Esther Lederberg, linocut print, 11" x 14" by Ele Willoughby, 2026
The 8th #PrinterSolstice2526 prompt is two, so I thought of duplicates. This reminded me of trailblazing microbiologist Esther Miriam Zimmer Lederberg (1922-2006) whose pioneering contributions to bacterial genetics include such fundamentals as the first successful implementation of replica plating (with her first husband, Nobel laureate Joshua Lederberg) which allows microbiologists to reproduce a pattern of microbes on different Petri dishes and, for instance, compare their response to various things put in each plate. Reading about how they would press a velveteen-covered disk onto the primary plate with microorganisms and then imprinting the secondary plate (or plates) with the same distribution of microbes, I recognized this as printmaking, so I was delighted to read that her biographer believes she was inspired by having worked in her father's print shop as an adolescent. She also discovered the lambda phage and the bacterial fertility factor F. While she and Joshua both were awarded the Pasteur Medal from the Society of Illinois Bacteriologists, Esther's contributions, including work she did on her own, were often misattributed to Joshua, and she was not included in his Nobel win, nor was she even ever offered a tenured position. In life, she cared more about the science than her reputation, but today microbiologists are working to make sure she gets more of the recognition she always deserved.
Microbiologist Esther Lederberg (née Zimmer, 1922-2007) made discoveries fundamental to modern understanding of bacterial gene regulation, recombination and exchange, but her work was both overshadowed by, and sometimes misattributed to her male collaborators.
Esther and her younger brother Benjamin were children of Orthodox Jewish Romanian immigrant, David and Pauline Geller Zimmer, herself the daughter of Romanian immigrants, who ran a print shop in the Bronx. Money was tight. The Zimmer children grew up helping in the shop during the Great Depression. David's siblings worked in the garment industry. Esther had a talent for language. Esther pleased her maternal grandfather by learning Hebrew, unlike her cousins, and won awards for French and Spanish at school. She graduated from Evander Childs High School when she was only 15, and won a scholarship to attend Hunter College, where she planned to study French or literature. Once there, she chose to switch to biochemistry, though teachers warned she would have trouble finding a job, as a woman. Nonetheless she found work as a research assistant working on Neurospora crassa, a red bread mold, with plant pathologist Bernard Oglivie Dodge. By the time she was 19 in 1942 she had graduated cum laude with a BSc in genetics.
She got a position with Alexander Hollander at the Carnegie Institution of Washington (later the Cold Spring Harbor Laboratory), continuing her work on N. crassa and making her first scientific publication. She won a fellowship for Standford in 1944 to work with George Wells Beadle and Edward Tatum (who together would later go on to win the 1958 Nobel in Physiology or Medicine with her future husband Joshua Lederberg). Tatum told her would only teach her genetics if she could work out why one of the Drosophila fruit flies in a bottle had different coloured eyes; she did this so well, he made her his Teaching Assistant. After summer school at Stanford's Hopkins Marine Station with microbiologist Cornelius Van Niel, she entered the master's program, and completed her M.A. in genetics with her thesis "Mutant Strains of Neurospora Deficient in Para-Aminobenzoic Acid" in 1946. She married one of Tatum's students at Yale, Joshua Lederberg, and moved to Yale's Botanical Laboratory. Joshua completed his doctorate in 1947 and was offered an assistant professorship at the University of Wisconsin, so the couple moved to Madison, Wisconsin. Esther enrolled in the doctoral program and was awarded a fellowship by the National Cancer Institute. Joshua developed a reputation as a brilliant thinker while Esther developed a reputation as a skilled expert experimentalist and they worked well as a team. Her 1950 doctoral thesis under supervision of plant geneticist R.A. Brink was titled "Genetic control of mutability in the bacterium Escherichia coli". She had already made some foundational discoveries of the fertility factor, but Joshua insisted she focus on completing her PhD, rather than follow up with further experimentation.
She spent most of the 50s at the University of Wisconsin, and in 1951 she discovered the lambda bacteriophage, a virus which infects and replicates within bacteria, and she published a detailed description in Genetics in 1953 with Joshua as the second author. He had asked her to wait before publishing because he felt it was not the top priority for the lab at that time. When Joshua won the 1953 Eli Lilly Award he told a reporter that Esther should have be recognized too. The lambda phage became a foundational discovery in molecular genetics, invaluable for understanding gene regulation and recombination. She incubated a mix of a parent E. coli K12 strain and a mutant E. coli K12 strain made with UV light and saw plaques, which indicated the presence of a bacteriophage. This type of virus would have been killed by UV light, so it must have come from the parent strain. She called this the lambda phage and found it had two lifestyles: either the typical, well-known phage lifestyle, the lytic cycle, where it rapidly made copies of itself inside the E.coli before bursting out (called lysis) or alternatively existing quietly as just another genetic marker within E. coli, without killing the cell. With her husband, she found that the quiescent form genetically mapped near the genes in the E. coli which metabolize lactose sugar (gal). The Lederbergs proposed that the lambda's genetic material integrates into the E. coli chromosome next to the gal genes, which let it replicate as a prophage along with the host bacteria's own DNA (a process called lysogeny). This was the first time this 2-part cycle had ever been described and today, the lambda phage is a key model for understanding other viruses (such as herpes simplex virus) which exhibit these split lytic-lysogenic lifecycles. To leave the host, the prophage needs to excise itself from the bacterial DNA and sometimes when this occurs the phage DNA is accompanied by some adjacent host DNA which the phage can then introduce into a new host; this is called specialized transduction. Esther presented her lambda studies, including λ lysogeny and specialized transduction in Canberra, at the Symposium of Bacterial and Viral Genetics in 1957, and her results on where it integrates, the fine-structure mapping of the gal locus in Montreal in 1958 at the 10th International Congress of Genetics.
While studying where the lambda prophage, she crossed bacteria with the prophage with strains without the prophage but will known genetic markers. She found that some crosses failed to form recombinants. She suspected something, a fertility factor, must be missing, writing that during her 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 names this F." She published with Luigi Cavalli-Sforza and Joshua. She was right and others' later research showed that F was a DNA sequence with genes which allow a bacterium to donate DNA to a recipient bacterium by direct contact or conjugation. This DNA sequence can be either an independent plasmid or integrated into the cell's chromosome. Likely because of the delay between her discovery of the fertility factor F and her follow-up experiments and publications, this work is often unfairly primarily attributed to Joshua in textbooks.
Microbiologists had been struggling to make identical geometrical configurations of microbes on multiple plates and tried using everything from toothpicks, paper, wire brushes and multi-pronged inoculators, until Esther and Joshua successfully implemented their simple solution to replica plating. Their process, pressing a plate of bacterial colonies onto sterile velvet and stamping them onto secondary plates of media with different ingredients to suit the traits needed for study (for instance, containing various antibiotics), mimics how a press works, like in Esther's father's shop! The first time she tried out the idea, she was inspired by her own powder puff, the velveteen pad in her makeup compact. It was, after all, designed to transfer powdered makeup to a person's face; maybe it could transfer configurations of microbes from plate to plate, so she tried it. Esther, whose family were garment workers, was the one familiar with textiles and she used this knowledge to source the best fabric for the job. Nonetheless, this method has also often been inaccurately credited to Joshua only. Since they could reliably replicate their plates, they were able to show, as previously demonstrated by Luria and Delbrück, that bacteriophage- and and antibiotic-resistant mutants spontaneously arose even in the absence of phages or antibiotics. These mutations were not occurring in response to their environment, as held by Lamarckism. Luria and Delbrück's work relied on mathematical arguments and had not gained traction but the simplicity of the Lederbergs' methods finally convinced their colleagues. Their method for replica plating remains a staple of microbiological laboratory work today.
In 1956, both Lederbergs jointly won the Pasteur Award for their contributions to science. In 1958, Joshua Lederberg shared the Nobel Prize for Physiology or Medicine for discovering bacterial conjugation, with Edward Tatum and George Beadle for their work with genetics. Joshua had discovered that bacteria do not only make identical copies of themselves; they sometimes reproduce by mixing genetic material, as occurs in sexual reproduction, to make something new. Esther, whose work, like discovering the fertility factor with allows this genetic mixing to occur, was essential to, or made in collaboration with Joshua's research, was not included in his win. Attending the formal ceremony in Stockholm, by his side, in her gown, only playing the role of scientist's spouse, must have been bittersweet. Esther became perceived as merely his research assistant. Joshua thanked her simply for her "companionship" in his acceptance speech. Castelli-Sforza 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."
In 1959 Esther and Joshua returned to Stanford, where Joshua became the head of the Genetics department. Esther could not be employed in the Genetics department because of anti-nepotism rules. Esther and two other women petitioned the dean of the medical school over the lack of female faculty. Eventually she got an untenured faculty position as a research associate professor in the Department of Microbiology and Immunology, where Esther worked for the rest of her career. This meant that her job was not secure and her short-term appointment was renewed on a rolling basis, dependent on her ability to secure grants. After their divorce in 1968, Esther had to fight to retain her position. She founded and directed the Plasmid Reference Center (PRC) from 1976 to 1986, where she organized, maintained, named, and distributed plasmids of various types including those coding for antibiotic-resistances, heavy-metal-resistance, virulence, conjugation, colicins, transposons and insertion sequences. Her sequential numbering system continued until her retirement. In 1974 she was effectively demoted and forced to transition to an adjunct professor of medical microbiology. She retired from the Department of Microbiology and Immunology in 1985 but continued as a volunteer at the PRC.
While not working as a scientist, Esther was a devoted amateur musician focusing on early music, playing medieval, Renaissance and baroque music on original instruments including several different sizes of recorder. She founded the Mid-Peninsula Recorder Orchestra, which plays music dating back to the 13th century, in 1962. A lover of the works of Charles Dickens and Jane Austen, she belonged to the Dickens Society of Palo Alto and the Jane Austen Society. Through her pursuit of early music, she met fellow enthusiast, engineer Matthew Simon newly arrived at Stanford in 1989, and they married in 1993. She died in 2006 of pneumonia and congestive heart failure at age 83. Esther always thought the science itself was more important than her reputation, but her second husband understood that her work was under-appreciated because she was a woman. Simon has worked tirelessly to make an extensive memorial website for Esther, so her story and role in the development of microbial genetics is not forgotten. The wealth of biographical information and documents there from her career has helped her biographers and microbiologists working to tell a more complete and accurate story of the development of their field.
References
Esther Lederberg, Wikipedia, accessed February, 2026.
Barron, Madeline. Esther Lederberg and the Rise of Microbial Genetics. American Society for Microbiology. October 4, 2023.
Joshua Lederberg, Wikipedia, accessed February, 2026.
Lederberg, J and E.M. Lederberg. Replica plating and indirect selection of bacterial mutants. J Bacteriol. 1952 Mar;63(3):399-406. doi: 10.1128/jb.63.3.399-406.1952. PMID: 14927572; PMCID: PMC169282.
Simon, Matthew. Esther M. Zimmer Lederberg Memorial Website. Accessed February, 2026
Steinmetz, Katy. Esther Lederberg and Her Husband Were Both Trailblazing Scientists. Why Have More People Heard of Him? Time Magazine. April 11, 2019.
"Women in Microbiology -Esther Lederberg" Live session from ASM Microbe 2017 hosted by Hazel Barton with guest Mark O. Martin interviewed by Rebecca V. Ferrell.
Zeldovich, Linda, Esther Lederberg changed our understanding of how bacteria breed. Popular Science, May 23, 2022.
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