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Linda Buck
Linda Buck
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Linda Buck Interview

Nobel Prize in Medicine

June 2, 2005
New York City

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  Linda Buck

It's something we almost take for granted, that we smell things, and react in different ways to different odors. When you were still a postdoctoral fellow at Columbia, you found in this commonplace experience not just a mystery to be solved, but something truly important to understand. Why is that?

Linda Buck: I was completely fascinated by this, and there was really nothing else I wanted to do more than to solve this problem.

Do you solve these problems by design? By trial and error?

Linda Buck: It's puzzle solving, and that's one of the things I love about doing science. It's really puzzle solving, and the other part of it is that what you find is so beautiful. Nature's designs are so elegant. I'm a very empirical scientist. I don't theorize, because what usually happens is that the answer, the biological mechanisms that are used, are usually far more elegant than the theories that people come up with. Of course, you have to have a hypothesis, or some kinds of ideas to begin to explore. For example, the idea that there are proteins in the nose that recognize odorants was a quite reasonable one, and there was some indirect evidence for it. The question was how to find them. What I decided to do was to try to find genes encoding these molecules. I think Richard Axel also agreed that this was the logical thing to do, so I set out to do that. Instead of looking for a job and getting a faculty position, I stayed on there, with his blessing. I actually looked for a job, and of course, I just said -- I didn't say I was going to work on Aplysia -- I said I'm going to do this, which of course, people would think was impossible, and I could never have gotten a grant to look for this, because who knows? Maybe I wouldn't have found the receptors. So I set out to do it, and I worked very hard to do this.

[ Key to Success ] Perseverance

That doesn't sound like a nine-to-five job.

Linda Buck: Oh, no.

At one point, I switched over to working until five a.m. so that I would have all the lab equipment to myself. And I worked very long hours, but I loved it, you know. So what you do is basically try to come up with an idea. How are you going to find what you're trying to find? And I tried several things before I hit on the right one. But it took taking a recently developed technique, and then changing that, modifying that, adding some layers onto that, and then pulling in some other way to analyze the data. So basically, I used PCR (polymerase chain reaction) which at that time was a relatively new technique, but I modified it, so that I developed a combinatorial PCR approach. I made the assumption that these proteins in the nose would be at least distantly related to other proteins that served as receptors or detectors on the surface of other cell types. There were some of these known, and there was some evidence that suggested that the proteins in the nose might transduce signals to the interior of the cell using similar mechanisms to some other receptors.

[ Key to Success ] Passion

Nobody had ever done this before. What inspired you, or led you to believe that this was an important thing to do?

Linda Buck: It wasn't as if I stood back and thought, "What's the most important thing?" I remember when I started graduate school that I did survey what was around me and decide what was the most important thing -- I thought -- to do. I think that that was in the backdrop, that I wanted to do something important. But I don't remember thinking, "This is an important thing! This is an important thing!" I might have done that, but I was always interested in taking on very challenging problems, and ones that I thought were important. I was never interested in taking small steps and adding bricks. I was always attracted to the bigger questions, and the challenges didn't bother me. This was actually a very high-risk project, and in retrospect, it was potentially suicidal. I didn't have to find the receptors. I mean potentially suicidal in terms of a career. But actually, that didn't matter to me at that time.

[ Key to Success ] Courage

Linda Buck Interview Photo
Linda Buck Interview Photo

Did you ever imagine that this long journey would take you to the Nobel Prize?

Linda Buck: No, I didn't really think that.

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