The Science of Collaboration

Time has turned one wall in Robert Weinberg's office at the Whitehead Institute for Biomedical Research into a family photo gallery. Across the room, a tangle of tropical plants has grown as thick as the record of his 20 years of collaborative research. Weinberg, a world-renowned biologist and cancer researcher, was a Massachusetts Institute of Technology professor in 1982 when David Baltimore, the Whitehead's first director, asked him to become a founding member of the fledgling institute in Cambridge, Mass. Baltimore laid out a vision of a research center that not only would allow scientists to pursue the work they loved but also encourage them to collaborate with colleagues in other disciplines. Weinberg liked what he heard and took a chance. "I came with no expectations," says Weinberg, winner of the 1997 National Medal of Science. "It turned out to be an excellent decision on my part." A few blocks away at the Whitehead/MIT Center for Genome Research, Chad Nusbaum sits in his office. Except for the physical map of the mouse genome on one wall, the room is decorated economically. Nusbaum came to the Whitehead four years ago, drawn by the same promise of scientific freedom and collegial cross-pollination that enticed Weinberg almost 20 years earlier. "I was really impressed and really excited," says Nusbaum, the center's co-director of sequencing and analysis. "I was immediately impressed by the quality of the operation. It was so far ahead of anything I had been involved with." By most measures, the Whitehead Institute and its impressive array of internationally renowned scientists is still regarded among the world's finest biomedical research centers. But on the eve of its 20th anniversary, any story about the Whitehead Institute is really a tale of two research centers. The established laboratories of its founding members and associate members have built the institute's 24-karat reputation and delivered to its doors the best and the brightest young scientists from across the globe. The newer and decidedly nontraditional Center for Genome Research, created in 1990, is balanced on the razor-edge of biomedical science. "The emphasis here is on providing an environment for fomenting great ideas and finding ways to move the earth, if necessary, to realize them," says Susan Lindquist, a professor of molecular genetics and cell biology from the University of Chicago who became the Whitehead's third director on October 15th. "We have some of the most extraordinary, talented, and visionary young people. They spark off each other to create new disciplines, new technologies, and new visions all the time." The initial goal of the independent, nonprofit research and teaching institute was to solve problems in biology that could one day be applied to new treatments for human disease. From the outset, the institute's leaders insisted that scientists collaborate across disciplines, something many traditional laboratories consider unholy. In 1990 Whitehead was ranked as the top research center in the world in genetics and molecular biology, according to Science Watch, from the Institute for Scientific Information. As of June 2001, it holds the number two spot behind the Salk Institute for Biological Studies in La Jolla, Calif. Whitehead has helped telescope the time between basic research and new drug therapies, Weinberg says. "Now often it happens in a matter of years rather than decades." As biology becomes what Lindquist calls "big science," it is a particularly exciting time at the Whitehead, considering the work being done at the Center for Genome Research. "We have been very advantageously positioned to take advantage of many developing things" coming out of the genome center, Weinberg says. "That has placed some labs in an auspicious position." Collaboration Key to Success Courtesy of Nadia S. Halim, Whitehead Institute for Biomedical Research Scientists work at "Gene Town," a former popcorn and beer factory transformed into the robotics-rich Center for Genome Research. Tucked away several blocks from the institute's Main Street building, the genome center is housed in an old popcorn and beer factory in a section of town quickly becoming known as "Gene Town." Founded in 1990 by Eric S. Lander, a former Rhodes scholar, mathematician, and biologist and Whitehead member, the genome center is really the vanguard of a new type of science. "Genetics, the study of individual genes, was quintessentially a child of the 20th century," Lander is quoted as saying in the most recent edition of the institute's annual report. "But in the 21st century we are moving beyond the study of individual genes to global views of all genes simultaneously, the field of genomics." The center is as spare in appearance as the Whitehead's main building is comfortable. Framed posters of the Mouse Genome Project and Deciphering the Genome, two research efforts involving the center, decorate its tiny reception area like pop art. Nusbaum's second floor office is crammed with more chairs than he can possibly use, plus two bicycles, a small round table, and a desk. It is a far cry from the corporate-like office suites a few blocks away. A thin, wiry man, Nusbaum came to the center just as sequencing became the next frontier in research. "We didn't have any preconceptions on how sequencing should be done," he says. The center planned to use robots to do the sequencing grunt work and quickly evolved through three generations of robots in 18 months. Today an army of robots handles almost all of the repetitious tasks. The scale of the enterprise was a big change for Nusbaum. "I was used to solving problems gene by gene," he says. "Eric's vision is not to think about a gene." Like others at the Whitehead, Nusbaum says the key to success is the willingness of world-class scientists to not only work together but to learn something new. "To succeed at Whitehead you have to be open minded and you have to understand another field," he says. "I'm an example of how communication is as important as expertise. The kind of leadership needed here is extremely broad." Part of that leadership comes from Nicole Stange-Thomann. She came to the center after completing her postdoctoral work at Yale University's department of molecular biophysics and biochemistry and a stint at a biotech company. Her job was trouble-shooting the center's technology problems and accelerating the Human Genome Project (HGP), which was in full swing at the time. She reinvented the center's library construction procedure and headed two project teams. She found that the scientists had too much work and not enough support. "My job was to do more high-quality trouble-shooting, finding out what could be better and looking at different things that could be better," she says. "We were doing an excellent job for what we had." Gene Town Opens to Other Species Courtesy of Nadia S. Halim, Whitehead Institute for Biomedical Research As HGP winds down, the center is embarking on a new mission--comparative genomics. Unlike other projects, where the center only provides raw data, Whitehead scientists want to be more involved in the comparative genomics research, maybe even teaming with a biotech company. The Whitehead is already evolving its mission by applying its raw data in-house to find the genetic markers for diseases such as cancer, diabetes, and inflammatory bowel disease. "There should be a strong hand-in-hand [relationship between] research results and finding meaningful information that can be eventually applied to biomedical research," Stange-Thomann says. And center scientists have plenty of work to do. Although unraveling the human genome was a magnificent enterprise, it doesn't actually reveal important information, like why a gene switches on and off or what a mutation means. Deciphering that information requires comparing the human genome with the genomes of other vertebrates and nonvertebrates for clues that will help them to understand normal genes. "By comparing you can see that new genes have arisen and you can correlate them to new and important innovations in humans," Stange-Thomann explains. "Understanding this is so important for our health. I still see this as basic research." Nusbaum agrees, adding that the genome sequence is more than just a linear string of letters. "It's an incredibly complicated and important and influential object," he says. "It's an infinitely deep mind and with many thousands of veins in it." By comparing the regions of the human, mouse, fish, shark, and fruit fly genes, researchers hope they will begin to understand the basis of both health and illness. "It's a fairly long-term project and I don't expect to see a solution for a long time," he says. "The goal is to push back the frontier of what we know. No matter how much we drill into it, there will be more there. We have printed an encyclopedia. Now we have to understand what is in it." The secrets of the human genome will be slowly revealed over the next decade, and Whitehead scientists assert that their interdisciplinary work with the private sector and with other academics will be critical. Already a simple analysis at the center has revealed many more types of cancers than was suspected. More importantly, center researchers are finding that the subdivisions of these cancers and their association with survival rates are very specific. "This will be critical in developing therapies and cancer survival rates," he says. "The genome revolution is going to come to medical science slowly over the next five to 10 years. But the effect is going to be profound. There is an amazing momentum building, pushing forward all of these things." Bob Calandra (rotoca@aol.com) is a freelance writer in Philadelphia.

The Science of Collaboration

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