Multidisciplinary Centers Take Up Challenges

Research universities and federal funding agencies are taking a new approach to cutting-edge research in life sciences: multidisciplinary teams of scientists. Already in 1999, two Ivy League universities have announced plans for new institutes that will bring together physical and biological scientists to tackle problems. Other major universities have embarked on similar initiatives within the past year. And a research institute that will open a campus in the Midwest next year plans to carry out multidisciplinary medical research. "There's a growing recognition that the time is ripe for physical science and engineering to come together with biological and medical sciences," says Steven Chu, a Nobel laureate who is professor of applied physics at Stanford University. "Biology has become very data-rich. You want to develop ways of analyzing the data." Multidisciplinary research in the life sciences "is indeed a general trend," agrees James Edwards, deputy assistant director of biological sciences at the National Science Foundation (NSF). The scientific community "is beginning to realize that many of the big, intractable problems we face require a multidisciplinary approach." Indeed, the NSF's biology division increasingly funds cross-disciplinary groups of researchers. "Our whole biocomplexity theme at NSF is built on the recognition that the living world is such a complex nexus of integrations that one really needs the perspective of various kinds of scientific disciplines," says Edwards. Bringing scientific fields together is hardly novel. After all, biochemistry and biophysics emerged as full-fledged disciplines from their foundation subjects more than three decades ago. However, the new centers take a different approach. They aim to integrate scientists with different backgrounds and skills in single buildings rather than cram a diversity of subject matter into individual brains. "We see a difference between multidisciplinary and interdisciplinary," explains George McLendon, chair of Princeton University's chemistry department. "In a multidisciplinary setup, one hopes to have individual disciplines that best represent the strengths of the individual scientists. In interdisciplinary situations, you have the danger of being neither fish nor fowl." Why have academic institutions chosen to set up their new centers now? "Biologists are moving beyond the era when they studied one gene, one protein, and one reaction," states Douglas Melton, who chairs the department of molecular and cellular biology at Harvard University. "The complexity that interests us all can be more thoroughly and incisively investigated by using several approaches. One might want to bring engineers, chemists, physicists, and computer scientists to understand how to design more effective experiments." Harvard plans to create a Center for Genomics and Proteomics, as part of an investment announced in January of more than $150 million in scientific research and education. In the same month, Princeton announced that it will put up $60 million to support the work of a new multidisciplinary Institute for Genomic Analysis. At Stanford, Chu is collaborating with biochemist James Spudich to promote what they call "Bio-X." This is a planned research center on the Stanford campus that will mingle disciplines as diverse as applied physics and clinical medicine. Other academic institutions have developed their own plans for centers that will combine disciplines. Last October, the University of Chicago announced its intention to build "a large new interdivisional laboratory for the biological and physical sciences." The Interdisciplinary Research Institute will sponsor "joint research projects at the boundary between the physical and biological sciences." The University of California, Berkeley, and the University of California, San Francisco, plan to set up a joint department of bioengineering. The new department will integrate Berkeley's strength in engineering with UCSF's clinical environment and basic health and medical sciences. The NSF, meanwhile, is organizing even more scattered multidisciplinary efforts. "We've funded many virtual groups, dispersed across several institutions," says Edwards. The trend to multidisciplinary efforts is not restricted to academic institutions. "Our idea is to create multidisciplinary teams," adds Nelson Pleau, chief administrative officer of the Stowers Institute for Medical Research, an organization that will open its doors next year in Kansas City, Mo.1 "The approach is a systems approach rather than a single-cell, single-gene, or single-protein approach," Pleau continues. "We expect to bring in scientists other than life scientists. We expect to bring in the cross-disciplinary fields to develop new research methods, tools, and technologies to use for both daily research and as intellectual property." It's no coincidence that several of the new multidisciplinary centers focus on genomics. "This second genetic revolution uses an array of technologies to understand how genes work and function together," says Edwards. "You need to involve engineers, physicists, and chemists, not only to make the devices to help understand these phenomena, but also to bring new ways of thinking about what's happening. Understanding the structure and pathways by which an organism fits together is an engineering phenomenon. Bringing an engineering rigor and an engineering approach to a network gives more than one can get from biology." Edwards points to one other factor that has enabled multidisciplinary approaches. "Information technology tools are available to allow us to do these large-scale genomewide kinds of analysis," he explains. "That means bringing computer scientists into the mix." The ability to frame problems that challenge multidisciplinary teams has occurred only recently. "One wouldn't have had enough information five years ago even to know what the right questions were, much less to start to attack some subset of them," says McLendon. Since then, however, molecular biologists and biotechnologists have made significant progress in understanding the human genome. That, says Melton, "has made it possible to ask questions about the richness of biological systems. The answer won't be a gene, but a network of genes." The new Harvard center plans, therefore, to go beyond the current practice of studying how single genes are regulated and how the proteins derived from them function. It will concentrate on understanding animal behavior, evolution, the multigenic basis of diseases and other complex phenomena, as well as the control of biological processes of this type via small molecules. The consequence of the center's work, explains Melton, will be that "one student can experimentally probe every member of a genome or proteome in a single experiment, and get an integrated picture of the response of an entire organism." Princeton's multidisciplinary institute will take a different approach. "Our strategy is to go one step further," says McLendon. "The challenge of the future lies in studying the principles that drive the integration of information in complex biological systems," explains Shirley Tilghman, a professor of life science who will serve as first director of the institute. "We hope to create an environment where scientists of all stripes, from biology, physics, chemistry, mathematics, and various fields of engineering, can work together to solve biological problems that depend on taking large amounts of information about genes, proteins, or structures, and revealing how they are integrated into a coherent whole." How will individuals in different disciplines collaborate? "We hope to create an interaction where we've got biologists who have a sense of the organism, chemists who bring spectroscopic skills, and physicists who bring mathematical insights to bear on the problem," says McLendon. "Each of us thinks of the problem in different, overlapping ways. We need a broader and deeper view to solve those problems. They're extraordinarily difficult for any single discipline to attack." So far, Stanford's Bio-X program is less defined. "We're right in the planning stages," says Chu. "We need to do fundraising, but it seems possible." Once the center is set up, says Spudich, "we want to mix smart people together in an interdisciplinary environment, and let nature take its course." Several major projects await the attention of teams in the new centers. One focuses on understanding how evolution selected the proteins that formed the building blocks of all genes. Fundamentally, this relies on chemistry. Another will examine how single cells integrate the sometimes contradictory external messages that they receive from the outside world. Here, specialists in complex circuits might provide some answers. And the study of biological processes that involve many genes demands expertise in mathematical modeling. Multidisciplinary research doesn't only use physical science to fulfill the ends of life science. Occasionally, the process is reversed. Chu, for example, has used DNA as a model system for studies of polymers. "Since the molecule is so long, one can image its fluorescence directly in an optical microscope," he explains. "The ability to visualize the molecule directly has opened up a new approach to the field, and we have been able to test several fundamental assumptions in polymer dynamics." Whether a particular line of research ultimately benefits life science or physical science, the multidisciplinary mode of operation offers a step beyond conventional R&D activities. "There is the advantage of having disparate disciplines under the same roof," says Edwards. "It leads to a more synergistic reaction." Peter Gwynne (Pgwynne767@aol.com) is a freelance science writer based in Marstons Mills, Mass. S. Bunk, "Stowers Institute Lays Ambitious Plans for K.C.," The Scientist, 12[19]5, Sept. 28, 1998.

Multidisciplinary Centers Take Up Challenges

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