Sandra Citi1, Douglas E Berg2. 1. Department of Cell Biology, Faculty of Sciences, University of Geneva , Geneva, Switzerland. 2. Department of Medicine, Division of Infectious Disease, University of California , San Diego, La Jolla, CA.
Abstract
Grete Kellenberger-Gujer was a Swiss molecular biologist who pioneered fundamental studies of bacteriophage in the mid-20(th) century at the University of Geneva. Her life and career stories are reviewed here, focusing on her fundamental contributions to our early understanding of phage biology via her insightful analyses of phenomena such as the lysogenic state of a temperate phage (λ), genetic recombination, radiation's in vivo consequences, and DNA restriction-modification; on her creative personality and interactions with peers; and how her academic advancement was affected by gender, societal conditions and cultural attitudes of the time. Her story is important scientifically, putting into perspective features of the scientific community from just before the molecular biology era started through its early years, and also sociologically, in illustrating the numerous "glass ceilings" that, especially then, often hampered the advancement of creative women.
Grete Kellenberger-Gujer was a Swiss molecular biologist who pioneered fundamental studies of bacteriophage in the mid-20(th) century at the University of Geneva. Her life and career stories are reviewed here, focusing on her fundamental contributions to our early understanding of phage biology via her insightful analyses of phenomena such as the lysogenic state of a temperate phage (λ), genetic recombination, radiation's in vivo consequences, and DNA restriction-modification; on her creative personality and interactions with peers; and how her academic advancement was affected by gender, societal conditions and cultural attitudes of the time. Her story is important scientifically, putting into perspective features of the scientific community from just before the molecular biology era started through its early years, and also sociologically, in illustrating the numerous "glass ceilings" that, especially then, often hampered the advancement of creative women.
Entities:
Keywords:
gender; glass-ceiling; lysogeny; phage genetics; recombination; restriction-modification; science history
Grete Kellenberger(-Gujer) was born Margaretha Gujer on November 12, 1919 in the village of Rümlang near Zürich. In the 1950s and 60s, she contributed importantly to establishing the international reputation of the University of Geneva as one of the first European Universities to develop research programs in the new field of molecular biology. She is renowned for studies of lysogeny, genetic recombination and DNA restriction-modification, in collaboration with Jean Weigle and Werner Arber (Nobel Prize 1978). Her formidable scientific acumen and achievements did not, however, result in her establishing a traditional academic career, nor did they result in a position that matched her scientific creativity and contributions. Rather, for most of her career she was paid only as a laboratory technician or research associate, often part-time and on soft money, and intermittently for a number of reasons, as summarized below. She died on March 13, 2011.Her story is important scientifically, one of creativity and productivity during the early and middle years of modern microbial and molecular genetics. It is similarly important sociologically, illustrating the numerous “glass ceilings” that confronted even the most creative women in western democracies in the mid-twentieth century, a history that is not sufficiently known among the far more empowered young women of today.
Family and education
Grete was raised in Rümlang, a small village near Zürich, the youngest of 3 children. Her father ran the local village post office. Her mother became ill with cancer, was bedridden for several years and died when Grete was 17. Grete attended elementary school in the village, and then, unlike most young villagers (and in general most Swiss contemporaries during those years), went on to higher studies. She enrolled in a classical humanist curriculum in the Girl's Gymnasium (Töchterschule, or high school) in Zürich, and graduated in 1939, shortly before the start of the Second World War in Europe, with a “maturity” diploma and the rank of best in class. She had dreamed of further literary studies, but could not pursue them because of limited family resources. Rather, she started work in an insurance company, Rentenanstalt, but enrolled a few years later (1942) in the Federal Polytechnic of Zürich (ETH) (Chemistry Section). She dropped out after 4 semesters, due in large part to wartime economic difficulties, and perhaps also to a lack of self-confidence. She then started work at the Lohnausgleichkasse (wage equalization fund) of Zurich, and in the following year (1945) married Eduard Kellenberger, a physics student whom she had met at the ETH.Grete and Eduard moved to Geneva in 1946, where he started PhD studies under the direction of Professor Jean Weigle, who had studied X-ray diffraction of mineral crystals, had helped design the first Swiss-manufactured electron microscope, and was Director of the University's Institute of Physics. Also in 1946 Grete (Fig. 1) gave birth to their only child, Elisabeth, who would later become a molecular biologist, and publish under the name of Elisabeth DiCapua, once in collaboration with her father.
First period in Geneva, 1948-1965, and pioneering phage studies: Collaborations with Eduard Kellenberger, Jean Weigle, Maria Zichichi
During their first years in Geneva Grete helped Eduard with his PhD project, which was to improve new, Swiss-made electron microscopes and to develop methods for examining structures of diverse types of living matter. They focused, in particular, on methods for preparing and photographing biological samples of many types, including bacterial cells and nucleoids (Eduard's PhD thesis). Grete was a co-author on several of the resulting publications. Life was exciting but also complicated professionally, in that, as Grete recalled, most physicists had little interest in electron microscopy and their EM group was consigned to one of the University's oldest buildings. Sample preparation was in a room next to the lab of botany professor Fernand Chodat, who had research interests in bacterial physiology, and who was the son of Robert Hippolyte Chodat, formerly Director of the University's Institute of Botany and a Rector of the University. The room for electron microscopy was several floors below the lab. Eduard wrote “In the darkness of the night we both” (himself and his technician Andrea de Stoutz) “were frequently frightened by the busts of the famous late professors placed along the staircase!” – perhaps in jest, but illustrating the hiatus between post-war biophysicists such as himself and their “new biology” vs. the University's tradition-bound senior faculty.Weigle suffered a heart attack in 1946, resigned his physics professorship in Geneva in 1948, moved to California, and joined the phage group of the great physicist-turned-biologist, Max Delbrück, at the California Institute of Technology. He returned to Geneva each summer to collaborate with Grete and other group members. In his first summer back (1949) he brought an idea from Caltech for a new research project: the genetic analysis of bacteriophages, especially λ, recently discovered by Esther Lederberg. Grete embraced this idea with passion and dedication, and in pursuing it, rapidly achieved scientific independence and creativity, as seen in her correspondence with Weigle, stored at Caltech (http://archives.caltech.edu). Based on their collaborative studies, Eduard was promoted to Group Leader of the University's new Institute of Biophysics and Director of the Center for Electron Microscopy. The Institute was housed from 1953 onward in the basement of the School of Physics, near the Arve river. Eduard and Institute members (Fig. 3) had numerous scientific interactions with bacteriologists at the Geneva-based World Heath Organization such as Ole Maaloe, an early member of the phage group and pioneer of quantitative bacterial physiology and also collaborated with biologists and physicians in the Faculties of Science and Medicine, using electron microscopy to better characterize their samples. That said, Grete recalled feeling that the University's biologists did not fully understand or perhaps respect the group's “new biology” (in translation) “thinking that the physicists know no biology, because they do not know the names either of plants, or animals,” and further wrote “We were something strange. And me, I was nothing, as I had never finished my studies.”
The USA (1965-1970) and in Geneva again (1971-1980)
Grete's professional and personal trajectory was dramatically altered in the mid-1960s. In 1965 Eduard started a sabbatical year as a “Regent” Invited Distinguished Professor at Kansas State University, in the lab of K. Gordon Lark (previously Eduard's Postdoc in Geneva). Eduard brought with him several group members (Fig. 6), including Grete, PhD student Uli Laemmli, and Edouard Boy de la Tour (nicknamed “Nadar” to distinguish him from Eduard Kellenberger, and in reference to the great nineteenth century French photographer Gaspard Félix Tournachon – initially called “Tournadar,” then Nadar). In January 1966, Grete wrote Zichichi that (in translation) “Eduard once asked me if I wanted to stay here while he “settles things in Geneva,”” and that “Gordon Lark wrote a grant application for “67 in which I am listed,” and “therefore, the future is as wide as the horizon of Kansas.” In reality, the marriage between Grete and Eduard had been in crisis for several years. It ended suddenly in the fall of 1966, with Eduard leaving Grete in Kansas and returning to Geneva. Grete was deeply wounded, and wrote Zichichi about her pain, and also about the possibility of leaving science: (in translation) “I am thinking about changing professions, to go to Sweden to learn embroidery. I also thought of going to New York to learn photography…in the end I thought that with the little money I have I could try to write theater for 2 or 3 years, this is what I really love.” But Grete was highly respected in the scientific community and received 3 job offers (letter to Zichichi of March 5, 1967): one in Dallas (attractive economically: $12,000 per year, with insurance, moving expense, supplements, etc., paid), one at the International Laboratory of Genetics and Biophysics in Naples (300,000 liras per month, an excellent salary at that time in Italy), and one from Lucien Caro, a French scientist with close ties to Geneva, for an independent position in his biophysics group at Oak Ridge National Laboratory in Tennessee. Grete considered going to Naples, since she loved Italy and Italians, had fond memories of Naples, and by then had an Italian son-in-law (Nicola DiCapua). However, in the end she accepted Caro's offer. Laemmli and Grete remained in Kansas for another 8 months and together analyzed T4 phage head assembly. Although Laemmli spent many hours with Grete as friend and collaborator, providing moral support, he did not then know that Grete did not have a doctorate nor even a University diploma (nor did Zichichi, despite their closeness, although Janine Séchaud and other group members in the 1950s were aware of this). After their final 8 months in Kansas Laemmli drove Grete and her possessions to Oak Ridge in his old Cadillac (Fig. 6), where she joined Caro's group, while Laemmli returned to Geneva.
In addition to Grete's collaborative articles with Eduard Kellenberger and Jean Weigle cited above, several other works also stand out, in particular those from her collaboration with Arber, Robert Weisberg, Berg, the Polish microbiologist Anna Podhajska (who had spent a year with Grete in the early 1970s) and Lucien Caro.Overall, Grete's greatest fundamental contributions in molecular biology included early evidence (using λb2) that prophage repression, induction and chromosome association (integration) involved separate physiologic events, and her demonstration of genetic recombination by DNA breakage and rejoining, rather than by the alternative and then popular replicative mechanism. Her 1961 article on recombination with Weigle was accompanied in PNAS by one with the same conclusions from Matthew Meselson and Jean Weigle. It is sad that although Grete's approach was more original and elegant, Weigle delayed Grete's completed manuscript while waiting for Meselson to finish his experiments, which confirmed what she had already shown. In the end, Meselson's article appeared just before Grete's, and is most cited in genetics textbooks. This may illustrate how a politico-academic editorial attitude could relegate contributions of women to the second level.But what to say of Grete's academic recognition? Grete had been offered the possibility of doing a PhD while she was in the US. But she was already 50, not particularly interested in a teaching position for which this degree would have been essential, and much preferred continuing with important experiments, rather than interrupting them to focus on course work and exams. Arber estimates that Grete certainly deserved a doctorate honoris causa, an idea that had circulated at the University of Geneva in the 1970s, and that Grete remembered as the initiative of Professors Alfred Tissières and Roger Weil. However, this was not followed through in the Faculty of Sciences, where Grete worked, although Laemmli says that he would have supported this idea, had somebody told him of it. It is good that the University's separate Faculty of Medicine clearly recognized Grete's major contributions to biomedical science and awarded her the “Prix Mondial Nessim-Habif” in 1979, shortly before her retirement.
Recognition and advancement: A gender perspective
Grete provided an example of a brilliant, productive female scientist who did not receive the career recognition (post, salary, independence) that her competencies, skills, and achievements deserved. Why? Can one blame her for limited self-esteem, academic ambition and leadership? Arber suggested that technically yes, it was “her fault” that she interrupted and never resumed her studies, and did not strive for the kind of independent academic career that was so typical of her male counterparts. How much did this stem: from the decision to help her husband early during their careers, especially for economic reasons? from the then-prevalent view in Swiss and other societies that submission to one's husband's needs was expected, especially of women from her working class socioeconomic background? and/or from her dream of (also) doing other things such as writing poetry and for the theater? It is important to frame Grete's life and career decisions in the context of her cultural and family background. Patriarchal stereotypes were extremely strong in Swiss culture and society, and may have had an important role in the choices that Grete made. Societal pressures and expectations that women should assume subordinate roles provided a strong implicit bias in determining the options that Grete considered, and in the attitudes of her contemporaries toward her career progression. Grete's department colleague Jean-David Rochaix, who came to know her in the mid-70s, noted that “one should not forget that it was very difficult at that time for a woman in science to be recognized, especially in Switzerland, where women did not obtain the right to vote at the federal level until the early 70s.” Obtaining a PhD for a woman would not necessarily lead to a professorial position either: for example, Janine Séchaud went to the US in 1960 for a successful postdoc with Streisinger, but upon her return to Geneva was happy to become a research associate and instructor (“Chargée de Cours”) until her retirement. So, the idea of an independent academic career may have looked too hard, or simply inappropriate, to Grete. Ironically, such a career probably would not have been so much easier had she sought to lead her own research group in a non-Swiss society. In the US before the 1972 passage of “Title IX” anti-discrimination legislation, for example, it was not uncommon for brilliant young science-oriented women to be discouraged from entering PhD programs; and for excellent, accomplished female PhD scientists to be passed over for academic jobs that would have been offered to them had they only been men. It is important to remember that this pattern, in turn, led to a paucity of role-models that would encourage young women to pursue academic careers. Furthermore, obtaining tenure for female junior faculty and staff scientists was also excessively difficult because they were asked to do much better than men of equivalent standing. Fortunately this pattern began changing in the US with “Title IX” legislation passage in 1972, which mandated that no federal funds could be awarded to institutions with patterns of anti-female discrimination. Despite such legislation there is still much gender-inequality in many countries, including Switzerland, and also the US, which ranked 26th and 19th, respectively, in the 2015 “glass ceiling index” of the quality of working women's environments in 29 countries.As additional illustration, at the University of Geneva, the first female Professor in a scientific discipline in the post-World-War-II period was Kitty Ponse, a brilliant endocrinologist, appointed in 1961. However, until 1967 Ponse and the philosopher Jeanne Hersch were the University's only female full professors. By the time of Grete's retirement (1980), the University of Geneva had only 8 female full Professors, and in 2016 there were 69 (18% of a total of 379), of which only 6 (7% of 83) were in the Faculty of Sciences.Given societal patterns and attitudes at the time, we can well imagine that Grete's choice to work modestly in her husband's shadow was considered appropriate, almost obligatory: to help her husband and thereby family, despite limiting her own advancement, and to continue in the stimulating collaboration with Weigle, who Grete admired for his French-style brilliance and flirtatious wit. Collectively, the intellectual challenge, the pleasure of identifying and solving puzzling and important problems, and the increasing international recognition (despite her reserve and her discomfort speaking in English) must have been enough to keep her going. Laemmli pointed out what an extraordinary and positive thing it was for a woman with no university degree to be accepted, recognized and treated as a peer by colleagues. However, this does not offset the fact that she had a far lower and less secure salary than her skills and competence deserved, and lacked independent access to the resources, students and other associates that would have more rapidly advanced her projects and ideas. So, one can only imagine what Grete would have accomplished had her great creativity been matched by great ambition, the unwavering support of her colleagues in promoting her advancement, and a post and resources that she so deserved – support that was, with only few exceptions, given automatically to her male peers.
Grete's personality and creativity
Grete (Fig. 7) was an exceptional woman: a complex personality, and above all very intelligent and creative, with a deeply developed critical thought, great imagination, and exceptional intuition. She was also kind and generous, and had a wonderful sense of humor. She nurtured team work in every sense during the early years of the Institute of Biophysics: scientifically, by freely sharing her ideas and skills with colleagues; and also socially, by organizing, for example, productive cake-and-croissant-coffee-breaks in which science was much discussed, and Christmas party shows with humorous satirical sketches.She made the lab atmosphere interesting, lively, exciting and happy for all. Two of her inventive, good-humored jokes illustrate this: in one Institute Christmas party, Nadar (Edouard Boy de la Tour), inspired by Grete, depicted a physics professor who was thin and tall in a photo-montage with his head attached to the body of a flying heron – to the delight of all, except perhaps the professor! Another time, Grete convinced a student to dress solely in black during experiments, lest reflections (radiation) from the white lab coat induce new unwanted mutations in the bacteria under study.Grete was reserved and discrete, and could appear shy, but also had great courage and asked pointed questions at seminars. She rarely displayed strong emotions. But Jean-David Rochaix remembers vividly her great joy and radiant smile when she learned that Werner Arber had received the Nobel Prize: it was one of the rare times that he remembered seeing Grete give free rein to her strong emotions. Her creativity was not limited to scientific research and the lab environment. Until age 30, she was recognized as a skilled pianist, but her piano was sold to finance a trip to a scientific meeting at Royaumont Abbey, north of Paris, for Eduard and herself. At age 50 she learned to play the guitar, and throughout her life she produced a large variety of creative works: her own clothes, letters full of humor, fictional stories (that she kept secret), original embroideries (Fig. 8), an illustrated story (“Bourribang,” with 24 watercolors), and a tape of songs for her grandchildren.
Salvador Luria (Nobel Prize 1968) said of her (31.5.1967): “She is well known and well appreciated for her contributions to molecular genetics and in fact one may say that she has exerted significant leadership in this field. Her more important contributions were those related to the analysis of deletion mutants of bacteriophage λ, which lead to one of the proofs of the physical basis of genetic recombination at the molecular level. […] She was responsible for training in bacteriophage research some of the best European geneticists.”In 2009, on the occasion of the 450th anniversary of the University of Geneva's founding, Grete was honored in the exhibition “Faces à Faces,” a project conceived and organized by Brigitte Mantilleri (Director of the University's Equal Opportunity Office) in close collaboration with Juliette Labarthe, to commemorate the personalities who contributed to its fame. The exhibition featured portraits on canvas by the Roger Pfund Workshop, that were placed in front of the windows of the University's Le Corbusier-inspired Uni-Dufour central administration building. Three canvases depicted Grete, as suggested by Pierre Spierer (former PhD student with Alfred Tissières, and later Professor, Dean of the Faculty of Sciences, and Vice-Rector of the University). In 2010 one of us (SC) suggested that the Department of Molecular Biology purchase one of Grete's canvases. That canvas now decorates the Department's seminar room in the building Sciences III, “face to face” with a canvas from the same exhibition depicting her former student and collaborator Werner Arber (Fig. 9): an artistic tribute to encourage women scientists of today and tomorrow!