No System, Just the Technology

I grew up in a science environment—my dad was a physicist and my mother was a mathematician. It was the default expectation that everyone would do science. Even when I was little I figured I'd be a professor. As a freshman at UC Berkeley I didn't know what courses to take. My sister said, “you should take biology, but you can't take biology until you take chemistry so you should take chemistry.” I got good grades in Chemistry 1, liked it, and decided to take more chemistry. My second year I took biology and every time I asked a question, they'd say, “that's a good question but you need to know biochemistry to understand that.” Biochemistry sounded sexy. I decided I'd major in it but discovered once I started taking the courses that it was ridiculously boring because all you do is memorize things from the book. I started taking physics and I found it ridiculously interesting because you could figure things out from first principles. I'd been avoiding physics because I didn't want to be just like my father. Then I took biophysical chemistry my third year with Wayne Hubbell, who was in the Chemistry Department. He was a great and inspiring teacher. I spent two years doing research with him as an undergraduate, plus another year after I graduated.

I thus had three posts in the ground: chemistry, where I was doing research; biochemistry, my major; and physics, which was a love I had discovered. I thought I'd do biophysics in graduate school because it was in between everything and the name sounded good. I ended up at Stanford University working with Harden McConnell; he had been Hubbell's advisor. A piece of advice I got from McConnell once that stuck in my mind was, “when in doubt, err on the side of generosity.” There are so many ethical issues that come up all the time in reviewing grants, papers, or students. He offered that rule to me and I took it to heart.

In graduate school, I never gave a moment's thought to what I would do later. When my boss said I should move on after I graduated, that was a new thought. I ended up getting lucky—someone in the lab that had a bigger view of the world than I told me I should consider Lee Hood at the California Institute of Technology (Caltech). I was so naive I didn't know what Caltech was, and I'd never heard of Lee Hood, other than the fact that he had coauthored a biochemistry text I used as an undergraduate. I got a couple of his papers and I thought they looked interesting. I decided I wanted to learn molecular biology, because at that time everything in the journals was about DNA and RNA, and if I wanted to be a scientist I should probably learn about them. I spent my first year at Caltech with Lee learning molecular biology by doing DNA sequencing. Within a few months I was totally demoralized doing this boring routine all the time. I thought I had trashed a previously promising career. Fortunately I got interested in a project to automate DNA sequencing using fluorescence detection, making that my main project. I developed new chemistry to tag DNA with fluorophores, built an instrument, and published a paper about automated DNA sequencing. It was a cool project that combined my graduate work in instrumentation and chemistry with an important need in molecular biology (and was my ticket to a job as a professor).

When looking for a job I thought I must be a biochemist because I worked on DNA. I had interviews in biochemistry departments, but on every visit there would come some moment when they'd say, “all that technology work you do is very interesting, but what'system' do you work on?” I would say, “no system, just the technology.” They wanted me to say I was going to study something like fruit fly differentiation, so I didn't get any job offers. Some people suggested I apply for analytical chemistry positions, which to me at the time was just the most boring course I ever took and not something I aspired to do. But I sent my C.V. to a few analytical places, including the University of Wisconsin, which liked me, and thought I was a new glitzy one of them because I worked on biology. This worked out well because analytical chemistry is a home for people like me who like to work on technology.

I change fields every few years for renewal because I get bored easily. I try to identify technical areas that are critical to biological research and to address them. My lab doesn't have a particular biological system that we pursue. Instead, we interact with a lot of different people who have biological problems to solve. The risk I have, being located in a chemistry department, is being isolated from biology and losing the ability to pick important problems. It enriches my research when I collaborate with biologists who are working on interesting and important problems, as I can use their needs to drive our labs' research directions.