Because of her groundbreaking discovery of the “DNA damage response,” professor emerita Evelyn M. Witkin, a bacterial geneticist at Rutgers for two decades, receives the prestigious Lasker Award for unveiling the medley of reactions that bacteria cells undertake to protect their genomes against external threats. Her research has contributed to understanding many diseases, including cancer.
The history of science is replete with stories of felicitous accidents, so it isn’t entirely surprising that Evelyn M. Witkin’s decision to enter the field of genetics was sparked as much by serendipity as scientific forethought. As an undergraduate studying zoology at New York University in the late 1930s, she was introduced to the writings of Soviet biologist Trofim Lysenko by a politically radical boyfriend, and she was intrigued by Lysenko’s theory that environment, rather than genes, controlled heredity. She figured the theory might make for an interesting research topic when she got to graduate school at Columbia University. But after her first genetics course there, she concluded that Lysenko was probably a fraud. Luckily for science, Witkin had also stumbled upon her life’s work.
This fall, after a career in genetics that would take her from Columbia to the Cold Spring Harbor Laboratory to New York’s Downstate Medical Center and, eventually, to Douglass College and the Waksman Institute of Microbiology at Rutgers, Witkin received the 2015 Albert Lasker Basic Medical Research Award, the highest U.S. honor in the medical sciences. Her work on the cellular response to DNA damage, for which she won the award, was genuinely groundbreaking and, in her own words, “illuminated some of the basic underlying mechanisms that happen in many diseases, including cancer.”
In 1941 when Witkin began her graduate research, the field of genetics was less than 75 years old. Researchers had yet to discover that DNA was genetic material, and the science of bacterial genetics had just been born. In 1943 Witkin read an unpublished paper by biophysicist Max Delbrück and microbiologist Salvador Luria proving that bacteria have genes like other organisms and found it revelatory—so much so that, by the end of the paper, she was jumping up and down with excitement. Given that bacteria replicate every 20 minutes or so, she realized, they would be wonderful subjects in which to study genetics.
Sensing her enthusiasm, Theodosius Dobzhansky, her adviser at Columbia, suggested she spend the summer of 1944 at the Cold Spring Harbor Laboratory on Long Island, one of the country’s preeminent institutes for the study of genetics at the time. Both Delbrück and Luria, who both went on to win a Nobel Prize, would be in residence that summer, and since Herman Witkin, the psychologist whom she’d married a year earlier, would be in Texas researching space orientation at the School of Aviation Medicine, she had no reason to remain in Manhattan.
Witkin had never taken a course in microbiology and knew virtually nothing about bacteria, but it didn’t take long for her to realize that she was where she ought to be. “It was heaven,” she once said. “You could feel the stirrings of the revolution in molecular biology beginning.” When she was ordered to induce mutations in bacteria using an ultraviolet lamp, she had no idea what she was doing but she was a quick study. Still, what happened next was entirely unexpected.
Witkin found that when one strain of E. coli bacteria was irradiated with UV light, all the bacteria in that strain died. But another mutant strain (known as B/r), exposed to the same UV dose, managed to survive—it had somehow become resistant to radiation. Witkin was intrigued. “I started to think about how mutations happen,” she says. She had also found the subject of her Ph.D. dissertation.
In her thesis, Witkin showed that UV exposure caused the cells in the first strain to stop dividing—which is why they eventually died. Over the course of her career, she built on this observation to establish what is now known as the DNA damage response, or the SOS response (so named for the universal distress signal). It’s a mechanism that protects the genomes of all living things, from bacteria to human beings. Exposure to radiation and other potentially lethal substances—a process that goes on ceaselessly in the bodies of bacteria and humans—damages the genetic coding in cells, rendering them unable to make copies of themselves. The SOS response detects that damage, temporarily halts cell division, and then a host of dormant genes “wake up” and begin to repair the cells. They do so by creating a new cell copier, which another scientist dubbed a “sloppier copier” for its tendency to make mistakes. Those mistakes are, in fact, mutations, cellular changes that can cause disease but are also crucial to the process of evolution, allowing organisms (including people) to adapt more successfully to the environment.
Witkin’s work inspired a new generation of researchers to continue to unlock the secrets of the SOS response. One of them, Stephen J. Elledge, today a professor of genetics at Harvard Medical School, went on to study the DNA damage response in yeasts and in human beings, and he shares the Lasker Award with Witkin. “His work is beautiful,” Witkin observed recently.
Witkin continued her work on the cellular response to UV radiation at Rutgers, where she arrived in 1971 and was associated with Douglass College for 12 years as a member of the Department of Biological Sciences. In the early 1980s, she transferred to the Waksman Institute and continued her research until her retirement in 1991 at age 70. “Retired” may be a misnomer in Witkin’s case. After leaving Rutgers, she maintained her involvement in the field of genetics, serving as a member of the advisory board of the Department of Molecular Biology at Princeton University. In a 2012 interview in the online journal PLoS Genetics, she admitted that “if I had a couple of million dollars to build a lab in my basement, I would have gone on. E. coli still has lots of secrets!”
Bacteria are only one of Witkin’s passions. Two others are the poet Robert Browning and his Victorian contemporary Charles Darwin. In 1997 she published a paper, “The Wonders of Darwin’s World,” detailing evidence that both men were influenced by a book published in 1678 by the English clergyman Nathaniel Wanley entitled The Wonders of the Little World, and she served as vice president of the New York Browning Society for three years, in the mid-2000s.
Over the course of her illustrious career, Witkin has received numerous awards, honors, and accolades. In 1977 she was elected to the National Academy of Sciences, one of its first female members. The next year, she became a fellow of the American Academy of Arts and Sciences and, two years later, was elected to the American Association for the Advancement of Science. In 2000 she received the Thomas Hunt Morgan Medal, which recognizes lifetime contributions to the field of genetics, from the Genetics Society of America; an article in the society’s journal praised both her “intellectual boldness and her personal modesty.” She received the National Medal of Science in 2002 for, according to the National Science Foundation, “her insightful and pioneering investigations on the genetics of DNA mutagenesis and DNA repair that have increased our understanding of processes as varied as evolution and the development of cancer.” Earlier this year, she won the Wylie Prize in biomedical sciences.
In spite of her history of professional recognition, Witkin says she was entirely unprepared for the call she received in June, alerting her that she’d won the Lasker (although the official announcement of the honor wouldn’t come until September 8). “You could have knocked me over with a soap bubble,” she says, speaking from the living room of her handsome two-story Princeton townhouse, with its hardwood floors, Oriental rugs, and comfortable furnishings. In a quiet courtyard not far from Princeton University, the house has been her home for 21 years. She lives there today with her 12-year-old cat, Jenny, and her love of all things feline is evident in several oil paintings, etchings, and collages that adorn the walls.
The call from the Lasker Foundation kicked off an unexpectedly busy summer. In addition to appearances on Charlie Rose and WNYC radio’s Leonard Lopate Show, Witkin wrote an article on her work for the journal Cell, participated in a video interview (for the Lasker Foundation), and spent much of the summer fielding questions from a writer with the foundation who was working on the citation for Witkin’s award. Her fellow honorees—Elledge and James P. Allison, who received the Lasker-DeBakey Clinical Medical Research Award for discovering and developing a cancer treatment that unleashes the immune system to fight cancer—were scheduled to appear with her on both the Lopate Show and Charlie Rose, but Elledge had to cancel due to illness and a minor accident kept Allison from the second. “So here I am at 94,” says Witkin, with a laugh. “One of these men is 25 years younger than I am, the other 35 years younger, and they both fell by the wayside. I was the only one standing.”
The award ceremony, on September 18, was attended by many of the former graduate students who worked with Witkin. Before coming to Rutgers, she’d never had graduate assistants, and she relished the experience of having them during her stints at Douglass and Waksman. And she was especially pleased to see them at the ceremony. “They helped in my research, and they deserved credit,” she says.
The Douglass years were good ones for Witkin. “The chair of the department, Charlotte Avers, had an enormous amount of energy and built this very diverse department,” she recalls. “I don’t think it was expected to be a high-level research department, but it was.” Transferring to Waksman in the early 1980s was a revelation: “It was set up for doing good research,” she says. “Rutgers was good to me.”
Witkin’s colleagues have long recognized not just her intellectual prowess, but also her courage in pursuing a field that, when she entered it, had hardly been invented. James Shapiro, a professor of microbiology at the University of Chicago, wrote of Witkin that “her fearless experiments into a totally unknown subject are a model for all young scientists.” She was a working mother before the term was coined, raising two sons while doing part-time research until her younger son graduated from high school. She never tired of the subject that earned her the Lasker Award. “I found that what I was doing was so compelling and interesting,” she said in a recent interview, “it never occurred to me I could do something else.” The world of science is extremely fortunate that it didn’t. •