Esther Lederberg
Encyclopedia
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 the lambda phage
, the relationship between transduction
and lambda phage lysogeny
, the development of replica plating
, and the 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.)
Zimmer thrived academically. She attended Evander Childs High School
in the Bronx, receiving honors for French and graduating at the age of 16. As an undergraduate, Zimmer worked at the New York Botanical Garden
, engaging in research on Neurospora crassa
with Bernard Ogilvie Dodge
. 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. 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. (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).
Symposia on genetics during the late 1940s and 50's, as well as later years.
Lederberg influenced and was influenced by such colleagues and friends as her mentor Edward Lawrie Tatum
, George Wells Beadle, Cornelius Van Niel
, Barbara McClintock
, Salvador Luria, André Lwoff, Jacques Monod
, François Jacob
, Werner Arber
, Erwin Chargaff
, Sol Spiegelman
, one-time director of Cold Spring Harbor Milislav Demerec
, Evelyn M. Witkin
, Max Delbrück
, Francis Crick
, James Watson
, Theodosius Dobzhansky
, Jim Crow, Luigi Luca Cavalli-Sforza
, Enrico Calef, M. B. Yarmolinsky, Mogens Westergaard, Aaron Novick, Bruce A. D. Stocker, Guido Pontecorvo
, Bernard Davis
, Alfred Hershey
, Eugene Nester, Allan Campbell, Alfred Sturtevant
, Gunther Stent
, Jonas Salk
, Tracy Sonneborn
, Sydney Brenner
, M. Laurance Morse, Julius Adler, Barbara J. Bachmann, Richard Feynman
, and many others.
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 bacterial Fertility Factor F (eventually publishing with Joshua Lederberg and Luigi Luca Cavalli-Sforza
), devised the first successful implementation of Replica plating
, helped discover and understand the genetic mechanisms of Specialized Transduction as well as generalized Transduction
, and was a major researcher in elucidating the genetic basis of Galactosemia
as well as Maltophilia. These contributions laid the foundation for much of the genetics work done in the latter half of the twentieth century.
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.)
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.
The intimate relationship between transduction and lambda phage lysogeny was a consequence of this work.
A permanent exhibit in the "DNAtrium" of The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology
honors Esther M. Zimmer Lederberg as the discoverer of lambda phage.
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:
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:
Eugene Nester said:
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:
At first, plasmids were of great interest due to their ability to confer inheritable resistance to antibiotics, thus were referred to as "R-Factors" or "R plasmids". As time passed, the nomenclature was changed to "Plasmids" (in general) to take into account other factors in addition to antibiotic resistance, such as genes for specific activity (gal, lac, ara, etc.) and temperature sensitivity. (For example, plasmid pSC304 used Kretschmer's protocol to establish temperature sensitivity. See P. J. Kretschmer and S. N. Cohen, 1977, J. Bacteriology, 130, 888-899.)
The PRC coordinated closely with the members of the Plasmid Nomenclature Committee (Royston Clowes, Stanley N. Cohen, Rob Curtiss III, Naomi Datta, Stanley Falkow, and Richard P. Novick), assigning prefixes to plasmids, and numbers to Insertion Sequences and Transposons.
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.
For a complete list of Esther Lederberg's professional memberships, see http://www.estherlederberg.com/Vita.html.
In 2010, Stanford University dedicated part of Clark Walk to Esther M. Zimmer Lederberg. (Clark Walk is a series of granite blocks that memorialize various Stanford scientists and events in the history of the Stanford School of Medicine, located between the Sherman Fairchild building and the Li Ki Shing Pavilion.)
A black granite block shows a photograph of Esther Lederberg in the laboratory, a page from one of her notebooks, and quotes from two close colleagues:
Len Herzenberg:
Stanley Falkow
:
In this memorial block, Stanford University explicitly attributes its information to the Esther Lederberg Memorial Web Site, "http://www.estherlederberg.com".
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. 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.” 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.” (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).“
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.) 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".
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
.
, 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 those two authors.
and botanical garden
s. 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.
For a list of all known papers authored or co-authored by Esther M. Zimmer Lederberg, see http://www.EstherLederberg.com/Papers.html.
Microbiologist
A microbiologist is a scientist who works in the field of microbiology. Microbiologists study organisms called microbes. Microbes can take the form of bacteria, viruses, fungi, and protists...
and immunologist and pioneer of bacterial genetics
Microbial genetics
Microbial genetics is a subject area within microbiology and genetic engineering. It studies the genetics of very small organisms. This involves the study of the genotype of microbial species and also the expression system in the form of phenotypes.It also involves the study of genetic processes...
. Notable contributions include the discovery of the lambda phage
Lambda phage
Enterobacteria phage λ is a temperate bacteriophage that infects Escherichia coli.Lambda phage is a virus particle consisting of a head, containing double-stranded linear DNA as its genetic material, and a tail that can have tail fibers. The phage particle recognizes and binds to its host, E...
, the relationship between transduction
Transduction (genetics)
Transduction is the process by which DNA is transferred from one bacterium to another by a virus. It also refers to the process whereby foreign DNA is introduced into another cell via a viral vector. Transduction does not require cell-to-cell contact , and it is DNAase resistant...
and lambda phage lysogeny
Lysogeny
Lysogeny, or the lysogenic cycle, is one of two methods of viral reproduction . Lysogeny is characterized by integration of the bacteriophage nucleic acid into the host bacterium's genome...
, the development of replica plating
Replica plating
In molecular biology and microbiology, replica plating is a technique in which one or more secondary Petri plates containing different solid selective growth media are inoculated with the same colonies of microorganisms from a primary plate , reproducing the original spatial...
, and the 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.Zimmer thrived academically. She attended Evander Childs High School
Evander Childs Educational Campus
Evander Childs Educational Campus is a cluster of public high schools located on the campus of the former Evander Childs High School in The Bronx, New York City...
in the Bronx, receiving honors for French and graduating at the age of 16. As an undergraduate, Zimmer worked at the New York Botanical Garden
New York Botanical Garden
- See also :* Education in New York City* List of botanical gardens in the United States* List of museums and cultural institutions in New York City- External links :* official website** blog*...
, engaging in research on Neurospora crassa
Neurospora crassa
Neurospora crassa is a type of red bread mold of the phylum Ascomycota. The genus name, meaning "nerve spore" refers to the characteristic striations on the spores. The first published account of this fungus was from an infestation of French bakeries in 1843. N...
with Bernard Ogilvie Dodge
Bernard Ogilvie Dodge
Bernard Ogilvie Dodge was an American botanist and pioneer researcher on heredity in fungi. Dodge was the author of over 150 papers dealing with the life histories, cytology, morphology, pathology and genetics of fungi, and with insects and other animal pests of plants...
. She received an A.B. at New York City’s Hunter College
Hunter College
Hunter College, established in 1870, is a public university and one of the constituent colleges of the City University of New York, located on Manhattan's Upper East Side. Hunter grants undergraduate, graduate, and post-graduate degrees in more than one hundred fields of study, and is recognized...
, 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
Cold Spring Harbor Laboratory
The Cold Spring Harbor Laboratory is a private, non-profit institution with research programs focusing on cancer, neurobiology, plant genetics, genomics and bioinformatics. The Laboratory has a broad educational mission, including the recently established Watson School of Biological Sciences. It...
) as a research assistant to Alexander Hollaender, with whom she worked on neurospora crassa
Neurospora crassa
Neurospora crassa is a type of red bread mold of the phylum Ascomycota. The genus name, meaning "nerve spore" refers to the characteristic striations on the spores. The first published account of this fungus was from an infestation of French bakeries in 1843. N...
as well as publishing her first work in bacterial genetics. In 1944 she won a fellowship to Stanford University
Stanford University
The Leland Stanford Junior University, commonly referred to as Stanford University or Stanford, is a private research university on an campus located near Palo Alto, California. It is situated in the northwestern Santa Clara Valley on the San Francisco Peninsula, approximately northwest of San...
, 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
Hopkins Marine Station
Hopkins Marine Station is the marine laboratory of Stanford University. It is located ninety miles south of the university's main campus, in Pacific Grove, California on the Monterey Peninsula, adjacent to the Monterey Bay Aquarium. It is home to nine research laboratories and a fluctuating...
under Cornelius Van Niel
Cornelius Van Niel
Cornelis Bernardus van Niel was a Dutch-American microbiologist. He introduced the study of general microbiology to the United States and made key discoveries explaining the chemistry of photosynthesis.In 1923, Cornelis van Niel married Christina van Hemert, graduated in chemical engineering at...
, she entered a master’s program in genetics. While at Stanford she worked with Edward Lawrie Tatum
Edward Lawrie Tatum
Edward Lawrie Tatum was an American geneticist. He shared half of the Nobel Prize in Physiology or Medicine in 1958 with George Wells Beadle for showing that genes control individual steps in metabolism...
of Yale on bacterial genetics. (Note: Tatum and George Beadle later split the 1958 Nobel Prize with her then-husband, Joshua Lederberg
Joshua Lederberg
Joshua Lederberg ForMemRS was an American molecular biologist known for his work in microbial genetics, artificial intelligence, and the United States space program. He was just 33 years old when he won the 1958 Nobel Prize in Physiology or Medicine for discovering that bacteria can mate and...
.) 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
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
.") 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 LaboratoryCold Spring Harbor Laboratory
The Cold Spring Harbor Laboratory is a private, non-profit institution with research programs focusing on cancer, neurobiology, plant genetics, genomics and bioinformatics. The Laboratory has a broad educational mission, including the recently established Watson School of Biological Sciences. It...
Symposia on genetics during the late 1940s and 50's, as well as later years.
Lederberg influenced and was influenced by such colleagues and friends as her mentor Edward Lawrie Tatum
Edward Lawrie Tatum
Edward Lawrie Tatum was an American geneticist. He shared half of the Nobel Prize in Physiology or Medicine in 1958 with George Wells Beadle for showing that genes control individual steps in metabolism...
, George Wells Beadle, Cornelius Van Niel
Cornelius Van Niel
Cornelis Bernardus van Niel was a Dutch-American microbiologist. He introduced the study of general microbiology to the United States and made key discoveries explaining the chemistry of photosynthesis.In 1923, Cornelis van Niel married Christina van Hemert, graduated in chemical engineering at...
, Barbara McClintock
Barbara McClintock
Barbara McClintock , the 1983 Nobel Laureate in Physiology or Medicine, was an American scientist and one of the world's most distinguished cytogeneticists. McClintock received her PhD in botany from Cornell University in 1927, where she was a leader in the development of maize cytogenetics...
, Salvador Luria, André Lwoff, Jacques Monod
Jacques Monod
Jacques Lucien Monod was a French biologist who was awarded a Nobel Prize in Physiology or Medicine in 1965, sharing it with François Jacob and Andre Lwoff "for their discoveries concerning genetic control of enzyme and virus synthesis"...
, François Jacob
François Jacob
François Jacob is a French biologist who, together with Jacques Monod, originated the idea that control of enzyme levels in all cells occurs through feedback on transcription. He shared the 1965 Nobel Prize in Medicine with Jacques Monod and André Lwoff.-Childhood and education:François Jacob is...
, Werner Arber
Werner Arber
Werner Arber is a Swiss microbiologist and geneticist. Along with American researchers Hamilton Smith and Daniel Nathans, Werner Arber shared the 1978 Nobel Prize in Physiology or Medicine for the discovery of restriction endonucleases...
, Erwin Chargaff
Erwin Chargaff
Erwin Chargaff was an American biochemist who emigrated to the United States during the Nazi era. Through careful experimentation, Chargaff discovered two rules that helped lead to the discovery of the double helix structure of DNA...
, Sol Spiegelman
Sol Spiegelman
Sol Spiegelman was an American molecular biologist. He developed the technique of nucleic acid hybridization, which helped to lay the groundwork for advances in recombinant DNA technology....
, one-time director of Cold Spring Harbor Milislav Demerec
Milislav Demerec
Milislav Demerec was a Croatian-American geneticist, and the director of the Department of Genetics, Carnegie Institution of Washington [CIW], now Cold Spring Harbor Laboratory from 1941 to 1960, recruiting Barbara McClintock and Alfred Hershey.Demerec was born and raised in Kostajnica...
, Evelyn M. Witkin
Evelyn M. Witkin
Evelyn M. Witkin, born Evelyn Maisel is an American geneticist whose research has been widely influential in the areas of DNA mutagenesis and DNA repair....
, Max Delbrück
Max Delbrück
Max Ludwig Henning Delbrück was a German-American biophysicist and Nobel laureate.-Biography:Delbrück was born in Berlin, German Empire...
, Francis Crick
Francis Crick
Francis Harry Compton Crick OM FRS was an English molecular biologist, biophysicist, and neuroscientist, and most noted for being one of two co-discoverers of the structure of the DNA molecule in 1953, together with James D. Watson...
, James Watson
James D. Watson
James Dewey Watson is an American molecular biologist, geneticist, and zoologist, best known as one of the co-discoverers of the structure of DNA in 1953 with Francis Crick...
, Theodosius Dobzhansky
Theodosius Dobzhansky
Theodosius Grygorovych Dobzhansky ForMemRS was a prominent geneticist and evolutionary biologist, and a central figure in the field of evolutionary biology for his work in shaping the unifying modern evolutionary synthesis...
, Jim Crow, Luigi Luca Cavalli-Sforza
Luigi Luca Cavalli-Sforza
Luigi Luca Cavalli-Sforza is an Italian population geneticist born in Genoa, who has been a professor at Stanford University since 1970 .-Books:...
, Enrico Calef, M. B. Yarmolinsky, Mogens Westergaard, Aaron Novick, Bruce A. D. Stocker, Guido Pontecorvo
Guido Pontecorvo
Guido Pontecorvo ForMemRS was an Italian-born geneticist.-Career:He fled to Britain in 1938.* Institute of Animal Genetics, University of Edinburgh, 1938-40 and 1944-45...
, Bernard Davis
Bernard Davis
Bernard David Davis was an American biologist who made major contributions in microbial physiology and metabolism. Davis was a prominent figure at Harvard Medical School in microbiology and in national science policy. He was the 1989 recipient of the Selman A...
, Alfred Hershey
Alfred Hershey
Alfred Day Hershey was an American Nobel Prize-winning bacteriologist and geneticist.He was born in Owosso, Michigan and received his B.S. in chemistry at Michigan State University in 1930 and his Ph.D. in bacteriology in 1934, taking a position shortly thereafter at the Department of Bacteriology...
, Eugene Nester, Allan Campbell, Alfred Sturtevant
Alfred Sturtevant
Alfred Henry Sturtevant was an American geneticist. Sturtevant constructed the first genetic map of a chromosome in 1913. Throughout his career he worked on the organism Drosophila melanogaster with Thomas Hunt Morgan...
, Gunther Stent
Gunther Stent
Gunther S. Stent was Graduate Professor of Molecular Biology at the University of California, Berkeley. He was born in Berlin as "Günter Siegmund Stensch"; the name was changed after the migration to the USA...
, Jonas Salk
Jonas Salk
Jonas Edward Salk was an American medical researcher and virologist, best known for his discovery and development of the first safe and effective polio vaccine. He was born in New York City to parents from Ashkenazi Jewish Russian immigrant families...
, Tracy Sonneborn
Tracy Sonneborn
Tracy Morton Sonneborn was an American biologist. His life's study was of the protozoan group Paramecium.-Non-Mendelian Inheritance:...
, Sydney Brenner
Sydney Brenner
Sydney Brenner, CH FRS is a South African biologist and a 2002 Nobel prize in Physiology or Medicine laureate, shared with H...
, M. Laurance Morse, Julius Adler, Barbara J. Bachmann, Richard Feynman
Richard Feynman
Richard Phillips Feynman was an American physicist known for his work in the path integral formulation of quantum mechanics, the theory of quantum electrodynamics and the physics of the superfluidity of supercooled liquid helium, as well as in particle physics...
, and many others.
Contributions to microbiology and genetics
Lederberg remained at the University of WisconsinUniversity of Wisconsin–Madison
The University of Wisconsin–Madison is a public research university located in Madison, Wisconsin, United States. Founded in 1848, UW–Madison is the flagship campus of the University of Wisconsin System. It became a land-grant institution in 1866...
for most of the 1950s. It was there that she discovered lambda phage, did early research on the relationship between transduction and Lambda phage
Lambda phage
Enterobacteria phage λ is a temperate bacteriophage that infects Escherichia coli.Lambda phage is a virus particle consisting of a head, containing double-stranded linear DNA as its genetic material, and a tail that can have tail fibers. The phage particle recognizes and binds to its host, E...
lysogeny
Lysogeny
Lysogeny, or the lysogenic cycle, is one of two methods of viral reproduction . Lysogeny is characterized by integration of the bacteriophage nucleic acid into the host bacterium's genome...
, discovered bacterial Fertility Factor F (eventually publishing with Joshua Lederberg and Luigi Luca Cavalli-Sforza
Luigi Luca Cavalli-Sforza
Luigi Luca Cavalli-Sforza is an Italian population geneticist born in Genoa, who has been a professor at Stanford University since 1970 .-Books:...
), devised the first successful implementation of Replica plating
Replica plating
In molecular biology and microbiology, replica plating is a technique in which one or more secondary Petri plates containing different solid selective growth media are inoculated with the same colonies of microorganisms from a primary plate , reproducing the original spatial...
, helped discover and understand the genetic mechanisms of Specialized Transduction as well as generalized Transduction
Transduction
Transduction is a mechanism whereby genetic material may be transferred from the genes of a bacterium to another bacterium. This may include the actual covalent-bonding of new genetic markers...
, and was a major researcher in elucidating the genetic basis of Galactosemia
Galactosemia
Galactosemia is a rare genetic metabolic disorder that affects an individual's ability to metabolize the sugar galactose properly. Although the sugar lactose can metabolize to galactose, galactosemia is not related to and should not be confused with lactose intolerance...
as well as Maltophilia. These 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.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.)
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.
The intimate relationship between transduction and lambda phage lysogeny was a consequence of this work.
A permanent exhibit in the "DNAtrium" of The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology
Massachusetts Institute of Technology
The Massachusetts Institute of Technology is a private research university located in Cambridge, Massachusetts. MIT has five schools and one college, containing a total of 32 academic departments, with a strong emphasis on scientific and technological education and research.Founded in 1861 in...
honors Esther M. Zimmer Lederberg as the discoverer of lambda phage.
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:
In terms of testing available markers ... the data showed that there was a specific locus for lysogenicity. ... 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.
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
Stanley Falkow
Stanley Falkow, PhD, is microbiologist and a professor of microbiology and immunology at Stanford University School of Medicine. He is sometimes referred to as the father of molecular microbial pathogenesis, which is the study of how infectious microbes and host cells interact to cause disease at...
all recount how Esther Lederberg provided them with the technical information necessary to successfully use this new methodology. From Alan Campbell:
Who successfully implemented the technique? Here Esther at least refined the process considerably. I remember (from her and others) that she was the one who went to the fabrics store and selected velvet of the best thickness, pile, etc. to give the cleanest prints.
Eugene Nester said:
I wanted to respond to your question about replica plating and who really invented it. I think it will be very difficult to answer that question in a convincing way. That technique was developed before I ever knew the Lederbergs ... I do know that Esther in all likelihood was responsible for getting the technique to actually work. She emphasized to me how important it was to use a particular kind of Italian velvet (or was it velveteen actually), so in my own mind I believe she was the key person in taking the idea to actual practice.
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:
It was brilliantly simple: creative discoveries often are. She thought of using ordinary velveteen from a yard goods store to serve as a kind of rubber stamp. The tiny fibers of the velveteen acted like hundreds of tiny inocculating needles. The pad was carefully kept in the same orientation and used to inocculate a series of agar plates containing different media containing antibiotics or supplemented with essential nutrients such as amino acids and vitamins. Esther and Joshua used this technique as an indirect selective method to prove the spontaneous origin of mutants with adaptive advantages. ...
All of these things foreshadowed our first meeting and I was appropriately in awe of her. I was just starting to use replica plating in my own work and Esther immediately told me what brand of velveteen to look for and to be sure to wash the velveteen before I used them and even what detergent to use to wash them.
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.At first, plasmids were of great interest due to their ability to confer inheritable resistance to antibiotics, thus were referred to as "R-Factors" or "R plasmids". As time passed, the nomenclature was changed to "Plasmids" (in general) to take into account other factors in addition to antibiotic resistance, such as genes for specific activity (gal, lac, ara, etc.) and temperature sensitivity. (For example, plasmid pSC304 used Kretschmer's protocol to establish temperature sensitivity. See P. J. Kretschmer and S. N. Cohen, 1977, J. Bacteriology, 130, 888-899.)
The PRC coordinated closely with the members of the Plasmid Nomenclature Committee (Royston Clowes, Stanley N. Cohen, Rob Curtiss III, Naomi Datta, Stanley Falkow, and Richard P. Novick), assigning prefixes to plasmids, and numbers to Insertion Sequences and Transposons.
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
- 1956 Society of Illinois Bacteriologists: Pasteur Award (with Joshua Lederberg; the first time the award was ever given to a team of researchers)
- 1969 American Cancer Society Dernham Postdoctoral Fellowship in Oncology (Senior Fellowship)
- President of the Stanford Chapter of Sigma XiSigma XiSigma Xi: The Scientific Research Society is a non-profit honor society which was founded in 1886 at Cornell University by a junior faculty member and a handful of graduate students. Members elect others on the basis of their research achievements or potential...
- Memberships in a number of other scientific societies; frequent invitee to Gordon Conferences; etc.
For a complete list of Esther Lederberg's professional memberships, see http://www.estherlederberg.com/Vita.html.
In 2010, Stanford University dedicated part of Clark Walk to Esther M. Zimmer Lederberg. (Clark Walk is a series of granite blocks that memorialize various Stanford scientists and events in the history of the Stanford School of Medicine, located between the Sherman Fairchild building and the Li Ki Shing Pavilion.)
A black granite block shows a photograph of Esther Lederberg in the laboratory, a page from one of her notebooks, and quotes from two close colleagues:
Len Herzenberg:
Joshua and Esther Lederberg established their own group and worked on bacterial genetics. Studying with Edward Tatum, they discovered sex, or genetic exchange in bacteria, which won him the Nobel Prize shortly after he arrived at Stanford. The process they developed became a way to transfer genetic information between bacteria.
Stanley Falkow
Stanley Falkow
Stanley Falkow, PhD, is microbiologist and a professor of microbiology and immunology at Stanford University School of Medicine. He is sometimes referred to as the father of molecular microbial pathogenesis, which is the study of how infectious microbes and host cells interact to cause disease at...
:
Esther Lederberg developed a method of replica plating using velveteen attached to a piston ring. The rings are pressed onto bacterial colonies and then stamped onto a series of plates. She advanced many of the early lab procedures and also discovered lambda phage, which became a widely used tool in microbial genetics.
In this memorial block, Stanford University explicitly attributes its information to the Esther Lederberg Memorial Web Site, "http://www.estherlederberg.com".
Professional challenges: gender discrimination
Stanley FalkowStanley Falkow
Stanley Falkow, PhD, is microbiologist and a professor of microbiology and immunology at Stanford University School of Medicine. He is sometimes referred to as the father of molecular microbial pathogenesis, which is the study of how infectious microbes and host cells interact to cause disease at...
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. These were exacerbated by her collaboration with then-husband Joshua Lederberg.
As Luigi Luca Cavalli-Sforza
Luigi Luca Cavalli-Sforza
Luigi Luca Cavalli-Sforza is an Italian population geneticist born in Genoa, who has been a professor at Stanford University since 1970 .-Books:...
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.” However, Joshua Lederberg
Joshua Lederberg
Joshua Lederberg ForMemRS was an American molecular biologist known for his work in microbial genetics, artificial intelligence, and the United States space program. He was just 33 years old when he won the 1958 Nobel Prize in Physiology or Medicine for discovering that bacteria can mate and...
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.” (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).“
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.) 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
Stanley Falkow
Stanley Falkow, PhD, is microbiologist and a professor of microbiology and immunology at Stanford University School of Medicine. He is sometimes referred to as the father of molecular microbial pathogenesis, which is the study of how infectious microbes and host cells interact to cause disease at...
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:
’Martha Chase, Daisy Roulland-Dussoix, and Esther Lederberg are women who participated in important discoveries in science. Martha Chase showed that phage genetic material is DNA not protein. Daisy Dussoix discovered restriction enzymes, and Esther Lederberg invented replica plating. Yet each of these discoveries is often credited to the male member of the team (Al Hershey, Werner Arber, and Joshua Lederberg, respectively). Using the resources of the library (at least five sources), write a five page paper that examines how history of science has treated each discovery (generally by Hershey, Arber, and Josh Lederberg, who all received the Nobel prize) and include your own appraisal of how you might have reacted to the reward structure in each case.
The unnamed Professor who posed this question noted that ‘(This one is a challenge! Feel free to reflect in your paper on why it might be so hard to find relevant information.)’
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".
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:
One of the frustrations of anyone directing a musical ensemble made up of volunteers is wondering who will show up for rehearsals and if all of the parts will be adequately covered. I never had to worry about Esther. Even after her health began to fail and she was required to use a walker, Esther seldom missed one of the orchestra's meetings, and she insisted on playing in the concerts that the orchestra presented despite her limited mobility.
Always conscious that much of Early Music was really dance music, Lederberg also studied Renaissance
Renaissance
The Renaissance was a cultural movement that spanned roughly the 14th to the 17th century, beginning in Italy in the Late Middle Ages and later spreading to the rest of Europe. The term is also used more loosely to refer to the historical era, but since the changes of the Renaissance were not...
and Elizabethan dance.
She loved symphonic music, opera, and the operettas of Gilbert and Sullivan
Gilbert and Sullivan
Gilbert and Sullivan refers to the Victorian-era theatrical partnership of the librettist W. S. Gilbert and the composer Arthur Sullivan . The two men collaborated on fourteen comic operas between 1871 and 1896, of which H.M.S...
.
Literature
Esther's taste in literature was eclectic; her library included both classics and contemporary works by such authors as Gore VidalGore Vidal
Gore Vidal is an American author, playwright, essayist, screenwriter, and political activist. His third novel, The City and the Pillar , outraged mainstream critics as one of the first major American novels to feature unambiguous homosexuality...
, Ursula K. Le Guin
Ursula K. Le Guin
Ursula Kroeber Le Guin is an American author. She has written novels, poetry, children's books, essays, and short stories, notably in fantasy and science fiction...
, and Margaret Atwood
Margaret Atwood
Margaret Eleanor Atwood, is a Canadian poet, novelist, literary critic, essayist, and environmental activist. She is among the most-honoured authors of fiction in recent history; she is a winner of the Arthur C...
. A scientist who could suspend disbelief enough to actually enjoy some 'science fiction', Esther nevertheless took issue with Michael Crichton
Michael Crichton
John Michael Crichton , best known as Michael Crichton, was an American best-selling author, producer, director, and screenwriter, best known for his work in the science fiction, medical fiction, and thriller genres. His books have sold over 200 million copies worldwide, and many have been adapted...
's handling of the alien antagonist in his novel, "Andromeda Strain". Her second husband, Matthew Simon, recounts:
Esther commented that "Crichton never got it right." I asked her what she meant, and she replied that if an extraterrestrial life form were caught in an outer space probe and brought back to Earth, whatever would counteract it would with high probability be caught along with it in the same probe, because living things are always surrounded in their environment by those things that counteract it. "They should simply have looked in the same net," she said. "They would have found what they needed to control the alien life form."
Lederberg also loved the works of Charles Dickens
Charles Dickens
Charles John Huffam Dickens was an English novelist, generally considered the greatest of the Victorian period. Dickens enjoyed a wider popularity and fame than had any previous author during his lifetime, and he remains popular, having been responsible for some of English literature's most iconic...
and Jane Austen
Jane Austen
Jane Austen was an English novelist whose works of romantic fiction, set among the landed gentry, earned her a place as one of the most widely read writers in English literature, her realism and biting social commentary cementing her historical importance among scholars and critics.Austen lived...
, and belonged to societies devoted to studying and celebrating those two authors.
Botany and botanical gardens
Lederberg maintained a lifelong love of botanyBotany
Botany, plant science, or plant biology is a branch of biology that involves the scientific study of plant life. Traditionally, botany also included the study of fungi, algae and viruses...
and botanical garden
Botanical garden
A botanical garden The terms botanic and botanical, and garden or gardens are used more-or-less interchangeably, although the word botanic is generally reserved for the earlier, more traditional gardens. is a well-tended area displaying a wide range of plants labelled with their botanical names...
s. 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
- Esther Lederberg, "Lysogenicity in Escherichia coli strain K-12, Microbial Genetics Bulletin, v.1, pp. 5-8 (Jan. 1950); followed by "Lysogenicity in E. coli K-12", Genetics, v.36, p. 560 (1951) (abstract). Papers available online at http://www.estherlederberg.com/LambdaW.html.
For a list of all known papers authored or co-authored by Esther M. Zimmer Lederberg, see http://www.EstherLederberg.com/Papers.html.