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Unformatted text preview: © 2004 Nature Publishing Group http://www.nature.com/naturegenetics C O M M E N TA RY Forensic genetics and ethical, legal and
social implications beyond the clinic
Mildred K Cho1 & Pamela Sankar2
Data on human genetic variation help scientists to understand human origins, susceptibility to illness and genetic
causes of disease. Destructive episodes in the history of genetic research make it crucial to consider the ethical and
social implications of research in genomics, especially human genetic variation. The analysis of ethical, legal and
social implications should be integrated into genetic research, with the participation of scientists who can
anticipate and monitor the full range of possible applications of the research from the earliest stages. The design
and implementation of research directs the ways in which its results can be used, and data and technology, rather
than ethical considerations or social needs, drive the use of science in unintended ways. Here we examine forensic
genetics and argue that all geneticists should anticipate the ethical and social issues associated with nonmedical
applications of genetic variation research.
Integrating ethical and social issues
Data on human genetic variation are being
generated and used to better understand
human origins, susceptibility to illness and
genetic causes of disease. The US National
Human Genome Research Institute
(NHGRI) recently proposed the next stage in
this work to carry forward and expand these
goals and to reaffirm a commitment, present
since the start of the Human Genome
Project, that appropriate uses of this information will be based on ethical, legal and
social science analysis1.
The history of destructive episodes in
genetic research makes this attention to the
ethical and social implications of genomics
research essential2. This is especially true of
human genetic variation research, because it
provides the opportunity to find the genetic
basis of individual and group differences.
The consideration of ethical, legal and social
1Stanford Center for Biomedical Ethics, 701A Welch Road, Suite 1105, Palo Alto, California
94304, USA. 2University of Pennsylvania,
Center for Bioethics, 3401 Market Street, Suite
320, Philadelphia, Pennsylvania 19104-3308,
USA. Correspondence should be addressed to
Published online 26 October 2004;
doi:10.1038/ng1434 S8 implications (ELSI) of genetic research will
not be maximally effective if it separates the
creation of knowledge from its uses or if it
sees the solution to appropriate uses of science as coming from a “cohort of scholars in
ethics, law, social science, clinical research,
theology, and public policy”1 rather than
emerging with and from the science. Thus,
ELSI analysis should be integrated into science, with participation of scientists; should
be conducted proactively, rather than after
scientific research projects are conducted;
and should anticipate and monitor applications of research. A collaborative effort that
centrally involves scientists and dialog
among many scientific communities is necessary to shape science for responsible uses,
because the way in which science is designed
and carried out fundamentally affects how it
can be used. Too often, the mere availability
of data and technology, rather than ethical
considerations or social needs, drives its use
in unintended ways; therefore, the awareness
and involvement of scientists in thinking
about downstream uses is needed at the earliest stages of research.
NHGRI is a leader in the concept of ELSI
analysis and recently involved scholars from a
diversity of backgrounds in planning largescale projects such as the HapMap3. Scholars
from anthropology, law, ethics and other dis- ciplines have had input in the earliest stages of
designing, carrying out and reporting genetic
research intended to identify genes involved
in diseases, protection against illness and
responses to drugs4. This multidisciplinary
approach was perceived to ‘slow’ the research
while issues such as informed consent, community consultation and benefits were ironed
out. But lack of attention to issues important
to the communities that are affected by the
research, and on whose behalf the research is
purportedly done, can also slow or even halt
research5,6 and breed deep distrust of scientists that can only hurt future efforts to carry
out or raise funding for future research.
Therefore, time spent making explicit the
ever-present ethical and social issues and
incorporating them into study design is better
conceptualized as an integral part of the
research process than as ‘extra’ time.
The HapMap has been an exemplar of
integrated and proactive ELSI analysis in
genetic variation research. Similar efforts
have been organized for other genetic
research projects, such as the development
of a pharmacogenetics research network
and database7 funded by the US National
Institutes of Health. Far less attention has
been paid to the application of genetic variation research for nonmedical purposes,
however. VOLUME 36 | NUMBER 11 | NOVEMBER 2004 N ATURE GENETICS SUPPLEMENT © 2004 Nature Publishing Group http://www.nature.com/naturegenetics C O M M E N TA RY
One example of the need for more involvement of geneticists in ELSI considerations is
in the application of human genetic variation
research for forensic uses, particularly criminal identification. The same kinds of data
that are used to analyze genetic differences
between humans for medical purposes are
also used in courts of law to determine identity. In a legal setting, the validity of certain
analytic methods and the data they produce,
especially those used to infer race from DNA
sequences, are particularly troubling.
Investigation’s DNA Advisory Board and
other associated technical and scientific
working groups have been active over the last
decade, insufficient attention has been paid
to the genetic, public policy or legal implications of these applications.
Over the last 10 years, the availability of
DNA samples and of techniques for rapid
DNA sequencing have created a vast body of
human genetic variation research for forensic
purposes. Standardized systems have been
developed and rapidly adopted worldwide
for determining whether DNA in a sample
from a suspect matches that in a sample from
a crime scene. The most commonly used systems in the US and the UK analyze fixed sets
of short tandem repeat (STR) loci8,9. Setting
laboratory error aside, lack of a match
between the STRs in a crime-scene sample
and those in the suspect’s DNA sample eliminates that person as a suspect.
Conversely, a match between the two sets
of STRs is typically presented as evidence
that crime scene DNA came from the suspect. But this conclusion cannot be made
with 100% certainty because the two samples are compared only at a limited number
of loci. Hence, all conclusions of identity or
nonidentity between two samples must be
probabilistic. It is in trying to improve the
precision of these probability calculations
that forensics brings in concepts of race
If samples from a crime scene and from a
suspect are determined to match at select
STR sites, the next step is to determine the
probability that this match could have
occurred by chance. This is called the match
probability, and its calculation requires
determining how commonly the alleles occur
at the analyzed loci. If the alleles in the crime
scene sample occur commonly, the chance is
higher that the sample could have come from
someone other than the suspect. But the crucial question is not only whether the alleles
are commonly found, but among whom?
That is, what is the relevant population for any given analysis on which to base an STR
allele frequency? Ideally, this probability
would be determined by analyzing the DNA
of the entire population of people who could
have conceivably left DNA at the crime scene
and then calculating the frequency of the pattern of the DNA at the crime scene sample in
this population. This is very impractical.
Alternatively, forensic geneticists typically
use reference databases categorized by race
and ethnicity to calculate probabilities.
The decision to use these databases was
stated in a report on forensic DNA typing
produced by the US National Research
Council (NRC)10–12. The NRC recommended that “[i]n general, the calculation of
a profile frequency should be made with the
product rule. If the race of the person who
left the evidence-sample DNA is known, the
database for the person’s race should be used;
if the race is not known, calculations for all
the racial groups to which possible suspects
belong should be made.”11
Despite the NRC’s recommendation, some
researchers continue to debate the use of the
product rule to calculate the probability of a
random match between crime scene sample
and suspect13. Concern has focused on the
assumption that the genetic loci that are analyzed occur independently in all populations12. But the capacity of these methods to
accurately and consistently distinguish individuals is less our concern here than the
assumptions about race that these methods
reinforce. For example, the NRC’s recommendation implies that (i) the ‘races’ of individuals whose DNA was analyzed to
determine allele frequencies in populations
or of suspects can consistently be assigned
and (ii) if the racial labels applied to crimescene samples and those applied to the populations with which they are compared are the
same, then the sample and populations will
be genetically similar.
Geneticists, most notably Eric Lander and
Bruce Budowle, were active participants in
the debate over how to calculate the probability of a random match14–16. The final article
in their exchange claims that “the scientific
issues have all been resolved”. But a series of
arguments and counterarguments about the
association between ‘race’ and patterns of
DNA markers has been unfolding in the
medical genetics literature over the last four
years, and these arguments are relevant to,
and should include, forensic geneticists. A
lively and constructive dialog, including people from various disciplines such as ethics,
history, and anthropology, has taken place
within the genetics research community
about whether genetic markers can be associ- NATURE GENETICS SUPPLEMENT VOLUME 36 | NUMBER 11 | NOVEMBER 2004 ated with, or used as a proxy for, race or ethnicity in various kinds of medical
research17–20. This debate includes the extent
to which population substructure exists21,22
and whether race and ethnicity are useful for
controlling for population substructure in
genotype-phenotype correlation studies23,24
or for identifying groups for tailored medical
treatments25,26. These dialogs have also
begun to address the clinical and social
implications of the inherent error in applying
probabilistic population data to individuals.
These conversations are directly relevant to
the forensic genetics community but have
not been widely extended into this group.
The assumption that socially fluid labels,
such as racial and ethnic categories, can be
assigned to individuals and populations
based on their genetics is problematic for
conceptual and practical reasons when
applied to forensics, just as it is problematic
when applied in the medical context18. The
calculation of a match probability for criminal identification purposes calls for assigning
race or ethnicity to a sample (often by undescribed methods), if ‘known’, and assigning
race or ethnicity to the reference populations
(also by unstandardized and poorly
described methods) from which allele frequencies are calculated. It then assumes that
these assignments correspond. That is, if a
sample is labeled as being from a ‘black’ individual, this person is considered genetically
equivalent in some way to populations
We know, however, that the use of such
labels varies widely over geographical time
and space, so that such correspondence is
not assured. For example, in the US, people
with ancestry from India are sometimes
labeled Asian and sometimes labeled white
or ‘Caucasian’27; they are not classified in the
same way in the UK as in the US20. Self-identification of race or ethnicity does not solve
the correspondence problem if the label on
the individual sample does not correspond
to the category assigned to data in DNA
databases. Self-identification also does not
solve the fluidity problem, because people
usually self-identify to categories imposed
externally (such as those used in the census),
and those labels constantly change.
Furthermore, we know that individual selfclassification is not stable; for example, one
US study found that one-third of people
change their own self-identified race or ethnicity in two consecutive years28.
There is an urgent need to expand this
debate into the field of forensics, for at least
two reasons. Both signal an extension of
DNA typing into new arenas of criminal S9 C O M M E N TA RY © 2004 Nature Publishing Group http://www.nature.com/naturegenetics identification. The first is a kind of ‘function
creep’ whereby the functions of DNA profiling are gradually expanded29 on a basis that is
scientifically controversial, if not questionable. The second is the US government’s
expansion of populations to whom these
techniques can be applied.
Analysis of STRs in human DNA was initially
developed to determine the identity or nonidentity of a sample of unknown origin with
a sample of known origin. In this way, crimescene samples could be compared with those
collected from suspects or victims of a crime,
or unidentified battlefield remains could be
compared with DNA samples collected from
enlisted soldiers to identify them.
The same kinds of analysis, however, have
now been used to create suspects where there
are none, with the new, stated assumption
that patterns of STRs are associated with visually identifiable physical characteristics. The
weak predictive power of the STR loci is
demonstrated in an article reporting “a
method for inferring the ethnic origin of a
DNA sample profiled using the SGM [second
generation multiplex]" in five British populations (classified in the paper as Caucasian,
Afro-Caribbean, Indian sub-continental,
Southeast Asian and Middle Eastern)30. In an
attempt “to discriminate between the ethnic
groups in the suspect population…a set of
10 000 profiles was simulated from each of the
five ethnic groups considered here, using
allele distributions estimated from the data.
For every profile in a set, its probability within
each ethnic group was estimated.”30 (Table 1).
Classifications into the five ‘ethnic’ groups
were assigned by police officers by visual characteristics: “The profiles included in the databases were therefore generated from criminal
justice (CJ) samples taken when individuals
were arrested for an offence. Designation of
ethnic group was by police officers and was
based on appearance rather than any knowledge of an individual’s ancestry.”30
This example brings up a number of areas
of debate about the relationship between
race, ethnicity and genes that have been
raised in the biomedical literature and should
also be addressed in the forensics literature.
First, the fluidity of racial and ethnic categories should be acknowledged. As has been
discussed at length in the medical literature,
racial and ethnic classification by appearance
is often inconsistent20,31. Thus, even if individuals could consistently be clustered into
groups by genetic profiles, the correlations
between visual and genetic classifications
(Table 1) would be low. S10 Nevertheless, this type of DNA analysis has
been used to create suspect pools based on
race, as in the case of a serial killer in
Louisiana. Police were looking for a ‘white’
male, but DNA from the crime scene suggested that the perpetrator was of “African
and American Indian ancestry”32, implying
that such a person could not be ‘white’.
In addition to the difficulties posed by the
social fluidity of race and ethnicity that make
them such problematic variables in genetic
research, several other issues have been raised
and debated in the medical literature. These
include (i) inadequate description of methods for assigning race and ethnicity to populations33–36; (ii) the problem of sampling
small or isolated populations and generalizing to larger groups such as ‘Africans’26; and
(iii) the validity of using small numbers of
genetic loci to group individuals by ancestry
when hundreds of markers might be necessary21,35. Non-STR genetic markers may have
a better correlation with phenotype37 but to
the extent that these correlations are made by
race, many of the concerns discussed above
Broadening DNA collection
At the same time that the analytic uses of
DNA collected for forensic purposes are
gradually expanding (under assumptions
that are being increasingly challenged in the
medical research community), the databases
of DNA data on criminals, with which suspect or victim DNA samples can be compared, are also expanding, to include people
other than those who were originally
intended to be included (sex offenders)38.
DNA evidence is now admissible in courts
of virtually all jurisdictions in the US and in
other countries39. In the US, STR profiles of
DNA collected from crime scenes are compared with DNA profiles collected locally
(including, but not limited to, those of suspects for the crime in question). If there is no
match with the local database, the profile can
be compared with state and then national
(National DNA Index System) collections. Together, the local, state and national databases are known as the Federal Bureau of
Investigation Combined DNA Index System
(CODIS) database, authorized by the DNA
Identification Act of 1994 (ref. 40) for law
enforcement purposes. According to the
CODIS website (http://www.fbi.gov/hq/lab/
codis/program.htm), “CODIS enables federal, state, and local crime labs to exchange
and compare DNA profiles electronically,
thereby linking crimes to each other and to
convicted offenders”. CODIS obtains DNA
profiles from individual states (now 49 states,
the US Army Crime Lab, the Federal Bureau
of Investigation and Puerto Rico). States
determine which DNA profiles are acceptable
for inclusion, now mostly convicted sex
offenders but increasingly many other categories of felons. Some states have expanded
their databases to include all felons or even
all arrested persons. As of April 2004, the
National DNA Index System contained
1,762,005 DNA profiles, including 80,302
crime-scene samples and 1,681,703 from
Recent legislative efforts suggest that this
number will probably increase rapidly. Bills
have been introduced in the US House of
Representatives and the Senate to give states
the authority to expand the CODIS database
so that it could potentially include DNA profiles from “arrestees and persons who have
been charged but not yet convicted, juvenile
offenders, and persons convicted of misdemeanors”41. The current California ballot
includes Proposition 69, which would
require “collection of DNA samples from all
felons, and from adults and juveniles
arrested for or charged with specified
crimes, and submission to state DNA database; and, in five years, from adults arrested
for or charged with any felony”42. Given that
the arrest pattern is already biased towards
racial and ethnic minorities41, the increased
inclusion of individuals in these groups in
DNA databases, even if they are not convicted of a crime, raises the potential for
future ‘identification’ of members of these Table 1 Misclassification table comparing true versus predicted ethnic group
True Predicted (%)
(1) (1) Caucasian (2) 56 9 (2) Afro-Caribbean
(3) Indian sub-continent (4) (5) 9 11 9 67 5 8 11 17 8 43 18 13 6 6 13 66 9 18 16 19 18 30 (4) Southeast Asian
(5) Middle Eastern (3)
15 Reprinted with permission from ref. 30. VOLUME 36 | NUMBER 11 | NOVEMBER 2004 N ATURE GENETICS SUPPLEMENT © 2004 Nature Publishing Group http://www.nature.com/naturegenetics C O M M E N TA RY
groups as seemingly established as perpetrators of a crime by what are actually probabilistic and scientifically evolving standards.
Information based on genetic variation
data has serious implications for individuals
and groups outside the clinical arena. Police
have used it to justify ‘DNA dragnets’ that
collected tissue samples from hundreds of
‘volunteers’, as in the Louisiana serial killer
case. The company that carried out the DNA
analysis in this case billed it as a success
because it “helped lead investigators to a suspect” (DNAPrint website, http://www.
plays_role.htm), Derrick Todd Lee. Others
claim, however, that “the Louisiana dragnet
didn’t catch Lee. That was done by alert
detectives who picked up a lead from an
unrelated case. But it did give the task force
investigating the murders the DNA of hundreds of innocent men.”
DNA dragnets are damaging to civil liberties, especially because DNA samples have
been taken without probable cause from people who are not suspects, not truly voluntarily43–45, and without provisions in the law for
destroying or returning them43,45. Although
technically the samples are collected from
volunteers, in practice the standards for sample collection are quite different from those
used for medical research. The typical
research consent process, which in many
countries requires oversight and approval by
institutional bodies, has explicit written provisions for withdrawing from the study and
disposition of data and tissue samples. In
contrast, the collection of DNA samples for
criminal investigation purposes has no provisions for destroying or returning samples
of those found innocent. Individuals have
had to sue in order to retrieve their tissue44–46. Furthermore, unlike medical
research, the consequences of declining to
‘volunteer’ a DNA sample in a dragnet are
social stigmatization, coercion or forcible
collection of tissue samples by other means45.
In at least one criminal investigation, those
who did not ‘volunteer’ to give DNA samples
were reportedly issued search warrants in
order to obtain DNA44. Those who decline to
‘volunteer’ face social ostracism because of
the belief that “if you don’t want to give your
DNA, you’ve got something to hide”44.
Attorney Barry Scheck, director of the
Innocence Project, which advocates using
postconviction DNA testing to exonerate the
wrongfully convicted, said, “It’s inherently
coercive when a policeman comes to your
door and says, ‘Give us a sample of your
blood and if you don’t give it to us, you’re a
suspect.’”44 Reasonable arguments could be made that
the standards of consent for taking DNA
samples for medical research do not apply in
their entirety to the taking of samples from
convicted felons47. But these arguments do
not similarly hold for taking DNA samples
from individuals who are not convicted of
crimes. Furthermore, it is clear that the term
‘voluntary’, in practice, means very different
things in the worlds of medical research and
criminal investigations. This discrepancy
could be damaging to legitimate uses of DNA
samples in both worlds.
The number of DNA profiles stored in
CODIS and the genetic tools to analyze them
will probably continue to grow, as will their
combined impact on the criminal justice system. Although the expanded collection of
DNA in itself should be a topic for public
debate, the issue here is the uses to which
these samples are put, envisioned and
enabled by medical and nonmedical genetic
research, and the role of scientists in shaping
these uses. Attributing racial and ethnic
labels to samples, a subject of considerable
and still unresolved debate in medical genetics, seems well on its way to acceptance in
forensics and the courtroom. Research that
aims to extend use of these labels to support
phenotypic or visual identification is still rare
but interest in it is strong. Misuse of genetic
research for nonmedical applications in the
volatile arena of race will severely erode the
public’s trust in the application of genetics to
health. This troubling prospect underscores
the need for medical and ELSI researchers to
look at applications of genetic research
beyond the lab and clinic and to widen the
dialog to a broader range of scientific and
COMPETING INTERESTS STATEMENT
The authors declare that they have no competing
Received 27 July; accepted 9 September 2004
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