Esther Lederberg, pioneer in microbial genetics, dies at Stanford at 83

STANFORD, Calif. - Esther Miriam Zimmer Lederberg, PhD, professor emeritus of microbiology and immunology at the Stanford University School of Medicine, 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 Stanford 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 his discoveries on how bacteria swap genes. 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 the field of 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 phage is a type of virus known as temperate, meaning that it can live for some time inside a cell rather than killing it immediately after reproducing. It became the model for animal viruses that have a similar life cycle, including some tumor viruses and herpes virus.

Lederberg laid the groundwork for demonstrating how phages can transfer genes between bacteria, and 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. Indeed, she worked with many of the top research scientists of the second half of the 20 th century, and several Nobel Prize winners, aside from Joshua Lederberg, could not have made their discoveries without the contributions she made to research. "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 of the City University of New York in 1942. She then moved to Stanford to study genetics and received her master's degree in 1946. That same year she wed Joshua Lederberg.

After receiving her master's degree, she spent a summer studying microbiology at Stanford's Hopkins Marine Station in Monterey and then went to the University of Wisconsin, where she received a U.S. 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 that is still widely used in genetics laboratories. The technique is an elegantly simple method using sterilized scraps of velvet. 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 can then be pressed in the same orientation onto a series of plates with various growth media, stamping duplicate colony patterns on each plate. By seeing which colonies could grow on which plates, the Lederbergs proved the spontaneous development of mutations in bacteria.

In 1959, Esther Lederberg returned to the Stanford School of Medicine, while Joshua assumed the chairmanship of the newly created department of genetics. She served as a professor of medical microbiology. The Lederbergs divorced in 1966.

Esther Lederberg continued her research in what is now the Department of Microbiology and Immunology at a time when women were scarce on the Stanford faculty. Her second husband, Matthew Simon, said that she petitioned the dean of the medical school to gain her position; to win him over, she offered to start in an untenured slot, though she felt she was overqualified for the job. 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, according to Kaiser. Countless 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 Stanford medical school from 1976 to 1986, one year after she officially retired in 1985. She was also the American Cancer Society Senior Dernham Fellow from 1968 to 1970.

Research associate Jonathan Hardy, PhD, a friend of Lederberg's for the last 25 years, recalled her wit and charm and her ability to hold an audience captive with her tales about the scientists with whom she had worked. "Esther was a cheery person 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," Hardy said.

Lederberg had a number of cultural interests outside of the scientific world. In particular, she 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 13 th 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, in her 38 th year of being a member of the group.

In addition to Early Music, Lederberg maintained an active involvement in medieval dance, the Palo Alto Dickens Fellowship and the Jane Austen Society. She was an avid supporter of conservation, and was a charter member of the Monterey Bay Aquarium.

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.

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