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David Botstein Prepares to Move Back East, Advises Biologists to Pick Up Bioinformatics

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David Botstein, one of the luminaries of the genomics world and a seminal figure in the development of microarrays, is packing up his Silicon Valley home and returning to his East Coast roots.

Last week, Princeton University announced that Botstein will head the Lewis-Sigler Institute for Integrative Genomics, arguably one of the most high-profile positions at the Ivy League school, starting next summer. Shirley Tilghman, Princeton’s president, was its founding director. The institute describes its mission as a mandate to develop novel approaches to the study of biology in a post-genomic era and to derive an understanding of how biological systems organize and integrate complex processes.

“This is an opportunity in an area that requires a lot of attention — undergraduate science teaching,” Botstein told BioArray News to explain why he accepted the position.

Botstein, who is chairman of the genetics department of Stanford University’s school of medicine, will begin his duties in Princeton on July 1, 2003, two months after the institute dedicates the $45 million, 90,000-square foot building that will house it.

Botstein helped set in motion the genomics revolution with a 1980 paper he co-authored, proposing a method for mapping genes that laid the groundwork for the Human Genome Project. Later, he helped guide the project as part of its advisory council, while leading the mapping and sequencing of the yeast genome in 1996.

This announcement may also signal the ending of a close research collaboration with cDNA microarray developer Patrick Brown, also of Stanford, who was Gilbert to Botstein’s Sullivan. The two produced no less than 44 published papers since 1995, 11 based on microarrays.

Botstein said that his departure to Princeton only accelerates an inevitable process, but that doesn’t make the split any easier.

“It’s fair to say that it was neither Pat’s nor my choice to split up,” he said. “For various reasons, Pat isn’t able to see his way to moving. The opportunity is there. I just turned 60 recently, so I think of this as a slightly-earlier-than-expected retirement. That said, by no means should anyone assume that there is no prospect that Pat and I won’t be doing things together at a distance. We will continue to profit from collaboration and interaction and having our frequently diverse points of view considered.”

Botstein will be leaving the Botstein Laboratory at Stanford and its many graduate researchers to try to teach undergraduates to look beyond Gaussian curves and consider the relationships between signal transduction pathways.

“The rate-limiting step in modern genomics is in understanding the data that you collect,” he said. “Biology has become an information science, it’s way more quantitative. It has become pretty clear to me that the place to start changing how biology is taught is in undergraduate school. I’m voting with my feet as to what I can do in the next decade or so that is left to me in my working life to make a difference.”

Botstein last taught undergraduate students 20 years ago, when he was at MIT, before leaving to work for two years at Genentech and then moving to the splendors of Stanford and becoming one of the world’s innovative thinkers.

Microarrays will be an important tool in the new curriculum he hopes to create.

“In many ways, [microarrays] are a poster child, if you like, for the genomics revolution,” he said. “I think they are only the first of many tools that will allow you to interrogate the genome over its entire length. They are, and have been, the basis for the first truly comprehensive look at organisms at work and I think there will be many more.”

Botstein said the volume of data that microarray based-research creates will compel biologists to learn how to understand the information that now gushes in gigabytes and terabytes.

“This is just the new way of looking at biology — a fundamental thing that requires of us that we really understand not only computation but figure out how to manipulate very large sets of data which are much truer representations of what the cells are doing and how the organisms are functioning than individual measurements of individual genes — no matter how cleverly chosen,” he said.

Those already at work in this field should demand specific bioinformatics tools, he said.

“You have to ask the statisticians and the bioinformaticians for the tools that will allow the biologist to browse the data and figure out for himself or herself what might be significant,” he said. “We [biologists] need to have the tools from the other side and we need to understand what a correlation coefficient is and we need to think in an n-dimensional space.”

Clearly, Botstein is a gifted scientist who in the twilight of a hugely successful career is moving to Princeton. Any parallel between him and the other Stein, the wire-hair mustachioed fellow who, a half century ago, made his own journey to southern New Jersey?

“Any comparison between this Stein and that Stein is completely inappropriate,” he said. “Now, I need to get away. My next appointment has just sat down and he’s a very distinguished Nobel Prize winner.”

— MOK

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