Esther Lederberg

Esther Miriam Zimmer Lederberg (December 18, 1922 – November 11, 2006) was an American microbiologist and a pioneer of bacterial genetics. Notable contributions include the discovery of the bacterial virus λ, the transfer of genes between bacteria by specialized transduction, the development of replica plating, and the discovery of the bacterial fertility factor F (F plasmid).

Lederberg also founded and directed the now-defunct Plasmid Reference Center at Stanford University, where she maintained, named, and distributed plasmids of many types, including those coding for antibiotic resistance, heavy metal resistance, virulence, conjugation, colicins, transposons, and other unknown factors.

Esther Miriam Zimmer was the first of two children born in the Bronx, New York, to a family of Orthodox Jewish background. Her parents were David Zimmer and Pauline Geller Zimmer. Her brother, Benjamin Zimmer, followed in 1923. A child of the Great Depression, her lunch was often a piece of bread topped by the juice of a squeezed tomato. Zimmer learnt Hebrew and she used this proficiency to conduct Passover seders.

Zimmer attended Evander Childs High School in the Bronx, graduating at the age of 16.She was awarded a scholarship to attend New York City's Hunter College starting that fall. In college, Zimmer initially wanted to study French or literature, but she switched her field of study to biochemistry against the recommendation of her teachers, who felt women struggled to get a career in the sciences.She worked as a research assistant at the New York Botanical Garden, engaging in research on Neurospora crassa with the plant pathologist Bernard Ogilvie Dodge.She received a bachelor's degree in genetics, graduating cum laude in 1942, at the age of 20.

After her graduation from Hunter, Zimmer went to work as a research assistant to Alexander Hollaender at the Carnegie Institution of Washington (later Cold Spring Harbor Laboratory), where she continued to work with N. crassa as well as publishing her first work in genetics. In 1944 she won a fellowship to Stanford University, working as an assistant to George Wells Beadle. She traveled west to California, and after a summer studying at Stanford University's Hopkins Marine Station under Cornelius Van Niel, she entered a master's program in genetics. Stanford awarded her a master's degree in 1946.That same year, she married Joshua Lederberg, a professor at the University of Wisconsin.

Lederberg next went to the University of Wisconsin to pursue a doctorate degree. From 1946 to 1949, she was awarded a predoctoral fellowship by the National Cancer Institute.Her thesis was "Genetic control of mutability in the bacterium Escherichia coli." She completed her doctorate under the supervision of R. A. Brink, in 1950.

Lederberg remained at the University of Wisconsin for most of the 1950s. It was there that she discovered lambda phage, did early research on the relationship between transduction and lambda phage lysogeny, discovered the E. coli F fertility factor with Luigi Luca Cavalli-Sforza (eventually publishing with Joshua Lederberg), devised the first successful implementation of replica plating with Joshua Lederberg, and helped discover and understand the genetic mechanisms of specialized transduction. These contributions laid the foundation for much of the genetics work done in the latter half of the twentieth century.

λ bacteriophage

Esther Lederberg was the first to isolate λ bacteriophage.She first reported the discovery in 1951 while she was a PhD student and later provided a detailed description in a 1953 paper in the journal Genetics.She was working with an E. coli K12 strain that had been mutagenized with ultraviolet light.When she incubated a mixture of the mutant strain with its parent E. coli K12 strain on an agar plate, she saw plaques, which were known to be caused by bacteriophages.The source of the bacteriophage was the parental K12 strain.The UV treatment had "cured" the bacteriophage from the mutant, making it sensitive to infection by the same bacteriophage that the parent produced.The bacteriophage was named λ.

The DNA of λ phage can incorporate into the chromosome of E. coli to become a prophage and subsequently replicate along with the DNA of the host bacterium. When the prophage is later prompted to leave the host, it must excise itself from the host DNA.Occasionally, the phage DNA that is excised is accompanied by adjacent host DNA, which can be introduced into a new host by the phage.This process is called specialized transduction.Lederberg's 1950 λ phage paper led to an understanding of specialized transduction.

Bacterial fertility factor F

The fertility factor (also known as F factor) is a bacterial DNA sequence harboring genes that allow a bacterium to donate DNA to a recipient bacterium by direct contact in a process called conjugation. The F factor is carried on an episome, which can exist either as an independent plasmid or integrate into the bacterial cell's genome.

Lederberg's discovery of F factor stemmed directly from her experiments to map the location of lambda prophage on the E. coli chromosome by crosses with other E. coli strains with known genetic markers.When some of the crosses failed to give rise to recombinants, she suspected that some of her E. coli strains had lost a "fertility factor."In her own words:

In terms of testing available markers ... the data showed that there was a specific locus for lysogenicity. ... In the course of such linkage [genetic mapping] studies,...one day, ZERO recombinants were recovered....I explored the notion that there was some sort of 'fertility factor' which if absent, resulted in no recombinants. For short, I named this F.A number of experiments were designed to clarify these observations.

Replica plating

The problem of reproducing bacterial colonies en masse in the same geometric configuration as on original agar plate was first successfully solved by replica plating, as implemented by Esther and Joshua Lederberg.Scientists had been struggling for a reliable solution for at least a decade before the Lederbergs finally implemented it successfully.Less efficient forerunners to the methodology were toothpicks, paper, wire brushes, and multipronged inoculators.

The Lederbergs used the replica-plating method to demonstrate that bacteriophage- and antibiotic-resistance mutants arose in the absence of phages or antibiotics.The spontaneous nature of mutations was previously demonstrated by Luria and Delbrück.However, many scientists failed to grasp the mathematical arguments of Luria and Delbrück's findings, and their paper was either ignored or rejected by other scientists. The controversy was settled by Lederbergs' simple replica-plating experiment.

Plasmid Reference Center

Esther Lederberg returned to Stanford in 1959 with Joshua Lederberg. She remained at Stanford for the balance of her research career, directing the Plasmid Reference Center (PRC) at the Stanford School of Medicine from 1976 to 1986.As director of the PRC, she organized and maintained a registry of the world's plasmids, transposons, and insertion sequences.

She retired from her position in the Stanford Department of Microbiology and Immunology in 1985, but continued her work at the PRC as a volunteer.

• 1956 Society of Illinois Bacteriologists: Pasteur Award (with Joshua Lederberg)
• 1959 Fulbright Fellowship in bacteriology to work at Melbourne University in Australia.
• 1969 American Cancer Society Dernham Postdoctoral Fellowship in Oncology (Senior Fellowship)
• Fellow of the American Association for the Advancement of Science
• President of the Stanford Chapter of Sigma Xi

In 1985, Lederberg was honored as an emeritus professor in microbiology and immunology at Stanford University.

Stanley Falkow said of Esther Lederberg that "Experimentally and methodologically she was a genius in the lab." However, although Esther Lederberg was a pioneer research scientist, she faced significant challenges as a woman scientist in the 1950s and 1960s.

Lederberg was excluded from writing a chapter in the 1966 book Phage and the Origins of Molecular Biology, a commemoration of molecular biology.According to the science historian Prina Abir-Am, her exclusion was "incomprehensible" because of her important discoveries in bacteriophage genetics.Abir-Am attributed her exclusion in part to the sexism that prevailed during the 1960s.

As Luigi Luca Cavalli-Sforza later wrote, "Dr. Esther Lederberg has enjoyed the privilege of working with a very famous husband. This has been at times also a setback, because inevitably she has not been credited with as much of the credit as she really deserved. I know that very few people, if any, have had the benefit of as valuable a co-worker as Joshua has had."

Like many other women scientists at Stanford University, Lederberg struggled for professional recognition. As her husband began his tenure as the head of the genetics department at Stanford in 1959, she and two other women petitioned the dean of the medical school over the lack of women faculty.She was eventually appointed a faculty position as Research Associate Professor in the Department of Microbiology and Immunology, but the position was untenured.According to Abir-Am, Esther had to fight to stay employed at Stanford after divorcing Joshua. Later in 1974 as a Senior Scientist, she was forced to transition to a position as Adjunct Professor of Medical Microbiology, which was effectively a drop in position.Her short-term appointment was to be renewed on a rolling basis and was dependent on her securing grant funding.

Esther Lederberg had cultural interests that went well beyond science.

Music

A lifelong musician, Lederberg was a devotee of early music. She played the recorder and in 1962 founded the Mid-Peninsula Recorder Orchestra, which plays compositions from the 13th century to the present.

Always conscious that much of early music was really dance music, Lederberg also studied Renaissance and Elizabethan dance.

She loved symphonic music, opera, and the operettas of Gilbert and Sullivan.

Literature

Esther's taste in literature was eclectic; her library included both classics and contemporary works by such authors as Gore Vidal, Ursula K. Le Guin, and Margaret Atwood.

Lederberg also loved the works of Charles Dickens and Jane Austen. She belonged to societies devoted to studying and celebrating these two authors, the Dickens Society of Palo Alto and the Jane Austen Society.

Botany and botanical gardens

Lederberg maintained a lifelong love of botany and botanical gardens. She encouraged the planting of indigenous plants such as poppies and lupins around the Stanford University campus, arguing that besides being beautiful, such plants would not need to be watered—an important consideration on a campus located in the San Francisco Bay Area, which experiences frequent droughts.

She married Joshua Lederberg in 1946; they divorced in 1968. She married Matthew Simon in 1993.

She died in Stanford, California, on November 11, 2006, from pneumonia and congestive heart failure at the age of 83.