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Esther Lederberg, pioneer in genetics, dies at 83

Courtesy of Matthew Simon

Esther Lederberg gives a lecture in Japan in 1962.

BY MITZI BAKER

Esther Miriam Zimmer Lederberg, PhD, professor emeritus of microbiology and immunology, whose more than half-century of studies opened the door for some fundamental discoveries in microbial genetics, died Nov. 11 at Stanford Hospital of pneumonia and congestive heart failure. She was 83.

A memorial service will be held at the Faculty Club on Nov. 30 from 4-6 p.m.

"She was one of the great pioneers in bacterial genetics," said Stanley Falkow, PhD, the Robert W. and Vivian K. Cahill Professor in Cancer Research. "Experimentally and methodologically she was a genius in the lab."

Lederberg is perhaps best known for her collaboration with her first husband, Joshua Lederberg, PhD, who in 1958 won the Nobel Prize for Physiology or Medicine for discoveries on how bacteria mate. But her work was extremely noteworthy in its own right, and she was a trailblazer for women scientists at Stanford and at large. "She was a real legend," said Lucy Tompkins, MD, PhD, the Lucy Becker Professor in Medicine and of Microbiology and Immunology.

Among Lederberg's achievements was the discovery of lambda phage, a virus that infects E. coli bacteria. She published the first report of it in Microbial Genetics Bulletin in 1951, and it quickly became a significant and widely used tool for studying genetic recombination and gene regulation.

"Her discovery of lambda has had a big influence in molecular genetics and virology," said Dale Kaiser, PhD, the Jack, Lulu and Sam Willson Professor of Biochemistry, Emeritus. "It led to quite a lot of work by a large number of people." He explained that lambda is a type of virus known as temperate, meaning that it lives for some time inside a cell rather than killing it immediately after reproducing. It became the model for animal viruses that have similar life cycles, including tumor and herpes viruses.

Lederberg laid the groundwork for demonstrating how phages can transfer genes between bacteria. Her findings were crucial to advancing the understanding of how genes are regulated, how pieces of DNA break apart and recombine to make new genes and how the process of making RNA from DNA is started and stopped. She worked with many of the top research scientists of the 20th century, and the discoveries of several Nobel Prize winners, aside from Joshua Lederberg, could not have been made without her contributions. "She developed lab procedures that all of us have used in research," said Falkow.

Born in the Bronx on Dec. 18, 1922, Lederberg obtained an AB at Hunter College in New York City in 1942. She then moved to Stanford to study genetics, receiving her master's degree in 1946. That year she wed Joshua Lederberg.

After receiving her master's degree, she spent a summer studying microbiology at Hopkins Marine Station and then went to the University of Wisconsin, where she received a United States Public Health Service Fellowship for research and earned her doctorate in 1950.

While at Wisconsin, Joshua and Esther Lederberg formed a team studying bacterial genetics. The Lederbergs developed the technique of replica plating in 1952, which is still widely used in genetics labs. The technique is an elegantly simple method using sterilized velvet scrap. The velvet pressed on the surface of a plate of bacterial colonies in a petri dish picks up some bacteria, like a stamp being pressed into an ink pad. The pad is then pressed in the same orientation onto a series of plates with varying growth mediums, stamping duplicate colony patterns on each plate. By seeing which colonies grew on which plates, the Lederbergs proved the spontaneous development of mutations in bacteria.

In 1959, Esther Lederberg returned to the School of Medicine, when Joshua became chair of the newly created Department of Genetics. The Lederbergs divorced in 1966.

As a professor in what is now the Department of Microbiology and Immunology, Esther Lederberg was doing research at a time when women were scarce on the Stanford faculty. Her second husband, Matthew Simon, said that she had to petition the medical school dean to gain her position; to win him over, she had to offer to start in an untenured slot, for which she felt she was overqualified. That was just one of many stories she had to tell about the challenges of being a woman scientist in the early days of genetic research. "She would recapitulate stories about how things really happened, which isn't always how it's reported in the scientific literature," said Falkow.

Lederberg was a seemingly limitless repository of information about the bacterial and phage strains that she worked with, said Kaiser. Researchers worldwide reaped the benefits of her methodical records and near-photographic memory of the details of her strains, he said. To facilitate collaboration, she directed the Plasmid Reference Center at the medical school from 1976 to 1986, one year after she officially retired in 1985.

Research associate Jonathan Hardy, PhD, a friend of Lederberg's, recalled her wit, charm and ability to hold an audience captive with tales about the scientists with whom she had worked. "Esther was cheery and had an excellent sense of humor, but I believe she would want to be remembered mostly as a scientist, which she was through and through until her very last days," he said.

In addition to her passion for science, Lederberg was intensely involved in the study and practice of Early Music—which includes the Medieval, Renaissance and Baroque periods of Western music—using original instruments. She founded the Mid-Peninsula Recorder Orchestra in 1962, which still draws amateur musicians in the area to play compositions from the 13th century to the present. In 2000, she was quoted by the San Francisco Chronicle as saying that she had always wanted to play the flute, but picked up a recorder on a whim and immediately fell in love. "You can begin anytime, even though it takes a lifetime to be good," she said at the time.

Through a common interest in Early Music, Lederberg met Matthew Simon and married him in 1993. She is survived by Simon and her brother Benjamin Zimmer.