Tuesday, March 24, 2009


First, I'd like to introduce Fredrick Bieber. He served on the Harvard
Medical School faculty for two decades where he directs and teaches courses in genetics, pathology and
forensic science. He has a long-standing interest in science, law and public policy. He served on the Social
Issues Committee of the American Society of Human Genetics, and is a member of the DNA Advisory
Board of the Federal Bureau of Investigation. He recently was appointed by the Solicitor General of
Canada to the legislatively mandated National DNA Advisory Committee of Canada to oversee certain
activities of the Royal Canadian Mounted Police. Dr. Bieber.
MR. BIEBER: Good morning. I was asked by Ira and David and Chris, who I thank very much
for inviting me, to try to form a bridge between some of the basic biology and medicine that applies to
human-identity testing and the work that you are concerned with in the courtrooms across the nation.
And in keeping with the theme that was started last night, I'd like to show this first slide and
really hopefully remind you that those of us, including myself, in medical genetics are not as the New York
magazine would imply, trying to create perfect people in our work in genetics and the hospitals and clinics.
In fact, if I were involved in such a project, I would have certainly worked on the ambiguous genitalia that
would certainly doom this particular new species to one generation. Some of you may have Ursula
LaGwynn's (ph) novel, A Path of Darkness where there are people who can morph to one or the other
depending on the circumstance.
But this is not really what genetics is all about, and I think from hearing the presentations last
night you understand that the media often takes one idea or concept and moves farther in the public line
than certainly the scientists or clinicians have in mind.
I'd like to start with a story after this slide, reminding that besides the work in forensics and
paternity that you're familiar with, there's a huge body of data and a large practice in genetics in all
modern countries that involves heart-wrenching and life decisions every day in the clinic and the hospitals
using the same technology for the diagnosis and treatment of disease, for the selection of the recipients of
bone marrow or organ transplants, and the identification of work casualties and the studying or rare and
endangered species.
All of these methods and concepts are similar, if not identical to what are used in the identity
testing that you use in the courtroom. And this fact I think often escapes interested persons in the public
who have the idea, because of so many of the challenges, that there's something apparently different about
the biology and the science and the practice of forensic genetics when, in fact, a new case almost a carbon
copy of that which we use in the clinics every day.
I want to tell you a story that unfortunately recurs and gives you some example of the kind of
work that got me interested in science and law and public policy. At one point, we saw a two-month-old
male with fractures, hernia, large liver, presenting at fifteen months with a third fracture, healing well later
Now in accordance with the laws in most states, when nurses or clinicians or educators or police
officers suspect child abuse of any kind, they must report this, and in a Massachusetts it falls under Chapter
51A. And these children are often removed from their parents' custody and placed in foster care. Here's a
photographic image for you of the radiograph showing the fractures of the long bones which would
certainly be startling to any nurse or clinician who saw such a patient.
There's a photograph on the right of the boy and his additional fracture. There's a problem here
however. As we would teach our medical students or nursing students in both medical centers. There's a
real laundry list in the so-called differential diagnosis of skeletal trauma that includes innocent trauma
normal variance, and a whole category of disorders that we call skeletal dysplasia. And as a medical
geneticist this is an area that we pay a lot of attention to, especially in infants who have skeletal changes
like those you saw on the x-ray.
It turns out that this child and many like him who have been taken from their parents across the
country and in other countries actually had a genetic disorder called osteogenesis imperfecta that is due to a
molecular defect in the production of collagen that forms the matrix of cartilage in bones and in fact was
not the victim of abuse. This particular child was put back in his parents custody after this diagnosis was
finally made.
Many times we use biochemical and molecular and DNA-based methods to perform diagnostic
tests on children like this in the hope of further injustice in that individual instant case. So I think you can
see that in the clinic we are not only concerned with the diagnosis and treatment of disease but also in the
justice system, and genetics plays a cardinal role every day of my work.
But we're here for this session for the next two days to talk about forensics, and I don't need to
remind you of the data in this slide of all of the methods that you've been involved in-- sex offender
tracking, the exculpation of wrongly accused and wrongly convicted or incarcerated suspects or individuals,
the identification of human remains, the identification of the possibility of serial offense, et cetera.
As you know DNA, that forms the basis for this identity testing, is derived from our parents in
the sperm and egg and can be found in most tissues in the body. And where nuclear DNA is not present,
mitochondrial DNA often is, and Bruce will have a word to say about that.
David wanted me to show you at least one photograph of the human chariotype, and I run a lab
that performs its testing at the Harvard Teaching Hospital where we actually look at the chromosome
patterns of patients or tumors in bone marrow from those patients to determine whether there's an extra
chromosome or missing chromosome, a deleted chromosome or a rearranged chromosome.
And all of our DNA, for those of you who aren't scientists, is packaged in these compartments
that we call chromosomes. We line them up in pairs and these chariotypes. And as you know, we get one
from each parent-- one from mom, one from dad. And we're actually in the forensics setting analyzing the
DNA, the double helix that is tightly wound around protein, pistones (ph), and packaged into these
chromosomes. So we're actually looking right at the molecular structure of the DNA.
And there are a number of methods to do this. I won't spend much time on this, but I think
historically you should be aware that there are several methods to type B and A in the identity testing
One is to cut the DNA at various points separated in a gel-based system and produce bands on
an RFLP-based system which behave in accordance to Mendelian's first and second laws so that we can
actually do paternity testings and include or exclude individuals in pedigrees like this. So all this work has
to be done just like it is in any genetic system.
These profiles, or these bands can be used to compare known samples, the so-called K-samples in
FBI lingo to the so-called Q samples, the question samples derived from crime scenes. And individuals or
their samples can be included or excluded with relative ease using these highly efficient separation
This work began in England actually in the 1980s when Alec Jeffries now knighted at Sir Alec
Jeffries first used this powerful method to actually exclude a false confessor to one or two brutal crimes
involving young teenage victims. And this work led to the conviction of Colin Pitchfork for the slaying
and sexual assault of both these girls. And this story is in The Blooding for those of you who aren't
familiar with that.
Nowadays a different separation method is used based on the fact that there are four-based pair
tandem repeats called STRs that exist throughout the human genome, and these size differences can also be
used in systems to produce patterns like the electrotherograms you see on this slide. There are typically 13
loci that are used worldwide--some countries use more, some use less-- that produce peaks and valleys like
this that can allow you to distinguish one sample of DNA from another.
This is a moving target, however. That is the technology, and there are new methods that may
automate or reduce the amount of lab wet bench work that's required, and watch the stock. This is not a
stock pit, but watch the stock of Nanogen, Apimetrics, Intel and Motorola because biochips or gene chips
as they're called will be taking off, I would predict, in the next few years because of the biological
applications of these micro-array systems that allow one to categorize literally hundreds of samples on a
single chip, a computer-sized chip.
And the chip readers are being made by Hewlett Packard which will allow us, as shown here in
some data from our lab looking at DNA from tumors and normal tissues from the endometrium to look at
what genes are expressed or not expressed in different human tissues at different times of the season,
different times of development.
We shouldn't forget our friends in the animal kingdom and the plant kingdom. There's a lab in
Ashland, Oregon that does this kind of testing on plant and animal DNA where it's relevant in the
investigation of crimes, sometimes involving humans. And I want to say just a couple of words before I
close about the courtroom issues that remain as I go to court to testify in evidentiary hearings-- these issues
shown here; they're in your handout-- are still coming up from time to time.
Much of this is technology as it moves has to pass through evidentiary hearings. Many of you
know the Frye decision by Hart. It's a two-page decision in 1923-- and this and other federal standards,
including Daubert, Kumo Tire and others, determine whether or not new evidence comes into the courts.
And for every article you could show like this where a court has admitted DNA evidence, this is
from the Boston Globe where the Supreme Court allowed it to come in. There are other cases where the
courts may rule otherwise in individual cases.
So the DNA wars have been fought throughout the country, including in Massachusetts. There
are staggering numbers that can be derived from a mathematical calculation of how rare or how frequent a
particular profile across many genetic loci would be. And these calculations make use of standard
population genetic theory and practice.
The numbers are quite imposing, and many individuals feel that mathematics could be a sorcerer
in our computerized society. And while it should assist the trier of fact, it shouldn't cast a spell over the
Larry Tribe at our law school wrote an article you should read as some point, called Trial by
Mathematics. It doesn't deal with DNA forensics at all, but the theme and ideology there is quite
interesting, and he argues in this review against these, of some forms of statistics in the Court. Other legal
scholars however have felt that the jury must be best informed, and that can only happen with proper data.
Some courts have ruled that experts can offer an opinion saying that a profile is unique. And this
court decision in the state of Washington dealt specifically with DNA population genetics. So this is a
changing platform as well.
I want to finish by inviting you to this about caveats in the interpretation of DNA evidence. We
hear from our friends all the time at work, did he do it; if the DNA matched, he must have done it. As I
would remind all of my own students, at the beginning and at the end of a lecture on forensic DNA,
finding someone's DNA at a crime scene doesn't tell us how it got there and when, no more than not
finding it doesn't mean that I wasn't there, okay.
So I don't think we can put all our eggs in the DNA basket. You know many stories, I'm sure,
about DNA from twins that would not be distinguishable even though their digital fingerprints would be,
is an exclusion, really an exclusion.
There are DNA mixtures that can be problematic to interpret. There are the missing third
parties. There are even odd cases where patients have had bone marrow transplants so that later on when
they're tested, the DNA from their peripheral blood lymphocytes actually reflects the DNA profile of the
donor of their bone marrow, rather than their own genomic DNA.
So there are enough instances like this that should require all of us to remember Louie Pasteur's
quote that Achance favors the prepared mind, and we really need to be thinking probably about these
matters. Thank you for your attention.

No comments:

Post a Comment