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Jeffrey M. Friedman, M.D., Ph.D. On the wall in Jeffrey Friedman's office hangs a piece of X-ray film—a black-spotted sheet that the Rockefeller University researcher developed at 5:30 one spring morning. The film told Friedman that he'd found what he and his colleagues had been searching for: ob, the gene that encodes the weight-regulating hormone leptin. “It was astonishingly beautiful,” he says of the data. Seeing the result, he jokes, “was the closest thing I've ever had to a religious experience.” Although these days he doesn't have time to personally develop X-ray films, Friedman has always enjoyed lab work. “I love the craft of it, working with your hands,” he says. And he appreciates that the busywork of doing experiments in the end produces “aesthetically pleasing results that mean something.” Friedman wasn't always gifted when it comes to handling test tubes. “I think I was below average,” he says. He used to set up the same experiment three days in a row, so if the first one didn't work, he'd have a backup. “I was like the Galloping Gourmet,” juggling different versions of the same dish, he says. “I got a lot of work done—but it wasn't pretty.” Friedman wasn't born an experimentalist—nor was he born with a burning passion to do science. Friedman more or less stumbled into his scientific career and his studies of obesity. “I have a friend who calls me 'the accidental scientist,'” he chuckles. As a young man, Friedman set out to become a physician. “Where I grew up, the highest form of human achievement was to become a doctor,” he says. “And I didn't strongly object.” So Friedman entered a six-year medical program out of high school and received his M.D. at the age of 22. At that point, he thought he'd do a one-year fellowship. “The good ones filled up well in advance,” he says, and by the time he got around to applying, Friedman found himself with “a year to kill.” During medical school, Friedman had enjoyed spending summers puttering in the lab. So he went to work with Mary Jane Kreek, an investigator at Rockefeller University who was studying addiction. At the time, researchers had recently discovered endorphins—opiatelike molecules made by the brain itself. Friedman was intrigued. “The idea that molecules can change complex behavior—that there are chemicals that influence how the brain works—was incredibly exciting,” he says. “Over the course of that year, I really came to love science,” says Friedman. “As a doctor, you're trained to absorb the facts you're given and accept them,” he says. “Science is almost the opposite. It's a frontier of discovery that's always moving. And I decided I wanted to do research.” While working with Kreek, Friedman found he needed to learn a technique that would allow him to measure endorphin concentrations in the brain. Kreek introduced Friedman to Bruce Schneider, another Rockefeller researcher, who was using a similar approach to study CCK, a hormone made by the gut and secreted in response to food. Some researchers thought that CCK might be the missing piece in the puzzle of the obese mouse. For decades, scientists had been studying a special strain of fat mice that appeared to lack a molecule that normal animals use to control their appetite. But Schneider didn't think that CCK fit the bill. “And I believed he was right,” says Friedman. Together he and Schneider showed that obese mice and normal mice produce the same amount of CCK, proving that the molecule could not be the long-sought-after appetite suppressant that was missing in the plump animals. The work whetted Friedman's appetite for obesity research, and when Friedman got his own lab at Rockefeller, he set out to find that factor—a task that would take eight years. “I believed that ob was going to make a hormone that regulates weight,” says Friedman. “That belief kept me at it for all that time.” At the same time, Friedman feared that someone would beat him to it. “I imagined lots of people were working on it. It was so interesting and important—how could people not be working on it?” So he fretted. “From '90 to '94, I never got a single phone call where my first thought wasn't that I was about to be told that someone else had landed on ob,” he says. “This is not a recipe for good mental health.” But Friedman hung in there, doing experiment after experiment. And on May 8, 1994, he got the result he was looking for. “It was amazing. It was absolutely exhilarating. I couldn't sleep at night for months just thinking about how unbelievably elegant and beautiful nature's solution to the calorie-counting problem is.” Later that morning, Friedman got a call from a cousin who'd scored third-row seats to a New York Knicks basketball game—the one in which John Starks dunked over Michael Jordan's head. After the notorious “Dunk Game,” Friedman went out to celebrate his scientific success over a pitcher of beer. “And on Monday we got back to work.” The researchers had a lot to do. They wanted to show that the product of the ob gene—leptin—was present in the blood and that it had the activity Friedman expected: an ability to make fat mice thin. The paper detailing these initial studies of ob made the cover of Nature magazine. Friedman's copy, which also hangs on his office wall, is autographed by Mark Messier, a center for the New York Rangers hockey team. A journalist who interviewed Friedman about the ob work was covering a Rangers game later that day, and she took the magazine along. “I always wonder what Messier must have thought” of the odd request, Friedman says. Friedman still attends games, but his real passion is science and the study of obesity. Since the early discoveries, he and other scientists have found that a certain percentage of obese people have defects that render them leptin deficient. Restoring their leptin brings their weight back to normal. “I like the idea that some people have benefited from my work,” says Friedman. “It gives me a real sense of gratification.” The desire to understand human obesity also drew Friedman to Kosrae, a small island in the South Pacific where the condition is epidemic. The locals have developed a taste for junk food, although what Friedman remembers most is the island's signature dish. “I must have had tuna and mangrove crab at every meal,” he says. Friedman loves to travel, but New York is his home. “Living in New York is like traveling all the time,” he says. “After being here 25 years, I can still walk down a street I've never walked down before. It's amazing. There's always a sense of surprise and exploration. Once you get a taste for it, it's hard to give up. When you leave New York, you feel like you're missing something.” It might have been a happy accident that brought Friedman to New York, to Rockefeller University, and to science. But it seems it's no accident that he has stayed. 10/04 |
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