Friday, May 2, 2014

PROFILES IN SCIENCE | ERIC LANDER Power in Numbers

http://www.nytimes.com/2012/01/03/science/broad-institute-director-finds-power-in-numbers.html?pagewanted=all&_r=0

CAMBRIDGE, Mass. — His Ph.D. is in pure mathematics, in a subfield so esoteric and specialized that even if someone gets a great result, it can be appreciated by only a few dozen people in the entire world. But he left that world behind and, with no formal training, entered another: the world of molecular biology, medicine and genomics.

Profiles in Science

Eric Lander
This is the sixth in an occasional series of articles and videos about leaders in science.
Rick Friedman for The New York Times
AN EXPERIMENT Eric Lander at the Broad Institute of Harvard and M.I.T., a research powerhouse that he founded.
FIRST PLACE Eric Lander, victorious at the 1974 Science Talent Search. The same year he made the American team in the Mathematics Olympiad.
Tony Cenicola/The New York Times
Dr. Eric Lander
As founding director of the Broad Institute of Harvard and M.I.T., he heads a biology empire and raises money from billionaires. He also teaches freshman biology (a course he never took) at M.I.T., advises President Obama on science and runs a lab.
Eric Lander — as a friend, Prof. David Botstein of Princeton, put it — knows how to spot and seize an opportunity when one arises. And he has another quality, says his high school friend Paul Zeitz: bravery combined with optimism.
“He was super smart, but so what?” said Dr. Zeitz, now a mathematics professor at the University of San Francisco. “Pure intellectual heft is like someone who can bench-press a thousand pounds. But so what, if you don’t know what to do with it?”
Eric Lander, he added, knew what to do. And he knew how to carry out strong ideas about where progress in medicine will come from — large interdisciplinary teams collaborating rather than single researchers burrowed in their labs.
So how did he end up at the Broad Institute, going from the most solitary of sciences to forging new sorts of collaborations in a field he never formally studied? What sort of person can make that journey?
Dr. Lander’s story can be told as a linear narrative of lucky breaks and perfect opportunities. But he doesn’t subscribe to that sort of magical thinking. To him, biography is something of a confection: “You live your life prospectively and tell your story retrospectively, so it looks like everything is converging.”
Yet given that limitation to recreating a personal history, Dr. Lander’s story is, at the very least, unusual.
A Math Club Standout
Now 54, Eric Steven Lander grew up in Flatlands, a working-class neighborhood in Brooklyn, raised by his mother — his father died of multiple sclerosis when Eric was 11.
“Nobody in the neighborhood was a scientist,” Dr. Lander said. “Very few had gone to college.”
His life changed when he took an entrance exam and was accepted at the elite Stuyvesant High School in Manhattan. He joined the math team and loved it — the esprit de corps, the competition with other schools, the social aspect of being on the team.
“I found other kids, ninth graders, who also loved math and loved having fun,” he said.
He was so good that he was chosen for the American team in the 1974 Mathematics Olympiad. To prepare, the team spent a summer training at Rutgers University in New Brunswick, N.J.
This was the first time the United States had entered the competition, and the coaches were afraid the team would be decimated by entrants from Communist countries. (Indeed, the Soviet Union placed first, but the Americans came in second, just ahead of Hungary, which was known for its mathematics talent.)
Dr. Zeitz was Dr. Lander’s roommate that summer. The two recall being the only teammates who did not come from affluent suburban families, and who did not have fathers. But Eric stood out for other reasons.
“He was outgoing,” Dr. Zeitz recalled. “He was, compared to the rest of us, definitely more ambitious. He was enthusiastic about everything. And he had a real charisma.” Team members decided that Dr. Lander was the only one among them whom they could imagine becoming a United States senator one day.
At first, though, it looked as if the young mathematician would follow a traditional academic path. He went to Princeton, majoring in mathematics but also indulging a passion for writing. He took a course in narrative nonfiction with the author John McPhee and wrote for the campus newspaper.
He graduated as valedictorian at age 20, won a Rhodes scholarship, went to Oxford and earned a mathematics Ph.D. there in record time — two years. Yet he was unsettled by the idea of spending the rest of his life as a mathematician.
“I began to appreciate that the career of mathematics is rather monastic,” Dr. Lander said. “Even though mathematics was beautiful and I loved it, I wasn’t a very good monk.” He craved a more social environment, more interactions.
“I found an old professor of mine and said, ‘What can I do that makes some use of my talents?’ ” He ended up at Harvard Business School, teaching managerial economics.
He had never studied the subject, he confesses, but taught himself as he went along. “I learned it faster than the students did,” Dr. Lander said.
Yet at 23, he was growing restless, craving something more challenging. Managerial economics, he recalled, “wasn’t deep enough.”
He spoke to his brother, Arthur, a neurobiologist, who sent him mathematical models of how the cerebellum worked. The models “seemed hokey,” Dr. Lander said, “but the brain was interesting.”
His appetite for biology whetted, he began hanging around a fruit-fly genetics lab at Harvard. A few years later, he talked the business school into giving him a leave of absence.
He told Harvard he would go to M.I.T., probably to learn about artificial intelligence. Instead, he ended up spending his time in Robert Horvitz’s worm genetics lab. And that led to the spark that changed his life.
Making the Leap
It was 1983, and while Dr. Lander was hanging around the worm lab, Dr. Botstein, at the time a professor at M.I.T., was growing increasingly frustrated. He had spent five fruitless years looking for someone who knew mathematics to take on a project involving traits like high blood pressure that were associated with multiple genes. For these diseases, the old techniques for finding traits caused by single genes would not work.
“I literally went around looking for someone who could help,” Dr. Botstein said. Finally, at a conference, another biologist said, “There’s this fellow, Lander, at Harvard Business School who wanted to do something with biology.”
Dr. Botstein hunted Dr. Lander down at a seminar at M.I.T., and pounced. The two connected immediately. “We went to a whiteboard,” Dr. Lander said, “and started arguing.”
Within a week, Dr. Lander had solved the problem. Then the two researchers invented a computer algorithm to analyze maps of genes in minutes instead of months. Soon, Dr. Lander had immersed himself in problems of mapping human disease genes.
He had long discussions with Dr. Botstein about the future of human genomics. It was a time, Dr. Botstein said, “when talk of sequencing the human genome was just beginning to get traction.” Dr. Lander wanted to know if there was any use for a mathematician in biology, and Dr. Botstein, who knew the challenges ahead, assured him there was.
“He had a sufficiently high opinion of himself,” Dr. Botstein said. “He thought that if anyone could do it, he could. He took a chance and dropped his Harvard job. It was clear that teaching economics would no longer be his career path.”
David Baltimore, a Nobel laureate who was then the head of the Whitehead Institute for Biomedical Research at M.I.T., was taken with Dr. Lander’s passion and abilities. He enabled Dr. Lander to become a fellow there and then an assistant professor in 1986.
That same year, Dr. Lander went to a meeting at the Cold Spring Harbor Laboratory on Long Island where leading scientists held the first public debate on the idea of mapping the human genome. Dr. Lander raised his hand and joined the discussion, impressing the others so much they invited him into their circle.
“It is very easy to be an expert in a new field where there are no experts,” Dr. Lander said. “All you have to do is raise your hand.”
Meanwhile, Dr. Botstein and Dr. Baltimore wrote to the MacArthur Foundation recommending Dr. Lander for a “genius” grant. He received it in 1987. He was 30.
“I tried to help him over the years in realizing his dreams.” Dr. Baltimore said. “And he’s been very successful in making that happen.”
Soon, Dr. Lander had become a central figure in the effort to sequence the human genome, leading the largest of the three centers that did most of the work. He combined his mathematics and the biology and chemistry he’d learned hanging out in labs. And he added insights about industrial organization, achieved in his business school days, to streamline the effort and control costs.
What he loved most about the work was the community he had craved, the team effort he had been searching for.
Even before the Human Genome Project ended, Dr. Lander was thinking of how to keep what he saw as a wonderful collaboration among scientists going. There were, by his count, about 65 collaborations among young scientists in Cambridge and Boston, all outside the usual channels.
“Something magical had happened,” Dr. Lander said. “People were coming together and taking on really bold problems.”
It may have had something to do with Dr. Lander’s personality. Gus Cervini, an administrator at Brigham and Women’s Hospital in Boston who worked for him for four years, used to call him “the sun.”
“He has this amazing influence or power on people,” Mr. Cervini said. “He had this ability to get people to really think big.
“When the sun shines on you, you feel like you can do anything.”
Persistence Rewarded
That power may have helped when Dr. Lander approached the presidents of Harvard and M.I.T. and proposed creating a permanent institute to continue the collaborative process that groups of scientists had been improvising. At first, he met with resistance, but he persisted.
Then Dr. Baltimore introduced him to the philanthropists Eli and Edythe Broad, who had made their fortune in real estate. The Broads (the name rhymes with code) visited Dr. Lander’s lab one Saturday morning in October 2002. A few months later, they agreed to invest $10 million a year for a decade, so Dr. Lander could start what he thought of as an experiment with a new kind of research institute.
The Broad Institute was to become a joint effort between Harvard and M.I.T., headed by Dr. Lander, that would encourage scientists to collaborate to solve big problems in biology, genetics and genomics.
Within 18 months, the Broads doubled their gift, to $200 million. In 2008, they contributed another $400 million as an endowment to make the institute permanent. Today the institute has about 1,800 collaborating scientists from the two universities and Harvard’s hospitals.
Its aims sound audacious: “Assemble a complete picture of the molecular components of life. Define the biological circuits that underlie cellular responses. Uncover the molecular basis of major inherited diseases. Unearth all the mutations that underlie different cancer types. Discover the molecular basis of major infectious diseases. Transform the process of therapeutic discovery and development.”
“Half the place is devoted to finding the basis of disease and half is devoted to trying to transform and accelerate the development of therapeutics,” Dr. Lander said. “It’s different from what you find in many university settings where you have many labs, each of whom does its own thing.”
The Broad is an experiment, Dr. Lander said, one that involves an institution and how to do scientific research. “This is in a sense a protected space to see if it works,” Dr. Lander said.
The institute is Dr. Lander’s passion, but hardly his only one. His days start and end in a gym on the second floor of his house, where he has an elliptical cross-trainer. He uses it for two 40-minute sessions, one in the morning and one at night, watching Netflix videos and burning — according to the machine — 1,000 calories a day. He reports that he lost 42 pounds last summer without changing his diet.
They bought the place, a converted schoolhouse, when his wife, Lori Lander, who is an artist, pointed out that it had a basketball court on the top floor — it could be a kind of neighborhood hangout, so the Landers would always know where their three children were.
After his morning workout, he sometimes goes to a local bakery where he can work quietly. He arrives at the Broad between 8 and 10 a.m. In the fall, he teaches introductory biology to a class of 700 M.I.T. students on Monday, Wednesday and Friday mornings. He often meets with graduate students and postdoctoral fellows in the afternoon to discuss their work.
Then he has his administrative duties and his meetings with philanthropists, trying to raise more money. He also spends 20 percent of his time in yet another role, as co-chairman of President Obama’s Council of Advisers on Science and Technology, which deals with topics like influenza vaccines, health information technology, science education and energy policy.
In the evening, around 6:30 or 7, he has dinner with his family. His wife cooks — Dr. Lander loves to cook but says he just does not have time.
He also reads — fiction, nonfiction, New Yorker articles — but has no patience with poor writing.
“I am very eclectic in my reading, but it has to be really well written,” he said. “That’s a huge barrier.”
On weekends he and his wife try to get to New York for the theater, another of his passions.
And he marvels at how his life has turned out. “I feel like it’s so incredibly lucky to end up here,” he said. “I could not have planned this. What if I hadn’t met David Botstein? What if I hadn’t gone to a meeting where the human genome was discussed? I have no idea. This is as random as it gets.
“It’s a very weird career.”

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