It Was Heaven: An Interview with Evelyn Witkin

Evelyn Witkin came of age at the dawn of bacterial genetics. In 1941 and with World War II looming, she began her PhD studies at Columbia University, and soon, with her very first experiment, she serendipitously cracked open a new field of research by discovering bacteria resistant to ultraviolet (UV) light. Witkin’s journey from UV resistance to DNA mutagenesis and repair spanned 50 years, taking her from Columbia University to Cold Spring Harbor Laboratory, and later from Downstate Medical Center (part of the State University of New York) to Rutgers University, from which she retired in 1991. Her original observations of filamentation associated with UV damage in E. coli and its suppression in a UVresistant mutant revealed the phenomenon of cell division checkpoint and were early harbingers of the cell’s SOS response to DNA damage. In the 1950s, Witkin discovered that the nature of the culture medium on which bacteria are grown postUV irradiation strongly influences the frequency of mutations that arise: high on media that promote active protein synthesis, but far lower on media that support protein synthesis only after a significant delay. Witkin studied the kinetics of this phenomenon, soon referred to as ‘‘mutation frequency decline’’ (Mfd), and showed that if protein synthesis is delayed or inhibited, genetic damage is corrected rapidly by an enzymatic repair mechanism (later proven to be excision repair of pyrimidine dimers), whereas if protein synthesis is enabled, abundant mutations are generated as products of error-prone repair, part of the manifold SOS responses. What is remarkable is that many of these early observations and hypotheses originated before it was even appreciated that DNA was the genetic material or that UV damaged DNA directly. Like other pioneering geneticists of that period— Barbara McClintock with her maize or Mary Lyon with her mice—Witkin brought tenacity and powerful skills of observation to develop a deep understanding of a fundamental problem in biology. Upon interview, I discovered that Witkin (Image 1) also infused a special attribute into every aspect of her life: joy. On a grey morning in early May, I made my way to her home at the end of a cobbled cul-de-sac, a half block from the Princeton campus, and she welcomed me with a strong cup of coffee and a youthful effervescence that belies her age. Though no longer practicing science, she has an active life involving historical research on Charles Darwin and Robert Browning, visits to her family in California, reading about cosmology with the Princeton Research Forum’s science book group, and, of course, graciously entertaining visitors like me. Gitschier: What prompted you to retire? Witkin: At the time, it was the law that you had to retire at 70. I was 70 in 1991, so do the arithmetic. Gitschier: Wow, you’re getting up there! You look fantastic! Witkin: Thank you. Anyway, I could have stayed on year-by-year at Rutgers, but I decided not to because I felt that the field was somehow getting away from me. And I didn’t want to push my luck with grants, because the way I like to work was not the way things were going at the time. I did most of my experiments myself with my own two hands; I had a small group, just two or three graduate students. I had no post-docs. And I felt that things had changed and one needed to have larger groups with various types of expertise represented. I had the same grant essentially since 1956! And I felt that I would have a hard time asking for money at that point. Gitschier: So you worked in the lab all through your sixties? Witkin: Oh gosh, yes. I mean I started in the ’40s. I was a graduate student from 1941 to 1947 when I got my PhD. And that was an interesting time to be starting. Especially at Cold Spring Harbor! Gitschier: I’ll bet. I’m very curious about your upbringing and how you met your husband. What was his name? Witkin: Herman A. Witkin. ‘‘Hy’’ was his nickname. I met him through my sister. She was a graduate student in psychology at New York University when I was an undergraduate [there]. As a matter of fact, I was a 16-year-old freshman when I met him. Gitschier: Did you grow up in Manhattan? Witkin: No. I was born in Manhattan, grew up there my first 9 years and then my mother re-married. My father had died when I was three. And when my mother remarried, we moved to Queens. My stepfather had just built a fabulously elegant ‘‘drug store’’, but it was a whole lot more than that. It had a food service, which was almost like a very good restaurant, and my mother supervised the food service. It was in the building that we moved into, actually—a big apartment. It was the most outlying part of Forest Hills; everything else was field beyond that point. You’d never know it now. And I commuted to high school, before there was a subway to Forest Hills on