David Botstein

First Person | David Botstein Courtesy of Frank Wojciechowski At the age of 60, David Botstein, microarray and genetics pioneer, is learning to play the cello. As a young man, Botstein seriously considered being a musician, but he knew the talent just wasn't there. "I did play the violin, badly," he admits. Yet his love of music is so ingrained--his brother, Leon, is music director for the American Symphony Orchestra--that even as an undergraduate at Harvard, he "ran with the musicians."

Jul 28, 2003
The Scientist Staff

First Person | David Botstein


Courtesy of Frank Wojciechowski

At the age of 60, David Botstein, microarray and genetics pioneer, is learning to play the cello. As a young man, Botstein seriously considered being a musician, but he knew the talent just wasn't there. "I did play the violin, badly," he admits. Yet his love of music is so ingrained--his brother, Leon, is music director for the American Symphony Orchestra--that even as an undergraduate at Harvard, he "ran with the musicians."

Botstein, who recently became head of Princeton's Lewis-Sigler Institute for Integrative Genomics, did not come to genetics easily. First it was engineering, then physics, then biochemistry. He found religion, so to speak, after reading the Molecular Basis of Evolution by nobelist Christian B. Anfinsen.

Botstein has no regrets. "I thought about [music] very seriously. It was pretty clear to me, being reasonable and objective about it, that I didn't have what it takes. There's nothing worse than going into something that [will be marred by] lifelong frustrations."

Tell us about your 'conversion' to biology.
It was just the time. I arrived at Harvard in 1959, just in time when Jim Watson was doing his number, saying how everything in biology would have to be reset to the beginning, and that you have to think of the flow of information from DNA to protein. And, I got caught up in that.

Where were you raised?
I was born in Switzerland, but I grew up in New York City. I came here when I was 7.

Are you a religious man?
No, it's 2003.

What do coworkers complain about you?
I talk too much.

Tell us about your connection with microarray technology.
Shortly after I arrived at Stanford ... Pat Brown [was making] these microarrays. We thought about how they could be used. The lowest hanging fruit, besides working with yeast on these things, was cancer. Pat and I made this joint lab, which we ran for 10 years.

Is the tag, "a don of yeast genetics," apt?
I think it is true. There is a very small group of people, of whom it's fair to count me in, who more or less, malice aforethought, produced the field. At a certain point in the early '70s, everyone was giving out free advice to young associate professors like myself. [They] said, "You need to do more than phages." We bet on yeast, and we won that bet.

What is your favorite paper?
This is like trying to choose among your children. I have a special fondness for the ones I did with my own hands. One of my favorites is a paper with [the late] Ira Herskowitz.1 Another paper is one that I am most famous for; it certainly was a paper that had impact.2 And the third, in which my role was a bit different, is about clustering of microarray data.3

What's the smartest thing you ever did?
I think it was to recognize, when I was still a relatively young guy, that I had to do something that I could do, and there was no point in doing something that I couldn't do. It just so happens that genetics worked perfectly for me; it was quantitative enough, and interesting, and I got in on the ground floor. What was the smart part about it, it was against conventional wisdom.

What was the dumbest?
I had a physicist who worked with me for a while, who was dealing with the problem of untangling DNA. He said there must be a way that the strands can pass through each other. I told him he was crazy, that you couldn't get the phosphodiesters apart. But in fact, his experiment could have led him to discover topoisomer-ases [enzymes that control and modify the topological states of cellular DNA]. It was a mistake I tried to learn from.

What goals do you have in your new job?
I want to try to do for the next generation what Jim Watson did for us. He said, "Don't worry about the details, follow the information." I want to say, "Don't worry about the molecular detail, worry about how it fits together." I want the institute ... [to take] a stab at the curriculum of the genomicist, or I would say general scientist of the future. We need more simulation and computational methods that allow you to look at the data set and ask, "What are the odds that that will arise on different models?" Most of my career, I've been heavily engaged in teaching. It's a suitable activity in this stage of my career.

What music do you have in your CD player now?
Bach's Cantata No. 4 (Christ lag in Todes Banden).

References
1. D. Botstein, I. Herskowitz, "Properties of hybrids between salmonella phage-p22 and coliphage lambda," Nature, 251:584-9, 1974.

2. D. Botstein et al., "Construction of a genetic-linkage map in man using restriction fragment length polymorphisms," Am J Hum Genet, 32:314-31, 1980.

3. M.B. Eisen et al., "Cluster analysis and display of genome-wide expression patterns," Proc Nat Acad Sci, 95:14863-8, 1998.

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