An Interview With DNA Forensics Authority Dr. Bruce Weir
William Neal Reynolds Professor of Statistics and Genetics
North Carolina State University
Sean Henahan, Access Excellence
Note: This interview was conducted in January 1995
The term DNA
fingerprinting was coined by British geneticist Alec Jeffreys only
ten years ago. Since that time, DNA forensics has become an important
tool in law enforcement. In some cases the DNA tests have helped convict
suspects, while in others the tests have exonerated suspects or overturned
previous convictions. Recent high profile court cases have put the spotlight
on DNA forensics and created the impression that there is a lack of agreement
among the experts on the reliability of this evidence. I spoke with Dr.
Bruce S. Weir, an expert witness for the prosecution in the OJ Simpson
case, about the methods and controversies surrounding DNA evidence.
Q: First, let's begin with a basic question, what do
we mean when we say DNA fingerprinting?
A: DNA fingerprinting, or DNA profiling as I prefer
to call it, characterizes a small portion of our DNA . It is a way of
identifying the DNA content of an individual. We think of fingerprints
as being unique to the individual. We know that even genetically identical
twins have different fingerprints. In contrast, DNA typing, because it
uses a very small fraction of the DNA, is certainly not unique.
Q: Let's imagine an hypothetical crime scene. When the technical people arrive at the crime scene, what do they do, what are they
looking for?
A: The people at the crime scene look for biological tissues,
such as blood stains on the ground and semen stains on clothing.
They may take swabs from the victim's body if rape is involved.
It is also possible to extract DNA from exotic things like the
saliva on the back of a postage stamp. If it is a very old crime,
they may obtain DNA samples from a skeleton.
Q: Wouldn't a drop of blood or other specimen at a crime scene be commingled with all kinds of other DNA from bacteria, flora
etc? How is this extraneous DNA excluded?
A: The methods used in forensic DNA are not so much concerned
with excluding extraneous DNA as in identification of human DNA.
The probes used are very specific for human DNA.
Q: Tell us a bit about the techniques used in forensic DNA
testing.. Are the laboratories using PCR to
look at allele combinations or RFLP (restriction fragment length polymorphisms)
or both? What are the advantages of the different techniques?
A: The laboratories use both techniques. The RFLP tests
were developed first and are better in the sense that they are much more
variable. There are many more variants in the population. A typical RFLP
will have 30 distinguishable types. The disadvantage of the RFLP method
is that it requires a relatively large amount of DNA along with radioactive
labeling visualized on a gel. To expose an X-ray film with a radioactive
labeled probe takes about a week. You have to do that for each system,
so the entire process can take many weeks. PCR techniques offer the advantage
of requiring only trace amounts of DNA and they can be done overnight.
Unfortunately, PCR systems currently in use are not very variable, allowing
typically only three of four variants.
Q: When laboratories use RFLP they are only looking for five orsix polymorphisms. Why not look for ten or 100 or 1000?
A: The State of N. Carolina uses eight polymorphisms. I believe by the time you have eight systems even with as few as 20
alleles, you are not going to gain anything by looking for more.
Q: A number of statistical techniques are now used to
confirm the reliability of these methods. Can you explain how the most
fundamental technique, the allele multiplication rule, is used to rate
the odds of a match between specimens?
A: If we want to come up with a figure for the frequency
of the pattern, we rely on statistical model. A DNA profile contains information
from let's say five RFLPS or five PCRs. This provides at least ten pieces
of information The entire profile has almost never been seen. Out of the
30,000 people who have been typed and their profiles put into database,
no two people have had same profile with five loci.. While the entire
profile has not been seen, each component has been seen quite often. Let's
say each variant at each locus occurs about ten percent of the time. So
say we have a ten band profile based on five loci, with each band occurring
ten percent of the time. We then multiply the ten numbers together to
gain a probability for that combination.
Q: It has been suggested that some factors could affect the
accuracy of that kind of probability calculation. For example,
some alleles are probably more likely to be seen in a given
racial or ethnic group. This led to a concept called the ceiling
principle. Can you explain this concept?
A: The ceiling principle was a method designed to be conservative in estimating probabilities, providing a frequency which would
not overstate the strength of the evidence. The DNA databases
used are designed to be representative of the entire population.
If a crime was committed in a particular area and the suspect in
a case belonged to a specific population group, the frequency for
a certain allele might be higher than for the population as a
whole. So it would prejudicial to the defendant to quote the
population-wide frequencies instead of the specific ones.
The ideal would be to have database tailored to every crime. That
is not practical, mainly because the population groups are not
well defined. So we are pretty much obliged to use the wider
population samples. There are ways to characterize the variation
in allele frequency across population subgroups using a statistical
method developed by population geneticists in the early 1950's.
We really would like to have samples from subgroups of the population
in order to be able to estimate how much they differ one from another.
Because these subgroups are ill-defined we can't sample them. So we fall
back on what is available, geographic sampling. The FBI has
samples from different States and has also compiled a worldwide
survey derived from databases compiled by forensic scientists
around the world. So we can compare the frequency of alleles in
different recognizable geographic groups.
We have found that any particular allele can have a frequency
that differs significantly from one population to another. It is
the frequency which differs, not whether that allele occurs in a
given population. However, the variants occur within all
populations. This leads us to believe that those variations
occurred before the divergence of the various human population
groups. So each individual allele frequency varies depending on
the population, but when we take a collection of say ten
alleles, the ups and downs tend to cancel out. We find that there
is not really a great deal of difference in the profiles we have
seen from one group to another. When we modify the product rule
appropriately by measures of population substructure, then the
ceiling principle is inappropriate. I think the ceiling principle
is poor science and I don't think it will be used in the future.
Q: Doesn't it seem that human error involved in the laboratory
work would be the weak link in the chain of DNA forensics?
A: There has been a lot of discussion about the potential for
human error. I would think the weak link would be right at the
beginning, for example, does the tube labeled 'crime scene blood
stain' reflect the true source of that material. The forensic
laboratories have a lot of safeguards built in, such as dual
observation of each step, and signing for custody of the
evidence. Forensic laboratories have a lot of experience in
taking care with evidence. But I take your point, if there is
going to be an error, it would be of the gross human kind, rather
than in technique.
Q: Modern science in general relies on publication of data in
peer reviewed journals, sharing raw data with other researchers
to confirm conclusions, etc. One criticism of forensic DNA
profiling as opposed to genetic susceptibility testing, is that
the methodologies have not passed through the usual channels of
peer review and comment.
A: In the early days that was true. Some people were very jealous about these data. However, the data are now routinely made
available to researchers. There is now an extensive bibliography
of studies available. The FBI, Lifecodes, Cellmark and other
laboratories have all published peer-reviewed scientific papers
explaining their protocols and methods of analysis. When they do
publish they are then obligated to make the raw data available.
Q: Several laboratories have established proprietary techniques in DNA profiling. Is one RFLP the same as the next? What are the
differences between the companies methods?
A: The RFLPs do differ from one laboratory to the next, but
the PCRs do not. Because the RFLPs are so variable, it is not trivial
to distinguish one variant from another. As a result, ad hoc methods are
used to accomplish this. We are talking about variations in length of
the regions. The regions examined may vary in length from 500 base pairs
up to 20,000 base pairs. They differ in the multiples of repeat units
of about ten. So if we are going to go from 500 to 20,000 in sets of ten,
we are talking about thousands of types, far too many to distinguish on
current gels. So binning strategies have been developed to amalgamate
alleles that are close together. Different laboratories use different
binning strategies.
Q: So it sounds like the ultimate in sensitivity and
specificity in DNA profiling would be a combination of RFLP plus a PCR?
A: Actually the ideal would be to use sequence data,
which is being used in some contexts. The Armed Forces Institute of Pathology,
for example, uses PCR mitochondrial sequence data to identify war remains.
This method can make very specific identification using only a few hundred
base pairs.
Q: It seems straightforward enough from the scientific
perspective what these tests are measuring and that they offer
high levels of reliability and accuracy. So why does there
appear to be so much debate on the validity of DNA forensics and
the statistical accuracy of DNA profiling?
A: There is a perception among the public that there is some
debate within the scientific community. I believe that there is no such
debate. When we look at the scientific literature, which is where science
is discussed, the published peer-reviewed papers are overwhelmingly in
favor of this technology and the protocols and analytic methods used.
Much of the current debate has been outside of the scientific literature.
It typically comes from court cases, where someone is on trial for a crime.
The defendant and prosecutors each have expert witnesses, so it looks
likes half of the scientists are one side and half on the other. This
is quite misleading and is not the way science operates. There are very
few people who have thought about and examined the issues carefully who
remain critical of DNA profiling.
BACKGROUND ON DR. WEIR
Research Expertise
Dr. Weir specializes in population genetics, the study of genetic
variation in human, animal and plant populations. Techniques he
pioneered has led to the development of statistical methods enabling
scientists to determine the probability that a DNA match linking a
person to a crime scene could have arisen from chance. The same
methods are used by medical researchers to locate genes that cause
diseases, such as cystic fibrosis.
Trial Experience
Weir has served as an expert witness on the statistical reliability
of DNA tests in 15 trials and pretrial hearings, including a trial in
1994 in Hillsboro, Ore., that resulted in a murder conviction. He also
served as an expert witness during the notorious
trial of O.J.Simpson.
Publications
Weir has published 94 articles; has edited or written four
books; and holds an editorial position at five periodicals,
including Genetics and American Journal of Human Genetics.
Dr. Weir authored landmark articles in Proceedings of the National Academy
of Sciences and American Journal of Human Genetics, using statistical
data from population studies to confirm the validity of DNA test results.
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