis of a few such repeats.
PCR provides excellent starting material for direct DNA sequencing, and
sequence analysis might ultimately be the approach used for personal
identification. But it will require improvements in automated sequencing
technology and the generation of larger databases on sequence variability.
POPULATION GENETICS RELEVANT TO THE

INTERPRETATION OF DNA TYPING
The finding that two samples of human tissue differ in their DNA patterns
leads to the conclusion that the two came from different persons. However, if the
two samples are indistinguishable with regard to the detected DNA patterns, two
possibilities exist: the two samples came from the same person (or from identical
twins), or the two samples came from different persons whose DNA patterns in
the target regions investigated are the same. Those two possibilities cannot be
distinguished. To provide the trier of fact—a judge or jury, for example—with
information for weighing the two possibilities, it has been traditional to us
statistics from population genetics to estimate the fraction of people in the
population who have the particular combination of DNA patterns. What is the
chance of picking at random a person who has the same genetic patterns as found
in the evidence sample? Obviously, the lower the probability, the stronger the
inference that the evidence sample is associated with a particular person who has
those patterns.
Thus, the central question in relation to forensic DNA typing is, What is the
probability that a person picked at random would match the evidence sample in
DNA patterns? Or, What proportion of persons in the same population as a
suspect have the same combination of DNA patterns as the evidence sample? In
answering the questions, the population frequencies of the patterns at the several
(often four) loci tested are multiplied together, on the assumption that they are
independent. Indeed, the alleles (two in a diallelic system) at each locus are
assumed to vary independently. Estimation of the frequencies of specific alleles
needed to answer the questions is based on population genetics.37 Experience with
blood groups, enzyme markers, and HLA types—including the genetic markers
used for forensic personal "identification" in the pre-DNA era—indicates that the
frequency of specific allele can vary widely among populations. That is
demonstrated in Figure 1-8 for the B blood-group allele; maps of the A and O
blood-group alleles show similar variability. It is to be expected that the
frequencies of the various alleles for the DNA polymorphisms also show
differences among populations. Thus, it might be critically important to pick the
right population with which to compare a given suspect's DNA.

INTRODUCTION 45
FIGURE 1-8 Distribution of gene for blood group B in Europe. Similar wide
variation is observed with genes for blood groups A and O. From Mourant et
al.,38 p. 266.
Estimating the Frequency of Alleles in Populations

As diagrammed in Figure 1-9, a diallelic system such as represented by
many RFLPs (Figure 1-3) gives rise to three genotypes that in the state of
Hardy-Weinberg equilibrium (see Chapter 3) are expected to have the following
frequencies: p2 (homozygotes for allele A1), 2pq (heterozygotes), and q2
(homozygotes for allele A2), where p is the frequency of allele A1 and q is the
frequency of allele A2. The frequency of each of the two alleles can be derived by
counting: e.g., each A1 homozygote has 2 A1 alleles, and each A1/A2
heterozygote has 1 A1 allele. Or the proportion of the A1 allele can be taken as
the square root of the frequency of A1 homozygotes. The two methods should
give closely similar results, if the population is in Hardy-Weinberg equilibrium.
A multiallelic system like that represented by VNTRs (Figure 1-10) gives
rise to many genotypes, as diagrammed in Figure 1-11; with five alleles, there are
15 genotypes [n(n + 1)/2]. Again, the frequency of each allele can be determined
by counting or, more easily, by taking the square

INTRODUCTION 46
p,q = proportion of A1 and A2 alleles, respectively, in the population -- p + q = 1

p2, 2pq, q2 =proportion of 3 genotypes -- p2 + 2pq + q2 = 1
where p2 = proportion of A1 homozygotes
2pq = proportion of heterozygotes
q2 = proportion of A2 homozygotes
FIGURE 1-9Punnett square (named for British geneticist) indicating frequency
of genotypes in diallelic RFLP system.
FIGURE 1-10 Schematic representation of alleles and genotypes in five-allele

VNTR system.

INTRODUCTION 47
FIGURE 1-11 A. Punnett square showing genotypes in single locus, five-allele

VNTR system, as schematized in Figure 1-10. B. A worked example: frequency
of each of 15 genotypes with allele frequencies indicated.

INTRODUCTION 48
root of the frequency of the homozygotes for the particular allele or half the
summed frequencies of the heterozygotes, which, in the case of the five-allele
system, will be of four types for each allele.
Population Substructure
It is intuitively obvious that relatives have genes in common. Thus, the
chance that DNA typing will yield a match with a suspect when the evidence
sample in fact came from a brother or other relative is considerable, especially if
only a few loci are tested.
The U.S. population is a conglomerate of many different population groups,
which might be viewed as extended families derived from all parts of the world.
The major ethnic groupings—white, black, Hispanic, Asian, etc.—are each
composites of many different subpopulations, which might have quite different
frequencies of the alleles used in forensic DNA typing. Allele frequencies
estimated from sampling of an overall ethnic group represent weighted averages.
Some of the component subpopulations might have allele frequencies quite
different from the mean values of the whole population. Further discussion of this
problem and recommendations for handling it are given in Chapter 3.
CHARACTERISTICS OF AN OPTIMAL FORENSIC DNA

TYPING SYSTEM
The methods of DNA typing continue to evolve as new ways to detect
individual variation are developed. Sequencing of DNA might ultimately be the
optimal method of personal identification, but that is still far from practical. It is
important that the flexibility to adopt new methods be retained as standardization
of DNA technology is developed (see Chapter 4) and databanks are created (see
Chapter 5).
Any method of forensic DNA typing, like methods for medical DNA and
other testing, should be rapid, accurate, and inexpensive. In addition, to achieve
maximal discrimination among individuals, forensic DNA typing requires the use
of markers with a high level of variability or polymorphism. Ideally, the high
degree of variability would be found in all the world's populations. The markers
and the probes used to detect them should have a unique sequence, so that each
probe hybridizes with only one part of the genome. Single-locus probes should be
used. The loci of the markers should be independent, e.g., on separate
chromosomes. The markers should, furthermore, come from noncoding and
therefore presumably nonfunctional parts of the genome, to avoid claims,
spurious or otherwise, of association of particular markers with particular
behavioral traits or diseases.
The automation of DNA typing might help to reduce its time and expense.
An advantage of speed and low cost is that one can test more parts

INTRODUCTION 49
of the genome. Even if a locus is only modestly polymorphic, its use in DNA
typing could have other advantages, such as complete unambiguity of scoring;
used in combination, such loci could demonstrate that the chance of a random
match is extremely low.
It must be emphasized that new methods and technology for demonstrating
individuality in each person's DNA continue to be developed. The methods
outlined in this chapter are likely to be superseded in efficiency, automatability,
economy, and other features by new methods. Care must be taken to ensure that
DNA typing techniques used for forensic purposes do not become "locked in"
prematurely. Otherwise, society and the criminal justice system will not be able to
derive maximal benefit from advances in the science and technology.
REFERENCES
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10. Cooper DN, Smith BA, Cooke HJ, Niemann S, Schmidtke J. An estimate of unique DNA
sequence heterozygosity in the human genome. Hum Genet. 69:201-205, 1985.
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14. Southern EM. Detection of specific sequences among DNA fragments separated by gel
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using restriction fragment length polymorphisms. Am J Hum Genet. 32:314-331, 1980.
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paternity determinations. Lancet. 1:574-576, 1988.
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1986.

INTRODUCTION 50
18. Higuchi R, yon Beroldingen CH, Sensabaugh GF, Erlich HA. DNA typing from single hairs.
Nature. 332:543-546, 1988.
19. Jeffreys AJ, Wilson V, Neumann R, Keyte J. Amplification of human minisatellites by the
polymerase chain reaction: towards DNA fingerprinting of single cells. Nucleic Acids Res.
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20. Erlich IIA, ed. PCR technology: principles and applications for DNA amplification. New York:
Stockton Press, 1989.
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1991.
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beta-S-globin allele by hybridization with synthetic oligonucleotides. Proc Natl Acad Sci
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color complementation assay. Proc Natl Acad Sci USA. 86:9178-9182, 1989.
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27. Wu DY, Ugozzoli L, Pal BK, Wallace RB. Allele-specific enzymatic amplification of beta-globin
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87:8923-8927, 1990.
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science. J For Sci. 35:1196-1200, 1990.
30. Myers RM, Maniatis T, Lerman I,S. Detection and localization of single base changes by
denaturing gradient gel electrophoresis. Methods Enzymol. 155:501-527, 1987.
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pair mismatches with hydroxylamine and osmium-tetroxide and its application to the study
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32. Nakamura Y, Leppert M, O'Connell P, Wolff R, Holm T, Culver M, Martin C, Fujimoto E, Hoff
M, Kumlin E, White R. Variable number of tandem repeat (VNTR) markers for human gene
mapping. Science. 235:1616-1622, 1987.
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globin anti HLA-DQ DNA with allele-specific oligonucleotide probes. Nature.
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approach to DNA typing. Nature. 354:204-209, 1991.
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and other polymorphisms. 2nd ed. Oxford: Oxford University Press, 1976.

DNA TYPING: TECHNICAL CONSIDERATIONS 51
2
DNA Typing: Technical Considerations
"DNA typing" is a catch-all term for a wide range of methods for studying
genetic variations. Each method has its own advantages and limitations, and each
is at a different state of technical development. Each DNA typing method
involves three steps:
1. Laboratory analysis of samples to determine their genetic-marker

types at multiple sites of potential variation.
2. Comparison of the genetic-marker types of the samples to determine
whether the types match and thus whether the samples could have
come from the same source.
3. If the types match, statistical analysis of the population frequency of
the types to determine the probability that such a match might have
been observed by chance in a comparison of samples from different
persons.
Before any particular DNA typing method is used for forensic purposes, it is
essential that precise and scientifically reliable procedures be established for
performing all three steps. This chapter discusses the first two—laboratory
analysis and pattern comparison—and Chapter 3 focuses on statistical analysis.
There is no scientific dispute about the validity of the general principles
underlying DNA typing: scientists agree that DNA varies substantially among
humans, that variation can be detected in the laboratory, and that DNA
comparison can provide a basis for distinguishing samples from different
persons. However, a given DNA typing method might or might not be
scientifically appropriate for forensic use. Before a method can be ac

cepted as valid for forensic use, it must be rigorously characterized in both

research and forensic settings to determine the circumstances under which it will
and will not yield reliable results. It is meaningless to speak of the reliability of
DNA typing in general—i.e., without specifying a particular method. Some states
have adopted vaguely worded statutes regarding admissibility of DNA typing
results without specifying the methods intended to be covered. Such laws
obviously were intended to cover only conventional RFLP analysis of single-
locus probes on Southern blots—the only method in common use at the time of
passage of the legislation. We trust that courts will recognize the limitations
inherent in such statutes.
Forensic DNA analysis should be governed by the highest standards of
scientific rigor in analysis and interpretation. Such high standards are appropriate
for two reasons: the probative power of DNA typing can be so great that it can
outweigh all other evidence in a trial; and the procedures for DNA typing are
complex, and judges and juries cannot properly weigh and evaluate conclusions
based on differing standards of rigor.
The committee cannot provide comprehensive technical descriptions for
DNA typing in this report: too many methods exist or are planned, and too many
issues must be addressed in detail for each method. Instead, our main goal is to
provide a general framework for the evaluation of any DNA typing method.
ESSENTIALS OF A FORENSIC DNA TYPING PROCEDURE
Scientific Foundations
The forensic use of DNA typing is an outgrowth of its medical diagnostic
use—analysis of disease-causing genes based on comparison of a patient's DNA
with that of family members to study inheritance patterns of genes or with
reference standards to detect mutations. To understand the challenges involved in
such technology transfer, it is instructive to compare forensic DNA typing with
DNA diagnostics.
DNA diagnostics usually involves clean tissue samples from known
sources. It can usually be repeated to resolve ambiguities. It involves comparison
of discrete alternatives (e.g., which of two alleles did a child inherit from a
parent?) and thus includes built-in consistency checks against artifacts. It requires
no knowledge of the distribution of patterns in the general population.
Forensic DNA typing often involves samples that are degraded,
contaminated, or from multiple unknown sources. It sometimes cannot be
repeated, because there is too little sample. It often involves matching of samples
from a wide range of alternatives present in the population and thus lacks built-in
consistency checks. Except in cases where the DNA evidence

excludes a suspect, assessing the significance of a result requires statistical

analysis of population frequencies.
Despite the challenges of forensic DNA typing, we believe that it is possible
to develop reliable forensic DNA typing systems, provided that adequate
scientific care is taken to define and characterize the methods. We outline below
the principal issues that must be addressed for each DNA typing procedure.
Written Laboratory Protocol

An essential element of any clinical or forensic DNA typing method is a
detailed written laboratory protocol. Such a protocol should not only specify
steps and reagents, but also provide precise instructions for interpreting results,
which is crucial for evaluating the reliability of a method. Moreover, the
complete protocol should be made freely available so that it can be subjected to
scientific scrutiny.
Procedure For Identifying Patterns

There must be an objective and quantitative procedure for identifying the
pattern of a sample. Although the popular press sometimes likens DNA patterns
to bar codes, laboratory results from most methods of DNA testing are not
discrete data, but rather continuous data. Typically, such results consist of an
image—such as an autoradiogram, a photograph, spots on a strip, or the
fluorometric tracings of a DNA sequence—and the image must be quantitatively
analyzed to determine the genotype or genotypes represented in the sample.
Quantitation is especially important in forensic applications, because of the ever-
present possibility of mixed samples.
Patterns must be identified separately and independently in suspect and
evidence samples. It is not permissible to decide which features of an evidence
sample to count and which to discount on the basis of a comparison with a
suspect sample, because this can bias one's interpretation.
Procedure For Declaring a Match

When individual patterns of DNA in evidence sample and suspect sample
have been identified, it is time to make comparisons to determine whether they
match. Whether this step is easy or difficult depends on the resolving power of
the system to distinguish alleles. Some DNA typing methods involve small
collections of alleles that can be perfectly distinguished from one another—e.g., a
two-allele RFLP system based on a polymorphism at a single locus. Other
methods involve large collections of similar alleles that are imperfectly
distinguished from one another—e.g., the hypervariable VNTR

systems in common forensic use, in which a single sample might yield somewhat
different allele sizes on repeat measurements.1 It is easy to determine whether two
samples match in the former case (assuming that the patterns have been correctly
identified), but the latter case requires a match criterion—i.e., an objective and
quantitative rule for deciding whether two samples match. For example, a match
criterion for VNTR systems might declare a match between two samples if the
restriction-fragment sizes lie within 3% of one another.
The match criterion must be based on the actual variability in measurement
observed in appropriate test experiments conducted in each testing laboratory.
The criterion must be objective, precise, and uniformly applied. If two samples lie
outside the matching rule, they must be declared to be either ''inconclusive" or a
"nonmatch." Considerable controversy arose in early cases over the use of
subjective matching rules (e.g., comparison by eye) and the failure to adhere to a
stated matching rule.
Identification of Potential Artifacts

All laboratory procedures are subject to potential artifacts, which can lead to
incorrect interpretation if not recognized. Accordingly, each DNA typing method
must be rigorously characterized with respect to the types of possible artifacts, the
conditions under which they are likely to occur, the scientific controls for
detecting their occurrence, and the steps to be taken when they occur, which can
range from reinterpreting results to correcting for the presence of artifacts,
repeating some portion of the experiment, or deciding that samples can be reliably
used.
Regardless of the particular DNA typing method, artifacts can alter a pattern
in three ways: Pattern A can be transformed into Pattern B, Pattern A can be
transformed into Pattern A + B; and Pattern A + B can be transformed into
Pattern B. It is important to identify the circumstances under which each
transformation can occur, because only then can controls and corrections be
devised. For example, RFLP analysis is subject to such artifacts as band shifting,
in which DNA samples migrate at different speeds and yield shifted patterns
(A→B), and incomplete digestion, in which the failure of a restriction enzyme to
cleave at all restriction sites results in additional bands (A→A + B).
Some potential problems can be identified on the basis of the chemistry of
DNA and the mechanism of detection in the genetic-typing system. Anticipation
of potential sources of DNA typing error allows systematic empirical
investigation to determine whether a problem exists in practice. If so, the range of
conditions in which an assay is subject to artifact must be characterized. In either
case, the results of testing for artifacts should be documented. Empirical testing is
necessary, whether one is considering a new method, a new locus, a new set of
reagents (probe or enzyme) for a

pre-existing locus, or a new device. Under some circumstances, even small

changes in procedure can change the pattern of artifacts.
Once potential artifacts have been identified, it is necessary to design
scientific controls to serve as internal checks in each experiment to test whether
the artifacts have occurred. Once the appropriate controls are identified, analysts
must use them consistently when interpreting test results. If the appropriate
control has not been performed, no result should be reported. When a control
indicates irregularities in an experiment, the results in question must be
considered inconclusive; if possible, the experiment should be repeated. A well-
designed DNA typing test should be a matter of standardized, objective analysis.
Sensitivity to Quantity, Mixture, and Contamination

Evidence samples might contain very little DNA, might contain a mixture of
DNA from multiple sources, and might be contaminated with chemicals that can
interfere with analysis. It is essential to understand the limits of each DNA typing
method under such circumstances.
Experiential Foundation
Before a new DNA typing method can be used, it requires not only a solid
scientific foundation, but also a solid base of experience in forensic application.
Traditionally, forensic scientists have applied five steps to the implementation of
genetic marker systems:2,3
1. Gain familiarity with a system by using fresh samples.

2. Test marker survival in dried stains (e.g., bloodstains).
3. Test the system on simulated evidence samples that have been
exposed to a variety of environmental conditions.
4. Establish basic competence in using the system through blind trials.
5. Test the system on nonprobative evidence samples whose origin is
known, as a check on reliability.
When a technique is initially developed, all five steps should be carefully

followed. As laboratories adopt the technique, it will not always be necessary for
them to repeat all the steps, but they must demonstrate familiarity and
competence by following steps 1, 4, and 5.4
Most important, there is no substitute for rigorous external proficiency
testing via blind trials. Such proficiency testing constitutes scientific confirmation
that a laboratory's implementation of a method is valid not only in theory, but also
in practice. No laboratory should let its results with a new DNA typing method be
used in court, unless it has undergone such proficiency testing via blind trials.
(See Chapter 4 for discussion of proficiency testing.)

Publication and Scientific Scrutiny

If a new DNA typing method (or a substantial variation on an existing one)
is to be used in court, publication and scientific scrutiny are very important.
Extensive empirical characterization must be undertaken. Results must be
published in appropriate scientific journals. Publication is the mechanism that
initiates the process of scientific confirmation and eventual acceptance or
rejection of a method.
Some of the controversy concerning the forensic use of DNA typing can be
traced to the failure to publish a detailed explanation and justification of
methods. Without the benefit of open scientific scrutiny, some testing
laboratories initially used methods (for such fundamental steps as identifying
patterns, declaring matches, making comparison with a databank, and correcting
for band shifting) that they later agreed were not experimentally supported. In
some cases, those errors resulted in exclusion of DNA evidence or dismissal of
charges.
TECHNICAL ISSUES IN RFLP ANALYSIS
Choice of Probes
A DNA probe used in forensic applications should have the following
properties:
• It should recognize a single human locus (or site), preferably one whose
chromosomal location has been determined.
• It should detect a constant number of bands per allele in most humans.
• It should be characterized in the published literature, including its
typical range of alleles, and its tendency to recognize DNA from other
species.
• It should be readily available for scientific study by any interested
person.
The committee recommends against forensic use of multilocus probes,

which detect many fragments per person. Because such probes might detect
fragments with quite different intensities, it is difficult to know whether one has
detected all fragments in a sample—particularly with small and degraded forensic
samples—and difficult to recognize artifacts and mixtures. Such problems
increase the difficulty of pattern interpretation. Multilocus probes increase the
risk of incorrect interpretation, and numerous single-locus probes, which do not
pose such problems, are available. The use of enough single-locus probes gains
the advantages of the single multilocus probes without the problems of
interpretation.

Southern Blot Preparation

The basic protocol for preparing Southern blots is fairly standard, but testing
laboratories vary in such matters as choice of restriction enzyme, gel length and
composition, and electrophoresis conditions. Such differences do not
fundamentally affect the reliability of the general method, but some enzymes
might require characterization (e.g., each restriction enzyme must be
characterized for sensitivity to inhibitors, for tendency to cut at anomalous
recognition sites under some conditions—often called "star activity"—and for
tendency to produce partial digestions), and differences in gels and
electrophoresis conditions will affect resolution of fragments and retention of
small fragments.
Questions have arisen concerning the use of ethidium bromide, a fluorescent
dye that binds to DNA and so allows it to be visualized. Some laboratories
incorporate ethidium bromide into analytical gels before electrophoresis; others
stain gels with ethidium bromide after electrophoresis. The committee strongly
recommends the latter, for two reasons:
• Ethidium bromide binds to DNA in a concentration-dependent manner

and has been shown to alter the mobility of fragments at high DNA
concentrations, thus decreasing the reliability of fragment-size
measurements.
• Staining after electrophoresis requires smaller amounts of ethidium
bromide, and that is preferable, because the dye is a known carcinogen
and thus poses problems of exposure and disposal.
Because there are several advantages and no drawbacks to staining after

electrophoresis, we conclude that there is no present justification for use of
ethidium bromide in analytical gels.
Identification of DNA Patterns

Identification of the DNA pattern of each sample should be carried out very
carefully. When analyzed with a single-locus probe, each lane will ideally show
at the most fragments derived from two alleles and nothing else. However,
complications can arise. To interpret such complications properly, an examiner
requires considerable knowledge and skill and might need to examine control
experiments.
Examination of a Control Pattern

Every Southern blot procedure should be applied to a known DNA sample
(in addition to the evidence samples in question), to verify that the hybridization
was performed correctly. If this control sample does not yield

a clean result that shows the correct pattern for a particular hybridization, the
result of the test hybridization should be discounted.
Single-Band Patterns
Sometimes, only a single band will be detected when two distinct alleles are
present. That might occur because the second allele is so small that it has
migrated off the end of the gel, because the second allele is similar in size to the
first allele and thus is not resolved, or because the second allele is much larger,
and larger fragments are preferentially lost in partially degraded samples.
When only a single band is found, the interpretation should always include
the possibility that a second band has been missed—i.e., that the pattern is
actually of a heterozygote, not a homozygote. (For statistical interpretation, the
frequency of a single-band pattern should be taken to be the sum of the
frequencies of all patterns containing this band. This is approximately twice the
allele frequency of the band.) In some cases, it could be important to interpret the
absence of a second larger fragment—e.g., when two samples match in a smaller
band, but the questioned sample lacks a second larger band. That could arise
either because the samples are from different persons or because the samples
come from the same person but the questioned sample is partially degraded.
Ideally, to distinguish these alternatives, one should determine whether a second
larger band could have been detected in the questioned sample by hybridizing the
membrane with a single-copy probe that detects an even larger monomorphic
fragment—i.e., one that is constant in all humans. In contrast, it would not be
sufficient simply to estimate the degree of degradation from the ethidium bromide
staining pattern of the sample.
Anomalous Bands
A sample might show more than two bands for various reasons. E.g., the
hybridization conditions were improper and caused the probe to hybridize to
incorrect fragments; the probe was contaminated with another sequence, which
caused it to recognize other fragments; the membrane was incompletely stripped
after a previous use, so a pattern seen on the previous hybridization is still being
detected; the restriction digestion did not proceed to completion, so the region
recognized by the probe is present in incompletely cut fragments of multiple
sizes; or the sample actually contains a mixture of multiple DNAs. The last
example is extremely important to recognize, because it can bear importantly on a
case. Whenever extra bands are observed, their origin should be determined.
The following clues provide a partial decision tree:

If the hybridization conditions were improper or the probe contaminated, the

pattern in the control DNA should be seen to be incorrect; the hybridization
should be repeated.
If the membrane was improperly stripped, the extra bands will be in the
same location as in the previous hybridization and might be present in the control
sample; the hybridization should be repeated.
If the restriction digestion was incomplete, one should see additional bands,
even with the use of monomorphic probes that typically give only a single
constant band. To ascribe extra bands to incomplete digestion, one should
therefore perform such a hybridization. If incomplete digestion has occurred, the
sample ideally should be re-extracted and redigested, and a new Southern blot
should be prepared. If that is not possible, because there is too little sample, it
will usually be difficult to get a reliable result.
If the samples are mixtures from more than one person, one should see
additional bands for all or most polymorphic probes, but not for a single-copy
monomorphic probe. Mixed samples can be very difficult to interpret, because the
components can be present in different quantities and states of degradation. It is
important to examine the results of multiple RFLPs, as a consistency check.
Typically, it will be impossible to distinguish the individual genotypes of each
contributor. If a suspect's pattern is found within the mixed pattern, the
appropriate frequency to assign such a "match" is the sum of the frequencies of
all genotypes that are contained within (i.e., that are a subset of) the mixed
pattern.
Another possible cause of extra bands is leakage between adjacent sample
lanes or misloading of two samples in a single lane. Such an occurrence can be
exceedingly difficult to detect and could result in an incorrect conclusion. It is
therefore important to leave a blank lane between a suspect sample and an
evidence sample, so that leakage can be detected and will not lead to false-
positive results.
Reporting of Anomalies
Examiners should document their interpretations of samples thoroughly in
writing. They should note all observed bands and any questionable densities that
they do not consider to be bands. Anomalous bands should be explained on the
basis of appropriate control experiments of the sorts described above.
Measurement of Fragments
Molecular-weight measurements of fragments should initially be made by
comparing band positions with known molecular-weight standards run in separate
lanes on the same gel (so-called external molecular-weight stan

dards). Measurements should be performed with a computer-assisted or

computer-automated system, in which the operator identifies the positions of the
bands with a digitizing pen or similar device that directly records them, visually
inspects them, or both. Computer-based procedures ensure appropriate
documentation of the measurement and promote objectivity.
External molecular-weight standards alone, however, are not sufficient,
because anomalies in electrophoresis can lead to errors in RFLP typing caused by
band shifting.5 Such anomalies can be due to differences in salt or DNA
concentrations among samples (which could be corrected by repeated extraction)
or to covalent or noncovalent modifications of the DNA (which might be
irreversible). Band shifting could cause two DNA samples from one person to
show different patterns or DNA samples from two different persons to show the
same pattern. Band shifting also makes it impossible to measure fragment sizes
relative to external molecular-weight standards, because the standards have
migrated at a different speed.
Band shifting is easy to detect by hybridizing the Southern blot with
monomorphic probes—that is, probes that detect constant-length fragments that
are always in the same position in all people. If several monomorphic fragments
are in the same position in both lanes, it is safe to assume that no band shifting
has occurred. If the monomorphic fragments are in different positions, band
shifting is present. The committee considers it desirable for all samples to be
tested for band shifting by hybridization with monomorphic probes that cover a
wide range of fragment sizes in the gel. That approach will eliminate the rare
production of a match by shifting of bands in an evidence sample to the same
positions as in a suspect sample. Testing laboratories now investigate the
possibility of band shifting only when they find two samples with patterns that
appear to be similar but shifted relative to one another. (Multiple monomorphic
probes might not be available for some systems and might need to be developed.)
Testing for band shifting is easy, but correcting it is harder. The best
approach is to clean the samples (by re-extraction, dialysis, or other measures)
and repeat the experiment in the hope of avoiding band shifting. When that is
impossible because too little sample is available or it fails (perhaps because of
covalent modification of the DNA), it is possible in principle to determine the
molecular weights of polymorphic fragments in a sample by comparing them with
monomorphic human bands in the same lane—so-called internal molecular-
weight standards. These monomorphic fragments are expected to have undergone
the same band shift, so they should provide an accurate internal ruler for
measurement. (Note that the polymorphic fragments and the internal molecular-
weight standards are visualized on separate hybridizations, but can be
superimposed on one another, if the external molecular-weight standards are used
to align the gels.)
In practice, however, the use of internal standards presents serious dif

ficulties. Accurate size determination requires a number of internal standards. If

band shifting caused all fragments to change their mobility by the same
percentage, one would need only a single monomorphic fragment to determine
the extent of shift. But band shifting appears to be more complex than that.
Different regions of the gel shift by different amounts.
Little has been published on the nature of band shifting, on the number of
monomorphic internal control bands needed for reliable correction, and on the
accuracy and reproducibility of measurements made with such correction. For the
present, several laboratories have decided against attempting quantitative
corrections; samples that lie outside the match criterion because of apparent band
shifting are declared to be "inconclusive." The committee urges further study of
the problems associated with band shifting. Until testing laboratories have
published adequate studies on the accuracy and reliability of such corrections, we
recommend that they adopt the policy of declaring samples that show apparent
band shifting to be "inconclusive." The committee recommends that all
measurement data be made readily available, including the computer-based
images and records. Any analytical software for image processing or molecular-
weight determination should also be readily available. All fragment sizes for both
known and questioned samples should be clearly listed on the formal report of the
testing laboratory.
Match Criteria
Current RFLP-based tests use VNTR probes that have dozens of closely
spaced alleles. On the one hand, the high degree of polymorphism increases the
power of the test to detect differences among persons. On the other hand, the
large number of alleles increases the complexity of matching samples, because
gels have little ability to resolve nearby alleles (which can differ by as little as 9
basepairs, so that, for practical purposes, the distribution of alleles can appear to
be continuous).
Because of the limited resolution, two samples from a single person will
often lead to slightly different measurements—e.g., 3.00 and 2.45 kilo-bases (kb)
in one case, 3.03 and 2.40 kb in another. To decide whether two samples match,
each laboratory must have a match criterion.6 The match criterion should provide
an objective and quantitative rule for deciding whether two patterns match—e.g.,
all fragments must lie within 2% of one another. When samples fall outside the
match criterion, they should be declared to be "inconclusive" or "nonmatching."
The match criterion must be based on reproducibility studies that show the
actual degree of variability observed when multiple samples from the same
person are separately prepared and analyzed under typical forensic

conditions. Some testing laboratories originally used matching rules that were
based on the average spacing of fragment sizes in each region of the gel, rather
than on actual studies of reproducibility. Other laboratories used purely visual
matching criteria. Both are inadequate. Each testing laboratory must carry out its
own reproducibility studies, because reproducibility varies among laboratories.
The precise match criterion of each laboratory should be made freely available to
all interested persons and should be stated in forensic reports.
The match criterion is also used in the calculation of allele frequencies. To
determine the probability that a matching allele was found by chance, one counts
the number of matching alleles in an appropriately chosen reference population.
For the calculation to be valid, the same match criterion must be applied in
screening the population databank and in comparing the forensic samples. Some
testing laboratories originally used less stringent rules for declaring a match
between forensic samples and more stringent rules for determining the frequency
of matching alleles in the databank; the effect was an overstatement of the
probability of obtaining a match by chance.
Some have advocated that testing laboratories, instead of using a match
criterion, should report a likelihood ratio—the ratio of the probability that the
measurements would have arisen if the samples came from the same person to the
probability that they would have arisen if they came from different persons. No
testing laboratories in the United States now use that approach. The committee
recognizes its intellectual appeal, but recommends against it. Accuracy with it
requires detailed information about the joint distribution of fragment positions,
and it is not clear that information about a match could be understood easily by
lay persons.
A laboratory's level of reproducibility can increase or decrease over time.
Reproducibility should be measured not only when a laboratory first implements
DNA typing, but continually on the basis of actual casework, as well as external
proficiency testing (see Chapter 4). One easy way is to record the fragment
measurements from the control samples of known DNA included on the
membrane and regularly examine the variability in these measurements. A
drawback of that approach is that the control pattern might become too well
known to the examiners. A slight variation would eliminate the problem.
Examiners would continue to use a fixed known control sample on every
membrane, but would also be given a blind control sample as a bloodstain to
analyze with each case. The latter sample would be randomly selected from a
collection of a few dozen known samples. The examiners would not know its
specific identity, but only a code number. They would compare the blind control
sample against the known patterns, to determine whether it matched to the
expected extent. Such an internal test of reproducibility would provide continuing
internal measurement of a

laboratory's reproducibility. It would likely be a powerful tool for quality control

in a laboratory. For convenience, blind control samples could be distributed by a
professional association or a private-sector firm. The committee recommends
that testing laboratories adopt such a system for continuing measurement of
reproducibility and that they regularly examine and report the results.
Recommendations for mandating such testing systems are discussed in Chapter 4.
Retention of Sample
Scientifically, the best way to resolve ambiguity is often to repeat the
experiment. The U.S. justice system guarantees opposing sides the right to have
repeat experiments performed by experts of their choice, whenever that is
possible. Accordingly, testing laboratories should measure DNA samples before
analysis (with accurate devices, such as fluorometers, as well as with ethidium-
stained "yield" gels) and should use only the quantity of DNA required for
reliable Southern blot analysis. When they can, they should retain enough of a
sample to repeat the entire analysis.
TECHNICAL ISSUES IN PCR-BASED METHODS

PCR is a relatively new technique in molecular biology, having come into
common use in research laboratories only in the last 4 years. Although the basic
exponential amplification procedure is well understood, many technical details
are not, including why some primer pairs amplify much better than others, why
some loci cause systematically unfaithful amplification, and why some assays are
much more sensitive to variations in conditions. Nonetheless, it is an extremely
powerful technique that holds great promise for forensic applications because of
its great sensitivity and the potential of its use on degraded DNA.
We discuss here two broad categories of technical issues concerning PCR
methods: issues related to the amplification step and issues related to the
detection of amplified product.
Technical Issues Related to Amplification
Amplification Conditions
The quality and specificity of amplification with PCR depends on the
amplification conditions: the amplification cycling program (temperatures,
mixture (e.g., primer, nucleotide, polymerase, and magnesium concentrations),
times, and number of cycles), the composition of the amplification and the
amount and nature of the target DNA in the sample (single-stranded or

double-stranded).7 In some cases, results can vary among thermocyclers from

different manufacturers, among thermocyclers of a single manufacturer, and even
among different sample wells in a single machine. It is therefore essential that
precise conditions be established for each typing system and that the system be
thoroughly characterized for its sensitivity to variations in these conditions. If an
assay yields spurious or confusing results under particular conditions, it may be
necessary to prescribe strict condition limits or to discard the assay altogether. No
PCR assay should be used until it has been rigorously characterized in this way.
Qualitative and Quantitative Fidelity

Ideally, PCR amplification products would faithfully represent the starting
material in the sample—both qualitatively and quantitatively. But that is not
always the case.
PCR amplification is known to result in misincorporation of nucleotides at
the relatively low rate of less than one per 10,000 nucleotides per cycle.8
Amplification is usually performed on a sample that contains a large number of
molecules; if the misincorporation is random, the low frequency of random errors
will not be detected in most systems and will pose no problem for the typing
result. Difficulties arise for systems in which the misincorporation is not random.
For example, DNA sequences that contain tandem repeat sequences—such as the
dinucleotide (CA)n or some VNTRs—present serious problems. Apparently, the
DNA polymerase can slip during amplification, introduce or delete copies of the
repeat, and produce a heterogeneous collection of fragments, often making
interpretation difficult. That drawback is unfortunate: such simple sequence
repeats tend to be highly polymorphic in the human population and so would seem
to be useful for forensics. Because there is no way to predict which PCR assays
will be subject to this problem, each assay must be thoroughly characterized.
In some cases, PCR can be qualitatively faithful but quantitatively
unfaithful, because some alleles amplify more efficiently than others. A sample
might contain a 50:50 mixture of two alleles and yield an amplified product with a
90:10 ratio.9 Differential amplification can arise through several mechanisms. It
has been observed in the amplification of allelic products of different sizes
(larger products tend to amplify less efficiently than shorter products) and in the
amplification of sequences that differ significantly in GC content (because of
differing denaturation efficiencies). In some cases, faithful amplification occurs
at some temperatures and differential amplification at other temperatures.8 The
possibility of differential amplification needs to be addressed in the design and
development of amplification protocols for each genetic-marker system. The
safeguards to

ensure that differential amplification does not occur should be defined and
documented.
Quantitative analysis of mixed samples with PCR might be problematic.
Suppose that PCR amplification reveals four alleles in a sample, and alleles 1 and 2
give a stronger signal than alleles 3 and 4. A conclusion that the two stronger
alleles correspond to one contributor with genotype 1/2 and the two weaker
alleles to a contributor with genotype 3/4 would be justified only if one had
demonstrated that the amplification and detection process yielded signals that
were directly proportional to the initial quantities of the alleles. If the locus were
subject to differential amplification, the conclusion might be unjustified. This
underscores the importance of characterizing possible differential amplification.
Ideally, primer pairs should amplify only the desired target locus. However,
nonspecific amplification can be seen, if one amplifies for extended cycle
numbers. Limits on the cycle number might be required as a safeguard against
nonspecific products.
Amplification Inhibition
Some forensic samples contain factors that inhibit amplification, either by
binding to the target DNA or by inhibiting the polymerase. In particular,
amplification inhibition is often seen with DNA from older bloodstains. It can
usually be remedied by re-extracting the DNA to remove the inhibiting factor, by
diluting the offending DNA, or by increasing the concentration of polymerase.
There is no evidence that any of those procedures affects typing adversely.
Nevertheless, the nature of inhibiting factors and the mechanism of the inhibition
effect deserve additional study. Each PCR system should be thoroughly
characterized on a range of simulated and known forensic samples, to document
any effect on reliability.
Contamination
One of the most serious concerns regarding PCR-based typing is
contamination of evidence samples with other human DNA. PCR is not
discriminating as to the source of the DNA it amplifies, and it can be exceedingly
sensitive. Potentially, amplification of contaminant DNA could lead to spurious
typing results. Three sorts of contamination can be identified, as set forth below;
each has its own solutions.
• Mixed samples. Some evidence samples occur as mixtures, e.g., sexual-

assault evidence, which often contains a mixture of semen and vaginal
fluids. In mixed samples that contain semen, it is possible to extract the

sperm DNA and the DNA of vaginal epithelial cells separately. That
allows the genetic contribution of the male and female to be
distinguished. However, there is one important caveat: if the sperm
fraction shows a genotype that matches that of the victim, one cannot
conclude that this represents the genotype of the perpetrator, inasmuch
as it could be due to residual vaginal epithelial cells. The problem should
disappear as PCR-based assays for more loci become available. For
other mixtures, such separation is not possible. For example, it is not
possible to separate the DNA contributed by different persons in mixed
bloodstains or in sexual-assault samples that involve two or more
perpetrators. Mixed samples are a reality of the forensic world that must
be accommodated in interpretation and reconstruction. As a rule, mixed
samples must be interpreted with great caution. Their interpretation
should always be based on results from multiple PCR assays, so that one
can check for consistency across various loci. Interpretations based on
quantity can be particularly problematic—e.g., if one saw two alleles of
strong intensity and two of weak intensity, it would be improper to
assign the first pair to one contributor and the second pair to a second
contributor, unless it had been firmly established that the system was
quantitatively faithful under the conditions used.
• Contamination from handling in the field and laboratory. It is
conceivable that DNA can be transferred to evidence samples or reaction
solutions through handling, either from the person doing the handling or
in transfer from other evidence samples. There are no hard data on the
amounts of DNA transferred by physical contact, but there are anecdotal
reports of experimenters who contaminated their PCR mixtures with
their own DNA. It is difficult to assess the likelihood of this sort of
contamination. Steps should be taken to minimize it, such as handling
samples with gloves and preparing solutions and processing samples in
separate areas. Contamination of solutions can be recognized with
appropriate positive-control and blank-control amplifications, which
should be used routinely. When a stain composed of blood, semen, or
other biological material is analyzed with PCR, it is important to analyze
unstained materials next to the stain with PCR as a control for
contamination.
• PCR product carryover contamination. The most serious problem is
contamination of evidence samples and reaction solutions with PCR
products from prior amplifications. Such products can contain a target
sequence at a concentration a million times greater, and even a relatively
small quantity could swamp the correct signal from the evidence
sample. Even the simple act of flipping the top of a plastic tube might
aerosolize enough DNA to pose a problem.
Many research and diagnostic laboratories have been afflicted with the
problem of PCR carryover. Contamination risks can be minimized by strict

adherence to sterile technique; the use of separate work areas for sample
processing, solution preparation, amplification, and type testing; the use of
separate pipettes in each area (pipettes are a major source of carryover
contamination); and maintenance of a one-way flow of materials from the
evidence-storage area to the sample-preparation area to the type-testing area.
Those precautions focus primarily on preventing PCR carryover
contamination. But it has become clear that carryover products from the PCR
reaction to another must also be eliminated. One way is to use the nucleotide
dUTP in place of dTTP in all PCR reactions.10 PCR products made in this
manner can be selectively destroyed by the enzyme uracil N-glycolase (UNG),
which excises dUTP. Accordingly, all evidence samples would be treated before
PCR amplification with UNG, to destroy contamination from previous PCR
reactions. The method holds promise, although it has not yet been extensively
tested in practice. Methods of detecting and preventing contamination from one
PCR reaction to another in forensic laboratories are generally still in their early
stages, and additional development should be encouraged.
As with contamination due to handling, carryover contamination can be
signaled by the appearance of product in blank controls and of mixed or
inappropriate types in samples and positive controls. Such controls should be
used rigorously. Moreover, it should be remembered that the controls are useful
for monitoring general contamination in the laboratory, not the accuracy of a
particular experiment. If a blank control is positive in one experiment, it indicates a
potential problem not just for that experiment, but for any experiment performed
at about the same time—even in a laboratory contaminated with PCR carryover,
blank controls do not necessarily become contaminated on every occasion. It will
be wise to repeat all work with samples that have never been exposed to the
PCR-typing laboratory.
In view of the problem of contamination due to handling and carryover,
laboratories must incorporate contamination control into their standard operating
procedures. And outbreaks of contamination and the steps taken to correct the
problem should be documented.
One of the best safeguards against contamination is to have DNA typing
independently performed in two laboratories, each starting with a piece of the
unprocessed evidence sample. Given the inexpensiveness of typing, serious
consideration should be given to independent replication of results—at least
during the early stages of this technology.
Issues Related to Detection of Amplified Product

Variation after PCR amplification can be detected in several ways. The most
popular detection schemes for nonforensic analyses are reverse dot hybridization,
analysis of PCR products for size variation with gel electro

phoresis, analysis of PCR products with gel electrophoresis after restriction-

endonuclease digestion, analysis for the presence of amplification after use of
allele-specific amplification primers, and analysis of the nucleotide sequence. No
matter what detection scheme is used, contamination of the test sample with a
second DNA sample or differential amplification of one allele in a sample that
contains two alleles at the test locus can produce an error in typing. Differential
amplification could result in the typing of a true heterozygote as a homozygote,
or the low level of hybridization of the second allele could suggest the presence
of a contaminating DNA in the test sample. A repeat PCR amplification and
analysis might be successful and pinpoint a problem in the first amplification
procedure. Besides those general problems, each detection format can entail its
own technical problems.
Reverse Dot Hybridization

In forensic analysis today, the single PCR-based kit available uses reverse
dot hybridization to detect variation at the HLA-DQ locus.11Reverse dot
hybridization is based on a yes-no detection scheme. Theoretically, the absence
of a signal in a dot means that the test allele is not present in the DNA sample,
and a signal in a dot indicates the presence of the test allele. An intermediate
signal in a dot—a signal that is considerably less intense than a second signal in
the test hybridization—can result from a second DNA sample's contaminating the
test sample, technical variation in the conditions of analysis (e.g., hybridization
temperature), or true heterozygosity for the allele that produces the intermediate
signal. Usually, such problems can be resolved through repeat experiments or by
comparing results from a number of loci with many alleles (such loci could shed
light on the nature of mixtures). If the DNA sample of a crime victim contains the
allele in question, it would suggest contamination as the source. If repeat of the
hybridization and washing procedures eliminates the intermediate signal, it would
suggest its spurious nature. Rarely, the origin of an intermediate hybridization
signal might remain unresolved; if the type of the sample is still questionable, the
data should be discarded.
Other Detection Methods

When restriction-enzyme digestion of a PCR product is necessary to
demonstrate alleles, the major pitfall is incomplete digestion. One can control the
problem in the test sample by using a restriction enzyme for which a constant site
that produces a fragment of constant size exists in the test fragment. For
example, suppose that digestion of a 500-bp PCR fragment by HaeIII yields a
constant 300-bp fragment and either a 200-bp fragment or 120-bp and 80-bp
fragments; a poor yield of the 300-bp frag

in a particular sample would suggest incomplete digestion of the PCR product.

Allele-specific amplification has been used in DNA diagnosis of genetic
disease. Diagnosis can be based solely on absence of an amplification product, so
it is a difficult technique to control adequately. Absence of a fragment can
indicate either failure of the amplification procedure or absence of the allele in
question from the test sample. If the former applies, a typing error would result.
For this reason, the committee recommends that this method not be used for
forensic analysis.
DNA sequence analysis of PCR products is commonly carried out either
manually or with automation. Some ambiguity of nucleotide sequence at one or
more positions is common and can signal DNA contamination or a technical
problem in the analysis. Another important problem occurs when the DNA
sequence of a fragment demonstrates variation at more than one position in the
nucleotide sequence. Because both alleles at a locus are sequenced in the
procedure, it is difficult to determine what fraction of the variation is contributed
by each allele. For example, if heterozygosity is observed at two positions in a
sequence, one cannot know, without further experimentation, whether one allele
contains both variants or each allele contains one.
New methods of detection of PCR products will surely be devised. Well-
controlled, extensive studies of the methods will be required before their use in
forensic science, and the quality-assurance procedures described in Chapter 4
will be important to ensure their rigorous testing and reliability.
Use of Kits
One commercial kit for forensic PCR analysis has been marketed. Other
such kits will probably be ready for commercial markets soon. The committee
sees a potential for introduction of unreliable kits and the misuse of kits. The
existence of a kit suggests ease of use and low chance of technical error. The
committee believes that nonexpert laboratories will run a significant chance of
error in using kits. We therefore recommend that a standing committee (discussed
later in this chapter) consider the issue of regulatory approval of kits for
commercial use in forensic DNA analysis. Even though no precedent exists for
regulation of tests in forensic applications, we believe that it might be necessary
for a government agency to test and approve kits for DNA analysis before their
actual forensic use.
Prospects of PCR-Based Methods

PCR analysis has a number of desirable features for forensic applications. It
requires very little DNA (less than for a Southern blot by a factor of 100-150) in
the evidence sample. It is thus feasible to amplify dozens of

loci. It generates a large quantity of relatively pure product that can be analyzed
with much greater precision than Southern blots, even down to the nucleotide
level. At the same time, it poses even more serious issues of proficiency, control,
and technology transfer than RFLP typing.
In summary, it is well established that one can greatly amplify a locus with
authenticity and that one can reliably detect alleles or sequence variation at the
amplified locus with any of a number of techniques. PCR analysis is extremely
powerful in medical technology, but it has not yet achieved full acceptance in the
forensic setting. The theory of PCR analysis, even though it is the analysis of
synthetic DNA, as opposed to the natural sample, is scientifically accepted and
has been accepted by a number of courts. However, most forensic laboratories
have invested their energy in development of RFLP technology and have left the
development of forensic PCR technology to a few other laboratories. Thus, there
is no broad base of experience in the use of the technique in identity testing.
Forensic PCR-based testing is now limited for the most part to analysis of
genetic variation at the DQ locus in the HLA complex. Potential ambiguities in
typing results cannot yet be checked by studying a number of other loci in the
same DNA sample. That shortcoming will be rectified with the addition of new
PCR markers for forensic analysis. However, it is clear that analysis of the DQ
locus with PCR can often provide useful information during the investigative
phase in the forensic setting.
In general, further experience should be gained with respect to PCR in
identity testing. Information on the extent of the contamination problem in PCR
analysis and the differential amplification of mixed samples needs to be further
developed and published. A great deal of this information can be obtained when a
number of polymorphic systems are available for PCR analysis. Ambiguous
results obtained with a number of polymorphic markers will signal contamination
or mixtures of DNA in a sample.
Quantification of PCR results needs to be explored, to make the results more
reliable. Laboratories that gain experience with PCR should determine the
relationship between cycle number and percentage of contaminating DNA easily
detected for each system used. Control primers that amplify small amounts of
DNA reliably and robustly need to be added to test amplifications. In general,
information derived from new polymorphic loci under standardized conditions
with easily quantifiable results or end points is needed. Considerable advances in
the use of PCR in forensic analysis can be expected soon; the method has
enormous promise.
NATIONAL COMMITTEE ON FORENSIC DNA TYPING

Forensic DNA typing is advancing rapidly. RFLP-based typing methods
continue to be refined and improved, PCR typing methods are being

used in some court cases, and other methods are being developed in scientific and
commercial research laboratories. Typing methods will continue to be replaced
with ever more sophisticated approaches for some time to come. These
developments hold great promise for increasing the sensitivity and reliability of
forensic DNA typing.
The rapidity of development creates a need to balance two competing
societal objectives. On the one hand, new technologies should be made available
quickly. On the other hand, forensic typing methods should not be used until their
soundness is established both in principle and in practice. The problem involves
both technology and technology transfer. Forensic DNA typing is drawing
methods from the cutting edge of molecular genetics, but must apply them to
quite different circumstances.
The committee believes that the field of forensic science would be best
served by the creation of a National Committee on Forensic DNA Typing
(NCFDT) to provide advice on scientific and technical issues as they arise.
NCFDT would consist primarily of molecular geneticists, population geneticists,
forensic scientists, and additional members knowledgeable in law and ethics. Its
charges would be to provide guidance about the power and limitations of DNA
typing methods, to identify potential problems and their solutions, to provide
guidance about whether new technologies are ready for practical use in the
forensic laboratory, and to provide advice concerning the regulation of kits for
forensic DNA typing. In addition (as discussed in Chapter 3), NCFDT would
provide advice on population genetics and statistical interpretation.
Such a committee could play a critical role in smoothing the acceptance of
DNA typing technologies in the courtroom while ensuring their reliability.
Although NCFDT would have no formal regulatory authority, we anticipate that
substantial influence would derive from its stature and the quality of its advice, so
that courts could look to its recommendations in making their decisions.
The present committee recommends that NCFDT be convened under the
auspices of an appropriate government agency. Because its task is fundamentally
scientific, we feel that the agency should be one whose primary mission is
scientific, rather than related to law enforcement. To avoid any appearance of
conflict of interest, an agency that uses forensic DNA typing itself would be
unsuitable. Two excellent choices would be the National Institutes of Health
(NIH) or the National Institute of Standards and Technology (NIST). NIH has
extensive experience in molecular biology, population genetics, and laboratory
practice. NIST has less direct experience in those fields, but has considerable
experience in evaluating technologies. Regardless of which agency convenes
NCFDT, we believe that the effort should have broad government support from
NIST, NIH, the National Science Foundation, the National Institute of Justice, the
Federal

Bureau of Investigation, and the State Justice Institute. NCFDT should also have
broad support from the American Society of Crime Laboratory Directors, the
Genetics Society of America, and the American Society of Human Genetics.
The creation of an expert advisory committee is a somewhat unusual step
for forensic science. However, we feel that it is the appropriate way to ensure
that the field can incorporate new developments promptly while maintaining high
standards.
SUMMARY OF RECOMMENDATIONS
• Any new DNA typing method (or substantial variation on an existing

method) must be rigorously characterized in both research and forensic
settings, to determine the circumstances under which it will yield
reliable results.
• DNA analysis in forensic science should be governed by the highest
standards of scientific rigor, including the following requirements:
— Each DNA typing procedure must be completely described in a detailed,

written laboratory protocol.
— Each DNA typing procedure requires objective and quantitative rules
for identifying the pattern of a sample.
— Each DNA typing procedure requires a precise and objective matching
rule for declaring whether two samples match.
— Potential artifacts should be identified by empirical testing, and
scientific controls should be designed to serve as internal checks to test
for the occurrence of artifacts.
— The limits of each DNA typing procedure should be understood,
especially when the DNA sample is small, is a mixture of DNA from
multiple sources, or is contaminated with interfering chemicals.
— Empirical characterization of a DNA typing procedure must be
published in appropriate scientific journals.
— Before a new DNA typing procedure can be used, it must have not only a
solid scientific foundation but also a solid base of experience.
• Regarding RFLP-based typing, the committee makes a number of

technical recommendations, including specific recommendations about
the choice of probes, the use of ethidium bromide in gels, controls for
anomalous bands, measurement of fragment sizes, controls for band
shifting, match criteria, and sample retention.
• Regarding PCR-based typing, the committee makes a number of
technical recommendations, including recommendations for thorough
characterization of each PCR assay for definition of the range of
conditions under

which it will perform reliably and for strict contamination measures and
other control procedures
• The committee strongly recommends the establishment of a National
Committee on Forensic DNA Typing under the auspices of an
appropriate government agency, such as NIH or NIST, to provide expert
advice primarily on scientific and technical issues concerning forensic
DNA typing.
REFERENCES
1. Balazs I, Baird M, Clyne M, Meade E. Human population genetic studies of five hypervariable
DNA loci, Am J Hum Genet. 44:182-190, 1989.
2. Culliford BJ. Determination of phosphoglucomutase types in bloodstains. J Forensic Sci Sociol.
7:131-133, 1967.
3. Culliford BJ. The examination and typing of blood stains in the crime laboratory. Washington,
4. Sensabaugh GF. Biochemical markers of individuality, pp. 338-415 in: Saferstein R, ed. Forensic
science handbook. Englewood Cliffs, New Jersey: Prentice-Hall, 1982.
McNally L, Baird M, McElfresh K, Eisenberg A, Balazs I. increased migration rate observed in DNA
from evidentiary material precludes the use of sample mixing to resolve forensic cases of
identity. Appl Theor Electrophoresis. 5:267-272, 1990.
6. Thompson WC, Ford S. The meaning of a match: sources of ambiguity in the interpretation of a
DNA print in forensic DNA technology, pp. 93152 in: Farley M, Harrington J, eds. Forensic
DNA technology. Chelsea, Michigan: Lewis Publishing, 1991.
7. Amheim N, Levenson CH. Polymerase chain reaction. C&E News68:36-47, October 1, 1991).
8. Erlich HA, Gelfand D, Sninsky J J. Recent advances in the polymerase chain reaction. Science.
252:1643-1651, 1991.
9. Comey CT, Jung JM, Budowle B. Use of formamide to improve amplification of HLA DQa
sequences. Biotechniqucs. 10:60-61, 1991.
10. Longo MC, Berninger MS, Harley JL. Use of uracil DNA glycosylase to control carryover
contamination in polymerase chain reactions. Gene.93:125, 1990.
11. Saiki RK, Walsh PS, Levenson CH, Erlich HA. Genetic analysis of amplified DNA with
immobilized sequence-specific oligonucleotide probes. Proc Natl Acad Sci USA.
86:6230-6234, 1989.

DNA TYPING: STATISTICAL BASIS FOR INTERPRETATION 74
3
DNA Typing: Statistical Basis for
Interpretation
Can DNA typing uniquely identify the source of a sample? Because any two
human genomes differ at about 3 million sites, no two persons (barring identical
twins) have the same DNA sequence. Unique identification with DNA typing is
therefore possible provided that enough sites of variation are examined.
However, the DNA typing systems used today examine only a few sites of
variation and have only limited resolution for measuring the variability at each
site. There is a chance that two persons might have DNA patterns (i.e., genetic
types) that match at the small number of sites examined. Nonetheless, even with
today's technology, which uses 3-5 loci, a match between two DNA patterns can
be considered strong evidence that the two samples came from the same source.
Interpreting a DNA typing analysis requires a valid scientific method for
estimating the probability that a random person might by chance have matched
the forensic sample at the sites of DNA variation examined. A judge or jury could
appropriately weigh the significance of a DNA match between a defendant and a
forensic sample if told, for example, that ''the pattern in the forensic sample
occurs with a probability that is not known exactly, but is less than 1 in 1,000" (if
the database that shows no match with the defendant's pattern is of size 1,000).
To say that two patterns match, without providing any scientifically valid
estimate (or, at least, an upper bound) of the frequency with which such matches
might occur by chance, is meaningless.
Substantial controversy has arisen concerning the methods for estimating

the population frequencies of specific DNA typing patterns.1-14 Questions have

been raised about the adequacy of the population databases on which frequency
estimates are based and about the role of racial and ethnic origin in frequency
estimation. Some methods based on simple counting produce modest
frequencies, whereas some methods based on assumptions about population
structure can produce extreme frequencies. The difference can be striking: In one
Manhattan murder investigation, the reported frequency estimates ranged from 1
in 500 to 1 in 739 billion, depending on how the statistical calculations were
performed. In fact, both estimates were based on extreme assumptions (the first
on counting matches in the databases, the second on multiplying lower bounds of
each allele frequency). The discrepancy not only is a question of the weight to
accord the evidence (which is traditionally left to a jury), but bears on the
scientific validity of the alternative methods used for rendering estimates of the
weight (which is a threshold question for admissibility).
In this chapter, we review the issues of population genetics that underlie the
controversy and propose an approach for making frequency estimates that are
independent of race and ethnic origin. This approach addresses the central
purpose of DNA typing as a tool for the identification of persons.
ESTIMATING THE POPULATION FREQUENCY OF A DNA

PATTERN
DNA "exclusions" are easy to interpret: if technical artifacts can be
excluded, a nonmatch is definitive proof that two samples had different origins.
But DNA "inclusions" cannot be interpreted without knowledge of how often a
match might be expected to occur in the general population. Because of that
fundamental asymmetry, although each new DNA typing method or marker can
be used for investigation and exclusion as soon as its technical basis is secure, it
cannot be interpreted with regard to inclusion until the population frequencies of
the patterns have been established. We discuss the issues involved in estimating
the frequency of a DNA pattern, consisting of pairs of alleles at each of several
loci.
Estimating Frequencies of DNA Patterns by Counting

A standard way to estimate frequency is to count occurrences in a random
sample of the appropriate population and then use classical statistical formulas to
place upper and lower confidence limits on the estimate. Because estimates used
in forensic science should avoid placing undue weight on incriminating evidence,
an upper confidence limit of the frequency should be used in court. This is
especially appropriate for forensic DNA typing, because any loss of power can be
offset by studying additional loci.

To estimate the frequency of a particular DNA pattern, one might count the
number of occurrences of the pattern in an appropriate random population
sample. If the pattern occurred in 1 of 100 samples, the estimated frequency
would be 1%, with an upper confidence limit of 4.7%. If the pattern occurred in 0
of 100 samples, the estimated frequency would be 0%, with an upper confidence
limit of 3%. (The upper bound cited is the traditional 95% confidence limit,
whose use implies that the true value has only a 5% chance of exceeding the
upper bound.) Such estimates produced by straightforward counting have the
virtue that they do not depend on theoretical assumptions, but simply on the
sample's having been randomly drawn from the appropriate population.
However, such estimates do not take advantage of the full potential of the genetic
approach.
Estimating Frequencies of DNA Patterns with the

Multiplication Rule(Product Rule)
In contrast, population frequencies often quoted for DNA typing analyses
are based not on actual counting, but on theoretical models based on the
principles of population genetics. Each matching allele is assumed to provide
statistically independent evidence, and the frequencies of the individual alleles
are multiplied together to calculate a frequency of the complete DNA pattern.
Although a databank might contain only 500 people, multiplying the frequencies
of enough separate events might result in an estimated frequency of their all
occurring in a given person of 1 in a billion. Of course, the scientific validity of
the multiplication rule depends on whether the events (i.e., the matches at each
allele) are actually statistically independent.
From a statistical standpoint, the situation is analogous to estimating the
proportion of blond, blue-eyed, fair-skinned people in Europe by separately
counting the frequencies of people with blond hair, people with blue eyes, and
people with fair skin and calculating their proportions. If a population survey of
Europe showed that 1 of 10 people had blond hair, 1 of 10 had blue eyes, and 1
of 10 had fair skin, one would be wrong to multiply these frequencies to conclude
that the frequency of people with all three traits was 1 in 1,000. Those traits tend
to co-occur in Nordics, so the actual frequency of the combined description is
probably higher than 1 in 1,000. In other words, the multiplication rule can
produce an underestimate in this case, because the traits are correlated owing to
population substructure—the traits have different frequencies in different
population groups. Correlations between those traits might also be due to
selection or conceivably to the action of some genes on all three traits. In any
case, the example illustrates that correlations within subgroups—whatever their
origin—bear on the procedures for estimating frequencies.

Unlike many of the technical aspects of DNA typing that are validated by
daily use in hundreds of laboratories, the extraordinary population-frequency
estimates sometimes reported for DNA typing do not arise in research or medical
applications that would provide useful validation of the frequency of any
particular person's DNA profile. Because it is impossible or impractical to draw a
large enough population to test calculated frequencies for any particular DNA
profile much below 1 in 1,000, there is not a sufficient body of empirical data on
which to base a claim that such frequency calculations are reliable or valid per
se. The assumption of independence must be strictly scrutinized and estimation
procedures appropriately adjusted if possible. (The rarity of all the genotypes
represented in the databank can be demonstrated by pairwise comparisons. Thus,
in a recently reported analysis of the FBI database, no exactly matching pairs of
profiles were found in five-locus DNA profiles, and the closest match was a
single three-locus match among 7.6 million basepair comparisons.)13
The multiplication rule has been routinely applied to blood-group
frequencies in the forensic setting. However, that situation is substantially
different: Because conventional genetic markers are only modestly polymorphic
(with the exception of human leukocyte antigen, HLA, which usually cannot be
typed in forensic specimens), the multilocus genotype frequencies are often about
1 in 100. Such estimates have been tested by simple empirical counting. Pairwise
comparisons of allele frequencies have not revealed any correlation across loci.
Hence, the multiplication rule does not appear to lead to the risk of extrapolating
beyond the available data for conventional markers. In contrast, highly
polymorphic DNA markers exceed the informative power of protein markers, so
multiplication leads to estimates that are less than the reciprocal of the size of the
databases.
Validity of Multiplication Rule and Population Substructure

The multiplication rule is based on the assumption that the population does
not contain subpopulations with distinct allele frequencies—that each individual's
alleles constitute statistically independent random selections from a common
gene pool. Under this assumption, the procedure for calculating the population
frequency of a genotype is straightforward:
• Count the frequency of alleles. For each allele in the genotype, examine a
random sample of the population and count the proportion of matching
alleles—that is, alleles that would be declared to match according to the
rule that is used for declaring matches in a forensic context. This step
requires only the selection of a sample that is truly random with
reference to the genetic type; it does not appeal to any theoretical
models.

It is essential that the forensic matching rule be precise and objective

—otherwise it would be impossible to apply it in calculating the
proportion of individuals with matching alleles in the population
databank. And it is essential that the same rule be applied to count
frequencies in the population databank, because this is the only way to
determine the proportion of random individuals that would have been
declared to match in the forensic context. (In the context of forensic
applications, an estimate of the probability of a match in DNA typing
has been termed conservative if on the average it is larger than the
actual one, so that any weight applied to the estimate would favor the
suspect. Thus, some laboratories use a more conservative rule for
counting population frequencies than for forensic matches—an
acceptable approach, because it overestimates allele frequency. The
converse would not be acceptable.)
• Calculate the frequency of the genotype at each locus. The frequency of a
homozygous genotype a1/a1 is calculated to be pa12 where pa1denotes
the frequency of allele a1. The frequency of a heterozygous genotype
a1/a2 is calculated to be 2pa1pa2, where pa1 and pa2 denote the
frequencies of alleles a1 and a2. In both cases, the genotype frequency is
calculated by simply multiplying the two allele frequencies, on the
assumption that there is no statistical correlation between the allele
inherited from one's father and the allele inherited from one's mother.
The factor of 2 arises in the heterozygous case, because one must
consider the case in which allele a1 was contributed by the father and
allele a2 by the mother and vice versa: each of the two cases has
probability pa1pa2. When there is no correlation between the two
parental alleles, the locus is said to be in Hardy-Weinberg equilibrium.
We should note that in forensic DNA typing, a slight modification is
used in the case of apparently homozygous genotypes. When one
observes only a single allele in a sample, one cannot be certain that the
individual is a homozygote; it is always possible that a second allele has
been missed for technical reasons. To be conservative, most forensic
laboratories do not calculate the probability that the sample has two
copies of the allele (which is pa12), but rather the probability that the
sample has at least one copy (which is 2pa1) leaving open the possibility
of a second allele. We endorse this procedure.)
• Calculate the frequency of the complete multilocus genotype. The
frequency of a complete genotype is calculated by multiplying the
genotype frequencies at all the loci. As in the previous step, this
calculation assumes that there is no correlation between genotypes at
different loci; the absence of such correlation is called linkage
equilibrium. (Some authors prefer to reserve the term linkage
equilibrium for loci on the same chromosome and to use the term
gametic phase equilibrium for loci on different chromosomes.) Suppose,
for example, that a person has genotype a1/a2, b1/b2, c1/

c1. If a random sample of the appropriate population shows that the frequencies
of a1, a2, b1, b2, and c1 are approximately 0.1, 0.2, 0.3, 0.1, and 0.2,
respectively, then the population frequency of the genotype would be estimated to
be [2(0.1)(0.2)][2(0.3)(0.1)][(0.2)(0.2)] = 0.000096, or about 1 in 10,417.
Again, the validity of the multiplication rule depends on the absence of

population substructure, because only in this special case are the different alleles
statistically uncorrelated with one another.
In a population that contains groups with characteristic allele frequencies,
knowledge of one allele in a person's genotype might carry some information
about the group to which the person belongs, and this in turn alters the statistical
expectation for the other alleles in the genotype. For example, a person who has
one allele that is common among Italians is more likely to be of Italian descent
and is thus more likely to carry additional alleles that are common among
Italians. The true genotype frequency is thus higher than would be predicted by
applying the multiplication rule and using the average frequency in the entire
population.
To illustrate the problem with a hypothetical example, suppose that a
particular allele at a VNTR locus has a 1% frequency in the general population,
but a 20% frequency in a specific subgroup. The frequency of homozygotes for
the allele would be calculated to be 1 in 10,000 according to the allele frequency
determined by sampling the general population, but would actually be 1 in 25 for
the subgroup. That is a hypothetical and extreme example, but illustrates the
potential effect of demography on gene frequency estimation.
Basis of Concern About Population Substructure

The key question underlying the use of the multiplication rule is whether
actual populations have significant substructure for the loci used for forensic
typing. This has provoked considerable debate among population geneticists:
some have expressed serious concern about the possibility of significant
substructure,2,4,9,10 and others consider the likely degree of substructure not great
enough to affect the calculations significantly.1,3,6,8,11,12,13
The population geneticists who urge caution make three points:
1. Population genetic studies show some substructure within racial

groups for genetic variants, including protein polymorphisms,
genetic diseases, and DNA polymorphisms. Thus, North American
Caucasians, blacks, Hispanics, Asians, and Native Americans are not
homogeneous groups. Rather, each group is an admixture of
subgroups with somewhat different allele frequencies. Allele
frequencies have not yet been homogenized, because people tend to
mate within these groups.

2. For any particular genetic marker, the degree of subpopulation

differentiation cannot be predicted, but must be determined
empirically.
3. For the loci used for forensic typing, there have been too few
empirical investigations of subpopulation differentiation.
In short, those population geneticists believe that the absence of substructure

cannot be assumed, but must be proved empirically (see Lewontin and Hartl10).
Other population geneticists, while recognizing the possibility or likelihood of
population substructure, conclude that the evidence to date suggests that the
effect on estimates of genotype frequencies are minimal (see Chakraborty and
Kidd12). Recent empirical studies concerning VNTR loci13,14 (Weir, personal
communication, 1991) detected no deviation from independence within or across
loci. Moreover, pairwise comparisons of all five-locus DNA profiles in the FBI
database showed no exact matches; the closest match was a single three-locus
match among 7.6 million pairwise comparisons.13These studies are interpreted as
indicating that multiplication of gene frequencies across loci does not lead to
major inaccuracies in the calculation of genotype frequency—at least not for the
specific polymorphic loci examined.
Although mindful of the controversy, the committee has chosen to assume
for the sake of discussion that population substructure may exist and provide a
method for estimating population frequencies in a manner that adequately
accounts for it. Our decision is based on several considerations:
1. It is possible to provide conservative estimates of population

frequency, without giving up the inherent power of DNA typing.
2. It is appropriate to prefer somewhat conservative numbers for
forensic DNA typing, especially because the statistical power lost in
this way can often be recovered through typing of additional loci,
where required.
3. It is important to have a general approach that is applicable to any
loci used for forensic typing. Recent empirical studies pertain only to
the population genetics of the VNTR loci in current use. However,
we expect forensic DNA typing to undergo much change over the
next decade—including the introduction of different types of DNA
polymorphisms, some of which might have different properties from
the standpoint of population genetics.
4. It is desirable to provide a method for calculating population
frequencies that is independent of the ethnic group of the subject.
Assessing Population Substructure Requires Direct Sampling

of EthnicGroups
How can one address the possibility of population substructure? In
principle, one might consider three approaches: (1) carry out population

studies on a large mixed population, such as a racial group, and use statistical
tests to detect the presence of substructure; (2) derive theoretical principles that
place bounds on the possible degree of population substructure; and (3) directly
sample different groups and compare the observed allele frequencies. The third
offers the soundest foundation for assessing population substructure, both for
existing loci and for many new types of polymorphisms under development.
In principle, population substructure can be studied with statistical tests to
examine deviations from Hardy-Weinberg equilibrium and linkage equilibrium.
Such tests are not very useful in practice, however, because their statistical power
is extremely low: even large and significant differences between subgroups will
produce only slight deviations from Hardy-Weinberg expectations. Thus, the
absence of such deviations does not provide powerful evidence of the absence of
substructure (although the presence of such deviations provides strong evidence
of substructure).
The correct way to detect genetic differentiation among subgroups is to
sample the subgroups directly and to compare the frequencies. The following
example is extreme and has not been observed in any U.S. population, but it
illustrates the difference in power. Suppose that a population consists of two
groups with different allele frequencies at a diallelic locus:
A a
Group I 0.5 0.5
Group II 0.9 0.1
If there is random mating within the groups, Hardy-Weinberg equilibrium
within the groups will produce these genotype frequencies:
AA Aa aa
Group I 0.25 0.50 0.25
Group II 0.81 0.18 0.01
Suppose that Group I is 90% of the population and Group II is 10%. In the
overall population, the observed genotype frequencies will be
AA = (0.9)(0.25) + (0.1)(0.81) = 0.306
Aa = (0.9)(0.50) + (0.1)(0.18) = 0.468
aa = (0.9)(0.25) + (0.1)(0.01) = 0.226
If we were unaware of the population substructure, what would we expect
under Hardy-Weinberg equilibrium? The average allele frequencies will be
A = (0.9)(0.5) + (0.1)(0.9) = ).54
a = (0.9)(0.5) + (0.1)(0.1) = 0.46
which would correspond to the Hardy-Weinberg proportions of

AA = (0.54)(0.54) = 0.2916
Aa = 2(0.54)(0.46) = 0.4968
aa + (0.46)(0.46) = 0.2116
Even though there is substantial population substructure, the proportions do
not differ greatly from Hardy-Weinberg expectation. In fact, one can show that
detecting the population differentiation with the Hardy-Weinberg test would
require a sample of nearly 1,200, whereas detecting it by direct examination of
the subgroups would require a sample of only 22. In other words, the Hardy-
Weinberg test is very weak for testing substructure.
The lack of statistical power to detect population substructure makes it
difficult to detect genetic differentiation in a heterogeneous population. Direct
sampling of subgroups is required, rather than examining samples from a large
mixed population.
Similarly, population substructure cannot be predicted with certainty from
theoretical considerations. Studies of population substructure for protein
polymorphisms cannot be used to draw quantitative inferences concerning
population substructure for VNTRs, because loci are expected to show different
degrees of population differentiation that depend on such factors as mutation rate
and selective advantage. Differences between races cannot be used to provide a
meaningful upper bound on the variation within races. Contrary to common
belief based on difference in skin color and hair form, studies have shown that the
genetic diversity between subgroups within races is greater than the genetic
variation between races.15 Broadly, the results of the studies accord with the
theory of genetic drift: the average allele frequency of a large population group
(e.g., a racial group) is expected to drift more slowly than the allele frequencies
of the smaller subpopulations that it comprises (e.g., ethnic subgroups).
In summary, population differentiation must be assessed through direct
studies of allele frequencies in ethnic groups. Relatively few such studies have
been published so far, but some are under way.16 Clearly, additional such studies
are desirable.
The Ceiling Principle: Accounting for Population

Substructure
We describe here a practical and sound approach for accounting for possible
population substructure: the ceiling principle.9 It is based on the following
observation: The multiplication rule will yield conservative estimates, even for a
substructured population, provided that the allele frequencies used in the
calculation exceed the allele frequencies in any of the population subgroups.
Accordingly, applying the ceiling principle involves two steps: (1) For each allele
at each locus, determine a ceiling frequency that is an upper bound for the allele
frequency that is independent of the

ethnic background of a subject; and (2) To calculate a genotype frequency, apply

the multiplication rule, using the ceiling frequencies for the allele frequencies.
How should ceiling frequencies be determined? We must balance rigor and
practicality. On the one hand, it is not enough to sample broad populations
defined as "races" in the U.S. census (e.g., Hispanics), because of the possibility
of substructure. On the other hand, it is not feasible or reasonable to sample every
conceivable subpopulation in the world to obtain a guaranteed upper bound. The
committee strongly recommends the following approach: Random samples of 100
persons should be drawn from each of 15-20 populations, each representing a
group relatively homogeneous genetically; the largest frequency in any of these
populations or 5%, whichever is larger, should be taken as the ceiling frequency.
The reason for using 5% is discussed later.
We give a simplified example to illustrate the approach. Suppose that two
loci have been studied in three population samples, with the following results:
Population 1 Population 2 Population 3
Locus 1
Allele a 1% 5% 11%
Allele b 5% 8% 10%
Locus 2
Allele c 3% 4% 4%
Allele d 2% 15% 7%
For the genotype consisting of a/b at locus 1 and c/d at locus 2, the ceiling
principle would assign ceiling values of 11% for allele a, 10% for allele b, 5% for
allele c, and 15% for allele d and would apply the multiplication rule to yield a
genotype frequency of [2(0.11)(0.10)][2(0.05)(0.15)] = 0.00033, or about 1 in
3,000. Note that the frequency used for allele c is 5%, rather than 4%, to reflect
the recommended lower bound of 5% on allele frequencies. Because the
calculation uses an upper bound for each allele frequency, it is believed to be
conservative given the available data, even if there are correlations among alleles
because of population substructure and even for persons of mixed or unknown
ancestry. This is more conservative, and preferable, to taking the highest
frequency calculated for any of the three populations.
The ceiling principle reflects a number of important scientific and policy
considerations:
• The purpose of sampling various populations is to examine whether

some alleles have considerably higher frequencies in particular
subgroups than in the general population—presumably because of
genetic drift. It is

matches at such alleles that might be accorded too much evidentiary

weight, if the general population frequency were used in calculating the
probability of a match.
• Determining whether an allele has especially high frequency does not
require a very large sample. A collection of 100 randomly chosen people
provides a sample of 200 alleles, which is quite adequate for estimating
allele frequencies.
• Genetically homogeneous populations from various regions of the world
should be examined to determine the extent of variation in allele
frequency. Ideally, the populations should span the range of ethnic
groups that are represented in the United States—e.g., English,
Germans, Italians, Russians, Navahos, Puerto Ricans, Chinese,
Japanese, Vietnamese, and West Africans. Some populations will be
easy to sample through arrangements with blood banks in the
appropriate country; other populations might be studied by sampling
recent immigrants to the United States. The choice and sampling of the
15-20 populations should be supervised by the National Committee on
Forensic DNA Typing (NCFDT) described in Chapter 2.
We emphasize, however, that it is not necessary to be comprehensive. The

goal is not to ensure that the ethnic background of every particular defendant is
represented, but rather to define the likely range of allele frequency variation.
• Because only a limited number of populations can be sampled, it is

necessary to make some allowance for unexamined populations. As
usual, the problem is rare alleles. Genetic drift has the greatest
proportional effect on rare alleles and may cause substantial variation in
their frequency. Even if one sees allele frequencies of 1% in several
ethnic populations, it is not safe to conclude that the frequency might
not be five-fold higher in some subgroups.
To overcome this problem, we recommend that ceiling frequencies be 5% or

higher. We selected this threshold because we concluded that allele frequency
estimates that were substantially lower would not provide sufficiently reliable
predictors for other, unsampled subgroups. Our reasoning was based on
population genetic theory and computational results, and we aimed at accounting
for the effects of sampling error and for genetic drift. The latter consideration was
especially important, because it scales inversely with effective population size
(i.e., small populations have larger drift) and because it accumulates over
generations. The use of such a ceiling frequency would correspond to a lower
bound of 5% on allele frequencies. Even if one observed allele frequencies of
about 1%, one would guard against the possibility that the frequency in a
subpopulation had drifted higher by using the lower bound of 5%. Thus, the
lowest frequency attrib

utable to any single locus would be 1/400 (1/20 × 1/20). In any case, it seems
reasonable not to attach much greater weight to any single locus.
• The ceiling principle yields the same frequency for a genotype,

regardless of the suspect's ethnic background, because the reported
frequency represents a maximum for any possible ethnic heritage.
Accordingly, the ethnic background of an individual suspect should be
ignored in estimating the likelihood of a random match. The calculation
is fair to suspects, because the estimated probabilities are likely to be
conservative in their incriminating power.
Some legal commentators have pointed out that frequencies should properly
be based on the population of possible perpetrators, rather than on the population
to which a particular suspect belongs.17,18Although that argument is formally
correct, practicalities often preclude use of that approach. Furthermore, the ceiling
principle eliminates the need for investigating the perpetrator population, because
it yields an upper bound to the frequency that would be obtained by that
approach.
Some have proposed a Bayesian approach,19,20,21 to the presentation of DNA
evidence. However, this approach, focusing on likelihood ratios, does not avoid
the kinds of population genetic problems discussed in this chapter. The
committee has not tried to assess the relative merits of Bayesian and frequentist
approaches, because, outside the field of paternity testing, no forensic laboratory
in this country has, to our knowledge, used Bayesian methods to interpret the
implications of DNA matches in criminal cases.
• Although the ceiling principle is a conservative approach, we feel that it

is appropriate, because DNA typing is unique in that the forensic analyst
has an essentially unlimited ability to adduce additional evidence.
Whatever power is sacrificed by requiring conservative estimates can be
regained by examining additional loci. (Although there could be cases in
which the DNA sample is insufficient for typing additional loci with
RFLPs, this limitation is likely to disappear with the eventual use of
PCR.) A conservative approach imposes no fundamental limitation on
the power of the technique.
DETERMINING ALLELE FREQUENCIES IN A POPULATION

DATABANK
For forensic purposes, the frequency of an allele in a laboratory's databank
should be calculated by counting the number of alleles that would be regarded as a
match with the laboratory's forensic matching rule, which should be based on the
empirical reproducibility of the system. This matching rule must account for both
the quantitative reproducibility of forensic

measurements in the testing laboratory and the quantitative reproducibility of the

population measurements in the laboratory that generated the databank. In
addition, the matching rule should reflect that one is making intergel
comparisons, which are typically less precise than intra-gel comparisons.
The above approach is sometimes referred to as ''floating bins," in that one
counts the alleles that fall into a "bin" centered on the allele of interest. Most
forensic laboratories in this country use the slightly different approach of "fixed
bins":22 One first aggregates alleles into a predetermined set of bins. Given an
allele in a forensic case, one must then compute its frequency by adding the
frequencies of all the bins that contain any alleles that fall within the window
specified by the laboratory's forensic matching rule. (All bin frequencies must be
added; it is not enough to take the largest of the bin frequencies.) This fixed-bin
approach is acceptable and might be more convenient in some settings, because
examiners need only consult a short table of bin frequencies, rather than search an
entire databank.
IMPLICATIONS OF GENETIC CORRELATIONS AMONG

RELATIVES
Because of the laws of Mendelian inheritance, the genotypes of biological
relatives are much more similar than those of random individuals. Parent and
child share exactly one identical allele at every locus, sibs share an average of one
identical allele per locus, and grandparent and grandchild share an average of 0.5
identical allele per locus. (Here, identical refers to identity by descent from a
common ancestor. Relatives can share additional alleles simply by chance.) These
facts have important consequences for DNA typing:
• The genetic correlation between relatives makes it possible to carry out

parentage and grandparentage testing. Paternity testing with DNA typing
is already an active industry in the United States, and grandmaternity
testing (with mitochondrial DNA, as well as nuclear genes) has been
used in Argentina to reunite families with children who were abducted
during the military dictatorship in the 1970s.23,24Relatedness testing
involves a question analogous to that asked in identity testing: What is
the chance that a randomly chosen person in the population would show
the degree of relatedness expected of a relative? The same basic
methods of population genetics apply, as discussed earlier.
• The ability to recognize relatedness poses a novel privacy issue for DNA
databanks. Many states are starting to compile databanks that record
patterns of DNA from convicted criminals, but not from other citizens,
with the hope of identifying recidivists. When a biological sample is
found at

the scene of a crime, its DNA pattern can be determined and compared
with a databank. If the unidentified sample perfectly matches a sample in
the convicted-criminal databank at enough loci, the probable perpetrator
is likely to have been found. However, a different outcome could occur:
the sample might match no entry perfectly, but match some entry at
about one allele per locus. Depending on the number of loci studied, one
could have a compelling case that the source of the sample was a first-
degree relative (e.g., brother) of the convicted criminal whose entry was
partially matched. (In practice, four loci would not suffice for this
conclusion, but 10 might.) Such information could be sufficient to focus
police attention on a few persons and might be enough to persuade a
court to compel a blood sample that could be tested for exact match with
the sample.
To put it succinctly, DNA databanks have the ability to point not just to
individuals but to entire families—including relatives who have committed no
crime. Clearly, this poses serious issues of privacy and fairness. As we discuss
more fully later (Chapter 5), it is inappropriate, for reasons of privacy, to search
databanks of DNA from convicted criminals in such a fashion. Such uses should
be prevented both by limitations on the software for search and by statutory
guarantees of privacy.
• Finally, the genetic correlation among relatives warrants caution in the

statistical interpretation of DNA typing results. Our discussion above
focused on the probability that a forensic sample would by chance match
a person randomly chosen from the population. However, the probability
that the forensic sample would match a relative of the person who left it
is considerably greater than the probability that it would match a random
person. Indeed, two sibs will often have matching genotypes at a locus—
they have a 25% chance of inheriting the same pair of alleles from their
parents and a 50% chance of inheriting one allele in common (which
will result in identical genotypes if their other alleles happen to match by
chance). Roughly speaking, the probability of a match at k loci will be
approximately (0.25 + 0.5p + 2p2)k in the general population, where p is
the average chance that two alleles will match (i.e., the apparent
homozygosity rate). Using p = 10% per locus for illustration, the
probability that two sibs match at two loci would be about 10% and at
four loci about 1%. Even for DNA profiles consisting entirely of very
rare alleles (p&sim;0%), the probability that two sibs will match at two
loci is about 6% and at four loci about 0.3%. In short, the probability
that two relatives will have matching genotypes is much greater than for
two randomly chosen persons. Whenever there is a possibility that a
suspect is not the perpetrator but is related to the perpetrator, this issue
should be pointed out to the court. Relatives of a suspect could be
excluded, of course, by testing their genotypes directly, provided that
their DNA could be obtained.

IMPLICATIONS OF INCREASED POWER OF DNA TYPING

COMPARED WITH CONVENTIONALSEROLOGY
Questions about the population genetics of DNA markers remain open, but
it is clear that the forensic scientist's discriminatory power has been substantially
expanded with the advent of DNA markers. Indeed, forensic laboratories are
routinely finding cases in which a suspect is included through conventional
serology but later excluded through testing with DNA markers. The FBI reports,
for example, that some 33% of suspects that match evidence samples according to
conventional serology turn out to be excluded through DNA typing (J. W. Hicks,
presentation to committee, 1990). Such outcomes represent a dramatic success of
the new technology and often lead to the exoneration of innocent suspects.
LABORATORY ERROR RATES

Interpretation of DNA typing results depends not only on population
genetics, but also on laboratory error. Two samples might show the same DNA
pattern for two reasons: two persons have the same genotype at the loci studied,
or the laboratory has made an error in sample handling, procedure, or
interpretation. Coincidental identity and laboratory error are different
phenomena, so the two cannot and should not be combined in a single estimate.
However, both should be considered.
Early in the application of the DNA approach, results from nonblind
proficiency studies suggested a high rate of false positives due to laboratory
error. One commercial laboratory reported one false match in 50 samples in each
of the first two blind proficiency tests conducted by the California Association of
Crime Laboratory Directors (CACLD).25 The error was attributed to incorrect
sample loading in the first test and to mixing of DNA samples (because of
reagent contamination) in the second. Another commercial laboratory reported no
false positives in the two CACLD tests, but is reported to have made errors
related to sample mixup in actual casework in New York v. Neysmith26 and in the
matter of a dead infant found in the Rock Creek area of Erie, Ill.27 A third
commercial laboratory made one error in 50 samples in the first CACLD test, but
none in later blind trial testing. Estimates of laboratory errors in more recent
practice are not available because of the lack of standardized proficiency testing.
Proficiency testing has also revealed important instances of false negatives.
In the second CACLD test, the second laboratory cited failed to detect that two
samples were 1:1 mixtures from two donors. Similarly, the first laboratory cited
failed to detect several 1:1 mixtures and, in one case, reported that a stain from
one person was a mixture. Those results raised serious questions about the
reliability of interpretation of mixed samples.

Especially for a technology with high discriminatory power, such as DNA

typing, laboratory error rates must be continually estimated in blind proficiency
testing and must be disclosed to juries. For example, suppose the chance of a
match due to two persons' having the same pattern were 1 in 1,000,000, but the
laboratory had made one error in 500 tests. The jury should be told both results;
both facts are relevant to a jury's determination.
Laboratory errors happen, even in the best laboratories and even when the
analyst is certain that every precaution against error was taken. It is important to
recognize that laboratory errors on proficiency tests do not necessarily reflect
permanent probabilities of false-positive or false-negative results. One purpose of
regular proficiency testing under standard case conditions is to evaluate whether
and how laboratories have taken corrective action to reduce error rates.
Nevertheless, a high error rate should be a matter of concern to judges and juries.
Reported error rates should be based on proficiency tests that are truly
representative of case materials (with respect to sample quality, accompanying
description, etc.). Tests based on pure blood samples would probably
underestimate an error rate, and tests based primarily on rare and extremely
difficult samples (which might be useful for improving practice) would probably
overestimate. Although the CACLD proficiency test was less than ideal (being
open, rather than blind, and not requiring reporting of size measurements), the
materials appear to have been representative of standard casework.
TOWARD A FIRM FOUNDATION FOR STATISTICAL

INTERPRETATION
Statistical interpretation of DNA typing evidence has probably yielded the
greatest confusion and concern for the courts in the application of DNA to
forensic science. Some courts have accepted the multiplication rule based on the
grounds of allelic independence, others have used various ad hoc corrections to
account for nonindependence, and still others have rejected probabilities
altogether. Some courts have ruled that it is unnecessary even to test allelic
independence, and others have ruled that allelic independence cannot be assumed
without proof. The confusion is not surprising, inasmuch as the courts have little
expertise in population genetics or statistics.
In reaching a recommendation on statistical interpretation of population
frequencies, the committee balanced the following considerations:
• DNA typing should be able to provide virtually absolute individual

identification (except in the case of identical twins), provided that
enough loci are studied and that the population-genetics studies are
developed with

appropriate scientific care. The importance of this long-term goal

justifies substantial investment in ensuring that the underlying
population-genetics foundation is firm.
• Statistical testimony should be based on sound theoretical principles and
empirical studies. Specifically, the validity of the multiplication rule in
any application depends on the empirical degree of population
differentiation for the loci involved. Adequate empirical data must be
collected, and appropriate adjustments must be made to reflect the
remaining uncertainties.
• It is feasible and important to estimate the degree of variability among
populations to determine ceiling frequencies for forensic DNA markers
and to evaluate the impact of population substructure on genotype
frequencies estimated with the multiplication rule.
• Careful population genetics is especially important for the development
and use of databanks of convicted-offender DNA patterns. Whereas the
comparison of an evidence sample to a single suspect involves testing
only one hypothesis, the comparison of a sample to an entire databank
involves testing many alternative hypotheses. Special attention must
thus be paid to the possibility of coincidental matches.
On the basis of those considerations, the committee reached conclusions,

which now will be discussed.
Population Studies to Set Ceiling Frequencies

In view of the long-term importance of forensic DNA typing, the
population-genetics foundation should be made as secure as possible.
Accordingly, population studies should be promptly initiated to provide valid
estimation of ceiling frequencies, as described above. Specifically, variation in
allele frequencies should be examined in appropriately drawn random samples
from various populations that are genetically relatively homogeneous. The
selection, collection, and analysis of such samples should be overseen by the
National Committee on Forensic DNA Typing (NCFDT) recommended in
Chapter 2.
Given the effort involved in drawing appropriate population samples and the
continuing need to type new markers as the technology evolves, the samples
should be maintained as immortalized call lines in a cell repository; that would
make an unlimited supply of DNA available to all interested investigators. We
note that preparation of immortalized cell lines through transformation of
lymphoblasts with Epstein-Barr virus is routine and cost-effective.
Transformation and storage can be handled as contract services offered by
existing cell repositories, such as the NIH-supported repository in Camden, N.J.

Such a cell repository would be analogous to that of the international

consortium Centre d'Etude du Polymorphisme Humain (CEPH)28 created in
1983. It holds some 1,000 samples from 60 reference families, which are used for
genetic mapping of human chromosomes. The cell lines have played an essential
role in the development of the human genetic-linkage map. The existence of a
common resource has also promoted standardization and quality control through
the ability to recheck samples. (We should note that the CEPH families
themselves are not appropriate for studying population frequencies, because they
represent closely related people in a small number of families.)
Substantial benefits will accrue to forensic DNA typing through the
availability of a reference collection that can be maintained at an existing facility
like the ones at the Coriell Institute of Medical Research and the American Type
Culture Collection. Although there is an initial investment in collecting,
transforming, and storing cells, the cost will be more than repaid in the broad and
continued availability of well-chosen samples for population studies of newly
developed DNA typing systems and the ability of investigators to confirm
independently the DNA typing that was done in another laboratory.
Reporting of Statistical Results

Until ceiling frequencies can be estimated from appropriate population
studies, we recommend that estimates of population frequencies be based on
existing data by applying conservative adjustments:
1. First, the testing laboratory should check to see that the observed
multilocus genotype matches any sample in its population database.
Assuming that it does not, it should report that the DNA pattern was
compared to a database of N individuals from the population and no
match was observed, indicating its rarity in the population. This
simple statement based on the counting principle is readily
understood by jurors and makes clear the size of the database being
examined.
2. The testing laboratory should then calculate an estimated population
frequency on the basis of a conservative modification of the ceiling
principle, provided that population studies have been carried out in
at least three major "races" (e.g., Caucasians, blacks, Hispanics,
Asians, and Native Americans) and that statistical evaluation of
Hardy-Weinberg equilibrium and linkage disequilibrium has been
carried out (with methods that accurately incorporate the empirically
determined reproducibility of band measurement) and no significant
deviations were seen. The conservative calculation represents a
reasonable effort to capture the actual power of DNA typing while
reflecting the fact that the recommended population studies have not
yet been undertaken. The calculation should be carried out as
follows.

For each allele, a modified ceiling frequency should be determined by (1)

calculating the 95% upper confidence limit for the allele frequency in each of the
existing population samples and (2) using the largest of these values or 10%,
whichever is larger. The use of the 95% upper confidence limit represents a
pragmatic approach to recognize the uncertainties in current population
sampling. The use of a lower bound of 10% (until data from ethnic population
studies are available) is designed to address a remaining concern that populations
might be substructured in unknown ways with unknown effect and the concern
that the suspect might belong to a population not represented by existing
databanks or a subpopulation within a heterogeneous group. We note that a 10%
lower bound is recommended while awaiting the results of the population studies
of ethnic groups, whereas a 5% lower bound will likely be appropriate
afterwards. In the context of the discussion of the ceiling principle, the higher
threshold reflects the greater uncertainty in using allele frequency estimates as
predictors for unsampled subpopulations.
Once the ceiling for each allele is determined, the multiplication rule should
be applied. The race of the suspect should be ignored in performing these
calculations.
Regardless of the calculated frequency, an expert should—given with the
relatively small number of loci used and the available population data—avoid
assertions in court that a particular genotype is unique in the population. Finally,
we recommend that the testing laboratory point out that reported population
frequency, although it represents a reasonable scientific judgment based on
available data, is an estimate derived from assumptions about the U.S. population
that are being further investigated.
As an example, suppose that a suspect has genotype A1/A2, B1/B2 at loci A
and B and that three U.S. populations have been sampled in the current
"convenience sample" manner and typed for these loci. The likelihood of a match
for this two-locus genotype would be estimated as follows:
Population 1 Population 2 Population 3 Derived frequency
750 persons 500 persons 200 persons
Locus A
Allele A1 0.003 0.013 0.042 Use 0.10
Allele A2 0.112 0.086 0.124 0.124 + 0.032 =
0.156a
Locus B
Allele B1 0.004 0.007 0.014 Use 0.10
Allele B2 0.228 0.078 0.218 0.228 + 0.021 =
0.249a
Loci A and B combined [2(0.10)(0.156)][2(0.10)(0.249)] = 0.001554
a The upper 95% confidence limit is given by the formula p + 1.96 , where p is the
observed frequency and N is the number of chromosomes studied.

A frequency of 0.001554 corresponds to about 1 in 644 persons. Addition of

two loci with about the same information content would yield a four-locus
genotype frequency of about 1 in 414,000 persons. Of course, if fewer than four
loci were interpretable, as is common in forensic typing, the estimated genotype
frequency would be much higher.
Significantly more statistical power for the same loci will be available when
appropriate population studies have been carried out, because the availability of
data based on a more rigorous sampling scheme will make it unnecessary to take
an upper 95% confidence limit for each allele frequency nor to put such a
conservative lower bound (0.10) on each allele frequency. Assuming that the
population studies do not reveal significant substructure, the 5% lower bound
recommended earlier should be used.
Finally, once appropriate population studies have been conducted and ceiling
frequencies estimated under the auspices of NCFDT, population frequency
estimates can be based on the ceiling principle (rather than the modified ceiling
principle discussed above). Such calculations can never be perfect, but we believe
that such a foundation will be sufficient for calculating frequencies that are
prudently cautious—i.e., for calculating a lower limit of the frequency of a DNA
pattern in the general population. In addition, new scientific techniques (e.g.,
minisatellite repeat codings29) are being and will be developed and might require
re-examination by NCDFT of the statistical issues raised here.
Our recommendations represent an attempt to lay a firm foundation for DNA
typing that will be able to support the increasing weight that will be placed on
such evidence in the coming years. We recognize that a wide variety of methods
for population genetics calculations have been used in previous cases—including
some that are less conservative than the approach recommended here. We
emphasize that our recommendations are not intended to question previous cases,
but rather to chart the most prudent course for the future.
Openness of Population Databanks

Any population databank used to support forensic DNA typing should be
openly available for reasonable scientific inspection. Presenting scientific
conclusions in a criminal court is at least as serious as presenting scientific
conclusions in an academic paper. According to long-standing and wise scientific
tradition, the data underlying an important scientific conclusion must be freely
available, so that others can evaluate the results and publish their own findings,
whether in support or in disagreement. There is no excuse for secrecy concerning
the raw data. Protective orders are inappropriate, except for those protecting
individual's names and other identifying information, even for data that have not
yet been published or for data

claimed to be proprietary. If scientific evidence is not yet ready for both scientific
scrutiny and public re-evaluation by others, it is not yet ready for court.
Reporting of Laboratory Error Rates

Laboratory error rates should be measured with appropriate proficiency tests
and should play a role in the interpretation of results of forensic DNA typing. As
discussed above, proficiency tests provide a measure of the false-positive and
false-negative rates of a laboratory. Even in the best of laboratories, such rates are
not zero.
A laboratory's overall rate of incorrect conclusions due to error should be
reported with, but separately from, the probability of coincidental matches in the
population. Both should be weighed in evaluating evidence.
Although mindful of the controversy concerning the population genetics of
DNA markers, the committee has decided to assume that population substructure
might exist for currently used DNA markers or for DNA markers that will be
used in the future. The committee has sought to develop a recommendation on the
statistical interpretation of DNA typing that is appropriately conservative, but at
the same time takes advantage of the extraordinary power of individual
identification provided by DNA typing. We have sought to develop a
recommendation that is sufficiently robust, but is flexible enough to apply not
only to markers now used, but also to markers that might be technically
preferable in the future. We point out that in using conservative numbers in the
interpretation of DNA typing results, any loss of statistical power is often offset
through typing of additional loci. The committee seeks to eliminate the necessity
to consider the ethnic background of a subject or of the group of potential
perpetrators.
• As a basis for the interpretation of the statistical significance of DNA

typing results, the committee recommends that blood samples be
obtained from 100 randomly selected persons in each of 15-20 relatively
homogeneous populations; that the DNA in lymphocytes from these
blood samples be used to determine the frequencies of alleles currently
tested in forensic applications; and that the lymphocytes be
"immortalized" and preserved as a reference standard for determination
of allele frequencies in tests applied in different laboratories or
developed in the future. The collection of samples and their study should
be overseen by a National Committee on Forensic DNA Typing.
• Sample collection and immortalization should be supported by feder

al funds, in view of the benefits for law enforcement in general and for
the convicted-offender databanks in particular.
• The ceiling principle should be used in applying the multiplication rule
for estimating the frequency of particular DNA profiles. For each allele
in a person's DNA pattern, the highest allele frequency found in any of
the 15-20 populations or 5% (whichever is larger) should be used.
• In the interval (which should be short) while the reference samples are
being collected, the significance of the findings of multilocus DNA
typing should be presented in two ways: 1) If no match is found with any
sample in a total databank of N persons (as will usually be the case),
that should-be stated, thus indicating the rarity of a random match. 2) In
applying the multiplication rule, the 95% upper confidence limit of the
frequency of each allele should be calculated for separate U.S. "racial"
groups and the highest of these values or 10% (whichever is the larger)
should be used. Data on at least three major "races" (e.g., Caucasians,
blacks, Hispanics, Asians, and Native Americans) should be analyzed.
• Any population databank used to support DNA typing should be openly
available for scientific inspection by parties to a legal case and by the
scientific community.
• Laboratory error rates should be measured with appropriate proficiency
tests and should play a role in the interpretation of results of forensic
DNA typing.
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29. Jeffreys A, MacLeod A, Tamaki K, Nell D, Monckton D. Minisatellite repeat coding as a digital
approach to DNA typing. Nature. 354:204-209, 1991.

ENSURING HIGH STANDARDS 97
4
Ensuring High Standards
Critics and supporters of the forensic use of DNA typing agree that there has
been a lack of standardization of practices and uniformly accepted methods for
quality assurance. The lack is due largely to the rapid emergence of DNA typing
and its introduction in the United States through the private sector.
As the technology developed in the United States, private laboratories using
widely differing methods (single-locus RFLP, multilocus RFLP, and PCR) began
to offer their services to law-enforcement agencies. During the same period, the
FBI was developing its own RFLP method, with yet another restriction enzyme
and different single-locus probes. Its method has become the one most widely
(albeit not exclusively) used in public forensic-science laboratories, as a result of
the FBI's national offering of free extensive training programs to forensic
scientists. Each method has its own advantages and disadvantages, databanks,
molecular-weight markers, match criteria, and reporting methods. In some
courts, there have been differences of opinion as to the reliability, acceptability,
and applicability of the various methods and particularly the degree of their
specificity or discriminating power.
Regardless of the causes, practices in DNA typing vary and so do the
educational backgrounds, training, and experience of the scientists and
technicians who perform these tests, the internal and external proficiency testing
conducted, the interpretation of results, and approaches to quality assurance.
It is not uncommon for an emerging technology to go without regulation
until its importance and applicability are established. Indeed, the de

velopment of DNA typing technology has occurred without regulation of

laboratories and their practices, public or private. The committee recognizes that
standardization of practices in forensic laboratories in general is more
problematic than in other laboratory settings: stated succinctly, forensic scientists
have little or no control over the nature, condition, form, or amount of sample
with which they must work. But it is now clear that DNA analytic methods are a
most powerful adjunct to forensic science for personal identification and have
immense benefit to the public—so powerful, so complex, and so important that
some degree of standardization of laboratory procedures is necessary to assure the
courts of high-quality results. DNA typing is capable, in principle, of an
extremely low inherent rate of false-positive results, so the risk of error will come
from poor laboratory practice or sample handling and labeling; and, because DNA
typing is technical, a jury requires the assurance of laboratory competence in test
results.
At issue, then, is how to achieve standardization of DNA typing laboratories
in such a manner as to assure the courts and the public that results of DNA typing
conducted and reported by a given laboratory are reliable, reproducible, and
accurate.
DEFINING THE PRINCIPLES OF QUALITY ASSURANCE

Quality assurance can best be described as a documented system of activities
or processes for the effective monitoring and verification of the quality of a work
product (in this case, laboratory results). A comprehensive quality-assurance
program must include elements that address education, training, and certification
of personnel; specification and calibration of equipment and reagents;
documentation and validation of analytic methods; use of appropriate standards
and controls; sample handling procedures; proficiency testing; data interpretation
and reporting; internal and external audits of all the above; and corrective actions
to address deficiencies and weigh their importance for laboratory competence. An
instructive example is Guidelines for a Quality AssuranceProgram for DNA
RFLP Analysis, developed by the Technical Working Group on DNA Analysis
Methods (TWGDAM).1
TWGDAM is a practitioners' group that comprises over 30 scientists who
work in DNA typing in 24 state, local, and federal forensic laboratories in the
United States and Canada. Its purpose is to assemble forensic scientists actively
involved with DNA typing methods and have them discuss the methods being
used, compare work and results, and share protocols. The FBI has subsidized and
hosted the meetings and plays a central role in the activities of the group.

The TWGDAM guidelines established functions to be followed

systematically in the RFLP typing procedure and cover many important aspects
of the laboratory process. In addition, they provide documentation designed to
ensure that DNA analysis is operating within the established performance criteria
and provide a measure of the overall quality of results. TWGDAM has also
published a more detailed description of the proficiency-testing portion of the
quality-assurance guidelines.2 The proficiency-testing guidelines for RFLP
analysis describe the necessary elements of open and blind proficiency testing,
including guidelines for documentation, review, and reporting of proficiency test
results and deficiency and corrective actions.3
The TWGDAM guidelines, however, are just guidelines—they must be
implemented in a formal, detailed quality-assurance program. The committee
recommends that laboratories engaged in forensic DNA typing adhere to the
TWGDAM guidelines for quality assurance and proficiency testing and
implement them in formal programs. Although we admire the TWGDAM
guidelines, we note that they do not go far enough in some ways. In some
important respects, the technical recommendations contained in Chapters 2 and 3
of this report exceed the TWGDAM guidelines and should be seen as augmenting
them.
TWGDAM is an excellent resource for forensic scientists and can play an
important role to complement the National Committee on Forensic DNA Typing
(NCFDT) recommended in Chapters 2 and 3. Whereas NCFDT should focus
primarily on the key issues of scientific foundations and technology transfer,
TWGDAM can serve as a forum for practitioners to discuss details of laboratory
practice. Although TWGDAM was originally an FBI initiative, it should be
restructured under broader auspices that represent the full range of forensic
laboratories and societies.
Finally, on the subject of quality assessment and quality control, we note
that the National Institute of Standards and Technology (NIST) has a program to
test and develop a series of standards and controls for use in DNA typing.
Because of its extensive experience in the development of standards, NIST can
play a highly important role in standardization by developing lists of approved
controls, equipment, and devices (including molecular-weight markers,
monomorphic markers, cell lines, and typing kits).
POTENTIAL METHODS FOR ENSURING QUALITY

The principles of quality assurance discussed above must be enforced
through appropriate mechanisms. Potential mechanisms include certification of
individuals, accreditation of laboratories, mandatory licensing, and funding
incentives contingent on adherence to standards. We discuss the advantages and
disadvantages of these in turn.

Certification of Individuals
In the certification approach, a certifying body dictates that fulfillment of
specified education, training, and experiential requirements be demonstrated by
documentation and examination. An examination can also include a laboratory
practicum. Individual certification has many advantages, but it is not adequate. A
person does not perform DNA typing tests in isolation. A person's ability to
produce high-quality results consistently depends heavily on the procedures,
reagents, equipment, management, and attitudes in the work environment. It is
impossible to separate a person from his or her organization and physical setting.
In addition, personal certification can be expensive and usually requires funding
support from the employing institution.
We recommend that the National Institute of Justice, given its interest in
training, develop training programs in association with the American Society of
Crime Laboratory Directors. Such a cooperative effort would allow continuity of
candidate selection, training, examination, and certification.
Laboratory Accreditation
Accreditation is a more comprehensive approach to regulation. It requires
that a laboratory demonstrate that its management, operations, individual
personnel, procedures and equipment, physical plant and security, and personnel
safety procedures all meet standards. Laboratory accreditation programs can be
voluntary or mandatory. Although voluntary programs can have a positive effect,
they suffer from the limitations that laboratories need not comply, that standard-
setting need not be open to public scrutiny, and that accreditation might be
contingent on membership in a professional organization. Accreditation programs
required by federal or state law provide a greater level of assurance.
Licensing of Laboratories
Licensing involves vesting, by the federal government or a state
government, of a regulatory body with the responsibility and authority to
establish a series of requirements that a laboratory must satisfy if it is to be
allowed to operate in a defined jurisdiction or to present evidence in its courts.
The licensing approach does not suffer the disadvantage of being voluntary. State
or federal laws can place sanctions on a laboratory that is not licensed by the
specified body. A potential drawback is that the development of such a program
can be time-consuming and expensive. In addition, licensing can be
anticompetitive and can discourage innovation. In the

case of state (as opposed to federal) regulation, there is the potential problem that
different practices will be mandated in different jurisdictions, although this can be
avoided if a few states take the lead and others follow suit by adopting similar
regulations or recognize other states' licensing. The most efficient path seems to
be for a federal licensing procedure to standardize the process for the nation and
avoid state licensing, which can be restrictive and redundant. The federal license
would be most cost-efficient and provide the field with a mechanism of quality
assurance.
Funding Contingent On Adherence to Standards

The ''stick" of licensing can be replaced by the "carrot" of funding. Such an
approach would provide an incentive for adhering to standards, reduce costs for
states and localities, and increase the number of laboratories able to afford DNA
typing. A medical specialty laboratory typically spends $1,000-3,000 per annum
for its licenses and accreditation. But the approach has numerous problems. The
use of an equitable funding formula within state eligibility requirements might be
problematic and controversial. Private laboratories would be unlikely to be
covered (or even to want to be covered) by such a program. Expanding the
number of practicing laboratories might decrease, not increase, the general
standard of practice for a complex technology. Most important, the funding
incentives alone do not provide an adequate guarantee of quality; they must be
backed up by a regulatory program.
QUALITY ASSURANCE IN RELATED FIELDS

It is useful to consider the experience with various approaches in related
fields. Medicine provides an appropriate analogy to forensic science, because it
involves the application of sophisticated scientific methods to serious decisions
that the practitioner must make on the basis of only partial information. Medicine
has general mechanisms for setting standards of education and training of people,
of laboratory practices and performance, and of quality assurance. The
mechanisms involve both voluntary standard-setting by professional
organizations and mandatory regulation through public licensing.
In pathology and laboratory medicine, the College of American Pathologists
(CAP) is the dominant standard-setting organization. It has its roots in pathology,
but has recently indicated its interest in working collaboratively with other
laboratory-based professional groups toward establishing standard-setting for
specialty laboratories. In medical genetics, the American Society of Human
Genetics (ASHG) operates a personnel-certification program for clinicians and
laboratory directors. ASHG recently agreed to

provide expert consultants to CAP to establish laboratory certification in

cytogenetics, biomedical genetics, and DNA-based diagnostics. In paternity
testing, the American Association of Blood Banks (AABB) has developed
laboratory-certification actions for protein typing methods and is establishing a
set of standards for clinical DNA testing laboratories. AABB has also entered into
discussions with CAP to codevelop proficiency testing for specialty laboratories.
Additionally, the American Society for Histocompatibility and Immunogenetics
has considered standards for histocompatibility testing, including DNA analysis.4
Mandatory government accreditation plays an essential role. Personnel
certification and laboratory licensing are required in medicine, and formal
requirements are set by state and federal regulatory bodies. Physicians,
physician's assistants, medical technologists, laboratories, and others are licensed
by states. Moreover, since 1967, a federal process of accreditation has been
mandated for medical laboratories under the Clinical Laboratory Improvement
Act (CLIA). In 1988, that process was expanded and restructured to enhance
performance of laboratories involved in human DNA diagnostic programs.
Officials responsible for implementing CLIA have recently initiated discussion
with CAP for the purpose of codeveloping proficiency testing.
Medical accreditation programs have substantial force behind them.
Government accreditation is mandated by law; private accreditation is often
mandated as a component of government regulation; and both kinds of
accreditation are required by third-party payers (e.g., insurance carriers) for
payment.
INITIAL EFFORTS TOWARD ESTABLISHING STANDARDS

IN FORENSIC DNA TYPING
Some initial efforts at developing accreditation and licensing standards for
forensic DNA typing are already under way, as follows.
The American Society of Crime Laboratory Directors (ASCLD) is a
professional organization of approximately 350 members that has represented
forensic-science laboratory directors since 1975. Although most forensic
laboratories in the United States are publicly funded and mandated by state or
federal statutes to examine physical evidence and perform forensic testing, a
voluntary laboratory-accreditation program has been in operation since 1985
through the auspices of the American Society of Crime Laboratory Directors-
Laboratory Accreditation Board (ASCLD-LAB), which is an independently
chartered organization affiliated with but separate from ASCLD. Some 77
forensic laboratories in the United States and in Australia are accredited by
ASCLD-LAB. Such accreditation is available to all public and private forensic
DNA laboratories, including ones that do not meet

the membership requirements for ASCLD. There has, however, been no listing of
laboratories that failed examination, had deficiencies, or were advised to
discontinue providing services, and that constitutes a flaw in voluntary laboratory
accreditation as carried out by ASCLD-LAB.
The New York state legislature has developed legislation to create a
licensing program that was recommended by the Governor's Select Commission
on DNA Typing, which was chaired by the state commissioner of criminal justice
and consisted of lawyers, molecular biologists, forensic scientists, and population
geneticists. It proposes that New York administer a licensing program with the
advice of a scientific review board and a DNA advisory committee. Those bodies
would consist of independent scientists in molecular biology and population
genetics with no ties to forensic laboratories, through financial relationships,
extensive collaboration, or provision of extensive testimony. This pioneering
effort is consistent with the leadership role that New York has assumed in other
laboratory testing—it is the national leader in the regulation of cytogenetics, for
example. Both houses of the New York legislature passed a bill establishing a
regulatory framework but it later was withdrawn. A similar bill has been
reintroduced in the current legislative session.
A third approach is reflected in legislation recently introduced in the U.S.
Congress "to provide financial assistance to state and local governments wishing
to upgrade their crime laboratories with DNA genetic testing capability"
contingent on their adherence to particular standards. The proposed law, entitled
the DNA Proficiency Testing Act (H.R. 339, introduced by Rep. Frank Horton),5
would promote increased quality assurance by providing grants from the
Department of Justice (DOJ) Bureau of Justice Assistance to state and local
forensic laboratories and mandating the FBI to publish "advisory standards for
testing the proficiency of forensic laboratories" and to carry out certification for
DNA proficiency-testing programs. The Bureau of Justice Assistance would
make grants to state or local forensic laboratories. Within 6 months of enactment,
the FBI would publish standards for testing the proficiency of laboratories that
conduct DNA typing. The standards would "specify criteria to be applied to each
procedure used by forensic laboratories to conduct analyses of DNA." The FBI
would revise the standards from time to time, as necessary.
Under H.R. 339, the FBI could approve a DNA proficiency-testing program
offered by a private organization, if the program satisfied the proficiency-testing
standards and the testing laboratory were prepared to issue to each forensic
laboratory that participated in the program a document that certified the
participation and specified the period for which the proficiency test applied to the
forensic laboratory. The FBI would have to withdraw approval for a DNA
proficiency-testing program if the program or testing laboratory failed to satisfy
the proficiency-testing standards.

In addition to those formal efforts for standardization now under

consideration, the FBI has promoted standardization through various programs
and initiatives.
• The FBI's Forensic Science Research and Training Center (FSRTC) in

Quantico, Va., developed the analytic methods most commonly used or
under development in forensic laboratories and promotes their
acceptance through an excellent training program. Since January 1989,
the FSRTC has provided training for over 200 forensic scientists from 74
state and local laboratories in the United States, South Korea, Turkey,
and Portugal.
• The FBI has initiated, sponsored, and hosted the TWGDAM meetings at
the FSRTC and published its guidelines.
• The FBI has proposed the establishment of a national DNA databank.
The proposal has serious implications for the standardization of
practices, in that its success would require participating forensic
laboratories to be capable of producing nearly identical results on a
given sample. That requirement would drive the forensic community to
adopt some standardized analytic methods, including molecular-weight
markers, probes, controls, and methods for allele measurement.
• The FBI provides educational and training opportunities (although it has
not indicated an interest in developing and implementing personnel or
laboratory testing programs for outside laboratories).
A REGULATORY PROGRAM FOR DNA TYPING
Components of a Suitable Program

In evaluating the relative merits of possible approaches, the committee
developed a list of general requirements that a regulatory program adopted for the
standardization of DNA typing technology should include. The ideal program
would contain mechanisms to ensure that:
• Individual analysts have education, training, and experience

commensurate with the analysis performed and testimony provided.
• Analysts have a thorough understanding of the principles, use, and
limitations of methods and procedures applied to the tests performed.
• Analysts successfully complete periodic proficiency tests and their
equipment and procedures meet specified criteria.
• Reagents and equipment are properly maintained and monitored.
• Procedures used are generally accepted in the field and supported by
published, reviewed data that were gathered and recorded in a scientific
manner.
• Appropriate controls are specified in procedures and are used.
• New technical procedures are thoroughly tested to demonstrate their

efficacy and reliability for examining evidence material before being

implemented in casework.
• Clearly written and well-understood procedures exist for handling and
preserving the integrity of evidence, for laboratory safety, and for
laboratory security.
• Each laboratory participates in a program of external proficiency testing
that periodically measures the capability of its analysts and the reliability
of its analytic results.
• Case records—such as notes, worksheets, autoradiographs, and
population databanks—and other data or records that support examiners'
conclusions are prepared, retained by the laboratory, and made available
for inspection on court order after review of the reasonableness of a
request.
• Redundancy of programs is avoided, so that unnecessary duplication of
effort and costs can be eliminated.
• The program is widely accepted by the forensic-science community.
• The program is applicable to federal, state, local, and private
laboratories.
• The program is enforceable—i.e., that failure to meet its requirements
will prevent a laboratory from continuing to perform DNA typing tests
until compliance is demonstrated.
• The program can be implemented within a relatively short time.
• The program involves appropriate experts in forensic science, molecular
biology, and population genetics.
The Role of Professional Organizations

One guarantee of high quality is the presence of an active professional
organization that is committed and able to enforce standards. Historically, the
professional societies in forensic science have not played a very active role—
certainly much less than medical societies. That has been due to a variety of
circumstances, including the fact that accreditation and proficiency testing can be
expensive and can lead to serious repercussions for laboratories with poor
performance. Voluntary programs have few incentives and offer relatively little
credibility for participating laboratories. Moreover, courts have not required
certification, accreditation, or proficiency testing for admissibility of evidence.
Together, those factors have worked against the development of rigorous
accreditation programs.
Recently, however, ASCLD-LAB has shown a substantial interest in
assuming an active role. At the annual meeting of ASCLD and ASCLD-LAB in
September 1990, the boards of both organizations passed—with near unanimity—a
resolution to expand requirements for accreditation of forensic-science
laboratories engaged in DNA typing, including mandatory proficiency testing at
regular intervals.6,7

Specifically, new standards require:
• Mandatory participation in an external proficiency-testing program

administered by a contractor that meets rigid specifications for adequacy
and reliability (it is envisioned that two sets of tests will be required each
year).
• The requirement that each examiner in a laboratory take proficiency tests
and submit results independently.
• Review of test results by ASCLD-LAB.
• Inclusion in the board's DNA Advisory Committee of both forensic DNA
scientists and leading experts in nonforensic DNA technology, to
provide guidance and advice in forensic DNA testing.
• Periodic on-site inspections of accredited laboratories.
• Documentation of conduct of internal, blind, and open proficiency
testing.
• Adherence to TWGDAM guidelines for quality assurance and
proficiency testing (endorsed by ASCLD and ASCLD-LAB).
• A mechanism to revoke or suspend accreditation on documentation of
unsatisfactory performance.
ASCLD has unanimously recommended that any forensic laboratory

engaged in DNA typing or actual case materials be accredited by ASCLD-LAB
for the typing method used. The committee supports the effort by ASCLD and
ASCLD-LAB, because it holds the promise of rallying the profession to enforce
high standards on its members. Of course, it remains for ASCLD-LAB to
demonstrate that it will actively discharge the role of accreditation and mandatory
proficiency testing. Any accreditation program would need to be advised by
persons without ties to forensic laboratories that are engaged in DNA typing, in
order to assure the public—especially defendants—that it is independent and
objective. To that end, program leadership should consist primarily of persons
who have no financial stake in the practice of forensic DNA testing.
The Role of Government

Voluntary accreditation programs are not enough. Because professional
organizations, such as ASCLD-LAB, lack regulatory authority, forensic
laboratories could avoid accreditation and still offer DNA typing evidence in
criminal proceedings. In view of the important public-policy goal that this
powerful technology be practiced only at the highest standard, compliance with
high standards must be mandatory. Two approaches should be used to accomplish
this, as set forth below.
First, courts should require that a proponent of DNA typing evidence have
appropriate accreditation—including demonstration of external, blind

proficiency testing (as well as other accreditation that might be mandated by

government or come to be generally accepted in the profession)—for its evidence
to be admissible. There is strong legal foundation for such a position. As a
number of courts have correctly recognized, the admissibility of scientific
evidence depends not just on a technology's being sound in principle, but on the
testing laboratory's having applied it in the case at hand according to generally
accepted standards. Courts should view the absence of appropriate accreditation
as constituting a prima facie case that the laboratory has not complied with
generally accepted standards. Until accreditation programs are fully
implemented, there will be a period during which some laboratories will not have
completed the accreditation process. In the interim, courts should require forensic
laboratories at least to demonstrate that they are effectively in compliance with
the requirements for accreditation as outlined by TWGDAM and by this report;
that would be taken as meeting generally accepted standards of practice.
Second, the federal government should adopt legislation requiring
accreditation of all forensic laboratories engaged in DNA typing. The committee
recommends the following approach:
• Establishing mandatory accreditation should be a responsibility of the

Department of Health and Human Services (DHHS), in consultation with
the Department of Justice (DOJ). DHHS is the appropriate agency,
because it has extensive experience in the regulation of clinical
laboratories through programs under the Clinical Laboratory
Improvement Act and has extensive expertise in molecular genetics
through the National Institutes of Health. DOJ must be involved,
because the task is important for law enforcement. However, the
committee feels that primary responsibility should rest with DHHS for
two reasons. First, DOJ lacks expertise in quality assurance and quality
control and in molecular or population genetics. Second, DOJ may be
perceived as an advocate for application of the technology. Oversight by
DOJ may not be perceived as providing adequate assurance to the public
or to a defendant facing prosecution by DOJ or affiliated agencies.
• DHHS, in consultation with DOJ, should contract with an organization to
create and administer an appropriate laboratory-accreditation program,
including proficiency testing. Preferably, the organization would be a
private professional group; that would avoid the creation of additional
government bureaucracy. One choice would be ASCLD-LAB, provided
that it followed through on its announced intentions to assume a more
active standard-setting role and demonstrated rigorous independence
from the laboratories that it would regulate. Another choice would be
CAP, which has unparalleled experience in administering such
laboratory-accreditation programs in a wide variety of fields.
Alternatively, the organization could be a government agency, provided
that it were not itself engaged in operat

ing forensic laboratories or closely tied to such a laboratory. Thus, NIST

might be appropriate, whereas the FBI and TWGDAM (suggested for
this role by H.R. 339) would not be.
• Mandatory accreditation falls within the interstate commerce clause,
inasmuch as the standard of practice of forensic DNA typing
laboratories profoundly affects citizens from states other than those of
the laboratories. Thus, even state forensic laboratories would be
covered.
• With the aid of an outside panel of experts, DHHS, in consultation with
DOJ, should periodically determine whether the accrediting organization
and the accreditation program are performing satisfactorily and, if not,
select a new organization.
As in medicine, federal legislation should not preclude additional state

licensing, but it might avoid the need for duplication of equivalent licensing
programs at multiple levels.
The committee considers mandatory accreditation to be essential for
ensuring high standards in DNA typing.
Support for Education, Training, and Research

In the long term, high quality in a field depends on first-rate programs of
education, training, and research. Such programs are crucial for developing the
necessary foundation of people and knowledge. The National Institute of Justice
(NIJ) is the appropriate organization for such efforts and for assisting in
education, training, and research. It is our opinion that NIJ has been given
inadequate financial resources to meet these needs and that the level of support
should be re-evaluated.
• Although standardization of forensic practice is somewhat problematic

because of the nature of the samples, DNA typing is such a powerful and
complex technology that some degree of standardization is necessary to
ensure high standards.
• Each forensic-science laboratory engaged in DNA typing must have a
formal, detailed quality-assurance and quality-control program to
monitor work, on both an individual and a laboratory-wide basis.
• The TWGDAM guidelines for a quality-assurance program for DNA
RFLP analysis are an excellent starting point for a quality-assurance
program, which should be supplemented by the additional technical
recommendations made in Chapters 2 and 3 of this report.
• TWGDAM should continue to function, playing a role complementary to
that of the National Committee on Forensic DNA Typing. To increase

its effectiveness, TWGDAM should include more independent technical

experts from outside the forensic community and should not be closely
tied to any forensic laboratory.
• Quality-assurance programs in individual laboratories alone are
insufficient to ensure high standards. External mechanisms are needed,
to ensure adherence to the practices of quality assurance. Potential
mechanisms include individual certification, laboratory accreditation,
and state or federal regulation.
• One of the best guarantees of high quality is the presence of an active
professional-organization committee that is able to enforce standards.
Although professional societies in forensic science have historically not
played an active role, ASCLD and ASCLD-LAB recently have shown
substantial interest in enforcing quality by expanding the ASCLD-LAB
accreditation program to include mandatory proficiency testing.
ASCLD-LAB must demonstrate that it will actively discharge this role.
• Because private professional organizations lack the regulatory authority
to require accreditation, further means are needed to ensure compliance
with appropriate standards.
• Courts should require that proponents of DNA typing evidence have
proper accreditation for each DNA typing method used. Lack of
accreditation should be considered to constitute a prima facie case that a
laboratory has not complied with generally accepted standards.
• In view of the compelling public interest in ensuring high standards for
DNA typing, the federal government should enact legislation to establish
a mandatory accreditation program. DHHS, in consultation with DOJ,
should be assigned responsibility for engaging an appropriate
organization to develop and administer the program. Possible choices
for such an organization include ASCLD-LAB, CAP, and NIST.
• NIJ does not appear to receive adequate funds to support education,
training, and research in this field properly. The level of funding should
be re-evaluated and increased appropriately.
REFERENCES
1. Technical Working Group on DNA Analysis Methods (TWGDAM). Guidelines for a quality
assurance program for DNA restriction fragment length polymorphism analysis . Crime Lab
Dig. 16(2):40-59, 1989.
2. Technical Working Group on DNA Analysis Methods (TWGDAM). Guidelines for a proficiency
testing program for DNA restriction fragment length polymorphism analysis. Crime Lab
Dig. 17(3):50-60, 1990.
3. Technical Working Group on DNA Analysis Methods (TWGDAM). Statement of the Working
Group on Statistical Standards for DNA Analysis. Crime Lab Dig. 17(3):53-58, 1990.

4. American Society for Histocompatibility and Humunogenetics. Standards for histocom-patibility

testing. ASHI Quart. 14(1), Winter-Spring, 1990.
5. H.R. 339, DNA Proficiency Testing Act of 1991, 102nd Congress, 1st Session. January 8, 1991.
6. Resolution of the ASCLD-LAB Delegate Assembly, Sept. 26, 1990.
7. ASCLD Board of Directors Resolution of Support, Sept. 27, 1990.

FORENSIC DNA DATABANKS AND PRIVACY OF INFORMATION 111
5
Forensic DNA Databanks and Privacy of
Information
DNA typing in the criminal-justice system has so far been used primarily for
direct comparison of DNA profiles of evidence samples with profiles of samples
from known suspects. However, that application constitutes only the tip of the
iceberg of potential law-enforcement applications. If DNA profiles of samples
from a population were stored in computer databanks (databases), DNA typing
could be applied in crimes without suspects. Investigators could compare DNA
profiles of biological evidence samples with a databank to search for suspects.
In many respects, the situation is analogous to that of latent fingerprints.
Originally, latent fingerprints were used for comparing crime-scene evidence with
known suspects. With the development of the Automated Fingerprint
Identification Systems (AFIS) in the last decade, the investigative use of
fingerprints has dramatically expanded. Forensic scientists can enter an
unidentified latent-fingerprint pattern into the system and within minutes compare
it with millions of people's patterns contained in a computer file. In its short
history, automated fingerprint analysis has been credited with solving tens of
thousands of crimes.1
This chapter examines whether similar databanks of DNA profiles should be
created and, if so, how and when.
COMPARISON OF DNA PROFILES AND LATENT

FINGERPRINTS
To identify key issues pertinent to the establishment of DNA databanks, it is
instructive to compare DNA profiles and latent fingerprints.

• Latent fingerprints are found at crime scenes much more commonly than
are body fluids that contain DNA. Latent-fingerprint analysis can be
useful in a wide range of crimes, including many murders, rapes,
assaults, robberies, and burglaries. However, the probative value of
latent fingerprints is often limited to establishing that a suspect was
present at a location—and that does not automatically imply guilt. DNA
analysis will be useful in more limited settings. DNA analysis will be
useful primarily in rapes (because semen is often recovered) and
murders (those in which either the perpetrator's blood was spilled at the
crime scene or the victim's blood stained the perpetrator's personal
effects—only the former will assist in identifying an unknown suspect).
Where it exists, DNA evidence will often be more probative than
fingerprints, in that the presence of body fluids is harder to attribute to
innocuous causes. That is especially true in rape cases, in which positive
identification of semen in the vagina is virtual proof of intercourse
(although it leaves open the issue of whether it was consensual).
Consequently, the potential utility of a DNA profile databank must be
evaluated in terms of the particular crimes to which it is primarily
suited.
• Fingerprints have a defined physical pattern independent of the method
of visualization, whereas DNA profiles are derived patterns that can be
constructed with various protocols (e.g., different restriction enzymes to
cut the DNA and different probes to examine different loci) that produce
completely different patterns that cannot be readily interconverted. The
advance of DNA technology will see the development of new protocols
that offer technical advantages but produce different and incompatible
patterns.
In a sense, current DNA profiles can be thought of as extremely small bits of a

person's fingerprints on all or some of the fingers. Different methods look at
different fingers or different locations on a finger. Only when DNA technology is
capable of sequencing the entire three billion basepairs of a person's genome
could a DNA pattern be considered to be as constant and complete as a
fingerprint pattern. Consequently, the development of DNA databanks is tied to
the standardization of methods. A national DNA profile databank can function
only if participating laboratories agree on standardized methods. However, the
creation of a databank with current methods could discourage the conversion to
newer, cheaper, and more powerful methods.
• The amount of information provided by latent fingerprints in an evidence

sample is essentially fixed—it depends primarily on the portion of the
finger(s) or palm found—and the forensic scientist uses all of it. DNA
typing of an evidence sample yields information in an amount
determined by the number of loci studied, so the forensic scientist has
substantial control over the amount of information to be obtained from a
sample. Conse

quently, the creation of a DNA profile databank would require decisions

about the extent of the DNA profile to be recorded.
• Fingerprints are more highly individualized than DNA profiles based on
the RELP technology being used in forensic laboratories. Consequently,
a match between an evidence sample and an entry in a DNA profile
databank should not automatically lead to the assumption of identity,
but should be confirmed by the examination of additional loci that are
not in the databank.
• Obtaining an inked fingerprint from a person is much less intrusive,
costly, and difficult than drawing a blood sample for DNA typing.
• Collection of fingerprints from known persons is inexpensive and
relatively easily accomplished by someone with minimal technical
background and training. In contrast, development of a DNA profile
from a blood sample is time-consuming and expensive and requires
extensive education, training, and quality-assurance measures.
Consequently, the number of people who can be included in a DNA
profile databank might be limited by economic considerations.
Categories of persons to include must be selected with due consideration
of costs and benefits.
• The computer technology required for an automated fingerprint
identification system is sophisticated and complex. Fingerprints are
complicated geometric patterns, and the computer must store, recognize,
and search for complex and variable patterns of ridges and minutiae in
the millions of prints on file. Several commercially available but
expensive computer systems are in use around the world. In contrast, the
computer technology required for DNA databanks is relatively simple.
Because DNA profiles can be reduced to a list of genetic types (i.e., a
list of numbers), DNA profile repositories can use relatively simple and
inexpensive software and hardware. Consequently, computer
requirements should not pose a serious problem in the development of
DNA profile databanks.
• Fingerprints provide no information about a person other than identity.
DNA typing can, in principle, also provide personal information—
concerning medical characteristics, physical traits, and relatedness—that
carries with it risks of discrimination. Consequently, DNA typing raises
considerably greater issues of privacy than does ordinary fingerprinting.
In short, ordinary fingerprints and DNA profiles differ substantially in ways

that bear on the creation and design of a national DNA profile databank.
CONFIDENTIALITY AND SECURITY

Confidentiality and security of DNA-related information are especially
important and difficult issues, because we are in the midst of two extraordi

nary technological revolutions that show no signs of abating: in molecular

biology, which is yielding an explosion of information about human genetics, and
in computer technology, which is moving toward national and international
networks connecting growing information resources.
Molecular geneticists are rapidly developing the ability to diagnose a wide
variety of inherited traits and medical conditions. The list already includes simply
inherited traits, such as cystic fibrosis, Huntington's disease, and some inherited
cancers. In the future, the list might grow to include more common medical
conditions, such as heart disease, diabetes, hypertension, and Alzheimer's
disease. Some observers even suggest that the list could include such traits as
predispositions to alcoholism, learning disabilities, and other behavioral traits
(although the degree of genetic influence on these traits remains uncertain).
Obviously, such information could lead to discrimination by insurance
companies, employers, or others against people with particular traits. In general,
the committee feels that DNA profile databanks should avoid the use of loci
associated with traits or diseases. That avoidance is the best guarantee against
misuse of such information. Current forensic RELP typing markers are not known
to be associated with particular traits or medical conditions, but they might be in
the future. Current PCR typing uses the HLA DQ locus, which is in a gene that
controls many important immunological functions and is associated with
diseases.
Even simple information about identify requires confidentiality. Just as
fingerprint files can be misused, DNA profile identification information could be
misused to search and correlate criminal-record databanks or medical-record
databanks. Computer storage of information increases the possibilities for
misuse. For example, addresses, telephone numbers, social security numbers,
credit ratings, range of incomes, demographic categories, and information on
hobbies are currently available for many of the citizens in our society from
various distributed computerized data sources. Such data can be obtained directly
through access to specific sources, such as credit-rating services, or through
statistical disclosure.2 ''Statistical disclosure" refers to the ability of a user to
derive an estimate of a desired statistic or feature from a databank or a collection
of databanks. Disclosure can be achieved through one query or a series of queries
to one or more databanks. With DNA information, queries might be directed at
attaining numerical estimates of values or at deducing the state of an attribute of a
person through a series of Boolean (yes-no) queries to multiple distributed
databanks.
Several private laboratories already offer a DNA-banking service (sample
storage in freezers) to physicians, genetic counselors, and, in some cases, anyone
who pays for the service. Typically, such information as name, address, birth
date, diagnosis, family history, physician's name and

address, and genetic counselor's name and address is stored with the samples.
That information is useful for local, independent bookkeeping and record
management. But it is also ripe for statistical or correlative disclosure. Just the
existence of a sample from a person in a databank might be prejudicial to the
person, independently of any DNA related information. In some laboratories, the
donor cannot legally prevent outsiders' access to the samples, but can request its
withdrawal. A request for withdrawal might take a month or more to process. In
most cases, only physicians with signed permission of the donor have access to
samples, but typically no safeguards are taken to verify individual requests
independently. That is not to say that the laboratories intend to violate donors'
rights; they are simply offering a service for which there is a recognized market
and attempting to provide services as well as they can. Much has been written on
statistical databank systems and associated security issues.3
Guidelines for release of DNA samples and disclosure of DNA typing
information must be designed to safeguard the rights of persons who, for one
reason or another, get involved in a DNA typing (see Chapter 7 for further
discussion) without burdening law-enforcement agencies and civil investigative
authorities with unnecessarily protective policies.
The need for safeguards of DNA information has not been completely lost
on lawmakers considering databank legislation. Some state legislation has
addressed the issue. For example, the Virginia law4 establishing a DNA profile
databank for convicted offenders states that
any person who, without authority, disseminates information contained in the

databank shall be guilty of a Class 3 misdemeanor. Any person who
disseminates, receives or otherwise uses or attempts to so use information in the
databank, knowing that such use is for a purpose other than as authorized by
law, shall be guilty of a Class 1 misdemeanor. Except as authorized by law, any
person who, for purposes of having DNA analysis performed, obtains or
attempts to obtain any sample submitted to the Division of Forensic Science for
analysis shall be guilty of a Class 5 felony.
That passage reflects recognition of the potential for abuse of information

derived from a sample (and of the sample itself) and incorporates sanctions to
preclude it. In the first legal test5 of the establishment of such databanks on
convicted felons, Chief U. S. District Judge James C. Turk upheld the Virginia
databank statute, offering the following opinion in regard to the issue of privacy:
The stored information is available only to law enforcement personnel in

furtherance of an official investigation of a criminal offense. Va. Code Ann.
Section 19.2-310.6 (1990). In addition, the identifying information is
disseminated to the law enforcement officer only if the sample provided by the
officer matches a sample in the databank. Id. The procedures followed

are sufficiently stringent such that no person, including a law-enforcement

official, may conduct random searches in the databank.
Although that is a good start, state laws should state explicitly the types of
uses that can be authorized. In particular, in addition to the points made in the
opinion just quoted, investigation of DNA samples or stored information for the
purpose of obtaining medical information or discerning other traits should be
prohibited, and violations should be punishable by law. Several states incorporate
some of those specific protections into their statutes establishing DNA profile
databanks. However, the committee urges all states to be systematic in defining
authorized uses of information in DNA databanks.
METHODOLOGICAL STANDARDIZATION
Because of the incompatibility between DNA typing methods, federal, state,
and local laboratories that wish to use a national DNA profile databank must all
adopt a single standardized method for analyzing samples—both databank
specimens and evidence specimens. Accordingly, the development of a national
DNA databank has the potential advantage of acting as a driving force for
standardization in forensic DNA typing, but the potential disadvantage of
ossifying a rapidly moving technology.
It is broadly agreed that current RFLP typing methods constitute simply an
initial approach that will be replaced in the next few years by procedures that are
much easier to automate, much less expensive, and more informative. Premature
development of a national databank based on current RFLP typing methods runs
the risk of perpetuating a "dinosaur" technology in the face of better techniques.
The committee believes that it is too early to launch a comprehensive
national DNA profile databank. However, it is appropriate to carry out pilot
programs based on RFLP technology with the FBI and states that have active
DNA typing efforts. The initial efforts should help to define the problems and
issues that will be encountered in the fashioning of a comprehensive program.
Such projects should be explicitly viewed as preliminary, with the clear
expectation that the databank will be supplanted in the next several years by
better methods.
Before even pilot projects can be begun, the degree of interlaboratory
reproducibility—which is essential to the success of a databank—should be
thoroughly documented. So far, there have been only a few interlaboratory-
reproducibility studies to compare the ability of different laboratories to measure
the same DNAs accurately under different circumstances. The National Institute
of Standards and Technology (NIST), in concert with the Federal Bureau of
Investigation (FBI) and the Technical Working Group on

DNA Analysis Methods (TWGDAM), sent samples to 22 laboratories in October

1990 (Dennis Reeder, personal communication, 1991); 12 laboratories have
reported so far. The greatest differences were reported to be slightly less than
5%. The preliminary results are encouraging, but need to be followed by more
extensive reproducibility testing before the efficacy of a national network based
on this method can be demonstrated. Moreover, the committee urges that
laboratories participating in any national databank be required to participate in
continuing proficiency and reproducibility studies (by carrying out blind
measurements of samples sent from a common source), to ensure that
reproducibility does not drift over time.
COST VERSUS BENEFIT

An analysis of the costs and benefits of establishing DNA databanks is
problematic at best. Costs will depend on a number of variables, such as
methods, numbers of loci used, and types and numbers of samples to be tested.
Benefits will depend on the populations included in the databank and the
likelihood of finding matches. Moreover, costs and benefits must be reckoned in
both monetary and nonmonetary terms.
Nonmonetary costs can include the risk of loss of privacy and the misuse and
abuse of genetic information. Nonmonetary benefits can include prevention of
future crimes. Those diverse elements cannot be weighed except in the context of
societal values.
Concerning monetary costs, it is helpful to recall the comparison between
latent fingerprints and DNA profiles. Collection of fingerprints from identified
persons is inexpensive and relatively easily accomplished by persons with
minimal technical training and background. Samples cost perhaps a few dollars;
the cost reflects the personnel time involved in taking and filing the fingerprints.
Although sample collection is simple, fingerprint databanks require sophisticated
and expensive computer hardware and software. A typical state automated
fingerprint identification system can cost $10 million. In contrast, DNA typing is
time-consuming, is expensive, and requires extensive education, training, and
quality-assurance measures. With current RFLP methods, blood must be obtained
by venipuncture at an estimated cost of $20/sample. Storage methods and costs
depend on the number of samples and the form in which they are preserved
(liquid or dried blood, extracted DNA pellet, buffy coat, etc.). In any case,
freezers, cryotubes, and labor can cost another $20/sample for storage. The cost
of RFLP analysis can be estimated from fees charged by private laboratories:
about $100-150/sample.6 Thus, a single DNA profile can cost about $120-170,
and constructing 10,000 DNA profiles could cost $1.2-1.7 million. However,
DNA typing databanks do not require highly sophisticated or expensive computer
hardware and software.

In short, ordinary fingerprints and DNA profiles have opposite economic

characteristics. Ordinary fingerprint databanks have low variable costs and high
fixed costs, and DNA typing databanks have high variable costs and
comparatively low fixed costs. Those considerations imply that different
decisions could be appropriate as to whether, when, and how to develop each kind
of databank. For example, because of the high variable cost per sample,
considerable thought must given to whose DNA profiles should be stored. To
maximize the "return per sample," one should concentrate on persons convicted
of crimes with documented high rates of recidivism, such as rape, as discussed
below.
Cost analysis is made more difficult by the rapidity of change in DNA typing
technology. For example, PCR-based methods might greatly reduce DNA typing
costs: blood samples might be replaced with simple buccal swabs (i.e., cheek
scraping); Southern blots might be replaced with non-gelbased formats;
complicated scoring of the problematic continuous allele system used in RFLP
analysis might be replaced with discrete mechanical allele scoring. Accordingly,
today's cost assessments must be viewed as tentative.
WHOSE SAMPLES SHOULD BE INCLUDED?

In deciding whom to include in a DNA profile databank, it is necessary to
consider the likely forensic utility of the data and the protection of individual
privacy. It is helpful to consider six categories of people.
Samples from Convicted Offenders

DNA profile databanks containing profiles of criminal offenders must be
justified on the basis of the likelihood of recidivism. The Bureau of Justice
Statistics7 found that, of the 108,580 persons released from prisons in 11 states in
1983, an estimated 63% were rearrested for a felony or serious misdemeanor
within 3 years, 47% were reconvicted, and 41% returned to prison or jail
(Table 5-1). They were charged with a total of 326,746 new offenses in the 3-
year period; more than 50,000 charges were related to violent offenses, including
approximately 2,000 homicides, 1,500 kidnappings, 1,300 rapes, 2,600 other
sexual assaults, 17,000 robberies, and 22,600 other assaults. Of the prisoners who
had been incarcerated for violent offenses, 60% were rearrested within 3 years
for similar offenses. Recidivism rates were highest in the first year. Four of every
10 released prisoners were rearrested in the first year; nearly one-fourth were
convicted of new crimes; and nearly one-fifth were returned to prison or sent to
jail. Most rearrests occurred in the states in which the prisoners were released,
although about 15% occurred in other states. Of course, high recidivism

rates alone do not demonstrate the utility of a databank of DNA profiles of

convicted offenders. One must also ask: What fraction of crimes committed by
repeat offenders do not themselves lead to rearrest and reconviction? What
fraction would end in rearrest and reconviction if a DNA profile databank were
available?
TABLE 5-1 Recidivism Rates of Prisoners Released in 11 States in 1983, by Most
Serious Offensea
Fraction of Prisoners, %, Who Within 3 Years Were:
Offense Fraction of Rearrested Reconvicted Reincarcerated
Prisoners, %
All offenses 100.0 62.5 46.8 41.4
Violent offenses 34.6 59.6 41.9 36.5
Murder 3.1 42.1 25.2 20.8
Negligent 1.4 42.5 27.9 21.8
manslaughter
Kidnapping .6 54.5 35.7 31.3
Rape 2.1 51.5 36.4 32.3
Other sexual 2.1 47.9 32.6 24.4
assault
Robbery 18.7 66.0 48.3 43.2
Assault 6.4 60.2 40.4 33.7
Other .4 50.1 33.2 31.4
Property offenses 48.3 68.1 53.0 47.7
Burglary 25.8 69.6 54.6 49.4
Larceny and theft 11.2 67.3 52.2 46.3
Motor vehicle 2.6 78.4 59.1 51.8
theft
Arson .7 55.3 38.5 32.3
Fraud 5.5 60.9 47.1 43.3
Stolen property 1.7 67.9 54.9 50.5
Other .8 54.1 37.3 33.9
Drug offenses 9.5 50.4 35.3 30.3
Possession 1.2 62.8 40.2 36.7
Trafficking 4.5 51.5 34.5 29.4
Other and 3.9 45.3 34.5 29.1
unspecified
Public-order 6.4 54.6 41.5 34.7
offenses
Weapons 2.2 63.5 46.7 38.1
Other 4.2 49.9 38.9 33.0
Other offenses 1.1 76.8 62.9 59.2
a Data from Beck and Shipley.7
The first question obviously is impossible to answer explicitly. However, the

FBI's Uniform Crime Reports states that there are about 20,000

murders and 100,000 forcible-rape cases per year. It is estimated that 30% of all
murder cases and 70% of all rape cases are never closed by arrest (John Hicks,
personal communication, 1990). It should also be pointed out that only an
estimated 50% of rapes are in fact even reported.
The second question is also difficult to answer, but it is clear that crimes of
most types will not afford the opportunity to recover relevant biological evidence
that will allow the police to identify an unknown suspect—i.e., the perpetrator's
own body fluids. They include larcenies, burglaries, and assaults, for which
ordinary fingerprints are frequently found. The major exception is rape, for which
semen samples can be recovered in many cases and might provide prima facie
evidence of sexual intercourse. In a small minority of homicides, blood, hair, or
tissue samples from the perpetrator are left at the scene of the crime (e.g., because
of a fight at the scene).
A DNA profile databank would thus be valuable primarily in investigating
forcible rape, although the databank would be useful for some other
investigations. State legislatures considering setting up such databanks should
weigh the benefits in terms of solved rape cases and the costs in terms of
collecting samples from persons likely to commit rapes (primarily, it seems,
convicted sex offenders). Initial state efforts to develop DNA profile databanks
were indeed aimed at sex offenders. Interestingly, some states rapidly expanded
their programs to include all convicted offenders—without explicit weighing of
the potential benefits of possessing such persons' patterns for solving crimes and
the potential costs.
The above discussion justifies the development of a databank of DNA
profiles of unknown subjects (open cases) and of offenders convicted of violent
sex crimes. Such a databank would provide law enforcement with a powerful tool
in linking sexual-assault cases through DNA profiles and tracking the activities
of serial rapists. In light of recidivism and the continuing increase in reported
rapes in this country, a databank of convicted sex offenders would provide
investigators with a logical first place to look for assistance in solving unknown-
offender sexual-assault cases.
Samples from Suspects

DNA typing profiles of suspects might also be useful in associating a person
with open or unsolved cases pending in other jurisdictions or states. Although a
suspect's DNA profile might ultimately be entered into a convicted-felon
databank, there would no doubt be a substantial period during which a suspect
might engage in other criminal activities. Thus, in the case of a serial rapist, a
person under suspicion and investigation for one offense, might be responsible
for several later offenses for which he is not suspected. Therefore, if a DNA
profile of a suspect is entered into a databank, it would be available to be
searched against future unsolved cases.

Samples from Victims

To protect their privacy, victims' DNA profiles should never be entered into a
national databank or searched against such a databank, with the possible
exception of cases of abduction, in which it might be desirable for the victim's
information to be stored and accessible to law-enforcement officials. In any
exceptional case, prior permission of the victim, the victim's legal guardian, or a
court should be required, and the victim's DNA should be removed from the
databank when it can no longer serve the purpose for which it was entered.
Samples from Missing Persons and Unidentified Bodies

This portion of the databank would contain DNA profiles from unidentified
bodies, body parts, and bone fragments. These would provide the greatest benefit
when DNA profiles from immediate relatives (parents) could be used to
reconstruct the DNA profile of a missing person for comparison. Although there
would be immediate benefits from the development of these types of data, the
actual number of relevant cases would be small, compared with the number of
sexual assaults by unknown persons.
Crime-Scene Samples from Unidentified Persons

DNA profile evidence found at the scene of a crime should be stored and
accessible to legally authorized investigators. Such samples might be useful for
recognizing serial or multiple crimes even before a perpetrator is found and will
be equally useful once a perpetrator has been identified. It might be useful to have
additional cross-referenced information accessible at the national level, including
modus operandi or other attributes for correlation as part of an investigation.
Samples from Members of the General Population

Some observers have suggested that a DNA profile databank should not be
limited to criminals, but should aim, at least in the long term, to store DNA
profiles from the entire general public. It is argued that many groups in the
general public are already required to be fingerprinted for various security and
identification purposes and the same justification could be applied to DNA
profiles; furthermore, if the databanks contained everyone, rather than just
previous offenders, the chance of identifying perpetrators would be much greater.
The committee does not find those arguments persuasive. For identification
and security purposes, DNA profiles would add nothing to ordinary

fingerprints, because ordinary fingerprints already provide a complete identifier

and are far more likely to be recovered in connection with security breaches than
are blood samples that are amenable to DNA analysis. As for identifying
perpetrators, there is no doubt that the system would have some effect. However,
Americans have generally been reluctant to allow the creation of national
identification systems, and DNA profiling poses a special risk of invasion of
privacy (concerning personal and medical traits). We caution against moving in
that direction. Finally, we note that current technology is far too expensive to
contemplate the creation of such a large databank.
Samples from Anonymous Persons for Population Genetics

The committee notes that statistical databanks of random population samples
are required for estimating allele frequencies, as described in Chapter 3. To
protect the privacy of persons whose only role is to make up a statistical sample,
their identities should never be retained in a databank, and the databanks should
never be searched for matches in connection with investigations.
SAMPLE STORAGE
Another difficult issue is the storage and maintenance of DNA samples
themselves (or any reusable products of the typing process), as opposed to DNA
profiles. In principle, retention of DNA samples creates an opportunity for misues
—i.e., for later testing to determine personal information. In general, the
committee discourages the retention of DNA samples.
However, there is a practical reason to retain DNA samples for short
periods. Because DNA technology is changing so rapidly, we expect the profiles
produced with today's methods to be incompatible with tomorrow's methods.
Accordingly, today's profiles will need to be discarded and replaced with profiles
based on the successor methods. It would be extremely expensive and inefficient
to have to redraw blood samples for retyping. We are therefore persuaded that
retention of samples after typing should be permitted for the short term—only
during the startup phase of DNA profile databanks. As databanks become
established and technology stabilizes somewhat, samples should be destroyed
promptly after typing.
INFORMATION TO BE INCLUDED AND MAINTAINED IN A

DATABANK
It is worth commenting on the nature of the information that should be stored
in a DNA profile databank.

• Submitting-agency information should include the location of the

agency, its telephone number, names of the analysts who conducted the
DNA typing, the name of the person who entered the data into the
databank, and agency contact information.
• Sample information should include entries that describe the type of
sample (body-fluid stain, tissue, or known blood sample) and a unique
sample identifier, the condition of the sample, unusual handling and
storage, and other factors that might affect the quality of the DNA and
the evaluation of partial patterns.
• The DNA type at a locus must be entered in standard nomenclature. For
example, for RFLP typing, fragment-size data from each locus
successfully probed should be entered as the number of basepairs
determined for each fragment. Sizing data for the human-DNA control
should also be entered.
• Entries into the convicted-offender files should include the name of the
offender, dates of offenses and convictions, and DNA profile data. Only
the profile index should be centrally stored. Case data should be stored
locally, and their distribution should be under the control of the local
agency.
RULES ON ACCESSIBILITY
Computer security should be ensured through use of the best available
practices and technologies. Access to the databank should be limited to a small
number of legally authorized persons and should be limited to what is required
for specific official investigations. All instances of access should be audited and
archived. An excellent discussion of computerized audit-trail systems is
available.8
If the computer system and associated databank are to be made available for
remote access by cooperating state and federal agencies, such as by telephone or
networked by other means, the access mechanism (i.e., the network switch)
should be made available only for specific, authorized remote-access sessions;
that is, the system should not be continuously available to remote users. This type
of limited access can be achieved either administratively or physically; it is a
simple and inexpensive means of safeguarding sensitive information and is
common practice in many national security situations. For example, secure
computers are virtually never connected to unsecured computers at national
defense laboratories; when newspaper headlines make statements that computers
at these facilities have been breached, it has been the case that the computers
were unsecured and not connected to the secure computers. In many cases, these
unsecured computers have telecommunication connections available to
employees for routine use, but they do not contain security information.

STATISTICAL INTERPRETATION OF DATABANK MATCHES

The distinction between finding a match between an evidence sample and a
suspect sample and finding a match between an evidence sample and one of many
entries in a DNA profile databank is important. The chance of finding a match in
the second case is considerably higher, because one does not start with a single
hypothesis to test (i.e., that the evidence was left by a particular suspect), but
instead fishes through the databank, trying out many hypotheses.
If a pattern has a frequency of 1 in 10,000, there would still be a
considerable probability (about 10%) of seeing it by chance in a databank of
1,000 people. Although there are statistical methods for correcting for such
multiple testing, the committee considers that approach unwise, because it
requires that the population frequency estimates of genotypes are accurate to a
degree that is unlikely to be achieved (because sample sizes are limited). There is a
far better solution: When a match is obtained between an evidence sample and a
databank entry, the match should be confirmed by testing with additional loci.
The initial match should be used as probable cause to obtain a blood sample from
the suspect, but only the statistical frequency associated with the additional loci
should be presented at trial (to prevent the selection bias that is inherent in
searching a databank). Forensic DNA typing laboratories should recognize that
they will require additional loci beyond those used in the databank to prove a case
against a suspect. Preparations should be begun now to have additional loci
characterized and available for general use before any DNA profile databank
comes into common use.
STATUS OF DATABANK DEVELOPMENT

There have already been state and federal efforts toward the creation of DNA
profile databanks. We review them briefly here.
State Level
According to a recent FBI survey,9 27% of 177 forensic science laboratories
responding indicated that they have legislative authority or a mandate to
construct a databank for their own jurisdictions to match DNA profiles. An
additional 38% believed that such authority or mandate was likely by 1991.
According to an Office of Technology Assessment survey conducted in late
1989,10 at least 17 states had passed or were considering legislation creating
statewide DNA databanks. The persons to be included in the databanks range from
sex offenders to all felons. Since the time of that survey,

the number has no doubt increased. Therefore, it is obvious that many state
legislatures recognize the potential benefit of a DNA databank as an important
investigative tool and that such databanks will become a reality. Many states are
already collecting samples in earnest, although at this writing no databanks are
operative.
Federal Level
The FBI and TWGDAM have proposed the creation of a national DNA
profile databank system, including one statistical and three investigative
databanks. The statistical databank would include DNA profiles of randomly
selected unrelated persons and would be built collaboratively and maintained by
the FBI for use by all forensic laboratories. The investigative databanks would
contain DNA profiles of body fluids from the scenes of crimes for which suspects
have been identified, convicted offenders, and bodies, body parts, and bone
fragments of unidentified persons. In the proposed national DNA profile databank
system, individual law-enforcement agencies (forensic laboratories) would
contribute DNA profiles (without personal information) to a centralized
databank, but retain absolute control of their own case records. The national
databanks would reference the sources of the profiles, but case data would be
secured and controlled by the state and local agencies.
In the national program, the FBI would play the lead role. It would
coordinate quality assurance with a technical advisory group to implement
appropriate guidelines; coordinate with other agencies that have a law-
enforcement interest in the development of the databank; provide hardware and
software for the databank server and for state access to the databank; provide
hardware to store and back up the databank server; provide training for states in
forensic DNA technology, quality control, and databank access; determine
formats for databank input and output; update index with new state and federal
submissions; assemble population data for all probes used and calculate and
disseminate population frequencies; and modify the system to accommodate new
DNA typing methods.
State and local agencies would be responsible for performing DNA analyses
of samples with consensus methods; submitting new information in a specified
format for incorporation into the databanks; guaranteeing the quality of their new
submissions; providing hardware and software for state image-analysis
workstations for telephone access to centralized index; maintaining centrally
indexed case files for as long as they remain in the index; and providing relevant
information from case files that are indexed centrally to other law-enforcement
agencies, which subscribe when requested.
Just as the Department of Defense keeps dental records and fingerprints
(with the FBI) of American soldiers, it is seeking funding to collect blood

samples from each soldier and establish a DNA profile databank. When a soldier
is killed and cannot be identified with usual methods, a sample of tissue, blood,
or bone marrow from the remains would be subjected to DNA analysis for
comparison with entries in the databank. There are 3.3 million active and reserve
members of the armed forces. Given the costs associated with the current
technology, a DNA databank of such scope would not be amenable to RFLP
analysis. The Armed Forces Institute of Pathology therefore proposes to begin
collecting and storing samples while working on the development of a DNA
analysis method, which when perfected will be much less expensive and time-
consuming than existing RFLP methods.
A databank of military personnel could also offer ancillary forensic
applications: criminal investigations conducted by criminal investigation
divisions of the armed forces could be aided in the same manner as those of other
law-enforcement agencies, identification of subjects for security purposes could
be enhanced, and identification of urine samples from disputed sources for drug
testing could be verified.
The present committee has not been asked to comment on this program; we
simply acknowledge its existence.
MODEL COOPERATIVE INFORMATION RESOURCE

Local autonomy as to databank structure and function is recommended, for
several reasons: a databank can be tailored to meet local needs, the local databank
administrator will not have to rely on outside entities for maintenance and
change, and security can best be managed with smaller, discrete, well-understood
databanks. That is not to say that standards and guidelines should be avoided. On
the contrary, very strict regulations, standards, and guidelines for all aspects of
the operation should be enforced and monitored. Databank requirements involve
determining what a system must accomplish; there are typically many alternative
implementation details that can accomplish the same goals.
The experimental protocols used to derive DNA profiles will probably
continue to change as the associated technologies continue to mature. That
presents a problem that is common in databank applications when the underlying
science is in flux: maintaining data integrity while keeping the system current
with the most appropriate technology. It will be challenging, but necessary to
ensure competence. In practice, that means designing for change, which requires
partitioning the problem into two domains—one that is relatively stable and one
that is relatively dynamic. For example, data within the sample context are
relatively stable, whereas those associated with experiments and derived data are
relatively dynamic.
Figure 5-1 is a high-level data flow diagram that shows one possible model
for the flow of information from state or regional laboratories to a

national information resource. Each state or region could have several

participating local facilities, but for simplification it is recommended that each
state or region have one official clearinghouse for locally derived information.
Regional facilities could range from situations where a state has several
laboratories serving a high-volume workload, as in California, to a regional group
of states that each have only periodic and low-volume workloads. All the locally
generated raw data and results would be stored
FIGURE 5-1 Hypothetical national information resource. Data flow starts with
forensic laboratories in various states that provide raw data. Data reduction
process provides information to national information resource databank. Merged
and reduced data are provided only to authorized users.

at the state or regional level. Thus, all the information concerning the sample,
experimental, and result contexts would be stored at the state or regional level;
only data associated with the result context would be accessed at the national
level. The box labeled ''Data Reduction Process" in the center of the figure ideally
represents a standardized method for DNA typing that all laboratories use.
The hypothetical national information resource shown in Figure 5-1does not
necessarily represent a physical entity, but could be simply a view of derived data
from all the various regional databanks. A view would be achieved by having
access software sitting "on top" of the various state or regional databanks. The
software would have distinctly different requirements for level of access to data
in the databank. For example, "outside views" would only need access to VNTR
profiles and some arbitrary identification number; no further information at this
first level of access would be required for initial identification searching.
• In principle, a national DNA profile databank should be created that

contains information on felons convicted of violent crimes with high
rates of recidivism. The case is strongest for felons who have committed
rape, because perpetrators typically leave biological evidence (semen)
that could allow them to be identified. The case is somewhat weaker for
violent offenders who are most likely to commit homicide as a recidivist
offense, because killers leave biological evidence only in a minority of
cases. The wisdom of including other offenders depends primarily on the
rate at which they are likely to commit rape, because rape is the crime
for which the databank will be of primary use.
There are a number of scenarios that illustrate the point that the databank
need not be limited to persons convicted of specified crimes.
• The databank should also contain DNA profiles of samples from

unidentified persons collected at the scenes of violent crimes.
• Databanks containing DNA profiles of members of the general
population (as exist for ordinary fingerprints for identification purposes)
are not appropriate, for reasons of both privacy and economics.
• DNA profile databanks should be accessible only to legally authorized
persons and should be stored in a secure information resource.
• Legal policy concerning access and use of both DNA samples and DNA
databank information should be established before widespread
proliferation of samples and information repositories. Interim protection
and sanctions against misuse and abuse of information derived from
DNA typ

ing should be established immediately. Policies should explicitly define

authorized uses and should provide for criminal penalties for abuses.
• Although the committee endorses the concept of a limited national DNA
profile databank, we doubt that existing RFLP-based technology
provides a wise long-term foundation for such a databank. We expect
current methods to be replaced soon with techniques that are simpler,
easier to automate, and less expensive—but incompatible with existing
DNA profiles. Accordingly, we do not recommend establishing a
comprehensive DNA profile databank yet.
• For the short term, we recommend the establishment of pilot projects
that involve prototype databanks based on RFLP technology and
consisting primarily of profiles of violent sex offenders. Such pilot
projects could be worthwhile for identifying problems and issues in the
creation of databanks. However, in the intermediate term, more efficient
methods will replace the current one, and the forensic community should
not allow itself to become locked into an outdated method.
• State and federal laboratories, which have a long tradition and much
experience with the management of other types of basic evidence, should
be given primary responsibility, authority, and additional resources to
handle forensic DNA testing and all the associated sample-handling and
data-handling requirements.
• Private-sector firms should not be discouraged from continuing to
prepare and analyze DNA samples for specific cases or for databank
samples, but they must be held accountable for misuse and abuse to the
same extent as government-funded laboratories and government
authorities.
• Discovery of a match between an evidence sample and a databank entry
should be used only as the basis for further testing using markers at
additional loci. The initial match should be used as probable cause to
obtain a blood sample from the suspect, but only the statistical frequency
associated with the additional loci should be presented at trial.
REFERENCES
1. Wilson T. Automated fingerprint identification systems. Law Enfore Technol. 1986. Aug-
Sep:17-20, 45-48.
2. Dalenius T. Towards a methodology and statistical disclosure control. Statistik Tid-skrift.
15:213-225, 1977.
3. Adam NR, Wortmann JC. Security-control methods for statistical databases: a comparative study.
ACM Comput Surv, 21:515-556, 1989.
4. Code of Virginia, Title 19.2-310.6. Unauthorized uses of DNA data bank; forensic samples;
penalties (1990, c. 669).
5.Jones v. Murray,763 F. Supp. 842 (W.D. Va. 1990).
6. Cellmark Diagnostics. Proposal for DNA databasing, Division of Criminal Investigation Forensic
Laboratory, South Dakota. Dec. 21, 1990.

7. Beck A, Shipley B. Recidivism of prisoners released in 1983. Bureau of Justice Statistics Special
Report NCJ-16261. Washington, D.C., 1989.
8. Lunt TF, Tamaru A, Gilham F, Jagannathan R, Neuman PG, Jalali C. IDES: a progress report.
Proceedings of the Sixth Annual Computer Security Applications , Tucson, Arizona: ACM
Press, 1990.
9. Miller J. The outlook for forensic DNA testing in the United States. Crime Lab Digest. 17(Suppl.
1 ):1-14, 1990.
10. U.S. Congress, Office of Technology Assessment. Genetic witness: forensic uses of DNA test.
OTA-BA-438. Washington, D.C.: U.S. Government Printing Office, 1990.

USE OF DNA INFORMATION IN THE LEGAL SYSTEM 131
6
Use of DNA Information in the Legal System
This chapter provides an overview of how DNA evidence might be used in

the investigation and prosecution of crimes and in civil litigation. The DNA
typing discussed in this chapter is mainly standard single-locus RFLP typing on
Southern blots without apparent band shifting; i.e., it is the technique most often
considered by the courts to date. We begin with a discussion of the investigation
stage, but devote most of our attention to admissibility. In that context, we review
some of the rapidly growing number of cases involving admissibility. Discussion
of case law is intended mainly to highlight specific issues and is not intended to
be comprehensive. Finally, we make a series of practical recommendations, with
judges especially in mind.
To produce biological evidence that is admissible in court in criminal cases,
forensic investigators must be well trained in the collection and handling of
biological samples for DNA analysis. They should take care to minimize the risk
of contamination and ensure that possible sources of DNA are well preserved and
properly identified. As in any forensic work, they must attend to the essentials of
preserving specimens, labeling, and the chain of custody and to any
constitutional or statutory requirements that regulate the collection and handling
of samples. The Fourth Amendment provides much of the legal framework for
the gathering of DNA samples from suspects or private places, and court orders
are sometimes needed in this connection.
Wherever possible, a preserved sample should be large enough to enable the
defense to obtain an independent RFLP analysis, but there should

almost always be enough at least for PCR analysis, a technique likely to be

widely used in forensics in the near future for amplification of the DNA in the
evidentiary sample. All materials relied on by prosecution experts must be
available to defense experts, and vice versa. The laboratories used for analysis
must be reliable and should be willing to meet recognized standards of
disclosure.
In civil (noncriminal) cases—such as paternity, custody, and proof-of-death
cases—the standards for admissibility must also be high, because DNA evidence
might be dispositive. The relevant federal rules (403, 702-706) and most state
rules of evidence do not distinguish between civil and criminal cases in
determining the admissibility of scientific data. In a civil case, however, if the
results of a DNA analysis are not conclusive, it will usually be possible to obtain
new samples for study. As in criminal cases, laboratories and other interested
parties must treat evidence according to established protocols.
The advent of DNA typing technology raises two key issues for judges:
determining admissibility and explaining to jurors the appropriate standards for
weighing evidence. A host of subsidiary questions with respect to how expert
evidence should be handled before and during a trial to ensure prompt and
effective adjudication apply to all evidence and all experts and are not dealt with
in this chapter.
ADMISSIBILITY
In the United States, there are two main tests for admissibility of scientific
information from experts. One is the Frye test, enunciated in Frye v. United
States.1 The other is a "helpfulness" standard found in the Federal Rules of
Evidence and many of its state counterparts. In addition, several states have
recently enacted laws that essentially mandate the admission of DNA typing
evidence.
The Frye Test

The test for the admissibility of novel scientific evidence enunciated in Frye
v. United States has been the most frequently invoked one in American case law.
A majority of states profess adherence to the Frye rule, although a growing
number have adopted variations on the helpfulness standard suggested by the
Federal Rules of Evidence.
Frye predicates the admissibility of novel scientific evidence on its general
acceptance in a particular scientific field: "While courts will go a long way in
admitting expert testimony deduced from a well-recognized scientific principle or
discovery, the thing from which the deduction is made must be sufficiently
established to have gained general acceptance in

the particular field in which it belongs."2 Thus, admissibility depends on the

quality of the science underlying the evidence, as determined by scientists
themselves. Theoretically, the court's role in this preliminary determination is
quite limited: it should conduct a hearing to determine whether the scientific
theory underlying the evidence is generally accepted in the relevant scientific
community and to determine that the specific techniques used are reliable for
their intended purpose.
In practice, the court is much more involved. The court must determine
which scientific fields experts should be drawn from. Complexities arise with
DNA typing, because the full typing process rests on theories and findings that
pertain to various scientific fields. For example, the underlying theory of
detecting polymorphisms is accepted by human geneticists and molecular
biologists, but population geneticists and statisticians might differ as to the
appropriate method for determining the population frequency of a genotype in the
general population or in a particular geographic, ethnic, or other group. The
courts often let experts on a process, such as DNA typing, testify to the various
scientific theories and assumptions on which the process rests, even though the
experts' knowledge of some of the underlying theories is likely to be at best that
of a generalist, rather than a specialist.
When a process is new and complex, a court should recognize that the
expertise of more than one discipline might be necessary to explain it. That is the
case when the admissibility of DNA evidence is judged as a matter of first
impression. Among the issues raised is the validity of the assumptions that (1)
except for identical twins, each person's DNA is unique, (2) the technique used
allows one to determine whether two DNA samples show the same patterns at
particular loci, and (3) the statistical methods used and the available population
databanks allow one to assess the probability that two DNA samples from
different persons would by chance have the same patterns at the loci studied.
Even if those assumptions are accepted, there is the important question of
whether (4) the laboratory's procedures and analyses in the case in question were
performed in accordance with accepted standards and provide reliable estimates
of the probability of a match.
Assumption 1—that, with the exception of identical twins, each person's
DNA is unique—is so well established in human molecular genetics that a court
is justified in judicially noticing it, even in the context of a Frye hearing.
Assumption 2—concerns the validity of procedures for extracting DNA from
samples of blood, semen, and other materials and analyzing it for the presence
and size of polymorphisms. With regard to application in scientific research, the
validity is sufficiently well established in the case of RFLP analysis with
Southern blots that judicial notice is also appropriate. With regard to the
application in forensic science, however, additional questions

of reliability are raised. For example, forensic DNA analysis frequently involves
the use of small, possibly contaminated samples of unknown origin, such as a
dried blood stain on a piece of clothing. Some experts have questioned the
reliability of DNA analysis of samples subjected to "crime scene" conditions. In
addition (as noted in Chapters 2 and 3), the details of the particular techniques
used to perform DNA typing and to resolve ambiguities evoke a host of
methodological questions. It is usually appropriate to evaluate these matters case
by case in accordance with the standards and cautions contained in earlier
portions of this report, rather than generally excluding DNA evidence. Of
particular importance once such a system of quality assurance is established
would be a demonstration that the involved laboratory is appropriately accredited
and its personnel certified. Some aspects (such as the validity of the theory
underlying RFLP analysis) might be so well established that judicial notice is
warranted. Others (such as quantitative correction of band shifting with a single
monomorphic fragment) might not be sufficiently well established to justify
admissibility.
Assumption 3—related to the adequacy of statistical databanks used to
calculate match probabilities—rests on unproven foundations. Many experts
question the adequacy of current databanks for making probability estimates, and
the use of multiplicative modes of combining probabilities are also open to
serious question (see Chapter 3). The solution, however, is not to bar DNA
evidence, but to ensure that estimates of the probability that a match between a
person's DNA and evidence DNA could occur by chance are appropriately
conservative (as described in Chapter 3).
The validity of assumption 4—that the analytical work done for a particular
trial comports with proper procedure—can be resolved only case by case and is
always open to question, even if the general reliability of DNA typing is fully
accepted in the scientific community. The DNA evidence should not be
admissible if the proper procedures were not followed. Moreover, even if a court
finds DNA evidence admissible because proper procedures were followed, the
probative force of the evidence will depend on the quality of the laboratory work.
More control can be exercised by the court in deciding whether the general
practices in the laboratory or the theories that a laboratory uses accord with
acceptable scientific standards. Even if the general scientific principles and
techniques are accepted by experts in the field, the same experts could testify that
the work done in a particular case was so flawed that the court should decide
that, under Frye, the jury should not hear the evidence.
The Frye test sometimes prevents scientific evidence from being presented
to a jury unless it has sufficient history to be accepted by some subspecialty of
science. Under Frye, potentially helpful evidence may be excluded until
consensus has developed.3 By 1991, DNA evidence had been considered in
hundreds of Frye hearings involving felony prosecutions

in more than 40 states. The overwhelming majority of trial courts ruled that such
evidence was admissible; there have been some important exceptions, however.
The first scientifically thorough Frye hearing concerning DNA typing was
conducted in People v. Castro,4 in which a New York trial court concluded that
the theory underlying DNA typing is generally accepted by scientists in genetics
and related fields, that forensic DNA typing has also been accepted and is
reliable, but that the technique as applied in the particular case was so flawed that
evidence of a match was inadmissible (although evidence of an exclusion was
admissible). The Castro court stated that the focus of the Frye test as applied to
DNA typing (or any other novel scientific evidence of similar complexity) must
include its application to the particular case. It held that flaws in the application
are not simply questions as to the weight to be given the evidence by the jury, but
go to admissibility as determined by the judge.5Castro determined that there were
serious flaws in the laboratory's declaration of a match between two samples, for a
number of reasons, including the presence of several anomalous bands. The court
did not credit the laboratory's explanation of the reasons for the anomalies and
criticized its failure to perform adequate follow-up testing. In addition, the court
concluded that the laboratory's population-frequency databank could not provide
an accurate estimate of the likelihood that the defendant was the source of the
DNA. The court's analysis and findings were careful, and they have generally
been approved by experts in the field.
In November 1989, the Supreme Court of Minnesota, deciding Statev.
Schwartz,6 became the first appellate court to reject the use of DNA evidence
analyzed by a forensic laboratory. In answering a certified question, the court
noted that "DNA typing has gained general acceptance in the scientific
community." Nevertheless, the court went on to hold that admissibility of specific
test results in a particular case hinges on the laboratory's compliance with
appropriate standards and controls and on the availability of its testing data and
results. It held that, "because the laboratory in this case did not comport with
these guidelines, the test results lack foundational adequacy and, without more,
are thus inadmissible." One matter that troubled the court was the failure of the
testing laboratory to reveal underlying population data and testing methods. The
court noted that the reliability of a test implies that it could be subjected to an
independent scientific assessment of the methods, including replication of the
test. Because such independent assessment had not occurred and could not take
place, owing to the laboratory's secrecy, the court held that the results were
inadmissible. In addition, the court was concerned that the testing laboratory (1)
had admitted having falsely identified two of 44 samples as coming from the
sample subject during a proficiency test performed by the California Asso

ciation of Crime Laboratory Directors and (2) had not satisfied relevant validation
protocols used by the FBI. In that regard, Schwartz makes a good case for
requiring laboratories to meet particular standards before they may provide
analysis of evidence to juries. Schwartzalso held that the use of population-
frequency statistics must be limited, because "there is a real danger that the jury
will use the evidence as a measure of the probability of the defendant's guilt or
innocence, and the evidence will thereby undermine the presumption of
innocence, erode the values served by the reasonable double standard, and
dehumanize our system of justice."7 The decision in Schwartzwas influenced by
Minnesota's unique position in limiting the use of probability estimates in trials.8
A new Minnesota statute not considered in Schwartz specifically requires
judges to admit population-frequency data generated by DNA testing. Thus, it is
not clear how influential Schwartz will be in its home state. Nevertheless, the
Minnesota judges' skepticism about statistical analysis is shared by other judges.
Particularly in regard to DNA typing, the manner in which probabilities should be
calculated requires great care.
In Cobey v. State,9 the Maryland Court of Special Appeals reached a
conclusion opposite to Schwartz, holding that evidence of DNA analysis from the
same laboratory that figured in Schwartz was admissible and finding that the
laboratory's databank was sound. The Cobey court was impressed by the absence
of expert testimony contradicting that in favor of admissibility. It did caution,
however, that "we are not, at this juncture, holding that DNA fingerprinting is now
admissible willy-nilly in all criminal trials." In 1989, Maryland became one of a
growing number of states to enact a law recognizing the admissibility of DNA
evidence.
Admissibility According to the Helpfulness Standard

The Federal Rules of Evidence, without specifically repudiating the Frye
rule, adopt a more flexible approach. Rule 702 states that,
if scientific, technical or other specialized knowledge will assistthe trier of fact
to understand the evidence or to determine a factin issue, a witness qualified as
an expert by knowledge, skill, experience,training, or education, may testify
thereto in the form of an opinionor otherwise.
Rule 702 should be read with Rule 403, which requires the court to
determine the admissibility of evidence by balancing its probative force against
its potential for misapplication by the jury. In determining admissibility, the court
should consider the soundness and reliability of the process or technique used in
generating evidence; the possibility that admitting the evidence would
overhwelm, confuse, or mislead the jury; and the proffered connection between
the scientific research or test result to be presented and particular disputed factual
issues in the case.10

The federal rule, as interpreted by some courts, encompasses Fryeby making

general acceptance of scientific principles by experts a factor, and in some cases a
decisive factor, in determining probative force.11 A court can also consider the
qualifications of experts testifying about the new scientific principle,12 the use to
which the new technique has been put,13 the technique's potential for error,14the
existence of specialized literature discussing the technique, and its novelty.15
With the helpfulness approach, the court should also consider factors that
might prejudice the jury. One of the most serious concerns about scientific
evidence, novel or not, is that it possesses an aura of infallibility that could
overwhelm a jury's critical faculties. The likelihood that the jury would abdicate
its role as critical fact-finder is believed by some to be greater if the science
underlying an expert's conclusion is beyond its intellectual grasp. The jury might
feel compelled to accept or reject a conclusion absolutely or to ignore evidence
altogether.16 However, some experience indicates that jurors tend not to be
overwhelmed by scientific proof and that they prefer experiential data based on
traditional forms of evidence. Moreover, the presence of opposing experts might
prevent a jury from being unduly impressed with one expert or the other.
Conversely, the absence of an opposing expert might cause a jury to give too
much weight to expert testimony, on the grounds that, if the science were truly
controversial, it would have heard the opposing view. Other possible difficulties
with the presentation of DNA expert evidence include the possibility of jury
confusion and an inordinate consumption of trial time.17 Nevertheless, if the
scientific evidence is valid, the solution to those possible problems is not to
exclude the evidence, but to ensure through instructions and testimony that the
jury is equipped to consider rationally whatever evidence is presented.
In determining admissibility with the helpfulness approach, the court should
consider a number of factors in addition to reliability. The first is the significance
of the issue to which the evidence is directed. If the issue is tangential to the case,
the court should be more reluctant to allow a time-consuming presentation of
scientific evidence that might confuse the jury. Second, the availability and
sufficiency of other evidence might make expert testimony about DNA
superfluous. And third, the court should be mindful of the need to instruct and
advise the jury to eliminate the risk of prejudice.18
Cases on Admissibility of DNA Evidence Under the Federal

Rules
As with the Frye rule, courts applying the federal rules or conforming state
rules must consider whether the particular techniques used in a particular case
pass scientific muster. Three federal courts have now conducted

thorough hearings on the admissibility of DNA evidence, with two courts finding
it admissible and one ruling it inadmissible.
The U.S. District Court for the District of Vermont conducted a detailed
analysis in United States v. Jakobetz.19 It reviewed the literature and FBI
practices. Despite a strong attack from the defense and its experts, the court found
that the DNA evidence was "highly reliable" and that its probative value
outweighed the potential for prejudice.20Strict application of the Frye test was
rejected in accordance with Second Circuit standards.21
After a thorough hearing that focused on FBI protocols, the U.S. magistrate
for the Southern District of Ohio in United States v.Yee22 also wrote a detailed
analysis with conclusions essentially tracking those in the Vermont case.
(Interestingly, an Arizona trial court considering the admissibility of DNA typing
in State v. Despain23carefully studied the transcript of Yee, but reached a
conclusion opposite to it. That might have been because it also reviewed the
transcript of another hearing in which four additional defense experts challenged
FBI protocols. Finding that there was a legitimate scientific controversy as to the
validity of DNA testing and that it had not gained general acceptance, the court in
Despain refused to admit evidence analyzed by the FBI laboratory.)
Most recently, the Superior Court for the District of Columbia reached the
opposite conclusion and held DNA typing inadmissible. In U.S.v. Porter24, the
court ruled that the technical reliability of DNA typing was generally accepted,
but that the FBI's method for calculating the probability of a coincidental match
was not. The court ruled that the scientific foundation of these probability
calculations bears on the admissibility (and not simply the weight) of the
evidence. Applying the Frye standard, the court found that "there is a controversy
within the scientific community [on this issue] which has generated further study,
the results of which will soon be available for scrutiny. It is after these studies and
others … when the court should be called upon to admit DNA evidence."
In addition, a number of state courts that apply analogues of the federal rules
have considered the admissibility of DNA evidence. In Andrews v. State,25 a
Florida court of appeals (the first higher-level state court to consider DNA
evidence) determined that the relevance approach was applicable under the
Florida evidence code that tracks the federal rules. The court admitted the
evidence presented by the plaintiff's three scientific experts, two of whom worked
for a private testing laboratory; the defense called no experts. The court
concluded that the DNA typing evidence offered by the plaintiff was clearly
helpful to the jury. With respect to the possibility of prejudice, the court found
that DNA typing is not particularly "novel," in that it had been used in
nonforensic applications for 10 years. The issue of differences between scientific
applications and forensic applications were not raised by the defense. The court
also noted the existence of specialized literature about the technique. As for the
possibility of erroneous test re

sults, the court credited testimony that an error in the testing process would mean
that there would be no result, rather than a false-positive or false-negative result.
The court also credited the efficacy of the laboratory's control runs and approved
the use of statistical data to determine the probability of a match.
In Spencer v. Commonwealth,26 the Supreme Court of Virginia affirmed a
trial court's finding that evidence derived from RFLP analysis was sufficiently
reliable to be admitted. The trial court heard testimony from three experts for the
prosecution in molecular biology and genetics. The defense called no expert
witnesses. The trial court credited testimony that there is no risk of false
positives, that the testing techniques are reliable and generally accepted in the
scientific community, and that the particular test was conducted in a reliable
manner.
At a later proceeding involving the same defendant, the Supreme Court of
Virginia held that evidence based on a sample analysis that used a PCR
technology was admissible. In discussing the standard for admitting novel
scientific evidence, it rejected the Frye test, asserting instead that the court should
make a ''threshold finding of fact with respect to the reliability of the scientific
method offered." Without discussing the details of the experts' testimony, the
court concluded that the evidence supporting admissibility was credible.27
A Delaware trial court held in State v. Pennell28 that DNA evidence was
admissible under a state statute similar to the federal rules, but refused to admit
probability statistics. There was no dispute about the underlying theory of DNA
typing or its general application in the particular case. The defendant challenged
the laboratory's claims that the population databank it used was in Hardy-
Weinberg equilibrium and that its "binning process" was valid. The defense held
that the state's experts' assessment of the probability of declaring a match was
overstated. The court accepted some of the defense contentions and faulted the
laboratory for its procedure. The state later introduced new evidence based on the
laboratory's revised procedure and a new databank. The court agreed to allow the
new evidence if the state would provide the raw data to the defendant, but the
state did not do so. The court expressed concern over testimony that the
measurements of allele size can depend on who is doing the measuring, and it
concluded that the state's evidence did not sufficiently support the probability
calculation.
Recent Appellate Opinions

As of February 1991, one federal and 10 state appeals from decisions to
admit DNA evidence had been decided. Eight of the state appellate courts upheld
trial courts' decisions to admit; the other two approved the scientific theory
underlying DNA typing, but one excluded the work of a particular laboratory
because of process unreliability, and one found that there was

sufficient controversy about the methods for assigning statistical weight so that
they could not be considered generally accepted. In the sole federal appellate
ruling, the Eighth Circuit Court of Appeals reversed a federal trial court's decision
to admit DNA typing evidence and directed the lower court to hold a full hearing
on admissibility.29In the spring and summer of 1990, an intermediate-level
appellate court in Texas30 and the supreme courts of South Carolina,31
Georgia,32North Carolina,33 and Massachusetts34 were among the courts that
considered the admissibility of DNA evidence. These opinions are of particular
interest, because they were issued after sustained debate in the legal and scientific
communities about possible flaws in DNA typing technology and possible
inadequacies in the population databanks. The courts in Texas, South Carolina,
Georgia, and North Carolina upheld the admissibility of DNA evidence;
Massachusetts rejected it because of concerns about the adequacy of population
genetic interpretation.
In Kelly v. Texas, the defendant appealed from a murder conviction,
challenging as error the trial court's admission of evidence that compared a semen
sample from the crime scene to a blood sample of the suspect. The defendant did
not challenge the principles of DNA typing or the general qualifications of the
state's five experts. He did attack the methods of the testing laboratory and the
statistical expertise of the witnesses. The appellate court was informed that
outside experts had twice verified the laboratory's procedures and results. In
upholding the trial court's decision to admit the evidence, the appellate court
specifically acknowledged the "validity" of the laboratory's techniques.
In July 1990, the Supreme Court of Georgia decided Caldwell v. State, a
death-penalty case. The appeal grew out of a trial court's decision after a Frye
hearing (that involved testimony by 10 experts) to admit DNA evidence. Both at
the Frye hearing and on the appeal, no challenge was made to the scientific
principles or general techniques used by the forensic laboratory. The focus was on
how the laboratory declared a match between samples, the validity of its
probability calculations, and its procedures to ensure quality control. In deciding
the appeal, the court first considered whether it was appropriate for the trial court
to use a Frye hearing to determine whether the laboratory had performed its test
with reliable techniques and in an acceptable manner. It concluded that, because
of the complexity of the issues and a lack of national standards, the inquiry was
appropriate. Although noting that errors, including false positives, could occur,
the court ruled that the laboratory's protocol was "adequate to meet these
concerns."
The court addressed how the laboratory had conducted a band shift analysis
and calculated the power of identity. Despite band shifting, the laboratory had
originally decided a match by visual examination. During the course of the trial,
as a result of criticism of that technique, it reana

lyzed the samples with a monomorphic probe. Such a probe provides an arguably
invariant reference point to analyze band shifts across samples. After review of
the testimony concerning the reanalysis, the appellate court concluded that this
approach to the problem of band shifting was acceptable.
The appellant in Caldwell also attacked the calculations that led the testing
laboratory to conclude that the chance that a randomly selected person would
have the same DNA pattern as that of the sample source and the suspect was 1 in
24,000,000. Only one of the 10 experts had actually examined the laboratory's
population databank, and he, a defense witness, insisted that it was not in Hardy-
Weinberg equilibrium. The court ruled that, in the absence of supporting
testimony, the probability statement generated by the laboratory assumptions
could not be accepted. But the court did accept the concept of appropriate
statistical calculations, which it erroneously thought did not depend on population
theory. (See the discussion of the population genetics question in Caldwell in
Chapter 3.)
In January 1991, the Supreme Judicial Court of Massachusetts, in
Commonwealth v. Curnin,34 became the second state supreme court to refuse to
admit DNA typing evidence. After being convicted of rape, in part on the basis of
DNA typing evidence, the defendant appealed, arguing that there was no general
agreement concerning test methods, use of control samples, or the need for a
testing laboratory to meet external performance standards. The high court did not
address those arguments, focusing instead on the "lack of inherent rationality" of
the process by which the testing laboratory concluded that 1 Caucasian in
59,000,000 would have the DNA pattern represented by the semen stain and the
defendant's blood. The court was particularly impressed by the testimony of an
expert for the defense who criticized the product rule as unsupported by the
laboratory's reference databank, raised the possibility of calculation errors due to
ignorance of population substructure, and explained why no assumption would be
made as to whether the relevant population was in Hardy-Weinberg equilibrium.
Despite its decision to reverse the trial court, the high court made clear that it
would not be surprised if the prosecution could correct the weaknesses of its
testimony. In the court's words, "it may even be that, by the time of the retrial of
this case the prosecution can support the admissibility of evidence of the
probability of the alleles disclosed by the DNA test being found elsewhere in the
human population. …"
Admissibility Statutes
Since 1987, the admissibility of DNA typing evidence was raised repeatedly
in the courts, largely in the context of Frye hearings. Challenges to admissibility
have become more sophisticated over the last 2 years. State legislatures have
recently begun to address the matter. Several states have

enacted laws that declare that appropriately performed DNA tests are admissible.
Although they do not specify what an appropriate test is, the statutes must have
been passed with single-locus RFLP analyses by Southern blotting in mind.
Arguably, some of them should not be interpreted as applying to technologies
that were not in general use and therefore could not have been evaluated by the
legislatures that passed the statutes. Such technologies could be validated by
amended statutes or by courts in Frye or Rule 702 hearings. For most purposes,
states with such laws have statutorily resolved disagreements over the scientific
reliability of DNA testing, although the questions of whether tests were
performed properly in a given case and of the adequacy of statistical calculations
based on test results probably remain subject to challenge.
The state laws are of two types. A number of states—including Arkansas,
Connecticut, Michigan, Montana, and New Mexico—now specifically admit
DNA evidence to assist in the resolution of paternity—noncriminal—cases (and,
by inference, probably other disputes concerning biological relationships).35
Louisiana, Maryland, Minnesota, Virginia, and Washington have enacted laws
that recognize the admissibility of DNA evidence in criminal cases.36
Maryland requires that the DNA report be delivered to the defendant 2
weeks before the criminal proceeding and specifies that the defendant may
require a witness who analyzed the sample to testify as to the chain of custody.
The Minnesota statute states that in any civil or criminal trial or hearing DNA
evidence is admissible without "antecedent expert testimony that DNA analysis
provides a trustworthy and reliable method of identifying characteristics in an
individual's genetic material upon a showing that the offered testimony meets the
standards for admissibility set forth in the Rules of Evidence"; a companion
provision specifically permits the admission of "statistical population frequency
evidence … to demonstrate the fraction of the population that would have the
same combination of genetic markers as was found in a specific human
biological specimen." Louisiana provides that "evidence of deoxyribonucleic acid
profiles, genetic markers of the blood, and secretor status of the saliva offered to
establish the identity of the offender of any crime is relevant as proof in
conformity with the Louisiana Code of Evidence.''
Legislative interest in DNA evidence remains active, and it is likely that
other states will enact laws generally favorable to its admissibility.
DNA DATABANKS ON CONVICTED FELONS: LEGAL

ASPECTS
Despite the scientific debate concerning some aspects of DNA typing
technology, by late 1990 at least 11 states had implicitly acknowledged its

potential value in forensic science by statutorily creating DNA databanks on

convicted felons.37 In general, the laws require that a person convicted of a felony
involving a sexual assault submit to phlebotomy before parole; the blood sample
is to be subjected to DNA typing and stored under the control of authorities. The
California law calls for the testing of felons convicted of murder and other
nonsexual felonies involving violence to a person. The Iowa law does not make
clear who will be tested. The Virginia law provides for testing of all convicted
felons.
Those laws were enacted because of the high rate of repeat felonious
behavior by convicted persons. For example, available data on Virginia offenders
shows that 36.3% of persons convicted of rape and 32.8% of persons convicted
of aggravated assault (including sexual assault) are convicted of another crime
within 5 years.38 The laws are premised on the fact that criminals sometimes
leave biological evidence at the crime scene and that the comparison of the
results of DNA typing of such samples with profiles stored in the forensic
laboratory might lead law-enforcement officials quickly to a prime suspect.
The creation of felon DNA databanks raises a number of challenging
constitutional questions, e.g., whether extracting blood for DNA analysis in
anticipation of future conduct is an unreasonable search or seizure under the
Fourth Amendment and whether the creation of such banks violates a privacy
right of the first-degree relatives of persons whose DNA samples are stored (see
Chapter 3). This committee is not prepared to recommend how these important
questions should be resolved, but recognizes that they deserve careful scrutiny. So
far, one federal district court has heard a challenge to the constitutionality of a
felon DNA databank. Its order for summary judgment favored the Virginia law.39
The committee did not conduct a detailed study of DNA databanks for law-
enforcement purposes. However, the committee does recognize that, as scientific
and technical concerns about DNA typing are resolved, it is highly likely that
databanks will proliferate, interconnect, and communicate. There is clearly a need
to conduct further studies on the issue. It will be important to measure the
perceived benefits of such databanks against possible harm. We must explore,
among other questions, the permissible purposes of such banks, how to minimize
invasion of legitimate privacy interests, and how to determine the appropriate
response when such interests are violated40 (see also Chapters 5 and 7).
ASSESSING THE ADMISSIBILITY OF EVIDENCE BASED ON

RESULTS OF FURTHERADVANCES IN DNA TECHNOLOGY
It is important to remember that "DNA typing" is a catch-all phrase for an
array of quite different technologies for measuring DNA variations among

persons. For some DNA typing methods, the technical basis is well accepted. For
others, important scientific questions must be resolved before they are appropriate
to use in court.
New developments in DNA technology probably will, and at first should, be
the subject of in limine hearings (those conducted by a court in deciding on
admissibility), as has been the case in recent instances when present technology
has been tested. As a general rule, generation of evidence with such new
technology should be encouraged if it is adequately supported in court hearings.
It is highly desirable that experts in molecular genetics and statistical analysis
review new developments and pass on them at a variety of conferences and
through published papers. Until there is some consensus in this field, results of
using new techniques may not be admitted; a testing period for the new
techniques will be needed to determine whether there are unforeseen errors or
difficulties, and it will take time to compile the necessary databanks. Otherwise,
the normal rules with respect to new developments can be relied on. In fact, new
developments should present less difficulty than has been posed by present DNA
typing technology, because much of the theory will have already been tested and
accepted by the courts.
The issue for courts will be to discern when a technology is so different as to
require a full admissibility hearing. Admissibility hearings might be required to
evaluate the underlying principle of a scientific method of identification, the
particular method for applying the principle, and the performance of a test in a
particular case. Regarding the underlying principles, there is, as we have noted,
no longer any question concerning the principle that DNA can be used to obtain
identification information; admissibility hearings need no longer address the
question. Regarding the particular method for applying the principle, the inquiry
will depend on the new method or technology. For example, use of a previously
unused DNA probe in the context of the basic RFLP technique might require an
admissibility hearing on whether the properties of the particular probe (e.g.,
pattern, sensitivity, or population genetics) are scientifically accepted. Methods
of correcting for shifted DNA patterns (that would otherwise fall outside the
usual matching rule) might require an admissibility hearing concerning whether
the correction procedure has gained scientific acceptance, inasmuch as this
substantially changes the method of declaring a match. The use of PCR
amplification for sample preparation might require a pretrial hearing on the
properties of the technique, because it introduces a novel issue considered by only a
few courts thus far—the synthesis of evidence by amplification. And the use of
various detection technologies for PCR products might require a pretrial hearing
about the characteristics of the detection method and its sensitivity to artifacts. In
each case, the court can properly limit inquiry to the substantially novel aspects
of the technology, focusing on whether

the method is accepted for scientific applications and whether it has been
validated for forensic identification. Minor changes in protocols will typically not
require pretrial hearings, unless they are likely to affect key issues (such as the
matching rule).
SUGGESTIONS FOR USE OF DNA EVIDENCE

Whatever statute or rule of evidence is applicable, some standards for
admissibility seem sound to the committee. In view of the importance of DNA
typing in both civil and criminal cases, the judge should determine, before
allowing DNA evidence to be introduced, that appropriate standards have been
followed, that tests were adequately performed by a reliable laboratory, and that
the appropriate protocols for DNA typing and formulation of an opinion were
fully complied with. In states without relevant statutes, the committee
recommends that the court judicially notice the appropriateness of the theoretical
basis of DNA typing by using this report, similar reports, and case law. As new
methods are used, the courts will have to assure themselves of their validity.
The problem that a court will have to focus on when a standard testing
approach is used is not general scientific theory, but actual application. In limine
hearings can be shortened considerably by stipulations, exchange of data by the
parties, and pretrial hearings to avoid unnecessary delay in trials. In the absence
of specific objections to laboratory procedures, a court may rely on evidence of
accreditation and certifications, a history of adequacy of testing by the
laboratory, and other assurances of careful practice. It is not necessary, at this
stage of development of DNA typing, to hold extensive admissibility hearings on
the general validity of the scientific techniques, although cases will still arise in
which the procedures used to report a match will be questioned.
It also might be necessary in a particular case to decide in advance whether
an expert will be permitted to characterize the probability of a match in
mathematical terms. As noted in Chapter 3, the use of the product rule (which
assumes the independence of the frequency distribution of the single-locus probes
and is the method by which the likelihood statement is generated) is
controversial. At present, courts should take a conservative approach concerning
the assumptions underlying the use of the product rule. A considerable degree of
discretion and control by the courts in these cases is recommended.
As a general matter, so long as the safeguards we discuss in this report are
followed, admissibility of DNA typing should be encouraged. There is no
substantial dispute about the underlying scientific principles. However, the
adequacy of laboratory procedures and of the competence of the experts

who testify should remain open to inquiry. Ultimately, DNA typing evidence
should be used without any greater inconvenience than traditional fingerprint
evidence.
DNA EVIDENCE AND THE VARIOUS PARTIES IN THE

LEGAL SYSTEM
The Jury
Because a jury might overvalue or undervalue scientific evidence, it is
appropriate where permitted for the judge to question DNA experts with an eye to
aiding the jury. The judge can explain to the jury the role of experts and the role
of the jury in evaluating the experts' opinions.
When probability statements are admissible, the judge should not be
expected to instruct the jury in detail on how probabilities are computed or how
probabilities available from an analysis of DNA material should be combined
with probability estimates based on more traditional testimony and other
evidence. Those matters are better left to the experts and to the lawyers on
summation. The court should encourage the use of charts, written reports, and
duplicates of materials that are relied on by the experts, so that the jury can be as
well educated as possible in the evaluation of DNA typing evidence. To that end,
the court should insist that technical terms be reduced to understandable lay
language and that scientific information be presented to the jury in the least
confusing form possible.
Special forms of charges are not required. DNA typing may be assessed
within the framework of normal forensic laboratory work and can be readily
handled with the present rules and forms of charges.
The Prosecutor
The prosecutor will work closely with the investigators and will normally
have access to adequately staffed and organized forensic laboratories. The
prosecutor should carefully supervise the investigation activities to ensure that
DNA typing evidence will be admissible, if it proves relevant.
The prosecutor has a strong responsibility to reveal fully to defense counsel
and experts retained by the defendant all material that might be necessary in
evaluating the evidence. That includes information on tests that proved
inconclusive, on retesting, and on the testing of other persons. Adoption of rules
or statutes that require the prosecutor to involve the defense in analysis of DNA
samples at the earliest possible moment is highly recommended.
The committee recommends going beyond what is required by the fed

eral rules of criminal procedure and of civil procedure in regard to disclosures

concerning DNA evidence. For example, data sheets and other materials obtained
from experts who are not designated to testify should be available freely without
the need for separate motions, because such materials are important for the
evaluation of the scientific evidence in the case of DNA typing. Such free
exchange of information, including access to databanks and to samples of
evidence DNA, should apply to defense and prosecution experts in both criminal
and civil cases.
The Defense
Defense counsel must have access to adequate expert assistance, even when
the admissibility of the results of analytical techniques is not in question, because
there is still a need to review the quality of the laboratory work and the
interpretation of the results. When the prosecutor proposes to use DNA typing
evidence or when it has been used in the investigation of the case, an expert
should be routinely available to the defendant. If necessary, he or she should be
able to apply for funds early in the discovery stages to retain experts without a
showing of relevance that might reveal trial strategy. Whenever possible, a
portion of the DNA sample should be preserved for independent analysis by the
defense.
The prosecutor should promptly reveal to defense counsel that DNA was
involved in the investigation and might be available for analysis at the trial.
Normally, the criminal-justice system will not provide for the appointment of
counsel for the defendant or for payment for experts until the defendant has been
arrested or charged. Where a sample of the defendant's tissue is sought for DNA
typing, application to the court for DNA experts should be possible even before
an arrest has been made.
In our judicial system, jurors are relatively independent. Nevertheless,
through limitations on the admissibility of evidence and on the form of its
presentation and through the use of a variety of instructions, the court exercises
considerable influence. DNA evidence, like other scientific and statistical
evidence, can pose special problems of jury comprehension. Courts and attorneys
should cooperate to facilitate jury understanding. Innovative techniques, such as
allowing jurors to take notes or ask questions, might be considered. Jargon should
be avoided, and information should be presented simply, clearly, and fairly.
Unless limited by law or court rules, judges should be free to pose questions to
witnesses when they feel that the answers might clarify the testimony. Reports
and relevant materials should be admitted into evidence so that they can be
studied by courts at their leisure. Finally, a judge would not be amiss in pointing
out to attorneys the wisdom of including jurors who are found to have a
background that enhances their ability to understand the expert testimony.

TESTING LABORATORIES
Other chapters have indicated appropriate standards for the operation of
testing laboratories and the collection and analysis of DNA samples. Uniformity
in reporting, completeness of reporting (including laboratory protocols and
written criteria for interpretation), and stringent quality assurance of laboratories
are essential. The court and the jury should have no reason to doubt the accuracy
of the processing of information. Laboratories and experts have a particular
responsibility to ensure that they are open and candid with the courts. Any
reservations about inadequacies or errors should be promptly revealed, and failure
to do that should be dealt with seriously. The court should not hesitate to exercise
contempt powers and exclude experts who have misled deliberately in the past.
Private trade associations and other appropriate groups should also apply pressure
to ensure accuracy and candor.
PROTECTIVE ORDERS
Protective orders should not be used to prevent experts on either side from
obtaining all relevant information, which can include original materials, data
sheets, software protocols, and information about unpublished databanks. A
protective order might be appropriate to limit disclosures by attorneys and experts
to third parties about proprietary information acquired in the course of a
particular case; but as a general rule, any scientific information used in a case
should be open to widespread scientific scrutiny. One exception might be when
the expert is involved in a current or recently completed study on which he or she
does not directly rely to develop an opinion. That will ensure that the expert does
not lose his or her opportunity to publish as a consequence of testifying.
Protective orders to prevent unnecessary intrusion into the privacy of such
persons as those who have been cleared after investigation or who are juveniles
are appropriate.
AVAILABILITY AND COST OF EXPERTS

Wide use of forensic DNA typing will have considerable costs. Laboratories
will be required to be funded by many states and the federal government. The
Commonwealth of Virginia, for example, has committed several million dollars
to its DNA forensic activities. Costs will be associated with upgrading the
databanks when new procedures replace old ones. Increased costs will also be
associated with the control, licensing, and oversight of laboratories and
technicians. Many experts will need to be available. The defense cost will be
substantially increased. Moreover, as DNA typing becomes more generally
available, jurors might expect it in situa

tions where it is impossible to produce. A failure to introduce DNA typing

evidence could lead to an inference of spoliation, i.e., the destruction or alteration
of evidence.
Of course, the early exclusion of suspects who have been cleared by DNA
typing evidence will reduce other costs to the judicial system. DNA evidence
might also obviate trials in some cases by proving identity fairly conclusively. In
general, however, the costs of the criminal-justice system will be increased.
We cannot now accurately estimate the cost of the widespread use of DNA
typing, but it can be expected to run into the tens of millions of dollars a year.
However, relative to the cost of operating the entire system, the cost of using
DNA evidence is minuscule. The quality of justice will be increased by full use
of DNA typing. In general, we believe that the expenditures are warranted by the
advantages to be expected.
Having carefully reviewed the issues, the committee offers the following
recommendations:
• Courts should take judicial notice of three scientific underpinnings of

DNA typing:
— The study of DNA polymorphisms can, in principle, provide a reliable

method for comparing samples.
— Each person's DNA is unique (with the exception of identical twins),
although the actual discriminatory power of any particular DNA test
will depend on the sites of DNA variation examined.
— The current laboratory procedure for detecting DNA variation
(specifically, single-locus probes analyzed on Southern blots without
evidence of band shifting) is fundamentally sound, although the validity
of any particular implementation of the basic procedure will depend on
proper characterization of the reproducibility of the system (e.g.,
measurement variation) and the inclusion of all necessary scientific
controls.
• The adequacy of the method used to acquire and analyze samples in a

given case bears on the admissibility of the evidence and should, unless
stipulated, be adjudicated case by case. In this adjudication, the
accreditation and certification status of the laboratory performing the
analysis should be taken into account.
• Because of the potential power of DNA evidence, authorities must make
funds available to pay for expert witnesses, and the appropriate parties
must be informed of the use of DNA evidence as soon as possible.

• DNA samples (and evidence likely to contain DNA) should be preserved

whenever that is possible.
• All data and laboratory records generated by analysis of DNA samples
should be made freely available to all parties. Such access is essential
for evaluating the analysis.
• Protective orders should be used only to protect the privacy of the
persons involved.
REFERENCES AND FOOTNOTES

1. Frye v. United States,293 F.2d 1013, 104 (D.C. Cir. 1923).
2. Frye v. United States,293 F.2d 1013, at 104 (D.C. Cir. 1923).
3. Gianelli PC. The admissibility of novel scientific evidence: Frye v. United States, a half-century
later, Colum L Rev, 811:'1197, 1226, 1980,
4. 144 Mise.2d 956, 545 N.Y.S. 2d 985 (Sup, Ct. 1989).
5. Id at 987.
6. 447 N.W. 2d 422 (Minn. 1989).
7. 447 N.W. at 426 (quoting State v. Carlson, 267 N.W.2d 170, 176 (Minn. 1980).
8. State v. Joon Kyu Kim,398 N.W.2d 544 (Minn. 1987).
9. 80 Md. App. 31,559 A.2d 391 (Md. App. 1989).
10. United States v. Downing,753 F,2d 1224, 1237 (3d Cir. 1985).
11. See, e,g., Kropinski v. World Plan Executive Council, 853 F, 2d 948, 956 (D,C, Cir, 1988); Novak
v. United States, 865 F.2d 718 (6th Cir. 1989); United States v, Smith, 869 F.2d 348, 352-54
(7th Cir. 1989).
12. E.g., United States v. Lushen, 614 F.2d 1164 (8th Cir.), cert. denied, 446 U.S. 939 (1980); United
States v. Williams, 583 F.2d 1194 (2d Cir. 1978), cert. denied, 439 U.S. 1117 (1979).
13. United States v. Hendershrot,614 F.2d 648 (9th Cir. 1980).
14. United States v. Williams,583 F.2d 1194 (2d Cir, 1978), cert, denied, 439 U,S. 1117 (1979).
15. State v. Hall,297 N.W.2d 80 (Iowa 1980).
16. See, e.g., People v. Marx, 54 Cal. App.3d 100, 111, 126 Cal. Rep. 3511, 356 (1975).
17. See United States v. Hearst, 412 F. Supp. 893 (N.D. Cal. 19761, aff'd, 563 F.2d 1331 (1977).
18. See, e.g., State v. Williams, 583 F.2d 1194 (2d Cir. 19781, cert. denied, 439 U.S. 1117 (1979)
(court's limiting instruction as to spectrographic voice identification stressed that jury could
disregard expert testimony and simply listen to the tapes and decide for themselves).
19. 747 F. Supp. 2511 (D. Vt. 1990).
20. Id at p,263.
21. ld at p.263.
22. United States v. Yee,ND, Ohio 129 FRD 692 (1990).
23. Superior Court of State of Arizona in the County of Yuma. No. 15589, February 12, 1991,
24. U,S. v. Porter,Superior Court of District of Columbia, Criminal Division, FO6277-89 (1991).
25. 533 So.2d 841 (Fla. App. 5 Dist. 1988).
26. 238 Va. 275, 384 S.E.2d 775 (Va. 1989).
27. Spencer v. Commonwealth, 238 Va. 295, 384 S, E. 2d 785 (1989).

28. 1989 WL 167430 at ll (Del. Super. Ct. Nov. 6, 1989) (Gebelein, J.).
29. U.S.v. Matthew Sylvester Two Bulls,918 F.2d 56 (8th Cir. 1990), 925 F. 2d 1127 (8th Cir. 1991)
(ca bane), vacated after death of defendant. See Weinstein, Rule 702 of the Federal Rules of
Evidence is sound; it should be amended (138 F.R.D. 1991) (discussing 7'wo Bulls).
30. Kelly v. Texas,No. 2089-026-CR (Ct. of Appeals, 2d District, Fort Worth, June 27, 1990).
31. State v. Ford,S.C., 392 S, E, 2d, 78.3 (1990).
32. Caldwell v. Stale,260 Ga. 278, 393 S.E. 2d. 436 (1990).
33. State v. Pennington,327 N.C. 89, 393 S.E. 2d 847 (1990).
34. Commonwealth v. Curnin,409 Mass. 218, 565 NE 2d 443 (1991).
35. Arkansas Act 723 (1989); Connecticut P.A. No. 89-360 (1989); Michigan Public Act 258 11989);
Montana Code Ann. Sect. 40-5-201 (1989); New Mexico Slat. Ann. Sect. 40-11-5 (1989).
36. Virginia Code Sect. 19.2-270.5; Louisiana Act 340 11989); Maryland Chap. 430 11989);
Minnesota Stat Sect. 634.23 (1989); Washington Chap. 350 (1989).
37. Cal. Penal Code 290.2; Colo. Code Ann. 17-2-201(g)(I); 111. Code Ann. 38 1005-4-3; S. Dak.
Code Ann. 23-544 et seq; Ariz. Code Ann. 3128. 1 Fla. Code Ann. 943.325; Iowa Code
Ann. 13.10; Minn. Code Ann. 609.3461; Nev. Code Ann. 176.111; Wash. Code Ann.
43.43.754; Virg. Code Ann. 19.2-310.2.
38. Report of the Joint Subcommittee Studying Creation of a DNA Test Data Exchange to the
Governor and the General Assembly of Virginia. Senate Document No. 29, Commonwealth
of Virginia, Richmond, 1990, p.I 1.
39. Lawrence R. Jones, el al. v.Edward W. Murray,Director of The Department of Corrections, et al.
W.D. Virginia, Civil No. 90-0572-R. Order for Summary Judgment, March 4, 1991.
40. See, in general, Ballantyne J, Sensabaugh G, Witkowski J., eds. DNA Technology arid Forensic
Science. Banbury Report 32. Cold Spring Harbor, New York: Cold Spring Harbor
Laboratory Press, 1989.

DNA TYPING AND SOCIETY 152
7
DNA Typing and Society
The introduction of any new technology is likely to raise concerns about its
impact on society. Financial costs, potential harm to the interests of individuals,
and threats to liberty or privacy are only a few of the worries typically voiced
when a new technology is on the horizon. DNA typing technology has the
potential for uncovering and revealing a great deal of information that most
people consider to be intensely private.
The federally established human genome program will yield an
unprecedented amount of genetic information and generate new databanks.1,2
Even apart from the human genome program, DNA technology is moving
forward; but this large-scale program, projected to take 10-15 years, is bound to
accelerate the acquisition of genetic information. At the same time, it contains a
mandate for examining the ethical, social, and legal implications of mapping the
human genome, with specific allocation of funds for examining these aspects.2 A
central concern raised by these developments is the safeguarding of the
confidentiality of personal genetic information. With greater understanding of the
human genome, the potential of misuse of DNA samples collected or preserved
for purposes of criminal justice will increase. The more databanks are
established, the greater the risk of breaches of confidentiality and misuse of the
information.3
The social, economic, and ethical concerns in this chapter overlap with the
legal aspects addressed in Chapter 6 and the issues in development and use of
databanks discussed in Chapter 5.

ECONOMIC ASPECTS
The forensic use of DNA technology will have various economic impacts.
The proliferation of DNA evidence in investigations and trials requires a fairly
rapid expansion in the number of reliable experts and laboratories. The cost of the
equipment, training and proficiency programs, supplies, and personnel will be
very large. For example, the three proposed regional laboratories in New York
state are estimated to cost $1.4 million per year.4 The Commonwealth of Virginia
has committed several million dollars over the last 3 years to its forensic DNA
activities (Paul Ferrara, personal communication, 1990). Material will have to be
stored for databanks and for checking suspects. Costs will be associated with the
upgrading and changing of databanks when new procedures are adopted. Those
costs will affect budgets for police, prosecutors, and courts. Indigent criminal
defendants might have a constitutional due-process right to have an expert
witness paid for by the government.
The courts themselves must be supplied with reliable assistance in
evaluating DNA material. In the federal system, the court can request an expert
or panel of experts to assist it, pursuant to Rule 706 of the Federal Rules of
Evidence. A special register of scientific experts can be maintained for ready
access. The government will generally have to bear this cost. However, if a
defendant can afford the cost and asks for expert assistance, the court can assess
some costs against the defendant and some against the state.
New costs will also be related to training and certification. The
implementation of any new technology requires training and certifying of
personnel. Additional costs will be incurred to develop mechanisms to ensure
quality control of laboratories that conduct forensic DNA testing.
New technology can grow and make ever larger fiscal demands on society.
It is difficult to predict the total cost of DNA testing when it becomes generally
available nationwide, but it is reasonable to expect it to amount to tens of millions
of dollars a year. That cost is unavoidable, but, given the present fiscal problems
at all levels of government, cannot be ignored. Setting up regional and
cooperative services is one way of controlling costs. It might not be feasible or
appropriate for some small forensic science laboratories to create their own DNA
testing capabilities. A major DNA testing center run by the FBI might reduce
costs to smaller localities. That potential reduction in monetary cost needs to be
balanced against the risks to privacy and confidentiality of having a powerful
federal law-enforcement agency in charge of DNA testing and storage of DNA
information. If laboratories come to share information, everything could
eventually become linked. At the same time, the risks that privacy and
confidentiality will be breached might be as great or greater with local

control, in that state laws governing the use of criminal records vary widely.
It is likely that the cost of criminal justice will be increased. In some cases,
however, early exclusion of suspects who have been cleared by forensic DNA
evidence will reduce cost in the judicial system. On balance, the increased costs
are small relative to the cost of operating the entire system. The committee
believes that the expenditures are warranted by the advantages to be expected.
ETHICAL ASPECTS
Ethical considerations regarding the use of DNA technology in forensic
science overlap with various issues addressed in social and legal analyses,5
including substantive and procedural rights of people and overall nonmonetary
costs and benefits likely to result from establishing the use of the new technology
in courtroom proceedings.
A threshold question for any ethical inquiry is whether the action or practice
under discussion is intrinsically wrong. An action or practice is intrinsically
wrong if it violates fundamental ethical principles. These have traditionally been
held to include prohibitions against enslavement, torture, gratuitous infliction of
harm on human beings, and modes of exploitation that use humans as merely a
means (usually without their knowledge or consent) to serve the ends of others.6
To hold that such actions or practices are intrinsically wrong is not to claim that
they can never be justified. For example, if torturing a terrorist who knows the
location of a bomb planted to kill a million people is the only way to avert the
tragedy, then torture might be justified. That would not yield the conclusion that
torture is ethically right, but rather would show that evil acts can sometimes—
albeit rarely—be justified as a means of preventing much greater harm.6
DNA technology in forensic science is unlikely to violate any fundamental
ethical principle of the type described above. Although DNA technology involves
new scientific techniques for identifying or excluding people, the techniques are
extensions and analogues of techniques long used in forensic science, such as
serological and fingerprint examinations, handwriting analyses, photography, and
examination of teeth. Ethical questions can be raised about other aspects of this
new technology, but it cannot be seen as violating a fundamental ethical
principle.
A new practice or technology can be subjected to further ethical analysis by
using two leading ethical perspectives. The first examines the action or practice in
terms of the rights of people who are affected; the second explores the potential
positive and negative consequences (nonmonetary costs and benefits) of the
action or practice, in an attempt to determine whether the potential good
consequences outweigh the bad.6

Moral Rights
Two main questions can be asked about rights: Does the use of DNA
technology give rise to any new rights not already recognized? Does the use of
DNA technology enhance, endanger, or diminish the rights of anyone who
becomes involved in legal proceedings? In answer to the first question, it is hard
to think of any new moral rights not already recognized that come into play with
the introduction of DNA technology into forensic science. The answer to the
second question requires a specification of the classes of people whose rights
might be affected and what those rights might be.
The people whose rights might be endangered or diminished seem to be
chiefly those who are suspected or accused of or indicted for a crime or involved
in other legal proceedings, such as paternity suits, denaturalization, or
immigration matters. Does use of DNA technology interfere with or diminish
their rights in any way? Might it enhance their rights? Which rights might be
endangered?
The current use of DNA technology appears to pose no greater threat to the
right to privacy than does normal fingerprinting, placement of photographs in
evidence, collection of blood or saliva samples, or other established forensic
techniques. DNA technology is not different in principle from those other
techniques, although it holds the promise of providing a more definitive
identification than most others (fingerprinting is likely to remain the best for a
while). If the use of DNA information can be strictly limited to defendant
identification, it involves no greater intrusion into the privacy of an accused
person than do traditional methods in forensic science, whose aim is to make as
definitive an identification as possible. Without strict limits, however, DNA
information can be more intrusive into privacy, in that it provides more
information about a person.
In some ways, the use of DNA information about suspects can be less
intrusive than traditional methods. ''Rounding up the usual suspects" by checking
a DNA sample against a computerized databank is both much easier and less
intrusive than rounding up the suspects themselves. But people who are rounded
up are made aware that they are under suspicion and can take protective steps.
Where databanks already exist, a fresh blood sample would have to be taken from
suspects for confirmation. Thus, it is a complex matter to determine whether the
rights of suspects are enhanced or endangered by the use of DNA evidence in the
forensic setting, which requires empirical evidence to be subjected to careful
analysis.
Concerns about intrusions into privacy and breaches of confidentiality
regarding the use of DNA technology in such enterprises as gene mapping are
frequently voiced, and they are legitimate ethical worries.1,6,7,8The concerns are
pertinent to the role of DNA technology in forensic science, as

well as to its widespread use for other purposes and in other social contexts. A
potential problem related to the confidentiality of any information obtained is the
safeguarding of the information and the prevention of its unauthorized release or
dissemination;5,7 that can also be classified under the heading of abuse and
misuse (discussed below), as well as seen as a violation of individual rights in the
forensic context.
People have a right not to be wrongly convicted of a crime. To protect that
right, a high standard of proof is imposed before a person may be found guilty. In
addition, techniques used in gathering and analyzing evidence must have proven
reliability (comprising accuracy, precision, specificity, and sensitivity) and should
be accepted by a consensus of the scientific community. If DNA technology is as
good as or better than other methods used to identify criminals and if the
implications and limitations of DNA evidence are recognized by judges and
jurors, its use should pose no greater danger to the rights of accused people than
the use of currently approved techniques of forensic identification. Moreover, the
reliability of DNA evidence will permit it to exonerate some people who would
have been wrongfully accused or convicted without it. Therefore, DNA
identification is not only a way of securing convictions; it is also a way of
excluding suspects who might otherwise be falsely charged with and convicted of
serious crimes.
Nonmonetary Costs and Benefits

The ethical perspective by which actions or practices are evaluated in terms
of their good and bad consequences is fundamentally sound. Nevertheless, it
suffers from both theoretical and practical difficulties.3Not only is it difficult to
predict good and bad results in advance of gathering sufficient evidence about
projected consequences, but it is also sometimes hard to weigh consequences,
even if they have already come about. For example, how is it possible to weigh
the good consequences of enabling positive identifications to be made with
greater certainty by using DNA technology against the bad consequences of
drawing mistaken conclusions in particular cases where laboratory techniques or
personnel are substandard? Even well-done tests can yield false positives. In
approximately 35% of cases performed by the FBI to date, the primary suspect
was excluded by DNA (tests on persons who had been prescreened). However,
that observation does not resolve the problem of weighing good consequences
against bad ones, although it does provide some information that could be used in
such weighing.
Another factor to be weighed in a consequentialist ethical analysis is whose
interests are to count and whether some people's interests should be given greater
weight than others'. For example, there are the interests of the

accused, the interests of victims of crime or their families in apprehending and

convicting perpetrators, and the interests of society. Whether the interests of
society in seeing that justice is done should count as much as the interests of the
accused or the victim is open to question. (Here there is an obvious overlap with
an ethical analysis from the perspective of rights, and assessment of the
consequences of instituting a new practice should include the effects of the new
practice on the rights of the people involved.)
Especially when a practice is new and information on projected
consequences is scanty, there are problems with relying on balancing the good
and bad consequences as a mode of ethical analysis.9 People who favor one
policy or practice predict a balance of good consequences over bad ones, and
detractors do the opposite.
One important factor contributing to uncertainty about the use of DNA
typing technology is the existence of disagreement among scientific experts.10
When experts disagree about the use of techniques or statistical methods (such as
extrapolations based on population genetics) or about the interpretation of data,
the uncertainty is of a different sort from uncertainty that stems simply from
scanty evidence drawn from actual consequences. The latter uncertainty can be
remedied by gathering more data before a technology is introduced as an accepted
standard. If controversy among experts persists, disagreements can erupt
whenever empirical evidence is analyzed and specific conclusions are to be
drawn.
An overall judgment that DNA technology in forensic science is superior to
existing forensic methods requires comparing intersubjectively verified scientific
evidence on the reliability and validity of the new method with evidence on the
other methods. Certainly, as a personal identification method, fingerprinting is the
definitive forensic technique and has many advantages. It has almost 100 years of
development, which has established empirically that a person has unique
fingerprints; fingerprints can even distinguish between identical twins.
Fingerprints are easily detected and developed, and large electronic fingerprint
databanks exist all over the world. A fingerprint is a directly observable
impression that does not generally involve extensive chemical or biochemical
manipulation. Rarely do fingerprint experts differ in conclusions reached after
examination of fingerprint evidence. The limitations of the technique are derived
from the fact that usable fingerprint evidence is left at crime scenes relatively
rarely and can indicate only the presence of a person at a scene.
Another method of identification commonly used in forensic laboratories is
forensic serology, i.e., analysis of physiological fluids for genetic markers, such
as ABO antigens, enzymes, and serum proteins. The major drawback of these
analyses is the degree of specificity provided. The usual battery of serological
tests might still allow characterization of a person only as a member of a larger
population sharing the same markers. Depending on the panel of tests, the
likelihood that a randomly selected person

will show the same markers as a person in question can range from 1 in 2 (such
as in type O) to 1 in several thousand (such as when many systems are typed and a
relatively rare type is found). The literature and case law on paternity disputes
suggest that a likelihood of 1 in 20 is reasonably corroborative and that a
likelihood of only 1 in 100 can strongly influence the triers of fact.
Thus, although conventional serology can exclude a person, it can also
include many members of a population group as the possible origin of a blood,
saliva, or seminal fluid stain. Conventional serology is further limited, in that
analysis of mixed-fluid stains in which two or more contributors are involved can
mask an individual donor. Similarly, only 75-80% of the population are secretors
(exhibit their ABO blood type in their other physiological fluids). Thus, the
combination of those factors severely limits the power of conventional forensic
serological examinations as an individual identifier. Results of serological
analysis also are more subjective and can give rise to differing conclusions when
interpreted by equally qualified scientists.
Hair evidence is often encountered in sexual assault and other violent
crimes. It is valuable as exculpatory evidence and can be informative as to
identity, but it lacks specificity. Although hair examiners can associate a hair with
racial characteristics and body source (trunk, head, or pubic area) the variations
among hairs on a given person make definitive association of a single hair with an
individual problematic. The microscopic comparison of hairs is also subjective
and can lead to differences of opinion among equally qualified experts. With the
advent of DNA technology, especially PCR amplification techniques, the use of
hair as an individual identifier will become more common.
Some other forms of individual identification are available to forensic
scientists, but have very limited application. For example, examination of teeth is
useful in identifying deceased persons or bite marks.
Providing scientific evidence that DNA technology is at least as reliable as
other forensic methods and is therefore more likely to result in definitive
identification or exclusion of persons suspected or accused of a crime satisfies
both the ethical concerns about individual rights and the conditions of an ethical
analysis based on weighing good and bad consequences. However, additional
assurances are required for the risk-benefit ratio to be favorable in each case in
which the technology is used. Therefore, a critical step in accepting the use of
DNA technology in criminal trials is establishing safeguards and seeking to
prevent abuses.
ABUSE AND MISUSE OF DNA INFORMATION

Even if a technology is scientifically sound and its use is ethically
permissible, it is necessary to seek to prevent abuses and misuses in prac

tice. Examples of abuses of DNA technology are unauthorized access to

databanks and unauthorized disclosure of information. An example of misuse is
the use of DNA information for purposes other than forensic—in other words,
going beyond the intended purpose of collecting and storing the information.
A major issue is the preservation of confidentiality of information obtained
with DNA technology in the forensic context.5,7 When databanks are established
in such a way that state and federal law-enforcement authorities can gain access
to DNA profiles, not only of persons convicted of violent crimes but of others as
well, there is a serious potential for abuse of confidential information.11 The
victims of many crimes in urban areas are relatives or neighbors of the
perpetrators, and these victims might themselves be former or future perpetrators.
There is greater likelihood that DNA information on minority-group members,
such as blacks and Hispanics, will be stored or accessed. However, it is important
to note that use of the ceiling principle (Chapter 3) removes the necessity to
categorize criminals (or defendants in general) by race for the purposes of DNA
testing and storage of information in databanks.
Maintaining DNA samples or information about ex-offenders and parolees
might be permissible, but requires justification. Even in a felon databank,
protections must be instituted. For example, a person's permission should be
obtained for the use of his or her DNA information outside the forensic context.
If there are no witnesses to a crime, law-enforcement agencies are likely to go
directly to the felon databank in their quest for probable suspects. The tendency to
use efficient and cost-effective means to solve crimes could result in reducing
safeguards, thereby eroding rights of ex-offenders and parolees.
Storage of DNA records of people who have not been convicted of a crime
raises ethical questions about the proper "ownership" of such information.11 DNA
information is personal and so should be treated as private, like information in a
person's medical record.8 Outside the forensic context, DNA information should
be stored in databanks and released only with the knowledge and explicit
permission of the person who is the subject of the information. As for storage of
forensic DNA information in databanks, some disagreements remain about
propriety and about the prospects for abuse (Chapter 5).
Even when the use of criminal databanks is limited to the local or regional
level, the potential for expansion raises questions of misuse. For example, should a
whole local population be subject to DNA typing when it is strongly suspected
that someone in the population left blood or other fluids at the scene of the crime?
Should this be seen as similar to a "frisk" or a simple search that requires a
warrant or as an intrusion into someone's body that requires a strong showing of
need? The potential for expanded

uses of DNA technology that would constitute serious intrusions into the privacy
of ordinary citizens requires the setting of guidelines that separate proper use from
misuse of the technology.
The release of DNA information on a criminal population for purposes other
than law enforcement also constitutes misuse. Employers and insurance
companies will certainly have an interest in DNA information on potential
employees or customers.1,8,9 Biomedical and behavioral scientists are likely to
want to screen felon databanks and develop new databanks to study various
characteristics of convicted offenders. Legal sanctions should be established to
deter the unauthorized dissemination or procurement of DNA information that
has been obtained for forensic purposes.
EXPECTATIONS
The introduction of a powerful new technology is likely to set up
unwarranted or unrealistic expectations. Various expectations regarding DNA
typing technology are likely to be raised in the minds of jurors and others in the
forensic setting10 (see Chapter 6).
For example, public perception of the accuracy and efficacy of DNA typing
might well put pressure on prosecutors to obtain DNA evidence whenever
appropriate samples are available. As the use of the technology becomes widely
publicized, juries will come to expect it, just as they now expect fingerprint
evidence, surveillance photographs, and audio and visual eavesdropping.
Moreover, prosecutors will not want to give defense attorneys the opportunity to
ask on summation, "If my client was the perpetrator, where is the DNA
evidence?"
Once a prosecutor produces DNA evidence, the defense will be under great
pressure to undermine it through the use of reports and experts, because of an
assumption that the jury would interpret a failure to call a defense expert as an
admission that the DNA evidence is persuasive. Mere cross examination by a
defense attorney inexperienced in the science of DNA testing will not be
sufficient.
Two aspects of DNA typing technology contribute to the likelihood of its
raising inappropriate expectations in the minds of jurors. The first is the jury's
perception of an extraordinarily high probability of enabling a definitive
identification of a criminal suspect; the second is the scientific complexity of the
technology, which results in laypersons' inadequate understanding of its
capabilities and failings. Taken together, those two aspects can lead to the jury's
ignoring other evidence that it should be considering.
Expectations regarding the power of DNA typing can lead to overlooking or
ignoring sources of error or mistakes in applying the technology. For example,
jurors' focusing on the probability of correctly identifying a per

petrator might lead them to discount the possibility of laboratory error, whether it
stems from incompetence or carelessness of personnel, malfunctioning
equipment, or unavoidable mistakes.
The efficacy and accuracy of a new technology typically are initially
demonstrated by the most highly competent and knowledgeable practitioners. As
DNA typing becomes routine, the quality of laboratories and personnel using it
might decrease while still meeting the standards required for accreditation or
licensing. However, the expectations of judges and juries might remain high,
because of the superior knowledge and competence of the initiators of the
technology. Later gains in experience and improved typing could lead to an
increase in quality.
As large felon databanks are created, the forensic community could well
place more reliance on DNA evidence, and a possible consequence is the
underplaying of other forensic evidence. Unwarranted expectations about the
power of DNA technology might result in the exclusion of relevant evidence.
Both prosecutors and defense counsel are entitled to benefit from the power
of DNA evidence, but they should not oversell it. DNA evidence is not infallible;
all laboratory work is subject to error; and, given current population databanks
and laboratory protocols, a witness or prosecutor will seldom (if ever) be justified
in stating that the probability that a reported DNA match involves someone other
than the suspect is so low as to make that possibility entirely implausible. Claims
that treat DNA identifications as though they are as reliable as fingerprint
identifications in the typical rape or murder case are unjustified; until technology
and databanks improve, they are likely to remain so.
Presentations suggesting to a judge or jury that DNA typing is infallible can
rarely be justified and should generally be avoided. However, there might be
instances where a prosecutor could legitimately argue that the DNA evidence
conclusively proves that the defendant committed the offense. Two examples are
illustrative:
• The victim is confined to an institution where access is limited to

relatively few male attendants. Semen taken from the vagina is subjected
to analysis and compared to blood samples from all possible males with
access to the victim. The defendant's known sample is the only profile
that matches the evidentiary sample. In this circumstance, the prosecutor
could well argue that only the defendant could have committed the
crime.
• In a prosecution for sexual assault of a child, again a limited number of
people might have access to the child, with only one possible donor
matching the evidentiary sample. Again, the prosecutor might argue that
the DNA evidence is conclusive.

ACCOUNTABILITY AND PUBLIC SCRUTINY

Because the application of DNA typing in forensic science is to be used in
the service of justice, it is especially important for society to establish
mechanisms for accountability and to ensure appropriate public scrutiny.
Accountability must be an issue in proficiency testing and accreditation.
There is reason to be skeptical of entrusting any important regulatory matters to a
self-regulating organization. Accordingly, any organization conducting
accreditation or regulation of DNA technology for forensic purposes should be
free of influence of private companies, public laboratories, or other organizations
actually engaged in laboratory work.
Private laboratories used for testing should not be permitted to withhold
information from defendants on the grounds that "trade secrets" are involved.
Alternatively, law-enforcement agencies could use only public laboratories for
testing, so that the issue of "trade secrets" would not arise.10 Critics of DNA
testing have suggested that the profit motive of private testing companies
undermines their reliability. Although that criticism might be justified when
companies are eager to market a product before it is ready, no general indictment
of private companies on this basis is justified.
Testing methods and data need to be made available for public scrutiny.
There has been a notable dearth of published research in forensic DNA testing by
scientists unconnected to the companies that market the tests. In contrast with the
research approach whereby new drugs and biomedical devices undergo controlled
trials of safety and efficacy, forensic science has used more informal modes of
evaluating new techniques. The process of peer review used to assess advances in
biomedical science and technology should be used for forensic DNA technology.
Whether in publications or in court, companies might be reluctant to reveal
their specific testing methods or the population data used to determine the
probability of a match, because they consider this information to constitute a
trade secret that could be exploited by competitors. However, the integrity of the
scientific method and judicial due process demand that such information be
revealed, particularly in criminal cases. The scientific community should require
that the same standards used to assess new findings in other sectors of science be
applied to DNA typing in the forensic setting.
INTERNATIONAL EXCHANGE
The need for international cooperation in law enforcement calls for
appropriate scientific and technical exchange among nations. As in other areas of
science and technology, dissemination of information about DNA

typing and training programs for personnel likely to use the technology should be
encouraged. It is desirable that all nations that will collaborate in law-
enforcement activities have similar standards and practices, so efforts should be
furthered to exchange scientific knowledge and expertise regarding DNA
technology in forensic science.
• In the forensic context as in the medical setting, DNA information is

personal, and a person's privacy and need for confidentiality should be
respected. The release of DNA information on a criminal population
without the subjects' permission for purposes other than law
enforcement should be considered a misuse of the information, and legal
sanctions should be established to deter the unauthorized dissemination
or procurement of DNA information that was obtained for forensic
purposes.
• Prosecutors and defense counsel should not oversell DNA evidence.
Presentations that suggest to a judge or jury that DNA typing is infallible
are rarely justified and should be avoided.
• Mechanisms should be established to ensure the accountability of
laboratories and personnel involved in DNA typing and to make
appropriate public scrutiny possible.
• Organizations that conduct accreditation or regulation of DNA
technology for forensic purposes should not be subject to the influence
of private companies, public laboratories, or other organizations actually
engaged in laboratory work.
• Private laboratories used for testing should not be permitted to withhold
information from defendants on the grounds that trade secrets are
involved.
• The same standards and peer-review processes used to evaluate advances
in biomedical science and technology should be used to evaluate
forensic DNA methods and techniques.
• Efforts at international cooperation should be furthered to ensure uniform
international standards and the fullest possible exchange of scientific
knowledge and technical expertise.
REFERENCES
1. U.S. Congress, Office of Technology Assessment. Mapping our genes—the genome projects: how
big, how fast? Washington, D.C.: U.S. Government Printing Office, 1988.
2. U.S. Department or Health and Human Services and U.S. Department of Energy. Understanding
our genetic inheritance: the U.S. Human Genome Project, the first five years FY 1991-1995.
Springfield, Virginia: National Technical Information Service, 1990.
3. President's Commission for the Study of Ethical Problems in Medicine and Biomedical

and Behavioral Research. Screening and counseling for genetic conditions. Washington,
4. DNA Report of New York State Forensic Analysis Panel. Albany, New York, 1989.
5. U.S. Congress, Office of Technology Assessment. Genetic witness: forensic uses of DNA tests.
Chapters 3-5. OTA-BA-438. Washington, D.C.: U.S. Government Printing Office, 1990.
6. Beauchamp TL, Childress JF. Principles of biomedical ethics. Chapter 2. 3rd ed.New York: Oxford
University Press, 1989.
7. de Gorgey A. The advent of DNA databanks: implications for information privacy. Am J Law
Med. 16:381-398, 1990.
8. Macklin R. Mapping the human genome: problems of privacy and free choice. Pp. 107-114in:
Milunsky A, Annas G J, eds. Genetics and the law. Ill. New York: Plenum Press, 1984.
9. President's Commission for the Study of Ethical Problems in Medicine and Biomedical and
Behavioral Research. Splicing life. Washington, D.C.: U.S. Government Printing Office,
1982.
10. Annas GJ. DNA fingerprinting in the twilight zone. Hastings Center Rep. 20:35-37, March/April
1990.
11. National Association of Attorneys General. Resolution, adopted at winter meeting. December
10-13, 1989, Phoenix, Arizona.

Organizational Abbreviations
AFIS Automated Fingerprint Identification Systems

ASCLD American Society of Crime Laboratory Directors
ASCLD-LAB American Society of Crime Laboratory Directors—Laboratory
Accreditation Board
ASHG American Society of Human Genetics
CACLD California Association of Crime Laboratory Directors
CAP College of American Pathologists
DHHS U.S. Department of Health and Human Services
DOJ U.S. Department of Justice
FBI Federal Bureau of Investigation
NCIC National Crime Information Center
NIH National Institutes of Health
NIJ National Institute of Justice
NIST National Institute of Standards and Technology
TWGDAM Technical Working Group on DNA Analysis Methods


GLOSSARY 167
Glossary
A single-letter designation of the purine base adenine; also used in diagrams to

represent a nucleotide containing adenine
Adenine a purine base; one of the four nitrogen-containing molecules present in
nucleic acids DNA and RNA; designated by the letter A
Allele one of two or more alternative forms of a gene
Allele fre- the proportion of a particular allele among the chromosomes carried by
quency individuals in a population
AMP-FLP amplified fragment length polymorphism
Autoradio- a photographic recording of the positions on a film where radioactive decay
gram(au- of isotopes has occurred
toradio-
graph;
autorad)
AutosomeY any of the chromosomes other than the sex chromosomes, X and
Band the visual image representing a particular DNA fragment on an autoradiogram
Band shift the phenomenon in which DNA fragments in one lane of a gel migrate at a
rate different from that of identical fragments in other lanes of the same gel
Basepair two complementary nucleotides held together by hydrogen bonds;
basepairing occurs between A and T and between G and C
Biallelic (see Diallelic)
Blot see Southern blot

GLOSSARY 168
C single-letter designation of the pyrimidine base cytosine; also used in

diagrams to represent a nucleotide containing cytosine
Chromosome the structure by which hereditary information is physically transmitted from
one generation to the next; the organelle that carries the genes
Controls tests performed in parallel with experimental samples and designed to
demonstrate that a procedure worked correctly
Cytosine a pyrimidine base; one of the four nitrogen-containing molecules in nucleic
acids DNA and RNA; designated by the letter C
Degradation the breaking down of DNA by chemical or physical means
Denatura- the process of unfolding of the complementary double strands of DNA to
tion form single strands
Deoxyri- the genetic material of organisms, usually double-stranded—composed of
bonucleic two complementary chains of nucleotides in the form of a double helix; a
acid (DNA) class of nucleic acids characterized by the presence of the sugar deoxyribose
and the four bases adenine, cytosine, guanine, and thymine
Diallelic variation showing only two forms with a frequency of more than 1%
DNA
Diploid having two sets of chromosomes, in pairs (compare haploid)
DNA deoxyribonucleic acid
DNA band the visual image representing a particular DNA fragment on an autoradiogram
DNA data- a collection of DNA typing profiles of selected or randomly chosen
bank individuals
(database)
DNA poly- an enzyme that catalyzes the synthesis of double-stranded DNA
merase
DNA probe a short segment of single-stranded DNA labeled with a radioactive or
chemical tag that is used to detect the presence of a particular DNA sequence
through hybridization to its complementary sequence
Elec- a technique in which different molecules are separated by their rate of
trophoresis movement in an electric field
Enzyme a protein that is capable of speeding up a specific chemical reaction but
which itself is not changed or consumed in the process; a biological catalyst
Ethidium an organic molecule that binds to DNA and fluoresces under ultraviolet light
bromide and is used to identify DNA
G single-letter designation of the purine base guanine; also used in diagrams to
represent a nucleotide containing guanine
Gamete a haploid reproductive cell

GLOSSARY 169
Gametic the state at loci on different chromosomes when the allele at one locus in the
(phase) gamete varies independently of that at the other loci; in gametic (phase)
equilibrium disequilibrium, a specific allele at one locus is associated with an allele at
another locus on a different chromosome with a frequency greater than
expected by chance (see linkage disequilibrium)
Gel semisolid matrix (usually agarose or acrylamide) used in electrophoresis to
separate molecules
Gene the basic unit of heredity; a sequence of DNA nucleotides on a chromosome
Gene fre- the relative occurrence of a particular allele in a population
quency
Genetic drift random fluctuation in allele frequencies
Genome the total genetic makeup of an organism
Genotype the genetic makeup of an organism, as distinguished from its physical
appearance or phenotype
Guanine a purine base; one of the four nitrogen-containing molecules present in
nucleic acids DNA and RNA; designated by the letter G
Haploid having one set of chromosomes (compare diploid)
Hardy- equilibrium the condition, for a particular genetic locus and a particular
Weinberg population, with the following properties: allele frequencies at the locus are
constant in the population over time and there is no statistical correlation
between the two alleles possessed by individuals in the population; such a
condition is approached in large randomly mating populations in the absence
of selection, migration, and mutation
Heredity the transmission of characteristics from parent to offspring
Heterozygotea diploid organism that carries different alleles at one or more genetic loci on
its homologous chromosomes
Heterozy- having different alleles at a particular locus; for most forensic DNA probes,
gous the autoradiogram displays two bands if the person is heterozygous at the
locus
HLA see human leukocyte antigen
Homology similarity between two structures or functions indicative of a common
evolutionary origin
Homozygote a diploid organism that carries identical alleles at one or more genetic loci on
its homologous chromosomes
Homozygous having the same allele at a particular locus; for most forensic DNA probes,
the autoradiogram displays a single band if the person is homozygous at the
locus
Human protein-sugar structures on the surface of most cells, except blood cells, that
leukocyte differ among individuals and are
antigen
(HLA)

GLOSSARY 170
important for acceptance or rejection of tissue grafts or organ transplants; the

locus of one particular class, HLA DQ, is used for forensic analysis with PCR
Hybridiza- the reassociation of complementary strands of nucleic acids, nucleotides, or
tion probes
Isotope an alternative form of a chemical element; used particularly in reference to
the radioactive alternative forms, or radioisotopes
Linkage disequilibrium the phenomenon in which a specific allele at one locus is
non-randomly associated with an allele at another locus
Locus (pl. the specific physical location of a gene on a chromosome
loci)
Marker a gene with a known location on a chromosome and a clear-cut phenotype
that is used as a point of reference in the mapping of other loci
Membrane the matrix (usually nylon) to which DNA is transferred during the Southern
blotting procedure
Molecular- DNA fragments of known size, from which the size of an unknown DNA
weight size sample can be determined
marker
Monomor- a probe that detects the same allele and hence the same pattern in everyone
phic probe
Multilocus a DNA probe that detects genetic variation at multiple sites; an autoradiogram
probe of a multilocus probe yields a complex, stripelike pattern of 30 or more
bands per individual
Mutagen a physical agent (e.g., x rays) or chemical agent that induces changes in DNA
Nucleic acid a nucleotide polymer of which major types are DNA and RNA
Nucleotide a unit of nucleic acid composed of phosphate, a five-carbon sugar (ribose or
deoxyribose), and a purine or a pyrimidine base
PCR polymerase chain reaction
Phenotype the physical appearance or functional expression of a trait
Point muta- an alteration of one nucleotide in chromosomal DNA that consists of
tion addition, deletion, or substitution of nucleotides
Polymerase an in vitro process that yields millions of copies of desired DNA through
chain reac- repeated cycling of a reaction that involves the enzyme DNA polymerase
tion (PCR)
Polymor- the presence of more than one allele of a gene in a population at a frequency
phism greater than that of a newly arising mutation; opera

GLOSSARY 171
tionally, a population in which the most common allele at a locus has a

frequency of less than 99%
Population a group of individuals occupying a given area at a given time
Probe a short segment of single-stranded DNA tagged with a reporter molecule,
such as radioactive phosphorus atom, that is used to detect a particular
complementary DNA sequence
Proficiency tests to evaluate the competence of technicians and the quality performance
tests of a laboratory; in open tests, the technicians are aware that they are being
tested, but in blind tests, they are not aware; internal proficiency tests are
conducted by the laboratory itself, and external tests are conducted by an
agency independent of the laboratory being tested
Protein a chain of amino acids joined by peptide bonds
Purine the larger of two kinds of bases found in DNA and RNA; a nitrogenous base
with a double-ring structure, such as adenine or guanine (compare
pyrimidine)
Pyrimidine the smaller of two kinds of bases found in DNA and RNA; a nitrogenous
base with a single-ring structure, such as cytosine, thymine, and uracil
(compare purine)
Quality as- a program conducted by a laboratory to ensure accuracy and reliability of
surance tests performed
Quality con- internal activities or activities according to externally established standards
trol used to monitor the quality of DNA typing to meet and satisfy specified
criteria
Recombinant fragments of DNA from two different species, such as a bacterium and a
DNA mammal, spliced into a single molecule
Replication the synthesis of new DNA from existing DNA
Restriction an enzyme that cleaves DNA molecules at particular base sequences
endonucle-
ase, restric-
tion enzyme
Restriction variation in the length of DNA fragments produced by a restriction
fragment endonuclease that cuts at a polymorphic locus
length poly-
morphism
(RFLP)
RFLP restriction fragment length polymorphism
RFLP technique that uses single-locus or multi-locus probes to detect variation in a
analysis DNA sequence according to differences in the length of fragments created by
cutting DNA with a restriction enzyme
Ribonucleic a class of nucleic acids characterized by the presence of the sugar ribose and
acid (RNA) the pyrimidine uracil, as opposed to the thymine of DNA
RNA ribonucleic acid

GLOSSARY 172
Serology the discipline concerned with the immunologic study of body fluids
Serum the liquid that separates from blood after coagulation
Sex chromo- chromosomes that are different in the two sexes and that are involved in sex
somes (x and determination
y chromo-
somes)
Sex-linked a genetic characteristic, such as color blindness, that is determined by a gene
characteris- on a sex chromosome and shows a different pattern of inheritance in males
tic and females; X-linked is a more specific term
Single-locus a DNA probe that detects genetic variation at only one site in the genome; an
probe autoradiogram that uses one single-locus probe usually displays one band in
homozygotes and two bands in heterozygotes
Somatic cells the differentiated cells that make up the body tissues of multicellular plants
and animals
Southern blot the nylon membrane to which DNA adheres after the process of Southern
blotting
Southern the technique for transferring DNA fragments that have been separated by
blotting electrophoresis from the gel to a nylon membrane
Standards criteria established for quality control and quality assurance; established or
known test reagents, such as molecular-weight standards
T single-letter designation of the pyrimidine base thymine; also used in
diagrams to represent a nucleotide containing thymine
Tandem multiple copies of an identical DNA sequence arranged in direct succession
repeats in a particular region of a chromosome
Taq poly- a DNA polymerase used to form double-stranded DNA from nucleotides and
merase a single-stranded DNA template in the PCR technique
Thymine a pyrimidine base; one of the four nitrogen-containing molecules present in
nucleic acids DNA and RNA; designated by the letter T
Uracil a pyrimidine in RNA
Variable repeating units of a DNA sequence for which the number varies between
number of individuals
tandem re-
peats (VN-
TR)
VNTR variable number of tandem repeats
Zygote diploid cell that results from the fusion of male and female gametes

Biographical Information on Committee

Members
VICTOR A. McKUSICK (Chairman) is University Professor of medical

genetics at Johns Hopkins. He received his M.D. from the Johns Hopkins
University School of Medicine. Dr. McKusick is the founding coeditor of the
international journal GENOMICS and served as founding president of the Human
Genome Organization (HUGO). Dr. McKusick is a member of the National
Academy of Sciences and served as a member of the Academy's Committee on
Mapping and Sequencing the Human Genome. He also belongs to the American
Society for Clinical Investigation, Association of American Physicians, American
Society of Human Genetics, American Philosophical Society, American
Academy of Arts and Sciences, Royal College of Physicians (London), and
Académie Nationale de Médecine (France).
C. THOMAS CASKEY is professor of medicine, biochemistry, and cell
biology, at Baylor College of Medicine and Henry and Emma Meyer Professor in
molecular genetics, director of the Institute for Molecular Genetics, and
investigator of the Howard Hughes Medical Institute. He received his M.D. from
Duke University. His research focuses on inherited disease and mammalian
genetics. Dr. Caskey's professional affiliations include membership in the
Institute of Medicine, National Academy of Sciences, American Society of
Human Genetics, Human Genome Organization, and Association of American
Physicians. He served as chairman of the Advisory Panel on Forensic Uses of
DNA Tests, U.S. Congress Office of Technology Assessment. Dr. Caskey
resigned from the committee on December 21, 1991.

PAUL B. FERRARA is director of the Virginia Division of Forensic

Science. He holds Ph.D. degrees in organic chemistry from Syracuse University
and from the State University of New York. After working as a research chemist
for du Pont, Dr. Ferrara entered the field of forensic science in the Northern
Virginia Police Laboratory, which became the Northern Virginia Regional
Facility of the statewide Forensic Laboratory System. He is a charter member and
past president of the Mid-Atlantic Association of Forensic Scientists, a member
of the Executive Board of the American Society of Crime Laboratory Directors
(ASCLD), and chairman of the DNA Implementation Committee of ASCLD.
MICHAEL W. HUNKAPILLER is vice president for science and
technology and general manager of Applied Biosystems Inc. He holds a Ph.D. in
chemical engineering from the California Institute of Technology. His research
focuses on the automation of procedures used in the structural analysis and
synthesis of proteins and DNA. Dr. Hunkapiller is the author of more than 100
publications and the inventor on more than 20 patents. His current professional
activities include service on the editorial boards of Technique, Genomics, and
Analytical Biochemistry, and he is a member of the American Association for the
Advancement of Science, American Chemical Society, and Human Genome
Organization. Dr. Hunkapiller resigned from the committee on August 17, 1990.
HAIG H. KAZAZIAN, JR. serves as director of the Center of Medical
Genetics at Johns Hopkins University School of Medicine. He is the Frank
Sutland Professor of pediatric genetics and professor of medicine and gynecology
and obstetrics at the medical school and professor of biology at the university.
His research has concentrated on mutation analysis in genetic diseases and he has
had a long interest in DNA diagnosis of genetic disease. Dr. Kazazian has served
on numerous NIH committees and editorial boards. He is a member of the
American Pediatric Society, American Society of Clinical Investigation,
Association of American Physicians, and the American Society of Human
Genetics.
MARY-CLAIRE KING is professor of epidemiology in the School of Public
Health of the University of California, Berkeley and of genetics in the
Department of Molecular and Cell Biology. She holds a Ph.D. in genetics from
the University of California, Berkeley. Dr. King's expertise is in human genetics,
genetic epidemiology, and population genetics. Her professional affiliations
include membership in many NIH committees and the American Association for
the Advancement of Science, American Epidemiological Society, Society for
Epidemiological Research, and American Society of Human Genetics.

ERIC S. LANDER is a member of the Whitehead Institute for Biomedical

Research, associate professor of biology at the Massachusetts Institute of
Technology, and director of the MIT Center for Genome Research. He received
his A.B. in mathematics from Princeton University and his Ph.D. in mathematics
from Oxford University. Dr. Lander's expertise is in human and mouse genetics,
molecular biology, population genetics, mathematics, and statistics. He has been a
MacArthur Fellow for research in human genetics and a Rhodes Scholar. He has
been a member of numerous NIH committees and has chaired the Genome
Research Review Committee for the National Center for Human Genome
Research. He also served on the Advisory Panel on Forensic Uses of DNA Tests
for the U.S. Congress Office of technology Assessment. Other professional
activities include service on the editorial boards of GENOMICS, Mammalian
Genome,Theoretical Population Biology, BioTechniques, and PCR Methods
andApplications.
HENRY C. LEE serves as director of the Forensic Science Laboratory of the
Connecticut State Police and professor of forensic science at the University of
New Haven. He received an M.S. and a Ph.D. in biochemistry from New York
University. Dr. Lee has been editor of the Hua-Lian Daily News and captain at
the Taipei Police Headquarters in Taiwan. He has conducted special training
activities in the various components of forensic science. His professional
memberships include those in the American Academy of Forensic Science,
American Society of Crime Laboratory Directors, International Association of
Forensic Science, Forensic Science Society (England), New York Academy of
Science, and International Homicide Detective Association.
RICHARD O. LEMPERT is Francis A. Allen Collegiate Professor of Law
and professor of sociology at the University of Michigan. Dr. Lempert has served
on National Science Foundation panels on law and social science and on the
global effects of environmental change. He has also served as a member, vice
chair, and chair of the National Research Council's Committee on Law and
Justice. He is a member of the American Sociological Association and the Law
and Society Association and has served the latter as editor of Law and Society
Review. He is now a trustee of the Law and Society Association and a member of
the editorial boards of Violence and Victims and The Law and SocietyReview.
RUTH MACKLIN serves as professor of bioethics in the Department of
Epidemiology and Social Medicine at the Albert Einstein College of Medicine.
She received her M.A. and Ph.D. in philosophy from Case Western Reserve
University. Dr. Macklin has published on medical ethics, and her

list of honors and awards includes an American Council of Learned Societies

fellowship and elected membership in the Institute of Medicine.
THOMAS G. MARR serves as senior staff investigator at the Cold Spring
Harbor Laboratory. He received his M.S. and Ph.D. in biology from Michigan
State University. The subjects of Dr. Marr's research studies include molecular
genetics analysis and databases. He is a member of the Human Genome Joint
Informatics Task Force, NIH/DOE, as well as the Technical Advisory Group-
Genome Database, Howard Hughes Medical Institute/The Johns Hopkins
University. Dr. Marr sits on the editorial board of Mammalian Genome, and his
other professional affiliations include membership in the American Statistical
Association, Association for Computing Machinery, and Institute of Electrical
and Electronic Engineers.
PHILIP R. REILLY is executive director of the Shriver Center for Mental
Retardation. He received his J.D. from Columbia University and his M.D. from
Yale University. Dr. Reilly has written numerous articles and several books,
including Genetics, Law, and Social Policy. He lectures on ethical issues in
genetic testing, paternity litigation, and DNA forensic science. Dr. Reilly also
served as a member of the National Research Council Committee on Public
Information in the Prevention of Occupational Cancer.
GEORGE F. SENSABAUGH, JR., is professor of forensic science and
biomedical sciences at the University of California, Berkeley. He received his
B.A. in philosophy from Princeton University and a doctorate in criminalistics
from the University of California, Berkeley. Dr. Sensabaugh serves on the
editorial boards of the Journal of Forensic Science, AmericanJournal of Forensic
Medicine and Pathology, Forensic Science Reviews, and Journal of Forensic
Science Society (Great Britain). He is a member of the American Association for
the Advancement of Science, American Academy of Forensic Science,
International Society for Forensic Hemogenetics, American Society of Human
Genetics, New York Academy of Science, and American Chemical Society.
JACK B. WEINSTEIN is U.S. district judge for the Eastern District of New
York. He has published treatises, books, and articles, primarily on evidence and
procedures. He is adjunct professor at the Columbia and Brooklyn law schools.
He served on the National Research Council Committee on Statistics and Law.

PARTICIPANTS 177
Participants
NORMAN ARNHEIM, University of Southern California

MICHAEL BAIRD, Lifecodes Corporation
BRUCE BUDOWLE, Federal Bureau of Investigation
ROBERT M. COOK-DEEGAN, Georgetown University
ROBIN COTTON, Cellmark Diagnostics
HENRY ERLICH, Cetus Corporation
SIMON FORD
DANIEL L. HARTL, Washington University School of Medicine
ROGER KAHN, Miami Metro Dade Police Department
Y. W. KAN, University of California, San Francisco
KENNETH KIDD, Yale University
ALAN LEVY, Fort Worth Tarrant County District Attorney's Office
GARY MARX, Massachusetts Institute of Technology
LAURENCE D. MUELLER, University of California, Irvine
THOMAS H. MURRAY, Case Western Reserve University
PETER J. NEUFELD
DENNIS REEDER, National Institute of Standards and Technology
BARRY SCHECK, Benjamin N. Cardozo School of Law
CHARLES TAYLOR, University of California, Los Angeles
BRUCE WEIR, North Carolina State University

PARTICIPANTS 178

INDEX 179
Index
A Band shifting, 54, 60-61, 140-141

Bayesian theory, 85
Abduction, 118, 121
Behavioral traits, 48, 114
Abuse of information, 19, 20, 24, 25, Bias in laboratory analysis, 53
114-116, 158-160 Blind testing,
Access to databanks, 18-19, 93-94, 123 see Proficiency testing
Accreditation of laboratories, 16, 17, Blood, 28, 89, 112, 120, 126, 142, 158
100-103, 105-108, 145, 162
Adenine, 2, 33
Admissibility of DNA evidence, 20-23,
52, 131-146
Allele frequency, 10-13, 14, 48, 62,
74-75, 77-79, 81-86, 91, 92-93, 122,
123
Alleles, 4, 32, 36
Allele-specific oligonucleotide probes, 42
American Association of Blood Banks, 102
American Society for Histocompatibility
and Immunogenetics, 102
American Society of Crime Laboratory
Directors, 17, 72, 100, 102-103,
105-106, 107
American Society of Human Genetics, 72,
101-102
American Type Culture Collection, 91
Amplification methods, 40-43, 63-65, 69
Andrews v. State, 138-139
Anomalous bands, 58-59
Appellate opinions, 139-141
Argentina disappearance cases, 86
Armed Forces Institute of Pathology, 126
Artifacts, 8, 54-55, 144
ASO (allele-specific oligonucleotide)
probes, 42
Assault, 112, 118-120, 143
Automated fingerprint identification sys-
tems, 17-18, 111, 113, 117 , 157
Automation,
see Computer technology
Autoradiography, 38-39, 53
Autosomes, 33

INDEX 180
databank samples, 113, 117, 118, Coriell Institute of Medical Research, 91

125-126, 143 Cost-benefit analysis,
Blood banks, 84 see Economics
Blood groups, 10, 27, 32, 43, 44, 88 Credit-rating services, 18, 114
Blot dotting, Criminal profile, 17-20, 86-87, 111-129,
see Reverse dot hybridization 142-143, 155, 159, 160
Bone, 121, 125, 126 Criminal records, 18, 114
Boolean searches, 18, 114 Custody cases, 20, 132
Buccal swabs, 118 Cytosine, 2, 33
Bureau of Justice Assistance, 103
D
C
Databanks, 15, 104
Caldwell v. State, 140-141 access to, 18-19, 93-94, 123
California Association of Crime Labora- allele frequency, 10, 74-75, 85-86, 91,
tory Directors, 88, 89 122, 124, 125
Carryover contamination, 58-59, 66-67 criminal profile, 17-20, 86-87, 111-129,
Ceiling frequencies, 13, 82-83, 84, 90-93 142-143, 155, 159, 160
Ceiling principle, 13, 14, 25, 82-85, 92, and legal proceedings, 135, 139, 140, 141
93, 158 privacy issues, 14, 17-20, 24-25, 32,
Cell repositories, 14, 90-91 86-87, 113-116, 121-122, 155 -156,
Census categories, 12 158-160
Centre d'Etude du Polymorphisme samples, 112-113, 116-123, 125-126, 143
Humaine, 91 sequence variability, 44
Certification of personnel, 16, 98, 100, see also Automated fingerprint identifi-
145, 153 cation systems;
Chain of custody, 131, 142 Cell repositories;
Civil cases, 20, 131-132 Computer technology;
Cleavage sites, 38, 54 Networks
Clinical Laboratory Improvement Act, 17, Defense counsels, 146, 147, 160, 161
102, 107 Defense laboratories, 123
Cobey v. State, 136 Demography,
College of American Pathologists, see Ethnic groups; Subpopulations
101-102, 107 Dental records, 125, 158
Commonwealth v. Curnin, 141 Department of Defense, 125-126
Computer technology, 44, 48-49, 60, 61; Department of Health and Human Ser-
see also Networks vices, 17, 107, 108
for databanks, 18, 113-114, 117, 123, 125 see also National Institutes of Health
Confidence limits, 9, 14-15, 75-76, 92 Department of Justice, 17, 107, 108
Confidentiality, see also Bureau of Justice Assistance;
see Privacy issues Federal Bureau of
Consequentialist ethical analysis, 24-25,
154, 156-157, 158
Constitutional issues, 20, 131, 143, 153
Contamination, 20, 52, 55, 131, 134
in PCR procedures, 65-67, 68, 70
in RFLP procedures, 58-59
Control primers, 70
Controls, in testing, 55, 57-58
for laboratory proficiency, 62-63
Convicted-felon DNA databanks, 17-20,
86-87, 111-129, 142-143, 155, 159,
160, 161
Cooperative services, 153
INDEX 181
Investigation; National Institute of Jus- see also Admissibility;

tice Rules of evidence
Dermatoglyphics, Exclusion of suspects, 75, 88, 135, 154, 156
see Fingerprinting Expert testimony, 21-23, 132-133,
Diagnostic DNA testing, 145-149, 153
see Disease testing External molecular-weight standards,
Diallelic RFLP systems, 4, 35, 36, 45, 46 59-60
artifacts, 54
match criteria, 53
Digestion procedures, 36-37, 38, 54 F
and anomalous results, 58-59 Federal Bureau of Investigation (FBI), 1,
in PCR analysis, 68-69 71-72, 103-104, 116, 153
in Southern blot preparation, 57 DNA databank, 10, 12, 77
Digital DNA typing, 43-44 DNA testing methods, 15, 28, 97
Digitizing pen, 60 Forensic Science Research and Training
Diploid genome, 2 Center, 104
Disclosure of information, 18-19, 24, Federal laboratories, 20, 116
114-115, 132, 148 Federal regulation, 101, 107-108
Discrimination issues, 114, 160 Federal Rules of Evidence, 21-23, 132,
Disease testing, 3, 6, 48, 52, 69, 79 136-139, 153
accreditation programs, 101-102 Fingerprinting, 17-18, 111-113, 120,
ethical issues, 24, 48 121-122, 125, 155, 157, 161
privacy issues, 18-19, 114-115, 116 compared to DNA typing, 29-31,
use of fingerprints, 29 111-113, 117-118
''DNA fingerprinting," 4, 28 see also Automated fingerprint identifi-
DNA Proficiency Testing Act, 103 cation systems
Documentation of laboratory procedures, "Floating bins,"; 86
59, 99, 105, 148 Fluorometry, 53, 63
Dot blotting, 42 Forensic Science Research and Training
Drug testing, 126 Center, 104
Due process, 153 Fourth Amendment issues, 20, 131
Fragment measurements, 59-61
Frequency calculations, 4-5, 9-15, 44-48,
E
74-86, 90-93
Economics of DNA testing, 48-49, and databanks, 124
148-149, 153-154 and legal proceedings, 141
and profile databanks, 113, 117-118, 120 Frequency theories, 85
Electrophoresis, 36 Frye v. United States, 21-22, 132-136, 138
in PCR procedures, 43, 67-68 Funding issues, 101, 153
in RFLP procedures, 37, 38, 57, 60
Employment discrimination, 114, 160
Endonuclease,
see Restriction enzymes
Enzyme markers, 44
Epstein-Barr virus, 90
Error rates of laboratories, 14, 15, 88-89, 94
Ethical issues, 24-25, 154-158
Ethidium bromide, 57, 58, 63
Ethnic groups, 9, 11-15, 25, 48, 75, 79-85,
91, 158
Evidence samples, 17, 23, 44, 87, 131-132
analysis procedures, 36, 53
contamination of, 55, 59, 65-66, 134
in databanks, 112-113, 121, 125
INDEX 182
G Information networks,
see Networks
Genetic disorders, In limine hearings, 144, 145
see Disease testing Inspections of laboratories, 106
Genetic drift, 82, 83-84
Insurance companies, 114, 160
Genetic mapping, 91, 152, 155 Internal molecular-weight standards, 60-61
Genetics Society of America, 72
International technology exchange, 25-26,
Genomes, 2-3, 9, 34 162-163
Genotypes, 32
Interstate commerce, and laboratory
Governor's Select Committee on DNA
accreditation, 108
Typing, New York, 103
Isotopic labeling, 37-38
Grandparentage86
Guanine, 2, 33
Guidelines for a Quality Assurance Pro- J
gram for DNA RFLP Analysis, 98-99
Jeffreys, Alex, 4, 40, 43-44
Judicial notice, 133-134, 145
H Jury presentations, 14, 20-23, 25, 89, 132,
136-137, 146, 147, 160 -161
Hair, 28, 120, 158 Juveniles, 148
Haploid genome, 3
Hardy-Weinberg ratios, 4-5, 11, 45, 78,
81-81, 91, 139, 141 K
Helpfulness standard of evidence, 21-23,
132, 136-137 Kelly v. Texas, 140
Heterogeneity of population, 82, 92 Kidnapping, 118, 121
Heterozygosity, 4, 36 Kits, for PCR analysis, 68, 69
frequency calculation of, 11, 45, 48, 78
and PCR analysis, 68, 69
L
and RFLP analysis, 38-40, 58
HLA (human leukocyte antigens), 10, 27, Laboratories, 8, 15, 18-19, 20, 28, 53-55,
32, 44, 68, 70, 114 97, 101, 105, 112, 116, 161, 162
Homicide, 19, 112, 118-120, 143 error rates, 14, 15, 88-89, 94
Homogeneity of populations, 12, 14, 84 and legal proceedings, 133, 135,
Homozygosity, 4, 36, 87 140-141, 145, 148
frequency calculation of, 11, 45, 48, 78, licensing, 100-101
79 protocols, 8, 53-55, 105, 112, 133, 135,
and PCR analysis, 68 140-141, 145, 148
and RFLP analysis, 38-40, 58 regulation of, 15, 16-17, 97-108, 162
Human genome project, see also Match criteria;
see Genetic mapping Proficiency testing; Technicians
Human leukocyte antigens, Laboratory Accreditation Board, Ameri-
see HLA can Society of Crime Laboratory
Hybridization, 37, 38, 40, 42, 48 Directors, 17, 102-103, 105-106, 107
and band analysis, 57-59, 60 Latent fingerprints, 17-18, 111-113
reverse dot, 42, 67, 68 Leakage between samples, 59
Hypervariable systems, see VNTR Licensing of laboratories, 100-101
I
Immigrants, 84, 155
Immortalized cell lines, 14, 90-91
Individual identification, 9, 28, 43-44,
74-75, 89-90, 113
from fingerprints, 29-31, 113

INDEX 183
Likelihood ratios, 85 O
Linkage equilibrium, 36, 78, 81, 91
Oligonucleotides, 40, 42
Organizations,
M see Professional organizations
Match criteria, 53-54

and PCR analysis, 43 P
and RFLP analysis, 61-63
Medical accreditation programs, 101-102 Paternity determination, 20, 85, 86, 102,
Medical diagnostics, 132, 142, 155, 158
see Disease testing Pattern analysis, 53, 57-59
Membrane transfer, 37, 38, 42, 58-59 PCR (polymerase chain reaction) analysis,
5-6, 7, 40-44, 63-70, 85 , 114, 132, 144
Mendel's law, 32, 36, 86
Military personnel, 125-126 commercial kits, 68, 69
Minisatellite repeat codings, 93 People v. Castro,135
Minority groups, Perpetrator populations, 13, 85
see Ethnic groups Phenotype, 32
Missing persons, 121 Pipettes, 67
Misuse of information, 19, 20, 24, Polymerase chain reaction,
114-116, 158-160 see PCR analysis
Mitochondrial DNA, 86 Polymorphism,
Molecular-weight standards, 59-61 see FRLP analysis;
Monomorphic probes, 60 VNTR
Multiallelic systems, Population frequencies, 9-15, 21, 44-48,
53, 74-85, 90-93, 157
see VNTR
Multilocus probes, 4, 10, 14-15, 40, 56 and databanks, 124
Multiple sources in sample, 52, 58, 59, and legal proceedings, 133, 135, 136,
65-66, 88, 158 139, 142, 145
Multiplex amplification, 42 Privacy issues, 14, 17-20, 24-25, 32,
Multiplication rule, 5, 10-15, 76-79, 86-87, 113-116, 121-122, 148 , 152,
82-83, 89, 92, 145 153, 155-156, 158-160
Mutations, 38, 52, 82 for databanks, 18-19, 86-87, 113-116,
121-122, 143, 158-160
Private laboratories, 15, 18-19, 20, 97,
N 101, 162
Probability,
National Committee on Forensic DNA see Frequency calculations
Typing, 8-9, 14, 16, 70-72, 84, 99 Probative value, of DNA evidence, 22, 52,
National Institute of Justice, 17, 71, 100, 134, 136-137
108 compared to fingerprints, 112
National Institute of Standards and Tech- Probes, 54, 56, 144
nology, 71, 99, 116-117 see also ASO probes;
National Institutes of Health, 17, 71, 90, Monomorphic probes;
107 Multiocus probes;
National Science Foundation, 71 Singlelocus probes
Native Americans, 12, 15, 78 Product rule,
Networks, 113-114, 116-117, 123, 125, see Multiplication rule
126-128, 153; Professional organizations, 16-17, 26, 63,
see also Computer technology; 100, 105-106, 148
Databanks Proficiency testing, 14, 15, 16-17, 55,
New York v. Neysmith, 88 62-63, 88-89, 94, 99, 103-108
Nonisotopic labeling, 37-38, 40 Profile repositories, 17-20, 86-87, 111-129
Nucleotides, 2-3, 33-35, 64
see also Oligonucleotides

INDEX 184
Proof-of-death cases, 20, 132 Rights of accused, 24-25, 154-157, 159

Proprietary data, 93-94, 148, 162 Robbery, 112, 118, 120
Prosecutors, 25, 146-147, 160, 161 Rule 403, 20, 22, 132, 136
Protective orders, 23, 93-94, 148 Rule 702, 20, 22, 132, 136-137
Protocols, 8, 53-55, 72, 105, 112 Rule 706, 20, 132, 153
Publication issues, 56, 93, 137, 138, 144, Rules of evidence, 20-23, 52, 132,
162 136-139, 141-142, 145, 153
Public laboratories, 15, 20, 28, 97, 116, 162
Public opinion, 25, 28, 107, 160
S
Saliva, 28, 142, 158
Q
Samples, 17-20, 36, 44, 53, 58-59, 60
Quality assurance, 15-17, 32, 97-109, 134, contamination of, 20, 52, 55, 59, 65-67,
153 68, 134
Quantitative analysis control, 57-58, 62-63
of pattern images, 53 in databanks, 116-123
see also Frequency calculations leakage, 59
mixed sources of, 52, 58, 59, 65-66, 88,
158
R reference, 14-15, 83-84, 90-91
Racial groups, retention of, 63, 122
see Ethnic groups storage, 18-19, 20, 90, 114-115, 117,
Radiocactive isotopes, 122, 159
see Isotopic labeling Sanctions, 100, 160
Rape, 19-20, 65-66, 112, 118-120, 143 Security of information, 18, 19, 24-25,
Reagents, 53, 54 113-116, 123
Recidivists, 19, 86, 118-120, 121, 143 Semen, 19, 27, 28, 36, 65-66, 112, 120
Red-cell enzymes, 27 Serial repists, 120
Reference samples, 14-15, 83-84, 90-91 Serology, 88, 157-158
Regional networks, 126-128, 153 see also Blood groups Serum protein,
Regulation, 15, 16-17, 97-98, 100-108, 27, 32
153-154, 162 Sex chromosomes, 33
of commercial kits, 69 Sex offenses, 19-20, 65-66, 118-120, 143
Relatives, 14, 25, 86-87, 121, 143 Single-band patterns, 58
Reliability of testing methods, 51-52, 71, Single-locus probes, 4, 5, 15, 23, 37,
88, 97, 106, 133-137, 156 38-40, 48, 52, 56, 57
Reproducibility of results, 85-86, Societies,
116-117, 135 see Professional organizations
Restriction digestion, Software
see Digestion procedures for databanks, 14, 18, 87, 117, 125, 128
Restriction enzymes, 3, 4, 34-38, 54, 57 for fragment measurement, 61
Restriction fragment length polymor- Soldiers, 125-126
phisms, Southern, Edwin, 3, 38
see RFLP analysis
Retention of samples, 63, 122
Reverse dot hybridization, 42, 67, 68
RFLP (restriction fragment length poly-
morphisms) analysis, 3-4, 34 , 35,
36-40, 56-63, 85, 98-99
and databanks, 19, 114, 116, 118
State law coverage, 52, 131-132
see also Diallelic RFLP systems;
Southern blots

INDEX 185
Southern blots, 5, 37, 38, 63 Uracil N-glycolase enzyme,

compared to PCR, 69-70 see UNC
preparation of, 3, 4, 57, 59 Urban areas, 25
validity as evidence, 23, 52, 131, 142 Urine, 28, 126
Spencer v. Commonwealth, 139
Sperm, 65-66
Standardization of methods, 8, 15-17, 26 V
and databanks, 112, 116-117, 126-128 Vaginal fluids, 65-66
and quality assurance, 97-109 Validity of methods, 51-52, 140, 145
see also Molecular-weight standards statistical, 75, 76-79, 90, 134, 140
"Star activity,"; 57 Variable number tandem repeat,
State Justice Institute, 71-72 see VNTR
State laboratories, 20, 28, 108, 116 Victim samples, 121
State regulation, 100-101, 108 Victims' rights, 25, 156-157
of databanks, 115-116, 120, 124-125, VNTR (variable number tandem repeat),
126-128, 142-143 4, 34-40, 45-48
State rules of evidence, 20, 21, 52, 132, and amplification, 42, 64
141-142 match criteria, 42, 53-54
State v. Despain138 and multiplication rule, 11-12
State v. Pennell, 139
State v. Schwartz, 135-136
Statistical analysis,
see Frequency calculations
Statistical disclosure, 18-19, 114-115
Subpopulations, 10-15, 48, 76, 77-85
Suspect samples, 20, 36, 53, 59
in databanks, 17-20, 86-87, 111-129,
142-143, 155, 159, 160
T
Technical Working Group on DNA Analy-
sis and Methods, 16, 98-99, 104,
106, 116-117
Technicians, 15, 16, 17, 25-26, 66, 97, 100
Technological advancement, 15, 55,
70-71, 143-145, 153
Technology transfer, 71
international, 25-26, 162-163
Thermocyclers, 64
Thymine, 2, 33
Trade secrets, 93-94, 148, 162
Twins, 29, 44
Training, 15, 16, 17, 25-26, 96, 104, 108,
125, 153
U
UNC (uracil N-glycolase enzyme), 67
Unidentified bodies, 121, 125, 126, 158
United States v. Jakobetz, 138
United States v. Porter, 138
United States v. Yee, 138

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DNA Technology in Forensic Science (1992)

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National Research Council 1992. DNA Technology in Forensic Science.

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Committee on DNA Technology in Forensic Science

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COMMITTEE ON DNA TECHNOLOGY IN FORENSIC

VICTOR A. McKUSICK, Chairman, The Johns Hopkins Hospital, Baltimore,

National Research Council Staff

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HAROLD E. VARMUS, Chairman, University of California, San Francisco,

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COMMISSION ON LIFE SCIENCES

BRUCE M. ALBERTS, Chairman, University of California, San Francisco,

National Research Council Staff

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The National Academy of Sciences is a private, nonprofit, self-perpetuating

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A STATEMENT BY THE COMMITTEE ON DNA TECHNOLOGY IN FORENSIC SCIENCE x

A Statement by the Committee on DNA

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2 DNA TYPING: TECHNICAL CONSIDERATIONS 51

3 DNA TYPING: STATISTICAL BASIS FOR INTERPRETATION 74

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Laboratory Error Rates 88

4 ENSURING HIGH STANDARDS 97

5 FORENSIC DNA DATABANKS AND PRIVACY OF INFORMA- 111

6 USE OF DNA INFORMATION IN THE LEGAL SYSTEM 131

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7 DNA TYPING AND SOCIETY 152

ORGANIZATIONAL ABBREVIATIONS 165

BIOGRAPHICAL INFORMATION ON COMMITTEE MEMBERS 173

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Characterization, or ''typing," of deoxyribonucleic acid (DNA) for purposes

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FIGURE 1 Diagram of the double-helical structure of DNA in a chromosome.

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FIGURE 2 Schematic representation of Southern blotting of single-locus,

That example illustrates what is called the product rule, or multiplication

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1. Laboratory analysis of samples to determine their genetic-marker

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• Any new DNA typing method (or a substantial variation of an existing

— Each DNA typing procedure must be completely described in a detailed,

• The committee strongly recommends the establishment of a National

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appropriate government agency or agencies to provide expert advice

STATISTICAL BASIS FOR INTERPRETATION