WikiPortallus: Esther Lederberg.html

Esther Miriam Zimmer Lederberg (December 18, 1922 - November 11, 2006) was an American microbiologist and immunologist and pioneer of bacterial genetics. Notable contributions include the discovery of lambda phage, the relationship between transduction and lambda phage lysogeny, the development of replica plating, and discovery of bacterial fertility factor F.

Lederberg also founded and directed the Plasmid Reference Center at Stanford University, whose collection contained plasmids of all types of genes, coding for antibiotic resistance, heavy metal resistance, virulence, conjugation, colicins, transposons, temperature sensitivity and other unknown factors. (Most of these plasmids have still not been thoroughly studied.)

Early years

Esther Miriam Zimmer was the first of two children born in the Bronx, N.Y. to David Zimmer and Pauline Geller Zimmer. (A 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.¹

Zimmer thrived academically. She attended Evander Childs High School in the Bronx, receiving honors for French and graduating at the age of 16. She received an A.B. at New York City’s Hunter College, graduating cum laude in 1942, at the age of 20.

After her graduation from Hunter, Zimmer went to work for the Carnegie Institution of Washington (later Cold Spring Harbor Laboratory) as a research assistant to Alexander Hollaender, with whom she worked on Neurospora crassa as well as publishing her first work in bacterial genetics.² 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. While at Stanford she worked with Edward Lawrie Tatum of Yale on bacterial genetics.³ ⁴ (Note: Tatum and George Beadle later split the 1958 Nobel Prize with her then-husband, Joshua Lederberg.) Stanford awarded her a Master of Arts in 1946.

She married Joshua Lederberg on December 13, 1946, after which she began work on her doctorate at the University of Wisconsin. (Her thesis was "Genetic control of mutability in the bacterium Escherichia coli.") Joshua Lederberg accepted a position there as Associate Professor. She completed her doctorate under the sponsorship of R. A. Brink, in 1950: the same year that she discovered the lysogenicity of lambda bacteriophage (see below).

Professional pioneers

Esther Lederberg attended the celebrated Cold Spring Harbor Laboratory Symposia on genetics during the late 1940s and 50's, as well as later years.

Contributions to microbiology and genetics

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

Lambda bacteriophage and transduction

Esther Lederberg was the first to isolate lambda bacteriophage, a DNA virus, from Escherichia coli K-12 in 1950. ⁶

Lambda phage genetic material consists of a double-stranded DNA molecule with 5' twelve-base-pair sticky ends (cos sites), which permit circularization of the DNA molecule. It shows a lytic cycle and a lysogenic cycle. Studies on the control of these alternative cycles have been very important for our understanding of the regulation of gene transcription. (The mechanism of integration of lambda DNA into bacterial DNA was first worked out by Esther's colleague and close friend, Allan Campbell, in 1962.⁷)

Lambda phage is considered a 'temperate bacteriophage': one whose genome incorporates with and replicates with that of the host bacterium. Uses for lambda include its application as a vector for the cloning of recombinant DNA; the use of its site-specific recombinase, int, for the shuffling of cloned DNAs by the 'Gateway' method; and the application of its Red operon, including the proteins Red alpha (also called 'exo'), beta, and gamma, in the DNA engineering method called recombineering.

Her 1950 lambda phage paper led to an understanding of transduction, which is important not only in explaining the transfer of bacterial resistance, but provides a major mechanism that can explain modes of evolution. ⁸

The intimate relationship between transduction and lambda phage lysogeny was a consequence of this work. ⁹

Bacterial Fertility Factor F

The Fertility Factor (also known as F Factor) is a bacterial DNA sequence that allows a bacterium to produce a sex pilus necessary for conjugation. The sequence contains 20 tra (for "transfer") genes and a number of other genetic sequences responsible for incompatibility, replication, and other functions. The F Factor is an episome, and can either exist as an independent plasmid or integrate into the bacterial cell's genome.

Esther Lederberg's discovery of F stemmed directly from her discovery of lambda as unexpected plaques on 'lac indicator agar' in the course of experiments on other material. In her own words:

Replica plating

Although there were other less efficient forerunners to the methodology (such as paper, or multipronged arrays using wire brushes, toothpicks, etc.), 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 M. Zimmer Lederberg.

Anecdotal credit is generally given to Joshua Lederberg for originating the idea of replica plating, but scientists had been struggling for a reliable solution for at least a decade before Esther Lederberg finally implemented it successfully.

Allan Campbell, Eugene Nester and Stanley Falkow all recount how Esther Lederberg provided them with the technical information necessary to successfully use this new methodology. From Alan Campbell:

In Falkow's case, this happened a few years after she first published the replica plating paper. At the memorial for Esther Lederberg, he spoke of the impact of replica plating, and his feelings upon meeting the originator of the technique:

Later contributions

Esther Lederberg returned to Stanford in 1959 with Joshua Lederberg. She remained at Stanford for the balance of her research career, founding and directing the Plasmid Reference Center (PRC) at the Stanford School of Medicine from 1976 to 1986.

She retired from her position in the Stanford Department of Microbiology and Immunology in 1985, but continued to run the PRC for almost another full decade after that.

Professional Honors

Professional Challenges: Gender Discrimination

Stanley Falkow said of Esther Lederberg that "Experimentally and methodologically she was a genius in the lab."¹⁵ However, although Esther Lederberg was a pioneer research scientist, she faced significant challenges as a woman scientist in the 1950s and 1960s. These were exacerbated by her collaboration with then-husband Joshua Lederberg.

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.” ¹⁶ However, Joshua Lederberg himself failed to mention Esther Lederberg’s name in his Nobel Prize acceptance speech of 1958. Unsurprising that despite the significant effect Esther Lederberg’s work had on twentieth-century microbiology, she was overshadowed by her husband's notoriety.

Esther Lederberg had to fight to gain a position on the Stanford faculty. Retained as a Senior Scientist, in 1974 she was forced to transition to a position as Adjunct Professor of Medical Microbiology “coterminous with research support.” ¹⁷ (Adjunct Professors are typically un-tenured.)

Allan Campbell noted the injustice of Stanford’s attitude toward women scientists in a letter of recommendation for Esther Lederberg, written in 1971: “I think she is a definite asset to the University and merits promotion according to the normal customs of your department (i.e., that your Committee on Women’s Promotions should recommend advancement on the same time schedule as a Committee of Men’s Promotions would advance a male scientist).“¹⁸

Both in high school and as an undergraduate at Hunter College, her proficiency with languages (French, Spanish), earned her many awards; she also started a French Club newspaper. When Lederberg's instructors learned that she wanted to study science rather than languages, they exerted great effort to persuade her not to go into a field where a woman was not allowed to succeed, with the possible exception of botany. (In fact, her career in science started with three internships doing botanical research at the New York Botanical Garden with B. O. Dodge between 1941 and 1942. She researched heterokaryosis in Neurospora tetrasperma.) ¹⁹ Lederberg felt that she should pursue her interests, genetics and microbiology.

Her situation was summed up best, and most publicly, upon Dr. Lederberg’s death in 2006. In his eulogy for Esther Lederberg, Stanley Falkow said that while preparing his remarks he had checked the internet and found “a suggested topic for a term paper to meet the requirements for a passing grade in a bioethics course in Pomona College." He read:

Twenty-first century science historians are beginning to look back on the mid-twentieth century as a time when researchers made great strides in the sciences, but lagged far behind in the area of gender discrimination. For a look at how science historian Pnina Abir-Am highlights the accomplishments of Esther M. Zimmer Lederberg and other under-credited female scientists, see the Brandeis University web site "Scientific Legacies".

Other Interests

Music. A lifelong musician, Lederberg was a devotee of Early Music. She was one of the founding members of the Mid-Peninsula Recorder Orchestra (affiliated with the San Francisco Early Music Society) in 1962, serving as its president for several years. At the memorial held for Dr. Lederberg at Stanford University, Frederick Palmer, musical director of the Mid-Peninsula Recorder Orchestra, spoke of Esther’s joy in this music, and her dedication to the MPRO:

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

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. A scientist who could suspend disbelief enough to actually enjoy some 'science fiction', Esther nevertheless took issue with Michael Crichton's handling of the alien antagonist in his novel, "Andromeda Strain". Her second husband, Matthew Simon, recounts:

Lederberg also loved the works of Charles Dickens and Jane Austen, and belonged to societies devoted to studying and celebrating these two authors.²⁴

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 as well as being beautiful such plants would not need to be watered -- an important consideration to a campus located in the San Francisco Bay Area, which has frequent droughts.

She married Joshua Lederberg in 1946; they divorced in 1966. She married Matthew Simon in 1993.

Esther Miriam Zimmer Lederberg died November 11, 2006, from pneumonia and congestive heart failure, at the age of 83.

Notable Papers

Footnotes

^ "Esther Lederberg Memorial Web Site: Anecdote #5"
^ Hollaender, A. and Zimmer, E. M., January 1945 (September, 1944), "The effect of ultraviolet radiation and X-rays on mutation production in penicillium notatum", Genetics Society of America 30(1):8
^ Lederberg, J., Tatum, E. L., Lederberg, E., 1946, "Gene Recombination in Escherichia coli", Nature 158:558
^ Tatum, E. L., Lederberg, E., Lederberg, J., 1947, "Gene Recombination in the Bacterium Escherichia coli", J. Bacteriology 53:673-684
^ She shot thousands of photographs of her colleagues at the Cold Spring Harbor Symposia and other scientific conferences. A special collection of her photographs is housed at Stanford at the Esther M. Zimmer Lederberg archive, and reproduced at http://www.estherlederberg.com/CSHL_List.html.)
^ "Lederberg, E. M., 1950, "Lysogenicity in Escherichia coli strain K-12", Microbial Genetics Bulletin, 1, pp. 5-9, Jan. 1950, Univ. of Wisconsin (Evelyn Maisel Witkin, Editor), Ohio State University, ISSN: 0026-2579, call No. 33-M-4, OCLC: 04079516, Accession Number: AEH8282UW" http://www.estherlederberg.com/LambdaW.html
^ Ann. Rev. Genet. 2007 41:1-11
^ Morse, M., Lederberg, E., Lederberg, J. 1956. Transduction in Escherichia coli K-12. Genetics 41:121-156
^ Records
^ The True History of Fertility Factor F
^ Deception
^ Gene Nester
^ Deception
^ The State: The Genotype: What's new
^ Esther Lederberg, pioneer in genetics, dies at 83
^ Records
^ op cit.
^ op cit.
^ Esther M. Zimmer Lederberg: Anecdotes
^ Deception
^ Speech by Dr. Stanley Falkow at Esther's Memorial, 11/30/2006
^ Speech by Fred Palmer at Esther's Memorial, 11/30/2006
^ "Esther Lederberg Memorial Web Site: Anecdote #11"
^^{citation needed}

Esther Lederberg.html

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