Christiane Nusslein-Volhard

Born 20th October, 1942 (Magdeburg, Germany)

Christiane Nüsslein-Volhard won the Nobel Prize in 1995, the sixth woman to do so. She was awarded the Prize on the basis of her groundbreaking research that showed how genes regulate the early development of fruit fly embryos. Her discoveries helped create the new discipline of developmental genetics and laid the foundation for understanding genetic defects in human embryos.

Christiane Nusslein-Volhard c. 1987 (Photo credit: Christiane Nusslein-Volhard)

Family

The second of five children, four girls and one boy, Christiane Nüsslein-Volhard is the daughter of Rolf Volhard, an architect, and Brigitte Haas Volhard, a nursery school teacher. Both parents came from large families and Nüsslein-Volhard spent her childhood surrounded by uncles, aunts and cousins, many of whom lived close by. Nüsslein-Volhard treasured staying with her maternal grandmother, Lies Haas-Möllmann, a woman of strong discipline and character who sacrificed her career as a painter to care for her family.(Nüsslein-Volhard)

Having little money of their own and few products to purchase in post-war German shops, Nüsslein-Volhard’s artistic parents devoted a lot of their energy to making toys and books for their children. The children were also encouraged to draw and paint and to make things for themselves, including their own clothes. Nüsslein-Volhard and her siblings also spent many happy hours playing music with their parents who were good musicians, with Nüsslein-Volhard playing the flute.(Nüsslein-Volhard)

Nüsslein-Volhard grew up in south Frankfurt in a flat that had a large garden and was located near a forest. She liked nothing better than to explore plants and animals and go bird-watching. The family also spent many vacations on a farm where Nüsslein-Volhard was allowed to look after the animals and help harvest the crops. All this fed Nüsslein-Volhard’s desire to become a biologist, a dream she held from when 12 years old. Her parents encouraged her ambition to become a biologist, endeavouring to find books on the topic for her to read. Nüsslein-Volhard was the only one in her family to develop a lasting interest in science. By contrast her sisters and brother followed in her parents’ footsteps, taking up careers in architecture, music and art. (Nüsslein-Volhard)

Neither of Nüsslein-Volhard’s parents were pushy as parents, but they expected their offspring to do well in school. Nüsslein-Volhard was close to her father and he took a keen interest in everything she did. She remembers, for example, him listening patiently to her explanations of what she was doing in mathematics and taking time to discuss Goethe’s scientific papers with her. Sadly he did not get to see Nüsslein-Volhard go to university because he died suddenly in February 1962, the day she did her last high school exam. Looking back she sees the secret of many successful women is having had a father who encouraged them.(van Bredow and Kullman).

Nüsslein-Volhard married young, in the mid-1960s. She met her husband while studying at the Johann-Wolfgang-Goethe University in Frankfurt. The couple did not remain married for long and did not have any children. Despite the brevity of her marriage, Nüsslein-Volhard retained her new hyphenated name. This was because she had already begun to publish under that name.(Resnik, May)

Education

While Nüsslein-Volhard enjoyed school and was recognised by her teachers to be an exceptional student, she seldom expended any effort and time on subjects that did not interest her. Her laziness in certain subjects was reflected in her final exams. She gained the lowest possible grades in Latin and physics and almost did not pass English. By contrast she was awarded high grades in German literature, mathematics and biology. These were her favourite subjects. She was fortunate to have inspiring teachers for all three of the subjects, most of whom were women. Nüsslein-Volhard particularly enjoyed learning about animal behaviour, genetics and evolution, topics her biology teacher introduced her to in her final year.

When Nüsslein-Volhard left school, in 1962, she briefly considered pursuing medicine. She soon dropped the idea after doing a month’s nursing course in a hospital. Instead she opted to study biology at Johann-Wolfgang-Goethe University in Frankfurt. The biology course and its students, however, proved disappointing. Nüsslein-Volhard much preferred the classes in maths and physics. Nonetheless, she soon realised that she could not continue these subjects because she found them too difficult, and her true interest was biology. By the summer of 1964 Nüsslein-Volhard had left Frankfurt for Tübingen to start a new course in biochemistry just begun at Eberhard-Karl University. Her living conditions in Tübingen were very basic - she had no central heating or hot water. Yet, she greatly enjoyed mixing with her fellow students and her studies, particularly the microbiology and genetics which she did in her final year. Nüsslein-Volhard was awarded a diploma in biochemistry in 1969.(Resnik, May)

Following her undergraduate degree, Nüsslein-Volhard began a doctorate at the Max-Planck-Institute for Virus Research in Tübingen. She was already familiar with the Institute, having attended seminars and lectures there on the newly emerging science of Molecular Biology. Her doctoral supervisor was Heinz Schaller, a chemist then working on isolating and characterising enzymes involved in nucleic acid biosynthesis and DNA replication. Nüsslein-Volhard investigated the interaction of RNA polymerase with promoter regions on the DNA of bacteriophages. The work was not easy because DNA sequencing was not yet possible. Nüsslein-Volhard nevertheless made a number of breakthroughs. First, she improved the methods to purify RNA polymerase, an enzyme that helps catalyse the transcription of RNA from DNA. Second, she characterised the initial step involved in the process of transcription.(Resnik, May)

Career

By the end of her doctorate, Nüsslein-Volhard began hunting for a fresh challenge. Based on her discussions with colleagues, she decided to switch to developmental biology. What interested her was finding morphogens, factors present in a fertilised egg that direct the development of an embryo. Drosophila, a fruit fly species, offered the best model for working on the issue. Scientists had been studying the fly for over a century to understand genetics and a range of other biological processes. The fruit fly is attractive for several reasons. Firstly, its is easy and cheap to maintain in the laboratory. Secondly, it has only a small number of chromosomes allowing for sophisticated genetic experiments. Thirdly, it has a short life-cycle. Finally, the fly produces large numbers of eggs that develop externally and hatch into segmented larvae within 24 hours.

Knowing very little about Drosophila or developmental biology, Nüsslein-Volhard approached Walter Gehring, a specialist in the area, based at the Biozentrum, the University of Basel, to become a postdoctoral researcher in his laboratory. Supported by a long-term fellowship from the European Molecular Biology Organization (EMBO), Nüsslein-Volhard began work in Gehrings laboratory in early 1975. Life in the laboratory was not easy at first because Nüsslein-Volhard was a novice at everything. But she soon picked up the genetics of Drosophila from colleagues and developed a number of tools to investigate embryonic development of Drosophila which at the time was not yet well known. She used these tools to isolate and study gradient mutants. In fact she found the flies so fascinating she began to dream about them at night. (Nüsslein-Volhard, 1995).

In 1977 Nüsslein-Volhard returned from Switzerland to Germany to continue her studies in the laboratory of Klaus Sander at Freiburg University who was an expert in embryonic patterning, the complex developmental process that helps transform a single-celled embryo into a finished multicellular organism. Sander was famous for being the first to describe morphogen gradients in the insect egg. Together with Margit Lohs-Schardin, Nüsslein-Volhard constructed a fate map of the Drosophila embryo and worked on the first gradient mutant involved in embryonic patterning in Drosophila which she had isolated in the Basel lab (Nüsslein-Volhard, 1995).

Nüsslein-Volhard left Freiburg in 1978 to set up a fly lab in the newly founded European Molecular Biology Laboratory, EMBL, in Heidelberg. This she did with Eric Wieschaus, a colleague she had met when in Basel. Sharing the same research interests and a technician, Nüsslein-Volhard and Wieschaus set out to identify the genes responsible for the initial developmental decisions of the Drosophila embryo. The aim was to mutate the genes at random and select the mutants that displayed an abnormal larval body pattern. Mutation rates were increased by feeding males with a potent agent for generating mutations and families set up which, after several generations of inbreeding, were scored for producing mutant embryos. Nüsslein-Volhard and Wieschaus then investigated the segmented pattern of mutated embryos for changes. This they did simultaneously using a dual microscope that allowed them to study each specimen together.

To identify most genes that fulfill these criteria, large numbers had to be scored. The two scientists developed a number tricks and tools to help speed up the process. One involved the construction of blocks of tubes which made4 it possible to collect eggs from several fly families simultaneously. Another made use of transparent agar plates to simplify the collection of the embryos. They also discovered a particular oil that was good for rendering the egg shell transparent. This was important because it enabled them to see and score the development of the embryos’ structures, segments and their polarity without further processing. (Nüsslein-Volhard)

Within three years Nüsslein-Volhard and Wieschaus had scored approximately 20,000 mutated families and collected about 600 mutants with an altered body pattern. Overall, they found that out of the approximately 5,000 genes that are essential for the survival of the fly, only 120 were important for the early developmental decisions. This collection of genes provided the basis of many further investigations in their and other laboratories, substantially contributing to the foundation of a new discipline, developmental genetics.(Wieschaus, Nüsslein-Volhard) A first report of the results describing 15 genes that control the formation of the segmented pattern of the Drosophila larva was published in Nature in October 1980. (Nüsslein-Volhard and Wieschaus).

Nüsslein-Volhard returned to Tübingen in 1981 to take up a junior position in the Friedrich-Miescher-Laboratory of the Max-Planck-Society where she continued her research on Drosophila embryos. She was interested in finding out how genes from the mother passed on instructing factors, morphogens, to the developing embryo. By 1988 she and Wolfgang Driever, her graduate student, demonstrated the first morphogen gradient that instructs other genes in a concentration dependent manner. (Driever, Nüsslein-Volhard)

In 1984 Nüsslein-Volhard became a director at the Max Planck Institute for Developmental Biology in Tübingen, a position she held until her retirement in 2014. Once there she launched work on vertebrates, using the zebrafish (Danio rerio) as her research model. She was curious to know if the model of embryo development found in the fruit fly (an insect) matched those in vertebrates.(Nüsslein-Volhard, 2012) Looking at a new organism involved developing a number of new tools, facilities and methods, but Nüsslein-Volhard relished the challenge. She soon found ways to streamline the work, which included making adjustments to the aquarium and feeding systems. (Brown)

By September 1992 Nüsslein-Volhard had 7,000 aquaria filled with fish in her laboratory and a team of 12 researchers. They systematically induced and isolated mutants with altered development as had been done before with Drosophila.(Resnik, May). This was a huge undertaking. It necessitated crossing mutagenised males with wild-type females and then mating the offspring to establish families and scoring their progeny for abnormal development during the first 5 days after egg deposition. By March 1994 the group had screened almost 4000 families. The team identified nearly 1200 mutants that affected the appearance of the fish larvae. (Nüsslein-Volhard, 2012). More recently her lab focused on the formation of the adult colour pattern of the fish with the aim of advancing the understanding of the genetic basis of the evolution of the form and structure of organisms.

Achievements

In 1995 Nüsslein-Volhard was jointly awarded the Nobel Prize in Physiology or Medicine together with Eric Wieschaus for identifying genes that control the development of the segmented pattern of Drosophila. They received the award together with Edward B Lewis, an American geneticist whose independent study of fruit flies at the California Institute of Technology established a cluster of genes that function as master regulators of the development of the embryo. By the time of the Prize was awarded it had become clear that many of the genes that Nüsslein-Volhard and Wieschaus had discovered were conserved in organisation and function in all multicellular animals. (Mancini) The Nobel Committee awarded the Prize on the basis that the scientists’ findings in Drosophila could pave the way to discovering genes that cause birth defects in humans and help understand the reasons behind miscarriage and improve the success rate of in-vitro fertilisation. Nüsslein-Volhard was the sixth woman, the first German one, to win the Nobel Prize.

In addition to her pioneering work on Drosophila, Nüsslein-Volhard is known for the breakthroughs she made with the zebrafish. (Nüsslein-Volhard, 1995) Following her research, zebrafish became a standard vertebrate research model throughout the world. It has proven useful because it shares many similarities in terms of body organisation with mammals, including humans, but unlike mammals is ideally suited for research, in terms of rapid embryonic development outside the maternal organism in large transparent embryos. (Resnik, May).

Aside her scientific achievements, Nüsslein-Volhard has helped numerous women scientists further their careers. She has done this both as a personal mentor and through the establishment of the Christiane Nüsslein-Volhard Foundation. This she set up in 2004 using her own money, generous support from sponsors including the Max-Planck-Society and funds from Unesco-L’Oreal’s Women in Science Program. Every year the Foundation provides funds to 15 talented young women of any nationality with children pursuing graduate or postdoctoral work in a German university or research institute. Directed towards women scientists at a make-or-break point in their careers, the funds are designed to release women from the time-consuming task of childcare and housework. Nüsslein-Volhard was inspired to create the Foundation based on her observation that doctoral female students with children had much less spare time to do extra work in her laboratory and attend conferences than their peers without children which often prevented them from advancing in their careers and dropping out of science. (Dreifus)

For Nüsslein-Volhard, the Foundation is just one step towards resolving the difficulties women face in science. Women not only often have to juggle the demands of the laboratory with that of housework and childcare but also discrimination. This she realises is not easy to tackle. She herself is highly familiar with the problem, having on more than one occasion suffered jealousy from male colleagues. One of her earliest experiences of this was when she was persuaded to become the second author on the publication that emerged out of her doctorate. The excuse she was given was that the first author, a man, had started the project and had a family and needed a career. This was despite the fact that Nüsslein-Volhard had in fact done almost all the work. (Dreifus) Nüsslein-Volhard links such attitudes to the wider sexism against women. As she commented in an interview in 2006, ‘There is terrible prejudice against women who are successful...If she's beautiful, she must be stupid. And if a woman is smart, she must be ugly -- or nasty. I think it makes some people feel better to learn I bake good chocolate cake.’(Dreifus)

This profile was written by Lara Marks with generous input from Christiane Nüsslein-Volhard.

References

Brown, K, ‘An interview with Christiane Nüsslein-Volhard’, Development , 144 (2017), 3851-4.

Dreifus, C, ‘Solving a mystery of life, then tackling a real-life problem’, The New York Times, 4 July 2006.

Driever, W, and Nüsslein-Volhard, C, ‘A gradient of Bicoid protein in the Drosophila embryo’, Cell, 54/1 (1988), 83-94.

Driever, W, and Nüsslein-Volhard, C, ‘The bicoid protein determines position in the Drosophila embryo in a concentration-dependent manner’, Cell, 54/1 (1988), 95-104.

Mancini, E, ‘The female Nobel winner: The enduring inspiration of that rarest of scientists’, Times Higher Education Opinion , (29 Sept 2017).

Nüsslein-Volhard, C, Biographical essay, Nobel Prize, 1995, https://www.nobelprize.org/nobel_prizes/medicine/laureates/1995/nusslein-volhard-bio.html

Nüsslein-Volhard, C, ‘The zebrafish issue of Development’, Development, 139 (2012), 4099-103.

Nüsslein-Volhard, C and Wieschaus, E ‘Mutations affecting segment number and polarity in Drosophila’, Nature , 287 (1980), 795-801.

Resnik, J, May, C, ‘Christiane Nusslein-Volhard (1942- )’, The Embryo Project Encyclopedia (16 Feb 2012).

von Bredow R and Kullmann, K, ‘Women are just as gifted in science as men', Spiegel Online (20 Aug 2015).

Wieschaus, E F and Nüsslein-Volhard, C, ‘The Heidelberg screen for pattern mutants in Drosophila: A personal account’, Annual Review Cell Developmental Biology , 32 (2016), 1–46.

Christiane Nusslein-Volhard: timeline of key events

Nusslein-Volhard shared the 1958 Nobel Prize for Medicine for discoveries relating to genetic control of early embryonic development.1942-10-20T00:00:00+00001995-01-01T00:00:00+0000Foundation created by Nusslein-Volhard, 1995 Nobel Prize winner, to cover the costs of housework and childcare for talented women scientists with children undertaking graduate or postgraduate work at German universities or research institutes2004-01-01T00:00:00+0000
Date Event People Places
20 Oct 1942Christiane Nusslein-Volhard was born in Magdeburg, GermanyNusslein-VolhardMax-Planck-Institute for Developmental Biology
1995Christiane Nüsslein-Volhard, Eric Wieschaus and Edward B Lewis jointly awarded Nobel Prize in Physiology or Medicine for illuminating the genetic control of embryonic developmentNusslein-Volhard, Wieschaus, Lewis 
2004Christiane Nusslein-Volhard Foundation establishedNusslein-VolhardMax Planck Institute

20 Oct 1942

Christiane Nusslein-Volhard was born in Magdeburg, Germany

1995

Christiane Nüsslein-Volhard, Eric Wieschaus and Edward B Lewis jointly awarded Nobel Prize in Physiology or Medicine for illuminating the genetic control of embryonic development

2004

Christiane Nusslein-Volhard Foundation established