Genetics, race, and evolution
the director of Princeton's new institute for genomics has to say
of the newest and most important initiatives at Princeton is a new
genomics center, where new scientific approaches to biology are
going to happen, according to Shirley M. Tilghman, the director
of the Lewis-Sigler Institute for Integrative Genomics.
"Biology is going
to make a transition from being a data-poor science to being a data-rich
science," Tilghman said. "We can now ask questions about
living systems that we could never ask before because we just didn't
have enough information." She added that biologists have been
functioning for the last 25 years by taking things apart and studying
each of the parts individually. "And now we sort of have a
sense that we are at the brink of being able to put the pieces back
Tilghman, who has been
at Princeton 14 years, said that the center has been up and running
for 18 months, and a new building, designed by Rafael Viñoly
(who also designed Princeton Stadium) is in the works.
In addition to research
activities at the institute, new undergraduate courses will be offered.
"There should be
a major impact on the curriculum as a result of the activities in
this institute. And not just in biology, but in physics, in chemistry,
and in computer science, because all of these sciences are going
to impinge on the way in which we go about answering the question
of how all the pieces we've been studying individually work together,"
Another thrust of the
institute will be various symposia. Last year bioinformatics was
the focus of one such gathering - taking a look at the intersection
between biology and computer science. This fall, another took place
that looked at the question of how chemists are coming at the problems
in biology. Another one, called from Physics to Biology, did the
same for physicists.
With the symposia, Tilghman
said, "we're trying to create the discussions and the dialogues
and the interfaces that will become reality once the building is
completed in two years. The other thing I'm very happy to say is
that we have forged alliances with the Center for Human Values,
and in particular with Peter Singer."
This alliance with Singer
yielded another gathering. Two speakers came to campus the beginning
of October to talk about the genetics of violent behavior, an interesting
issue from a scientific perspective but one which also has major
bioethical implications, said Tilghman.
Human genome project
The latest big news in
the field of genomics was splashed across all the newspapers across
the country a few months ago: the decoding of the human genome.
When asked how Princeton
fits in with the human genome project, Tilghman, who for the last
several years has chaired the External Advisory Committee at the
National Institutes of Health that has overseen both mouse and human
genome sequences, smiled. "I actually spend a lot of my time
thinking about how the federal project is going. The sequencing
is being done in highly specialized centers, at five large institutions
across the world as well as in the few smaller centers. But we always
made it clear as we thought about the Institute here at Princeton
that the Institute was not going to actually sequence. What the
Institute was going to do was to essentially take advantage of the
sequence and to move forward at how do we use this sequence to understand
new things about biology."
Now that pretty much
all the parts of the human genome have been identified, the next
step is what is called annotation, or figuring out what the parts
do. Tilghman keeps a ready metaphor for the nonscientist.
"Think of it as
a kid with a radio. What biologists have been doing is what the
kid does when he or she takes a radio apart. The genome project
has identified all the parts. We can say with some confidence that
yeast has 6,000 genes, in other words, there are 6,000 products
that go into making a yeast cell a yeast cell. The number for human
is still being hotly debated. It could be as small as 40,000, it
could be as large as a 100,000. Someplace in that range. Now what
the genome project has done has at least given us a chemical identity
of those parts. But that's different than knowing what each part
"So it's just like
the kid who has all the parts on the table, and the kid's looking
at this and saying 'Well, this part you know looks like a screw,
and I guess it is a screw. But this part, I've never seen anything
that looks like this part. What does this part do?' And that's where
we are today in the year 2000. We have all these parts on the table.
Some of them we know a great deal about because we've been studying
them for 25 years. But actually a shocking percentage of them we
don't know anything about what they do. We just know they're there."
Figuring out what the
parts do will be one of the thrusts of the research at the Institute.
One way to go about it is to make a mutation in the gene and then
see what goes wrong when that gene isn't working. Scientists then
deduce what the function of that gene is.
"Genetics is a great
tool, but not a perfect tool," Tilghman said. For instance,
in the mouse genome, which is her particular area of research, she
studies a gene that if mutated completely deletes the gene. "Nothing
bad happens to the mouse. Now that is a conundrum because this gene
is in all mammals. It is highly conserved. Evolution wants that
gene there. And yet when we take it away nothing happens. It could
be that it so important that there's another gene that will compensate.
It's a back-up. So that's why genetics isn't a perfect tool."
Another tool is biochemistry,
where scientists can purify the product of the gene and then try
and understand what it's biochemical property is.
But Tilghman hopes that
at the Institute, some of the research will be broader. One of the
newest researchers at the institute is Saeed Tavazoie, who approaches
the annotation in this way. As Tilghman explains, " The idea
is to say, 'Let's see if we can take all of the genes and figure
out what they do, what each one does, but do it in a sort of multiplexed
way. So that we can actually get the answers to a lot of genes at
once instead of one gene at a time.'"
But the Institute is
really going to go further. "We're going to try and pretend
that all that annotation has happened. And we're going to say, 'Now
that all the parts have labels and all the labels are meaningful,
how can we use that information to know the logic behind a cell
responds to its environment. We know that a cell has to respond
to many, many signals in its environment, and we study them by studying
them one at a time. But we've never asked in totality how does the
cell respond to them all at once. Because that's what happens in
real life. So we're trying to actually jump beyond where the science
is right now and anticipate what the key problems are going to be
in five years.'"
Once the genome is understood,
it is absolutely irrefutable that it will lead to practical, clinical,
and disease prevention discoveries, said Tilghman.
on the genetic level
Another realization coming
from the genome project might have a profound effect on social understanding.
"From a scientific perspective," Tilghman said, "there
is no such thing as race. You cannot scientifically distinguish
a race of people genetically from a different race of people. Now
you can find a gene that affects skin color, and you can
show that this gene has one form in people of African descent and
is different form of people, let's say , of Danish descent. But
that's just one little change. That doesn't make them a race. If
you look at all the other things in their DNA that determine all
the ways in which we're the same, in fact the two DNAs are indistinguishable.
So it seems that there
is only one race: the human race. "There are variants,"
Tilghman said, "and the variants we pay more attention to are
the variants that are visible to us. But in fact the variants that
probably matter much more than whether your skin is black or your
skin is white are variants that predispose you to breast cancer.
And those occur in all populations; variants that predispose you
to heart disease; variants that predispose you to Alzheimer's disease.
And those do not track by race. So the important ones are not the
And where does that
Another area in which
scientists find confirmation on the genetic level is the area of
evolution. When asked if Tilghman believes in the theory of evolution.
She smiled again and nodded emphatically. "Oh yeah. I'm a scientist,
so I spend my life evaluating information and asking whether that
information supports or doesn't support various models. If one looks
at the question of evolution, in my opinion, the evidence is overwhelming.
Most people who've looked at it objectively believe that that's
And how does a scientist
answer the question of how did life start? Tilghman said, "Well,
I'm an atheist. So I look for scientific explanations, and I think
that we don't have a definitive answer to that question as scientists
. What we have is now I think a reasonable idea of what the conditions
on earth were at the time when the first biological molecules were
arising, were appearing. We don't know the order in which those
molecules appeared, and in fact that's a very contentious field
right now in early evolution. There are people who favor the idea
that the first molecules were RNA-like. There are people who believe
the first molecules were protein-like. Both can sort of show you
experiments that would argue in favor of their particular idea.
How it really happened we don't yet I think have a clear idea, and
yet I think the fact that we can create these molecules in test
tubes that mimic those conditions tells us it's plausible that that
in fact is how life evolved. It's a fascinating problem."
By Lolly O'Brien
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