INTERVIEW

Richard M. Losick

Interviewed by Emma Patten-Hitt

This article also appears in BioMedNet's Conference Reporter.

Posted May 25, 2001 · Issue 103

Background

Biography
Richard Losick joined the Harvard faculty in 1972 and is currently Maria Moors Cabot Professor of Biology. He has served as chair of both the Department of Molecular and Cellular biology and the Department of Cellular and Developmental biology. He received his undergraduate degree in chemistry from Princeton University in 1965 and his Ph.D. in biochemistry from the Massachusetts Institute of Technology four years later. Losick's research has focused on gene expression and development in simple organisms, such as the unicellular bacterium Bacillus subtilis and the filamentous bacterium Streptomyces coelicolor, which are accessible to genetic manipulation. He is a member of the National Academy of Sciences and is on the editorial boards of Cell and Science.

What event led you into research?

Some successful scientists I know started relatively late in life. They came into it after they were undergraduates. But in my case I've always been fascinated in how things work, especially how biological things work. When I was a kid I was fascinated with how a salamander's tail could regenerate. As I got older, I came into the view that one should always work with the simplest organism possible. I have always been fascinated in science. There was no real event that got me started in it, and I never doubted what I wanted to do.

What do you consider to be your greatest achievement and why?

My earliest interest in bacteria focused on gene transcription - how genes were turned on and off. An important mechanism that has proved to be pervasive among bacteria involves a protein called sigma, which directs promoter recognition by RNA polymerase. I was at Harvard when sigma was discovered in Jim Watson's lab. But I was one of the first to identify other alternative members of the sigma protein. What was very exciting, though, was that bacteria did not have one form of sigma but several. This meant that they could be thought of as regulatory proteins that could direct recognition of different classes of genes. This is what I feel is my most important contribution: that I discovered the first alternative sigmas in bacterial viruses and bacteria themselves. That was in the 1970s.

The other aspect that has dominated much of my career is that I thought these sigmas would be especially important in differentiation and that they could turn on whole blocks of genes in different cell types. And this has been very true. This has been my idea right from the beginning and it turned out to be generally true, even more than we expected.

Has anybody in science especially inspired you during your career?

I've had wonderful mentors my whole career who have had a big influence on me. When I was an undergraduate, I worked in the lab of a man named Charles Gilvarg at Princeton University. He was a wonderful scientist who not only was very clever but had a deep sense of scientific rigor. I learned a lot about things, such as what a "control" was. In fact, I worked in bacteria while in his lab, and he introduced me to the scientific method during that time.

While I was a graduate student at MIT, I worked on bacterial cell surfaces in the lab of Phil Robbins. He was a man who loved to work at the bench himself. He enjoyed doing experiments with his own hands, and I admired that enormously. The project that he worked on was in collaboration with Salvadore Luria at MIT, one of the greats in the field of bacteriology. Luria was an extremely inspiring figure to me.

Why do you study B. subtilis?

My view about science is that if you want to study a biological problem, you should pick the simplest organism and the most accessible organism that illustrates that problem. My strongest interest in biology is how cells develop and undergo differentiation. B. subtilis is perhaps the simplest and most accessible organism on the planet for doing this. It has a nice cytology and a lot is known about it.

The old view of a bacterium was that it was a kind of amorphous vessel with enzymes floating around in it. And one of the things that's been exciting in microbiology in the last five to seven years is the realization that proteins have addresses inside cells.

There was this view that bacteria were too small to see what was going on inside. But in fact, fluorescence microscopy can reveal a lot of what's going on inside the cell. Then green fluorescent protein came along; it had a huge effect because you could look into living cells and see great detail. Vital membrane dyes have also become very important because it means you can look at where proteins are in living cells and you can even watch them over time.

What advice would you give to someone who is beginning a science career?

If he or she is an undergraduate, and they think they are interested in science, they should get into the lab and stay there, not just do a rotation over the summer. When you are a graduate student you have to decide to tough it out. Most of science is failure, so you have to have the right attitude.

The rewards that come only after a long period of time should be enough to keep you going, and you should not get too discouraged by the fact that most things don't work. You have to love it and to like working with your hands. You must be prepared to work on a problem for a long time and be misled. But in the end, if you stick with it, you can learn something new about nature that nobody ever knew before. Few things in life are as rewarding as that.

Emma Patten-Hitt is a freelance writer based in Atanta, Georgia. She has a Ph.D. from Emory University in nutrition with a molecular biology emphasis, and is about to complete a master's degree in technical communication.