Evelyn M. Witkin

Evelyn M. Witkin (born March 9, 1921, New York City, New York, U.S.—died July 8, 2023, Plainsboro Township, New Jersey) American geneticist whose groundbreaking research on mutagenesis (the induction of mutations) in bacteria provided insight into mechanisms of DNA repair, the fundamental process by which living organisms maintain their genetic integrity in order to survive. Witkin’s discoveries were central to the basic understanding of how bacteria adapt to their environment, including how they survive exposure to ultraviolet (UV) radiation and antibiotics (see antibiotic resistance). Her discoveries played a key role in the elucidation by other researchers of DNA-damage responses in eukaryotic cells.

Education and early discoveries

Maisel was raised in Manhattan and later Queens in New York City. At age 16 she began undergraduate studies at New York University (NYU) and in 1941 completed a bachelor’s degree there. She planned to remain at NYU for graduate studies, but a suspension received during her senior year for protesting against NYU’s acquiescence to segregation in Southern schools during athletic events caused her to enroll instead at nearby Columbia University, where she earned a master’s in 1943. That same year she married psychologist Herman A. Witkin, with whom she later had two children.

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Evelyn remained at Columbia to carry out her doctoral research, working in the laboratory of Ukrainian American geneticist Theodosius Dobzhansky, who was widely known for his influential research on genetics and evolution in Drosophila flies. In 1943, for a class assignment, Dobzhansky asked Witkin to report on a paper by biologists Salvador Luria and Max Delbrück. The paper described the first experimental evidence for the existence of mutable genes in bacteria. Witkin was intrigued by the finding and decided to spend the following summer studying bacterial genetics at Cold Spring Harbor Laboratory under the guidance of Dobzhansky’s colleague, Croatian American geneticist Milislav Demerec. In initial experiments, Witkin induced mutations in Escherichia coli bacteria using UV light and performed the first successful isolation of UV-resistant E. coli mutants. In 1944, Witkin having completed her course work at Columbia and Dobzhansky’s laboratory being unequipped for bacterial research, she returned to Cold Spring Harbor to pursue her thesis work. She subsequently discovered that UV-sensitive E. coli cells become elongated and filamentous and are prevented from undergoing cell division prior to dying from UV irradiation. The observation would prove critical to her later work. Witkin graduated with a Ph.D. from Columbia in 1947.

Research on UV mutagenesis and the SOS response

In 1949, following postdoctoral studies at the American Cancer Society, Witkin resumed the study of bacterial genetics at Cold Spring Harbor. In 1955 she joined the faculty of medicine at the State University of New York Downstate Medical Center. There in the early 1960s she discovered that UV mutagenesis in E. coli could be reversed through dark exposure, a phenomenon that she described as “dark repair” in order to distinguish it from photoreactivation (the elimination of UV mutagenic effects via visible light-dependent enzymatic reactions). She also built on her earlier observations in UV-sensitive E. coli, proposing in 1967 that the UV-induced block of cell division was due to the inhibition of a DNA replication enzyme that, if left active, would otherwise introduce mutations into DNA during the replication process. That possibility was considered in Croatian French biologist Miroslav Radman’s model of so-called SOS replication, which he initially proposed in 1970 by memorandum to Witkin. According to Radman, SOS replication provides bacteria with a means of surviving sudden and extensive DNA damage, and it displays unique characteristics—it is inducible (triggered by DNA damage), requires the synthesis of new proteins, and is controlled by genes known as lexA and recA.

After learning of Radman’s SOS model, Witkin worked to identify a common control mechanism in bacteria that regulates the seemingly disparate cellular responses to UV mutagenesis. Her work supported the idea that the control mechanism involves lexA, which under normal conditions represses the activity of SOS response genes, and recA, which responds to DNA damage by eliminating lexA repression. Other researchers subsequently confirmed her findings and applied them to the study of DNA repair mechanisms in other organisms.

Awards and honours

Witkin received many awards and honours during her career, including the National Medal of Science (2002) and the Albert Lasker Basic Medical Research Award (2015). She was elected to the U.S. National Academy of Sciences in 1977 and the American Academy of Arts and Sciences in 1978. In 1979 she was named the Barbara McClintock Professor of Genetics at Rutgers, where she retired in 1991 as professor emerita.