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.
1 Early years
2 Contributions to microbiology and genetics
2.1 λ bacteriophage and specialized transduction
2.2 Bacterial Fertility Factor F
2.3 Replica plating
2.4 Later contributions
3 Professional honors
4 Professional challenges: gender discrimination
5 Other interests
Botany and botanical gardens
6 Notable papers
8 External links
Esther Miriam Zimmer was the first of two children born in the Bronx,
New York, to 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
Zimmer thrived academically. She attended Evander Childs High
School in the Bronx, receiving honors for French and graduating at
the age of 16. 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 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 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
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
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
Contributions to microbiology and genetics
Lederberg remained at the
University of Wisconsin
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 and specialized transduction
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.
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
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
Her 1950 lambda phage paper led to an understanding of specialized
A permanent exhibit in the "DNAtrium" of The Eli and Edythe L. Broad
Massachusetts Institute of Technology
Massachusetts Institute of Technology 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 carried on an
episome, which 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
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.
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.
Scientists had been struggling for a reliable solution for at least a
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
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
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.
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. Bacteriol., 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
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.
1956 Society of Illinois Bacteriologists: Pasteur Award (with Joshua
Fulbright Fellowship in bacteriology to work at Melbourne
University in Australia.
American Cancer Society
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.
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 Ka 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
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.
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.
Professional challenges: gender discrimination
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.
Luigi Luca Cavalli-Sforza
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."
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
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)."
Esther Lederberg had cultural interests that went well beyond science.
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 and Elizabethan dance.
She loved symphonic music, opera, and the operettas of Gilbert and
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
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 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
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.
Joshua Lederberg in 1946; they divorced in 1968. 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
^ Ware, Doreen. "Pioneering Women in STEM". National Science
Foundation. Retrieved 10 March 2016.
^ a b "Stanford Magazine - Article". alumni.stanford.edu. Retrieved
^ a b "Esther Lederberg, Pioneer of Bacterial Genetics". Small Things
Considered. Retrieved 2016-09-21.
^ a b c d "Miriam Esther Lederberg". What is Biotechnology?. Retrieved
19 March 2017.
^ Simon, Matthew. "Agreement: Use of the Esther M. Zimmer Lederberg
Memorial Website". www.estherlederberg.com. Retrieved
^ a b c d e f g Alic, Margaret (1999). "Esther Miriam (Zimmer)
Lederberg 1922-". In Proffitt, Pamela. Notable Women Scientists.
Farmington Hill, Michigan: Gale Group. pp. 320–322.
^ Hollaender, A.; Sansome, E.R.; Zimmer, E.; Demerec, M. (1945).
"Quantitative irradiation experiments with Neurospora crassa. II.
Ultraviolet irradiation". American Journal of Botany. 32 (4):
^ a b Maugh II, Thomas H. (30 November 2006). "Esther Lederberg, 83;
helped unlock mysteries of bacteria and viruses". Los Angeles Times.
Retrieved 24 March 2017.
^ "Scientific Legacies: Esther Miriam Zimmer Lederberg (1922-2006)".
Scientific Legacies. Retrieved 24 March 2017.
^ a b c Gottesman ME, Weisberg RA (2004). "Little lambda, who made
Microbiology and Molecular Biology Reviews : MMBR. 68
(4): 796–813. doi:10.1128/MMBR.68.4.796-813.2004.
PMC 539004 . PMID 15590784.
^ Lederberg J, Cavalli LL, Lederberg EM (1952). "Sex Compatibility in
Escherichia Coli". Genetics. 37 (6): 720–30. PMC 1209583 .
^ Lederberg, Joshua; Lederberg, Esther (1952). "
Replica plating and
indirect selection of bacterial mutants". Journal of Bacteriology. 63
(3): 399–406. PMC 169282 . PMID 14927572.
^ Lederberg EM, Lederberg J (1953). "Genetic Studies of Lysogenicity
in Escherichia Coli". Genetics. 38 (1): 51–64. PMC 1209586 .
^ Hayes W (1980). "Portraits of viruses: bacteriophage lambda".
Intervirology. 13 (3): 133–53. doi:10.1159/000149119.
^ Morse, M.; Lederberg, E.; Lederberg, J. (1956). "Transduction in
Escherichia coli K-12". Genetics. 41: 121–156.
^ click "Fertility Factor F" in the navigation pane of the frameset
^ a b c click "Replica Plating" in the navigation pane
Special Topics > Plasmid Reference Center >
^ University of Wisconsin. Dept. of Genetics. Ashman, R. Bruce,
Editor, "The Genotype" No. 40, 1955-1956; see 
^ See also personal correspondence from Dr. Falkow at
^ Esther Lederberg, pioneer in genetics, dies at 83
^ Abir-Am PG (1999). "The First American and French commemorations in
molecular biology: from collective memory to comparative history".
Osiris. 14: 324–70. doi:10.1086/649312. PMID 11971293.
^ "Gender Discrimination: only an adjunct!"
^ "Letter of Endorsement from Allan Campbell, January 18, 1971"
^ "Esther Lederberg, 83, a Founder of Bacterial Genetics". The New
York Sun. November 9, 2006. Retrieved 24 March 2017.
^ Speech by Fred Palmer at Esther's Memorial, 30 November 2006
Esther Lederberg Memorial Web Site: Anecdote #11"
^ Russell, Sabin. "Professor
Esther Lederberg -- Scientist". SFGate.
Retrieved 1 September 2017.
Stanford Archives posted many of Lederberg's photographs and images of
her documents to its
Flickr page: .