Evelyn Witkin, who studied how cells repair DNA, dies at 102

Evelyn Witkin, who paved the way for advances in cancer treatment and genetics by conducting groundbreaking studies on the DNA-damage response, the mechanism by which cells detect and respond to damage from chemicals, radiation and other threats, died July 8 at a rehabilitation center in Plainsboro Township, N.J. She was 102.

The cause was complications from a fall, said her son, Joseph.

When Witkin launched her scientific career in the 1940s, the structure of DNA was a mystery, its function was barely known and the field of bacterial genetics was just getting started. Working with E. coli cultures at Cold Spring Harbor Laboratory on Long Island, and later at Rutgers University in New Jersey, she helped demonstrate the way in which organisms detect damage to their genome and put out a biological distress signal, triggering rescue efforts in a fight for survival.

“Her work underpins our understanding of DNA damage and DNA repair in all living organisms, from bacteria to humans, and for understanding how DNA damage and DNA repair affect cancer and aging,” said Richard H. Ebright, the laboratory director at Rutgers’s Waksman Institute of Microbiology, in a 2021 interview with the university.

Witkin’s pathbreaking research began in 1944, when she started investigating genetic mutations in bacteria by irradiating E. coli cells with ultraviolet light. The UV dosage was too strong — it was her first experiment with bacteria, on her first day at work at Cold Spring Harbor — and destroyed virtually all of the cells. Yet four colonies continued to grow.

“At this point, I asked, ‘Why did they survive? Maybe a mutation made them resistant,’” she recalled in a 2015 interview with the New York Times.

Her studies of mutations led her to pinpoint genes that were usually silent in E. coli cells, but were activated when the DNA was damaged. By the early 1970s, she was collaborating with another scientist, Miroslav Radman, who had been similar leads at the Free University of Brussels. “We pooled our information,” she said, “and decided that this was the tip of a very interesting iceberg.”

Together, Witkin and Radman developed what became known as the SOS response theory, outlining the ways in which cells attempt to survive and reproduce in the face of DNA damage that threatens their destruction. Witkin said that she and her colleagues counted more than 40 genes that are activated when DNA is damaged, and which initiate a ballet of chemical processes intended to help cells endure.

Witkin continued to study the SOS response until 1991, at age 70, when she said she was forced to step down because she had reached what was then the mandatory retirement age for Rutgers faculty. She received the Thomas Hunt Morgan Medal for lifetime achievement in genetics in 2000, the National Medal of Science in 2002, and in 2015 was awarded the Wiley Prize in Biomedical Sciences as well as the Albert Lasker Basic Medical Research Award, a top honor in medical research. She shared both those awards with Stephen Elledge, who had applied her research to more complex organisms, including human beings.

“If I had a couple of million dollars to build a lab in my basement, I would have gone on,” she told the scientific journal PLOS Genetics in 2012, lamenting that she had to step away from her research. “E. coli still has lots of secrets.”

The younger of two children, Evelyn Ruth Maisel was born in Manhattan on March 9, 1921, to Jewish immigrants from Eastern Europe. Her father, a pharmacist, died when she was 3; her mother, a homemaker, remarried a few years later and moved the family to the Forest Hills neighborhood of Queens, where her stepfather ran a drugstore.

As a young girl, Witkin was fascinated by Sinclair Lewis’s Pulitzer Prize-winning novel “Arrowsmith,” about a young doctor with a zeal for medical research. The book “made science seem so romantic and rewarding and wonderful,” she recalled in a Lasker prize interview, and after she enrolled at New York University at age 16 she began studying biology.

She also got involved in campus activism. During her senior year, in 1940, she helped lead a protest against the university’s treatment of Black athletes, who were left at home when the school’s sports teams traveled to compete against segregated universities. (The practice was widespread in college athletics in the years before World War II, with segregated schools in the South typically making the request.)

When the football team’s star fullback, Leonard Bates, was barred from traveling to a game against the University of Missouri because he was Black, Witkin and six other students circulated a petition protesting the policy. About 2,000 students picketed the administration building, chanting “Bates must play!,” according to a subsequent account in the Times.

“NYU responded by suspending us for three months,” Witkin told the newspaper. “I could not graduate with my class. I lost the graduate assistantship they’d offered me for the following year.”

In search of a new graduate program, she went uptown to Columbia University, where Russian-born geneticist Theodosius Dobzhansky agreed to take her on as a student. “He’d never had a female graduate student before,” Witkin recalled, “and thought that would be pretty good.”