From: Chuck Gierhart Evolution is not an act of faith. It is an act of
observation. It's story is told in the fossil record and your RNA and DNA.>>
The head of the Human Genome Project is a devout Christian and true believer
in stem cell research. by David Ewing Duncan (published online February 20,

Francis Collins is changing the way we think about DNA. First he helped
decode the human genome. Now he oversees a research empire at the National
Human Genome Research Institute (part of the sprawling National Institutes
of Health), leading the race to find disease-causing sequences hidden in our
genes, doling out hundreds of millions in grant money each year, and
defending controversial science in the charged politics of Washington, D.C.

A devoted Christian, Collins defends evolution and embryonic stem cell
research in his new book, The Language of God: A Scientist Presents Evidence
for Belief (Free Press, 2006). He dismisses religious extremists and
scientist-atheists as equally shrill and believes that both sides push their
beliefs on a public who prefers that science and religion remain separate.

In college Collins found biology boring and trained as a chemist, only to
become a physician and then a famed gene hunter at the University of
Michigan at Ann Arbor, where he identified the gene for cystic fibrosis and
helped find the gene for Huntington's disease. He blazed into the public eye
in the late 1990s during the bruising competition to sequence the human
genome; he ran the $3.7 billion public effort while J. Craig Venter
conducted a parallel effort using private funds. After much scientific
mudslinging, the two sides declared a tie in 2000 and were feted jointly at
the White House.

Moving beyond mere code breaking, Collins has been focusing on the recently
completed International HapMap Project, a genomic atlas of clusters of
disease-causing snippets of DNA. The project catalogs human variability and
identifies patterns of genes that are linked to health and disease.

DISCOVER contributing editor Duncan spent an afternoon with Collins in his
offices at the NIH. Collins, a lanky man in well-worn beige jeans and a
flannel shirt, has an aw-shucks breeziness about him-an ease that belies his
status as one of the most powerful scientists in the world.

In your book, you stake a middle ground between the view that there is only
science and the idea that an intelligent being directs human affairs. How do
you strike a balance?
We live in an unfortunate time when the Richard Dawkins crowd says religion
is silly, and other people say evolution is silly. Most people don't agree
with either extreme. The dominant position in the past for most working
scientists was a middle ground: You use the tools of science to understand
how nature works, but you also recognize that there are things outside of
nature, namely God, for which the tools of science are not well designed to
derive truth. The middle-ground position is that there is more than one way
to find truth, and a fully formed effort to try to answer the most important
questions would not limit you to the kinds of questions that science can
answer, especially the eternal one: Why are we all here, anyway?

You're a born-again Christian who suggests that therapeutic cloning could be
acceptable. Some other devout people consider it fundamentally immoral. What
do you see differently?
There is a difference between doing research on an embryo that was generated
by sperm and egg coming together, which is the way human beings are created,
versus the very bizarre laboratory phenomenon of taking a nucleus from a
skin cell or the udder cell of a sheep and putting it into an environment
that takes it back in time to its stem cell state. In public discourse,
they're both called embryos. Even though the somatic cell nuclear transfer
approach is a very different biological phenomenon, in many people's minds
it has been all blurred together. As a result, we've really missed out on a
chance for a much more thoughtful, nuanced discussion, and we're still
trying to recover from that.

What kind of reaction has your book provoked?
I didn't know quite what to expect, but the response has been amazing. Most
of the large volume of letters and e-mails I have received have been
encouraging and positive, both from the scientific community and from the
religious community. A few scientists have written that it is inappropriate
for a scientist to write about harmony with faith, because they think that
faith already has too much power in the United States. A few conservative
Christians have been stridently critical about my endorsement of theistic
evolution. Most heartwarming have been a few dozen very personal messages
from individuals who had been struggling with whether they were forced to
make a choice between science and faith and were relieved to hear that it is
possible to embrace both.

What did you think you were in for when you signed on to the Human Genome
Project in 1993?
When I came here, I don't think that one person out of 10 actually believed
that we would sequence the human genome by 2005. We were feeling our way in
the dark-we didn't have the methods, the people, the confidence. We were
really struggling.

What exactly is a gene?
That's a good question. You ask 100 molecular biologists that and you'll get
110 answers. I have a pretty classic answer-a gene is a well-defined segment
of DNA that encodes for a protein. Some genes also code for segments of
proteins. The key thing is for a gene to have an exon [a stretch of DNA that
transcribes into RNA]. There are also pseudo-genes that encode RNA but have
no apparent function. They are holdovers.

Why does the body keep those around?
It's like junk in your basement. Some of it could be thrown out, but some of
it you keep around in case some day you need it.

What are you finding about the importance of known genes versus the "junk
DNA" in between them?
We're learning a lot about this. At the NIH we have a project called
ENCODE-Encyclopedia of DNA Elements. It's a coordinated effort among 30 labs
to identify all of the parts of the human genome that have biological
activity, including the so-called junk DNA. We have found that there is a
lot more action. There are transcription factors happening and RNA being
made. We still don't know if all of this activity is actually doing
something or if it's the equivalent of background noise, but we're working
to find out.

Now that the human genome has been sequenced, what more is there to learn
about genetics?
That was just the beginning. Back in 1997, two colleagues and I wrote a
paper about the promise of having a really rich catalog of human genetic
variation. I thought that was something we should strive for. I didn't think
we'd get there this quickly! That project, called HapMap, got started in
2002 with scientists from six countries aiming to lay out how variation is
organized across all the human chromosomes in four different populations.

What is a HapMap, and why is it so important?
A haplotype is a stretch of DNA with a particular combination of genetic
spellings that vary among different people. Haplotypes in vulnerable gene
regions can be responsible for increasing risk of disease. The idea of the
HapMap Project was to define the spelling differences in the human
population-there are about 10 million of these, called SNPs, or single
nucleotide polymorphisms-and how they are organized into haplotype
neighborhoods in the genome.

How does that help you learn about disease?
Searching for genetic variations that predict an increased risk of disease
can be terribly difficult and expensive. If you had to test all 10 million
SNPs in hundreds or thousands of cases and controls for a disease, it would
be completely impractical and unaffordable. HapMap provides a valuable
shortcut, as it defines the neighborhoods within which the SNP spellings are
tightly correlated. In each neighborhood, you can identify a small number of
"tag SNPs" that serve as a proxy for all the others that you didn't test.
That way, instead of having 10 million things to sample, you can sample
using about 300,000. That's what we're doing now, when we look for diabetes
genes in my lab, and that's what the whole world is doing with this map for
lots of other common diseases.

Has linking genes to diseases become easier since you began your career at
the University of Michigan?
Searching for diabetes genes is much harder than anything I did in Michigan.
At that time, I was looking for genes for Mendelian conditions, like cystic
fibrosis and Huntington's disease: There's one single gene, and if you have
the misspelled version of the gene, you are extremely likely to get the
disease. Whereas for heart disease or schizophrenia or diabetes, no single
gene is going to have a very large effect-these are complex diseases with
many genetic and nongenetic causes.

The underlying science is also, frankly, rather tough to explain. Is there a
way to describe all of this more simply?
Not really, and it hasn't helped our cause that we geneticists give
inscrutable names like "haplotype" to our concepts. This really doesn't help
when you're trying to explain this science to the public, or to Congress.

The race to decode the human genome sparked a lot of debate about whether
public efforts or private companies are better suited for handling such huge
science projects. Which side won?
The evidence is absolutely clear that large genomic data production projects
should be public efforts. These data sets can stimulate research in both the
public and private sectors if they are immediately made available to all
scientists, without any barrier to access. This can be readily seen by the
success of the Human Genome Project, and the subsequent public sequencing of
more than two dozen other animal genomes, the HapMap, the Mammalian Gene
Collection, and the rest. No company sees big genome data generation
projects with private subscriptions as a viable business plan anymore.

Are these big biology projects increasingly international?
I think genomics has led that charge. The genome project was an
international effort. Scientists from six countries agreed to the same
standards and joined forces. That was unprecedented. The HapMap project was
the same way.

One recent report suggested that the United States may not be the leading
economy by 2050. India and China may pull ahead, and biotech will be a big
part of that advance. Do you agree?
It's clearly a possibility. India's primary strength has been computation,
and they've been slower to join projects in human genomics, in part because
of the restriction that no samples can leave the country. That policy is
understandable, because there was a time when there was a lot of "biopiracy"
going on, if you want to call it that. But now, in this more open
environment where international collaboration means sharing samples, they
are rethinking this. We've had intense collaboration with China for six or
seven years-Yang Huanming, director of the Beijing Genomics Institute, was a
contributor to the sequencing of the human genome. China has quickly figured
out where they want to go with this, and they've done a good job of it.


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