HOME

TheInfoList



OR:

Esther Miriam Zimmer Lederberg (December 18, 1922 – November 11, 2006) was an American
microbiologist A microbiologist (from Greek ) is a scientist who studies microscopic life forms and processes. This includes study of the growth, interactions and characteristics of microscopic organisms such as bacteria, algae, fungi, and some types of para ...
and a pioneer of bacterial genetics. She discovered the bacterial virus λ and the bacterial fertility factor F, devised the first implementation of
replica plating Replica plating is a microbiological technique in which one or more secondary Petri plates containing different solid (agar-based) selective growth media (lacking nutrients or containing chemical growth inhibitors such as antibiotics) are inocul ...
, and furthered the understanding of the transfer of genes between bacteria by
specialized transduction Transduction is the process by which foreign DNA is introduced into a cell by a virus or viral vector. An example is the viral transfer of DNA from one bacterium to another and hence an example of horizontal gene transfer. Transduction does ...
. Lederberg also founded and directed the now-defunct Plasmid Reference Center at
Stanford University Stanford University, officially Leland Stanford Junior University, is a private research university in Stanford, California. The campus occupies , among the largest in the United States, and enrolls over 17,000 students. Stanford is conside ...
, where she maintained, named, and distributed
plasmids A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; how ...
of many types, including those coding for
antibiotic resistance Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. All classes of microbes can evolve resistance. Fungi evolve antifungal resistance. Viruses evolve antiviral resistance. ...
, heavy metal resistance,
virulence Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ...
,
conjugation Conjugation or conjugate may refer to: Linguistics *Grammatical conjugation, the modification of a verb from its basic form * Emotive conjugation or Russell's conjugation, the use of loaded language Mathematics *Complex conjugation, the change ...
,
colicins A colicin is a type of bacteriocin produced by and toxic to some strains of ''Escherichia coli''. Colicins are released into the environment to reduce competition from other bacterial strains. Colicins bind to outer membrane receptors, using them ...
,
transposons A transposable element (TE, transposon, or jumping gene) is a nucleic acid sequence in DNA that can change its position within a genome, sometimes creating or reversing mutations and altering the cell's genetic identity and genome size. Tran ...
, and other unknown factors. As a woman in a male-dominated field and the wife of Nobel laureate
Joshua Lederberg Joshua () or Yehoshua ( ''Yəhōšuaʿ'', Tiberian: ''Yŏhōšuaʿ,'' lit. 'Yahweh is salvation') ''Yēšūaʿ''; syr, ܝܫܘܥ ܒܪ ܢܘܢ ''Yəšūʿ bar Nōn''; el, Ἰησοῦς, ar , يُوشَعُ ٱبْنُ نُونٍ '' Yūšaʿ ...
, Esther Lederberg struggled for professional recognition. Despite her foundational discoveries in the field of microbiology, she was never offered a tenured position at a university. Textbooks often ignore her work and attribute her accomplishments to her husband.


Early years

Esther Miriam Zimmer was the first of two children born in the
Bronx The Bronx () is a borough of New York City, coextensive with Bronx County, in the state of New York. It is south of Westchester County; north and east of the New York City borough of Manhattan, across the Harlem River; and north of the New Y ...
, New York, to a family of
Orthodox Jewish Orthodox Judaism is the collective term for the traditionalist and theologically conservative branches of contemporary Judaism. Theologically, it is chiefly defined by regarding the Torah, both Written and Oral, as revealed by God to Moses on ...
background. Her parents were David Zimmer, an immigrant from Romania who ran a print shop, and Pauline Geller Zimmer. Her brother, Benjamin Zimmer, followed in 1923. Zimmer was a child of the
Great Depression The Great Depression (19291939) was an economic shock that impacted most countries across the world. It was a period of economic depression that became evident after a major fall in stock prices in the United States. The economic contagio ...
, and her lunch was often a piece of bread topped by the juice of a squeezed tomato. Zimmer learned
Hebrew Hebrew (; ; ) is a Northwest Semitic language of the Afroasiatic language family. Historically, it is one of the spoken languages of the Israelites and their longest-surviving descendants, the Jews and Samaritans. It was largely preserved ...
and she used this proficiency to conduct Passover seders. Zimmer attended Evander Childs High School in the Bronx, graduating in 1938 at the age of 15. She was awarded a scholarship to attend New York City's
Hunter College Hunter College is a public university in New York City. It is one of the constituent colleges of the City University of New York and offers studies in more than one hundred undergraduate and postgraduate fields across five schools. It also admin ...
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 that a woman would have more difficulty pursuing a career in the sciences. She worked as a research assistant at the
New York Botanical Garden The New York Botanical Garden (NYBG) is a botanical garden at Bronx Park in the Bronx, New York City. Established in 1891, it is located on a site that contains a landscape with over one million living plants; the Enid A. Haupt Conservatory, ...
, engaging in research on '' Neurospora crassa'' with the plant pathologist
Bernard Ogilvie Dodge Bernard Ogilvie Dodge (18April 18729August 1960) 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, ...
. She received a bachelor's degree in genetics, graduating ''cum laude'' in 1942, at the age of 19. After her graduation from Hunter, Zimmer went to work as a research assistant to
Alexander Hollaender Alexander Hollaender (9 December 1898 – 6 December 1986) was one of the world's leading researchers in radiation biology and in genetic mutations. In 1983 he was given the Enrico Fermi Award by the United States Department of Energy for his cont ...
at the
Carnegie Institution of Washington The Carnegie Institution of Washington (the organization's legal name), known also for public purposes as the Carnegie Institution for Science (CIS), is an organization in the United States established to fund and perform scientific research. Th ...
(later
Cold Spring Harbor Laboratory Cold Spring Harbor Laboratory (CSHL) is a private, non-profit institution with research programs focusing on cancer, neuroscience, plant biology, genomics, and quantitative biology. It is one of 68 institutions supported by the Cancer Centers ...
), where she continued to work with ''N. crassa'' and published her first work in genetics. In 1944 she won a fellowship to
Stanford University Stanford University, officially Leland Stanford Junior University, is a private research university in Stanford, California. The campus occupies , among the largest in the United States, and enrolls over 17,000 students. Stanford is conside ...
, working as an assistant to
George Wells Beadle George Wells Beadle (October 22, 1903 – June 9, 1989) was an American geneticist. In 1958 he shared one-half of the Nobel Prize in Physiology or Medicine with Edward Tatum for their discovery of the role of genes in regulating biochemical even ...
and Edward Tatum. When she asked Tatum to teach her
genetics Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar work ...
, he initially demurred until he made her determine why, in a bottle of ''
Drosophila ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many speci ...
'' fruit flies, one fly had different colored eyes than the others. This she worked out so successfully that Tatum made her his . She later traveled west to California, and after a summer studying at Stanford University's
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 (United States) on the Monterey Peninsula, adjacent to the Monterey Bay Aquarium. ...
under
Cornelius Van Niel Cornelis Bernardus van Niel (also known as Kees van Niel) (November 4, 1897 – March 10, 1985) was a Dutch-American microbiologist. He introduced the study of general microbiology to the United States and made key discoveries explaining the ...
, she entered a master's program in genetics. Stanford awarded her a master's degree in 1946. Her M.A. thesis was entitled "Mutant Strains of ''Neurospora'' Deficient in Para-Aminobenzoic Acid". That same year, she married
Joshua Lederberg Joshua () or Yehoshua ( ''Yəhōšuaʿ'', Tiberian: ''Yŏhōšuaʿ,'' lit. 'Yahweh is salvation') ''Yēšūaʿ''; syr, ܝܫܘܥ ܒܪ ܢܘܢ ''Yəšūʿ bar Nōn''; el, Ἰησοῦς, ar , يُوشَعُ ٱبْنُ نُونٍ '' Yūšaʿ ...
, then a student of Tatum's at
Yale University Yale University is a private research university in New Haven, Connecticut. Established in 1701 as the Collegiate School, it is the third-oldest institution of higher education in the United States and among the most prestigious in the w ...
. Lederberg moved to Yale's Osborn Botanical Laboratory and then to the
University of Wisconsin A university () is an institution of higher (or tertiary) education and research which awards academic degrees in several academic disciplines. Universities typically offer both undergraduate and postgraduate programs. In the United Stat ...
after her husband became a professor there. There she pursued a doctorate degree. From 1946 to 1949, she was awarded a predoctoral fellowship by the
National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. T ...
. Her thesis was "Genetic control of mutability in the bacterium ''
Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...
''." She completed her doctorate under the supervision of R. A. Brink in 1950.


Contributions to microbiology and genetics

Lederberg remained at the
University of Wisconsin A university () is an institution of higher (or tertiary) education and research which awards academic degrees in several academic disciplines. Universities typically offer both undergraduate and postgraduate programs. In the United Stat ...
for most of the 1950s. It was there that she discovered
lambda phage ''Enterobacteria phage λ'' (lambda phage, coliphage λ, officially ''Escherichia virus Lambda'') is a bacterial virus, or bacteriophage, that infects the bacterial species ''Escherichia coli'' (''E. coli''). It was discovered by Esther Leder ...
, did early research on the relationship between transduction and lambda phage lysogeny, discovered the ''E. coli'' F fertility factor with
Luigi Luca Cavalli-Sforza Luigi Luca Cavalli-Sforza (; 25 January 1922 – 31 August 2018) was an Italian geneticist. He was a population geneticist who taught at the University of Parma, the University of Pavia and then at Stanford University. Works Schooling and po ...
(eventually publishing with Joshua Lederberg), devised the first successful implementation of
replica plating Replica plating is a microbiological technique in which one or more secondary Petri plates containing different solid (agar-based) selective growth media (lacking nutrients or containing chemical growth inhibitors such as antibiotics) are inocul ...
with Joshua Lederberg, and helped discover and understand the genetic mechanisms of
specialized transduction Transduction is the process by which foreign DNA is introduced into a cell by a virus or viral vector. An example is the viral transfer of DNA from one bacterium to another and hence an example of horizontal gene transfer. Transduction does ...
. These contributions laid the foundation for much of the genetics work done in the latter half of the twentieth century. Because of her work, she is considered to be a pioneer in bacterial genetics. In 1956, Esther and Joshua Lederberg were honored for their fundamental studies of bacterial genetics by the Society of Illinois Bacteriologists, which awarded them the Pasteur Medal.


λ bacteriophage

Esther Lederberg was the first to isolate λ
bacteriophage A bacteriophage (), also known informally as a ''phage'' (), is a duplodnaviria virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν ('), meaning "to devour". Bac ...
. 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. Her studies showed that λ had both a typical lifestyle in which the phage rapidly made many copies of itself before bursting out of the ''E. coli'' host and an alternative lifestyle in which the phage existed quietly within ''E. coli'' as just another genetic marker. Esther and Joshua Lederberg demonstrated that λ, in its quiescent form, genetically mapped near the ''E. coli'' genes required for metabolism of the sugar
galactose Galactose (, '' galacto-'' + ''-ose'', "milk sugar"), sometimes abbreviated Gal, is a monosaccharide sugar that is about as sweet as glucose, and about 65% as sweet as sucrose. It is an aldohexose and a C-4 epimer of glucose. A galactose molecu ...
(''gal''). The Lederbergs proposed that the genetic material of λ physically integrated into the chromosome next to the ''gal'' genes and subsequently replicated as a
prophage A prophage is a bacteriophage (often shortened to "phage") genome that is integrated into the circular bacterial chromosome or exists as an extrachromosomal plasmid within the bacterial cell. Integration of prophages into the bacterial host is th ...
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 Transduction is the process by which foreign DNA is introduced into a cell by a virus or viral vector. An example is the viral transfer of DNA from one bacterium to another and hence an example of horizontal gene transfer. Transduction does ...
. Following publication of her studies on λ over several years, Lederberg presented her findings at international conferences. In 1957, Lederberg gave a talk on λ lysogeny and specialized transduction at the Symposium of Bacterial and Viral Genetics in
Canberra Canberra ( ) is the capital city of Australia. Founded following the federation of the colonies of Australia as the seat of government for the new nation, it is Australia's largest inland city and the eighth-largest city overall. The ci ...
, Australia. In 1958, she presented her findings on the fine-structure mapping of the ''gal'' locus at the 10th
International Congress of Genetics The International Congress of Genetics (ICG) is a five yearly conference for geneticists. The first ICG was held in 1898. Since 1973 It has been organized by the International Genetics Federation (IGF). The aim of the congress is to reflect on pro ...
in
Montreal Montreal ( ; officially Montréal, ) is the second-most populous city in Canada and most populous city in the Canadian province of Quebec. Founded in 1642 as '' Ville-Marie'', or "City of Mary", it is named after Mount Royal, the triple- ...
, Canada.


Bacterial fertility factor F

Lederberg's discovery of the fertility factor (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 enetic mappingstudies,...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.
Later work by others showed that the 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 Conjugation or conjugate may refer to: Linguistics *Grammatical conjugation, the modification of a verb from its basic form * Emotive conjugation or Russell's conjugation, the use of loaded language Mathematics *Complex conjugation, the change ...
. The DNA sequence encoding the F factor can exist either as an independent
plasmid A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; how ...
or integrate into the bacterial cell's chromosome.


Origin of mutations

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 implemented it successfully. Less efficient forerunners to the methodology were toothpicks, paper, wire brushes, and multipronged inoculators. Biographer Rebecca Ferrell believes that the method Lederberg invented was likely inspired by using her father's press at his work, pressing a plate of bacterial colonies onto sterile velvet, after which they were stamped onto plates of media with different ingredients, depending on the desired traits the researcher wished to observed. 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 the 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 A transposable element (TE, transposon, or jumping gene) is a nucleic acid sequence in DNA that can change its position within a genome, sometimes creating or reversing mutations and altering the cell's genetic identity and genome size. Tran ...
, and
insertion sequences Insertion element (also known as an IS, an insertion sequence element, or an IS element) is a short DNA sequence that acts as a simple transposable element. Insertion sequences have two major characteristics: they are small relative to other transp ...
. She initiated the system of naming insertion sequences and transposons sequentially beginning with IS''1'' and Tn''1''. The sequential numbering continued until her retirement. 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.


Professional challenges: gender discrimination

Microbiologist Stanley Falkow said of Esther Lederberg that " perimentally 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. After her foundational discoveries of the F factor and λ in graduate school, Joshua Lederberg stopped her from conducting additional experiments to follow up on her discoveries. According to Esther, Joshua, as her thesis advisor, wanted her to finish her PhD dissertation. Her graduate school advisor, R.A. Brink, may not have recognized the significance of her discoveries. She may have been fully recognized for her discoveries if she were allowed to pursue them immediately. Instead, the delay hurt her legacy as an independent research scientist, and her findings on bacterial sex are now credited primarily to her husband. In fact, most textbooks highlight Joshua Lederberg's role in the discoveries made jointly with Esther. The lack of credit Esther Lederberg is given for development of the replica plating technique has been cited as an example of the Matilda effect, in which discoveries made by women scientists are unfairly attributed to their male colleagues. By the time Joshua won the Nobel Prize in 1958, the research centers that were recruiting him saw Esther as his wife and research assistant rather than an independent scientist. 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 Luigi Luca Cavalli-Sforza (; 25 January 1922 – 31 August 2018) was an Italian geneticist. He was a population geneticist who taught at the University of Parma, the University of Pavia and then at Stanford University. Works Schooling and po ...
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." Her husband Joshua did acknowledge her work and contributions. When the couple attended the 1951 Cold Spring Harbor Symposium, he discussed Esther's doctoral work on ''E. coli'' and acknowledged her as second author. Ferrell notes, however, that he did not later acknowledge her work when he wrote an autobiographical account of their discovery of genetic recombination in bacteria. Lederberg was an advocate for herself and other women during the early years of feminism's second wave. 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 demotion. Her short-term appointment was to be renewed on a rolling basis and was dependent on her securing grant funding.


Other interests

A lifelong musician, Lederberg was a devotee of
early music Early music generally comprises Medieval music (500–1400) and Renaissance music (1400–1600), but can also include Baroque music (1600–1750). Originating in Europe, early music is a broad musical era for the beginning of Western classi ...
and enjoyed playing medieval, Renaissance, and baroque music on original instruments. She played the
recorder Recorder or The Recorder may refer to: Newspapers * ''Indianapolis Recorder'', a weekly newspaper * ''The Recorder'' (Massachusetts newspaper), a daily newspaper published in Greenfield, Massachusetts, US * ''The Recorder'' (Port Pirie), a news ...
and in 1962 founded the Mid-Peninsula Recorder Orchestra, which plays compositions from the 13th century to the present. Lederberg also loved the works of
Charles Dickens Charles John Huffam Dickens (; 7 February 1812 – 9 June 1870) was an English writer and social critic. He created some of the world's best-known fictional characters and is regarded by many as the greatest novelist of the Victorian er ...
and
Jane Austen Jane Austen (; 16 December 1775 – 18 July 1817) was an English novelist known primarily for her six major novels, which interpret, critique, and comment upon the British landed gentry at the end of the 18th century. Austen's plots of ...
. She belonged to societies devoted to studying and celebrating these two authors, the Dickens Society of Palo Alto and the Jane Austen Society.


Personal life

She married
Joshua Lederberg Joshua () or Yehoshua ( ''Yəhōšuaʿ'', Tiberian: ''Yŏhōšuaʿ,'' lit. 'Yahweh is salvation') ''Yēšūaʿ''; syr, ܝܫܘܥ ܒܪ ܢܘܢ ''Yəšūʿ bar Nōn''; el, Ἰησοῦς, ar , يُوشَعُ ٱبْنُ نُونٍ '' Yūšaʿ ...
in 1946; they divorced in 1968. In 1989, she met Matthew Simon, an engineer who shared her interest in early music. They married in 1993 and remained married for the rest of her life. She died in Stanford, California, on November 11, 2006, from
pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severit ...
and
congestive heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, ...
at the age of 83.


See also

*
Timeline of women in science This is a timeline of women in science, spanning from ancient history up to the 21st century. While the timeline primarily focuses on women involved with natural sciences such as astronomy, biology, chemistry and physics, it also includes women f ...


References


External links

* {{DEFAULTSORT:Lederberg, Esther Miriam Zimmer American microbiologists Phage workers Hunter College alumni Jewish American scientists Jewish women scientists American women biologists Women microbiologists 1922 births 2006 deaths Women inventors Stanford University alumni University of Wisconsin–Madison alumni 20th-century American women scientists 20th-century American scientists 21st-century American scientists Scientists from the Bronx 20th-century American Jews 21st-century American Jews 21st-century American women scientists