David Botstein's contributions to molecular biology—including the development of techniques used for mapping the human genome, elucidation of yeast and phage genetics, and advancement of microarray technology—caught our attention. Curious to know more, BioTechniques contacted him to find out about the ambitions, character, and motivations that led to his success.

A Teacher and a Researcher

What are your most significant insights and how did they come to you?

With Myron Levine at the University of Michigan, I worked on bacteriophage P22. I started with DNA replication and then continued with its genetics and physiology. This project continued in my own lab at the Massachusetts Institute of Technology (MIT) and resulted in the first demonstration of an essential circular DNA intermediate in replication of a linear genome. Because it was a small field, my P22 work culminated in a pretty complete description of the molecular biology of this phage.

In another interesting project I did with Ira Herskowitz, we showed that two viruses that infect different species of bacteria (Escherichia coli and Salmonella) could nevertheless recombine. I also worked on basic genetic technology—knocking out yeast genes, shuttling mutations in and out of yeast genomes, and using transposons to do these things in bacteria. A group of us figured out how to map human disease genes using DNA markers (RFLPs) in the late 1970s.

And of course, I just realized whom I was talking to! At BioTechniques, you must be interested in microarrays. Pat Brown and I collaborated in developing uses for microarrays and a method for extracting biological information from the mass of data they generate.

What was your biggest professional obstacle and how did you overcome it?

I guess I would say that my only real obstacles arose from academic politics. Many people are deeply conservative regarding change and often do things that just don't make sense. But this became much less of an issue as I advanced to positions of authority where I had the leverage to start new programs.

Do you go against conventional wisdom?

I have been criticized for having a short attention span and not being very focused. But it all depends on what your goal is. It is important to stay motivated. Science should be fun. So during my career, when I found something else that was more fascinating, I had to pursue it. It was the only way I could continue doing really good science, so it has been beneficial overall. The only disadvantage of this is that it is not viewed favorably by grant reviewers.

You have achieved success in so many areas. What would you say is your greatest contribution to the field?

My greatest contributions are in the people who trained with me. Teaching keeps you grounded on what's important. I am as much a teacher as a researcher.

What are the most important goals you are currently working towards?

I am strongly focused on why fewer students choose to become scientists. A goal of the Lewis-Sigler Institute is to rethink undergraduate science education. We serve students who are interested in science, not just studying it so they can get into medical school. I am trying to see if restoring rigor and keeping math in the science classes will inspire more top students to go into science for its own sake.

At Lewis-Sigler, the students who are interested in science are kept together at the beginning and allowed to differentiate into chemists, biologists, or physicists as they go along. Not everyone can be everything, but I hope that this educational structure will facilitate communication between disciplines. Students trained this way should be able to converse in several fields while contributing to some. To attain this goal, we put our money towards education and collaboration.

We also aim to make resources available to everyone. In order to be trained in state-of the-art biology, students need access to microarrays, mass spectrophotometers, high-throughput Solexa sequencing instruments, etc. The Center for Quantitative Biology provides these resources for routine student use.

What interests or hobbies do you have outside the classroom and lab?

I play the cello. In music and in science, you need to follow your intuition to understand what things should look and sound like. In elementary education today, there is a misunderstanding that music and art are optional, but they are not. They bring order and mental discipline just as biology and math do. The topics build upon and enhance each other and are as essential as physical exercise.

What has been the highlight of your career so far?

The highlights are my students and the success the alumni have achieved.

Also, a couple of years back, some of my former students hosted a birthday party for me. It was meant to be a surprise, but I had some suspicions in advance. My former students and postdocs attended. It really meant a lot to me.