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HARVARD GAZETTE ARCHIVES Mixing Disciplines for New Solutions By Alvin Powell
For much of his 34 years, Dari Shalon has been lining up challenges and knocking them down. There were the twin master’s degrees from MIT in business and engineering; the stint as a team leader for the construction of the Daedalus human-powered airplane, which set three world records in a flight between Crete and Santorini in 1988; his Stanford Ph.D. in biotechnology engineering; his co-development of DNA chip technology; and his role as founder, president, and chief executive officer of a biotech firm that developed and marketed commercial versions of the DNA chip. Oh, and somewhere in there, he commanded tanks in the Israeli Army. All this augurs well for Harvard’s new Center for Genomics Research, which named Shalon its first director this year. If the past is any guide and making the Center a success is Shalon’s latest challenge, just sit back and watch the journal articles and patents fly. "Dari is an unusual and extremely talented man who is bringing focus and imaginative energy to the Center for Genomics Research," said Dean of the Faculty of Arts and Sciences (FAS) Jeremy Knowles. "His eclectic background in engineering, business, and biology, and his successes in both academic and corporate settings, make him wonderfully appropriate for our interdisciplinary venture in genomics."Multidisciplinary Problems For his part, Shalon said he’s always been intrigued by problems that require expertise in several disciplines to solve, from complex military operations to directing the Center for Genomics Research, which will bring together experts in biology, chemistry, physics, computing, applied math, and engineering to examine biological systems. "We will be developing the next -generation tools for understanding biological systems by integrating the work of the brightest researchers at Harvard," Shalon said. In addition to research, the center will put together genomics courses to introduce the cross-disciplinary work being done there. What Shalon is striving to do at Harvard, he’s already accomplished on a personal level. While studying engineering at MIT, Shalon became intrigued by biological systems. He observed biologists at work in the lab and saw that they spent more of their time generating data than analyzing it. The problem, he realized, is the difficulty of obtaining information from biological systems. Gaining the information, he thought, is as much an engineering problem as it is a biological problem, and he began to get involved in modeling complex systems. "I wanted to take a look at the mother of all complex systems and that’s biology," Shalon said. "We’re just scratching the surface. I think we have job security for at least two generations."The First DNA Chip His cross-discipline work continued at Stanford, where his doctoral program combined biochemistry, genetics, bioinformatics, and engineering. It was while at Stanford that Shalon and Patrick Brown devised the first DNA chip, a new device hailed as a revolutionary breakthrough that can be used to analyze thousands of genes at once. The chip depends on the fact that genes encode messenger RNAs that carry the instructions for making proteins. By measuring the amounts of different messenger RNAs, researchers can tell how active different genes are. The chip itself contains rows of dots, with each dot containing the DNA sequence from a known gene. The chip is washed with a fluorescently labeled solution of messenger RNA from the cell being studied. The dots glow in different colors depending on how much of the corresponding messenger RNA is present in the sample. By examining the different colors on the chip – black, blue, yellow, and red –researchers can discern different levels of activity of the cell’s genes. Knowing which genes are active and which are not will allow researchers to zero in on specific genes that are active in cancer cells, for example, or to develop new drugs that more specifically target genes responsible for certain illnesses. Chips have already been developed containing 10,000 different genes, and chips containing all 100,000 or so human genes are not far off. The large amount of information held by a single chip can provide researchers with data in a few hours that, using older techniques, would have required painstaking research over months or years to gather. In addition, the large amount of data provides new opportunities to use statistical analysis to examine biological problems. "Right now we have a very limited understanding how to predict biological systems," Shalon said. "Using information from the DNA chip, we build databases, series of snapshots of cells – normal, sick, under stress – that improve our scientific understanding and which will eventually lead to more accurate medical diagnoses. It’s really become a system analysis problem." After creating the DNA chip, Shalon licensed the technology from Stanford and started a company, Synteni Inc., in California’s Silicon Valley, to commercialize the technology. Shalon headed the company from 1994 until 1998, when it was sold to Incyte Pharmaceuticals Inc. for $90 million. Shalon stayed on for a year after the purchase to help with the transition. Finding the Best Minds For his next challenge, Shalon wanted to work with the best minds in the field. He thought he would do that in another biotech start-up firm. But as he began to investigate, he realized the best minds aren’t necessarily in the business world. "I came to realize that many of the world’s smartest people aren’t for hire. They’re in an academic environment. They’re not in it for the money. They’re in it because of the love of research," Shalon said. "There is a commitment and incredible talent here, and an openness to doing things in a different way. It is a combination I couldn’t resist." The Center for Genomics Research is the brainchild of a "summer science group" of faculty colleagues convened in the summer of 1998 by FAS Dean Knowles. The group, called together to identify critical and emerging fields of research, proposed creating several research clusters that would draw expertise from different academic departments, allowing the sharing of facilities and equipment. Two centers, the Center for Genomics Research and a Center for Imaging and Mesoscale Structures, are already in being. Professor of Biochemistry and Molecular Biology Douglas Melton, who served on the summer science group, said the Center’s goals are lofty, but he believes Shalon is up to the task. "The success of the Center depends on leadership, energy, and commitment, and we’re extremely fortunate that Dari is our new director," Melton said. "Creating a new research center and fostering interactions with different disciplines within the College and Medical School is a big challenge and it’s a perfect fit for Dari." Since Shalon started at the center earlier this year, he, together with Melton and Professor of Chemistry Stuart Schreiber, the Center’s scientific co-directors, have been working on crafting its structure and physical facilities. Plans are on the drawing board for a new life sciences building on the site of the current Gibbs building. That new facility, which will extend under the courtyard between Gibbs and the Fairchild Biochemistry Building, will contain, among other facilities, office and laboratory space for the new Center for Genomics Research. Research fellows from different disciplines will staff the Center, Shalon said. He envisions an open floor plan that will encourage discussions and the flow of ideas between faculty and fellows, among biologists, chemists, and engineers. "Physical proximity is important," Shalon said. "Great things will happen when a physicist talks to a biologist who talks to a chemist."
Copyright 1999 President and Fellows of Harvard College |
