Big Man in Genes
"Medicine's Springboard: Perceptions from a
Few Consummate Geneticists"]
By Gillian McCallion
| Portrait by Rich Riggins
The head of the
prestigious McKusick-Nathans Institute of Genetic Medicine talks about
why even school children must begin to understand some of the basics of
and I have been downstairs to grab a cup of rum and butter coffee. He
has removed his tie, undone his top button, checked his e-mail and we
are ready to talk. He slides across his perfectly ordered office to fiddle
with an expensive-looking stereo, explaining that he once read an article
on the virtues of playing music in one's office. Apparently it makes awkward
silences less awkward. In general, he chooses classical music. No one
can be offended by that. "I'd better turn this off," he says now.
Chakravarti is the
new Henry J. Knott Professor and director of the McKusick-Nathans Institute
of Genetic Medicine. At 47, some might suggest, he is young to hold such
a position. His track record suggests age has never been an issue.
in the United States from his hometown of Calcutta, India, in 1974 on
the day Nixon resigned. He'd finished an undergraduate degree in statistics
and mathematics and was headed for the University of Texas in Houston
to do a doctorate in human genetics. Three years later, he was cited among
the "who's who of students at American colleges and universities." By
1989 he'd become an integral part of the team that identified the gene
responsible for cystic fibrosis.
Chakravarti is perhaps
best known for his analyses of the genetic predisposition and molecular
mechanisms involved in such common and complex human diseases as diabetes,
heart disease and mental illness. He is somewhat less well-known for an
Indian cookbook he authored during his graduate student years, "Not Everything
We Eat Is Curry." One year ago, he arrived in Baltimore from Cleveland's
Case Western Reserve University, handpicked by a blue-ribbon committee
as the first head of the McKusick-Nathans Institute of Genetic Medicine.
With him were his wife Shukti, an assistant professor of medicine, and
their two daughters Priya, 13, and Indira, 8.
As the world propels
into an era in which genetic knowledge will become crucial to the practice
of medicine, Chakravarti talked about how he views his role at the helm
of the prestigious institute.
There was a lot
of speculation about who'd be chosen to head up this Institute of Genetic
Medicine. Any thoughts on why you got the job?
One reason may be that I come from both a computational and an experimental
genetics background. Also, genetics has changed. It's gone from the study
of the importance of genes in single gene disorders, which, although very
important, affect relatively small numbers of patients, to the study of
genes that affect common disorders which are subject to the influence
of multiple genes. We're all interested in these common disorders but
not very many geneticists know and understand them in molecular terms.
I believe my previous work is important to this understanding.
gene disorders are the so-called complex diseases?
Yes, traits like hypertension, heart disease or mental illness. These
are common chronic disorders. The importance of genes in these disorders
is not in doubt but the way in which these genes play out their roles
is very much in doubt.
What's been your
big contribution in this area?
I was one of the first few scientists to vocalize the importance of genomics
in the study of complex traits which was largely descriptive before that.
I also recognized the details of some of these common complex traits and
the methods by which they could be identified and understood including
the use and importance of studying genetic variation in SNPs (single nucleotide-polymorphisms).
But neither of these is my greatest contribution. That is yet to come,
It sounds like
you have a professional Holy Grail?
I have no single Holy Grail, but it would be great to know, even in a
single disorder, why we need mutations at more than one gene to elicit
a disease effect. I think we need that conceptual understanding even in
one system. We have the beginnings of this in some cancers but not for
Are we close?
Yes, I think we are near. Perhaps in a year or two we'll have some understanding
of what the meaning of a complex disorder is. We call these diseases complex
because we're ignorant about the biochemical nature of their genes and
mutations and the nature of the interactions that lead to such intricate
biochemical behavior. We need genomics technology, but to crack the genetic
basis of complex diseases we'll also need to understand the basis for
complex inheritance. Once we do that, I suspect we'll start understanding
the general rules of the nature of these disorders.
Changing to a
new university can't be easy. What persuaded you to come to Hopkins?
That's actually fairly simple. I wanted to make some changes in human
genetics. If you want to do that, the institution really matters. This
sounds odd but despite all the hoopla there aren't a lot of institutions
that really appreciate what genetics is and what it can do. My colleagues
at Hopkins do. Secondly, Hopkins is close to many other fantastic institutions
along the east coast, and to the NIH. Thirdly, it's possible to attract
an excellent caliber of trainee here.
the core group you want to put together must be taking up a lot of your
time-not only the trainees you want to bring in, but also your genetics
faculty. Do you have some underlying principles for choosing your faculty?
The most important
is to gather together individuals who believe in the same kinds of changes
I do and who are outstanding scientists. Genetics is a very young field,
at least in its modern incarnation, so my bias is to bring in many more
junior faculty than senior. Junior scientists are more adaptable to change
and they're also the repositories of all this new information.
The three areas
we plan to concentrate on are complex disorders, epigeneticswhich
is the study of why two entities that have the same sets of genes and
the same form still can have different behaviorsand developmental
genetics. We need faculty members who are very well versed and comfortable
with all the new technologies. In general, biologists aren't. Ideally,
we need faculty who can bring in expertise in genomics, in computational
biology and in manipulating the actions of multiple genes simultaneously.
You've said you
want to help the public think about genetics in a new way. What exactly
do you mean?
My goal is simply to change the way we do human genetics, to make human
genetics much more real in the clinical realm and to make genetics of
the human a much more intrinsic part of both basic research and education.
Do you think
scientists in general have a good track record when it comes to educating
the public about their work?
I think they're much better today than they used to be, but I'll go out
on a limb and say in general scientists have not been very interested
in educating other people about what they do and why they are doing it.
It just hasn't been high on their list of priorities.
Is there any
reason why it's necessary for the average person to have an idea of what
goes on in scientific research?
At one point, people believed that science was completely serendipitous.
Newton didn't have to spend much money to have an apple drop on his head.
Einstein was so brilliant that great ideas just occurred to him, but that's
not how we practice science now. Science happens because of a very persistent
and thoughtful and highly structured way of doing experiments, a very
thorough way of sifting through nature. And because we do it this way
it requires great amounts of public support. There is no longer the perfect
trust that once existed between the public and scientists. As scientists,
we need to be much more transparent. Individual scientists need to speak
to and write for the public at large explaining what they do, even when
they have no exciting discovery to report.
You've even talked
about wanting the institute to form relationships with elementary schools.
Isn't the science education that our children are receiving satisfactory?
My children are taught many more aspects of science than I ever was, although
clearly a few decades have passed since then. In terms of biology there
seems to be an emphasis on ecology and population biology. The brain is
not really covered in depth. Children know about genes but not really
in any meaningful way. It's probably a question of time but it is an area
of concern to me. The only way of having a scientifically aware society
is by giving people the relevant information. Getting anything into the
school curriculum is a fairly difficult process. But there are many organizations
working in this area and one has to keep at it.
How about teaching
the medical world about advances in genetics?
Yes, I am quite concerned about educating our colleagues. The word genetics
is too broad and we have to emphasize much more specificity. We have to
teach physicians, for example, why all these modern advances make sense
and why they are important to the lives of their patients.
Would you say
that this general lack of understanding about genetics is your biggest
I tend not to focus on frustrations; I wouldn't be doing this job
if I didn't believe that one could make a difference. But I do think the
aspect that I probably find most frustrating and really the biggest challenge
is that knowledge of genetics is really very non-randomly distributed
among the constituency that needs to understand it.
And that constituency
Scientists and physicians first of all. Various scientists understand
genetics to varying degrees. Some clearly believe that genetics is no
more than a set of tools. Genetics is much more than that. It is an intellectual
construct, it's a way of viewing the world through the lens of variation.
What makes genetics unique isn't that it's defined by a set of codes-all
biological systems are. In the case of genetics, though, this code and
changes to it are inherited. And it is this feature that affects variations
in gene functions that form the basis for most human diseases.
But if genetic medicine
is going to become a reality, politicians also have to understand it.
There are major questions concerning privacy, confidentiality and insurability
that need to be dealt with. There are clearly a few members of the government
who understand it very well but the vast majority don't believe it's important
enough to warrant their attention. So the most frustrating aspect is that
scientific fixes may come before societal fixes.
The current administration
in Washington certainly appears to have some ideas that could affect genetic
The previous administration
was more knowledgeable about these issues but it was not knowledgeable
on day one. I think that whatever the administration, the outcome really
depends on whether or not it has some articulate people who understand
the issues and can get the president's and Congress' attention.
Right after they
finished mapping the genome, scientists and the press made a lot of claims
about the impact that was going to have on medicine and research. What's
In science we like things to be pre or post something-in this case pre
or post genome. I actually don't think we are post-genome. I think that
this is the beginning of the genome age, merely after we have the sequence.
We have yet to show how best to interpret it and use it. The most obvious
implication is that we have to change the way we do the science. In the
past we haven't considered how a genome's worth of biological information
impacts, for instance, the metabolism of glucose or the way in which tumors
metastasize. How do we do this? It's one thing to conceptualize it but
to be able to do it practically and to make the thinking and the technology
widely available… that's a challenge.
Let's end with
a personal question. What do you do when you're not working?
These days, I spend as much time as I can with my family. I didn't do
enough of that in the past. But this job is really tough and if I'm not
careful, I could burn myself out.