The
sequencing of the human genome was a decade and a half in the making and
undeniably represents one of the great achievements of modern science. To
geneticists and biologists it also represents the opportunity to elucidate, for
the first time ever, the genetic basis of human variation and the genes that
underlie common human diseases. Some researchers are just now phrasing the
questions they want to ask of the genome sequence. Others, like geneticist Eric
S. Lander of the Whitehead Institute, Cambridge, Massachusetts, have known the
questions for 15 years and have spent much of the intervening time working on
the sequence so that they could get their answers.
As director for the Whitehead's
Center for Genome Research, Lander was first author on the seminal sequence
publication from the International Human Genome Sequencing Consortium. The
report, published last February in Nature
(409: 860-921, 2001) has already been cited more than 600 times. As the lead
story in this issue recounts, the paper's first-year citation total
was far and away the highest of any publication since Science Watch began tracking such figures eight years ago (a total
rivaled, of course, only by the Science
paper published the same week, reporting data from the privately funded
human-genome project). But Lander's
impact on the field of human genetics goes far beyond this single paper. His
appearance in the table in the lead
story of this issue marks his second consecutive
placement in the annual Science Watch
listing of hot scientists, based on his contribution to five highly cited
papers published over the last two years. In total, Lander now has two papers
with over 1,000 citations each (with another at 900-plus and counting—see the
table on page 4) and two dozen more with more than 100.
Lander, 45, received his bachelor's
degree in mathematics from Princeton and was awarded a Rhodes Scholarship to
Oxford University, where he received his doctorate in mathematics in 1981. He
spent the next nine years as assistant and associate professor of economics at
the Harvard Graduate School of Business Administration. He started working at
the Whitehead Institute as a Whitehead fellow in 1986. Lander is also professor
of biology at the Massachusetts Institute of Technology and a scientific
founder of Millennium Pharmaceuticals.
From his office at the Whitehead
Institute,
Lander spoke with Science
Watch correspondent Gary Taubes.
It might seem irrelevant now, but what kind of mathematics did you study? And
how did you end up teaching at Harvard Business School?
I did algebraic combinatorics, applications of group representational theory to
coding theory. I studied with Peter Cameron at Oxford. As for business school,
I loved math and always enjoyed doing it, but I didn’t want to do it as a
career because it's a fairly monastic career, and I'm not a very good monk. I
wanted to do something else but wasn't sure what. Through a series of accidents
a former professor of mine at Princeton introduced me to a statistician at
Harvard Medical School who introduced me to Howard Raiffa at the business
school, where they said, “We'll give you a job teaching managerial economics.”
So I took them up on the offer and,
while I was there, I learned genetics and molecular biology.
Was there one particular incident that got you started?
I was writing a book, derived from my thesis, on information theory. I guess
someone suggested I should look at neurobiology, because there's a lot of
information in the brain. I started reading some mathematical neurobiology and
realized that I didn't understand wet neurobiology, so I had to read that, and
to understand that I had to learn cellular biology, but to understand that, I
had to learn molecular biology. It was an infinite regression that concluded at
genetics, and I'm still there. When I finally feel I have learned genetics, I
should get back to these other problems. But I'm still trying to get the
genetics right.
Along more up-to-date lines, what was the hardest challenge in getting the
human genome sequenced?
Probably coordinating lots of different things at once. It's a complex process
that involves 20 different things working: getting the right clone selected,
for instance, working out the procedures to prepare the DNA, working out
robotics of many many different sorts, working out different kinds of
biochemistry, hiring people, training people, doing computational analysis. The
hardest part was coordinating all 20 pieces, which all have to work. It's not
as if there was one extraordinary hard part and everything else was easy. Any
one of the 20 things could have been the rate-limiting step. We had to manage
them all simultaneously, like juggling 20 balls at once. We had a spectacular
group of colleagues and everybody got really good at juggling. By the end of
the project, everything was working really simply, beautifully, and smoothly.
But that's how it always works. It's like trying to fly an aircraft while
you're still attaching pieces to it. You have people crawling out on the wings,
changing the propellers and things. Finally, when you're just about ready to
land it, you have the whole thing in perfect working order.
Was it a difficult transition going from a bench scientist to running such a
large project?
To some extent, but I still also do an awful lot of individual research. I
guess the accident of having taught at the business school for nine years, and
having taught a course for three years on managing science-based businesses,
helped me out. continued
.
