Christiane Nüsslein–Volhard

German biologist Christiane Nüsslein–Volhard (born 1942) is known for her ground breaking discoveries about how genes control the early development of embryos. She shared the 1995 Nobel Prize for Medicine (with Edward B. Lewis and Eric F. Wieschaus), and was the first German woman to win a Nobel Prize in science.

Nüsslein–Volhard was born on October 20, 1942, in Magdeburg, Germany, while World War II was raging in Europe. She was the second of five children of Rolf Volhard, an architect, and Brigitte (Haas) Volhard, a musician and painter. She grew up in a flat in Frankfurt, Germany, in a rustic environment and within a family that appreciated art and music. By age twelve, however, Nüsslein–Volhard decided she wanted to be a biologist, given her keen interest in plants and animals. All of her siblings went on to pursue artistic or architectural careers.

Still, her artistic surroundings influenced her sense of observation, which would benefit her in more advanced scientific research, particularly that of fruit fly embryos. She recalled her childhood as happy and stimulating, thanks to supportive parents. Her parents provided her with appropriate books and listened to her ideas. But Nüsslein–Volhard still learned how to play the flute and draw, despite her scientific inclinations.

In high school, she was an admittedly mediocre student, but only because she often felt compelled to pursue her own interests and studies. Still, she enjoyed her teachers and her classes, particularly biology. At the end of school, she gave a speech, "On Language of Animals," which was influenced by Konrad Lorenz and German biologists who studied animal behavior.

While she was in high school, her father died on February 26, 1962. After finishing high school, she wanted to study biology and become a researcher. Once she considered entering medicine, but after doing a one–month course as a nurse in a hospital, she knew she would never enjoy working as a physician.

Obtained Numerous Degrees

She attended Johann Wolfgang Goethe University in Frankfurt and received degrees in biology, physics, and chemistry in 1964. That year, she learned of a biochemistry curriculum that was starting at the Eberhard–Karls University in Tübingen, Germany, so she left family and friends behind. She earned a degree in biochemistry from the university in 1968 and a Ph.D. in biology and genetics in 1973. She also had a chance to attend seminars and lectures from scientists of the Max–Planck Institute, including Gerhard Schramm, Alfred Gierer, Friedrich Bonhöffer, and Heinz Schaller. They were teaching the latest advances in protein biosynthesis and DNA replication.

In 1975, she moved to Basel, Switzerland to conduct her postdoctoral work. She also held research fellowships at the Max–Planck Institute for Virus Research in Tübingen and at the Albert Ludwigs University in Freiburg, Germany. During her education, she never found her gender to hinder her scientific pursuits. From Heinz Schaller, she got her first real training in a laboratory. She was his first graduate student. She recalled that, as he was a chemist, Schaller taught her to think in "quantitative terms, yields, and completeness of reactions."

She was married briefly as a young woman and changed her name to Nüsslein–Volhard. She had no children. After she divorced, she kept her husband's last name because it had already become associated with her developing scientific career.

Nobel Research

In 1978, after Nüsslein–Volhard finished her post–doctoral fellowships in Switzerland and Freiburg, Germany, she accepted her first independent research position at the European Molecular Biology Laboratory in Heidelberg, Germany. She served its head group for the next two years. Also finishing his training at the laboratory was Eric F. Wieschaus, the developmental biologist with whom Nüsslein–Volhard would later share the Nobel Prize.

The two researchers found they had a common interest in Drosophila, or fruit flies, so they decided to work together. Their goal was to discover how a newly fertilized fruit fly egg developed into a fully segmented embryo. "I immediately loved working with flies," she recalled in the autobiography she wrote for theNobel Committee when she received her Nobel Prize in 1995. "They fascinated me, and followed me around in my dreams."

Actually, their ambitions went well beyond mapping the development of a simple fly. In the broader sense, they wanted to find out how a single–cell egg, or the immediate union of a spermcell and egg, developed into a complex organism; that is, they wanted to find out how cells knew how to eventually become a specific body part such as a hand, an eye, or skin. Nüsslein–Volhard and and Wieschaus would base their experiments on the pioneering genetic research Edward Lewis conducted in the 1940s. However, the collaborators would soon open up a whole, new area for research into human birth defects.

The fruit fly was appropriate to their purpose, as it has fast embryonic development and would not slow down their research. They first set out to isolate the genes responsible for the initial growth of the embryo, an unprecedented and daring strategy. Nüsslein–Volhard and Wieschaus were not sure they could even isolate the specific genes.

They proceeded with their research by feeding male fruit flies sugar water laced with chemicals that would destroy their deoxyribonucleic acid (DNA). Subsequently, when the male flies mated, the females often produced embryos that were dead or mutated.

For a year, Nüsslein–Volhard and Wieschaus studied these altered embryos under a microscope equipped with two viewers that enabled them to examine an embryo together. Eventually, they identified the genes that directed cells to become a specific body part of the fly, and they found that the mutated genes often altered the embryo's natural body plan. Nüsslein–Volhard could distinguish even the most minute deviation and could tell whether it would affect how the embryo would develop.

The two researchers published the results of their experiments in the 1970s. Essentially, they had discovered which genes were essential to normal development. One of their significant findings was that only few identifiable genes controlled development.

The collaborators published several more papers over the next few years that reported further discoveries, including how a mother's genes pass on genetic codes to a developing embryo. They called the codes morphogens and explained that these released chemicals that essentially tell other genes where to go and what to do.

The results of their research had widespread implications. The Nobel committee said that their work with fruit flies helped scientists understand the causes of birth defects in human beings, as similar genes exist in humans and perform similar functions as they develop. Nüsslein–Volhard's and Wieschaus's research could lead to the discovery of genes that could explain birth defects in humans. In addition, it could help improve in–vitro fertilization and eventually explain the cause of miscarriages.

The collaborators' work sparked the launching of an international project to map out a genetic blueprint for all life forms. In 1995, Nüsslein–Volhard received the Nobel Prize for Medicine with Wieschaus and Lewis. Lewis, who was with the California Institute of Technology until his death in 2004, had been analyzing genetic mutations in fruit flies since the 1940s and had published his results independently from Nüsslein–Volhard and Wieschaus.

Previous to winning the Nobel, in 1991, Nüsslein–Volhard and Wieschaus received the Albert Lasker Medical Research Award, which is considered second only to the Nobel in prestige.

Following publications about the work, Nüsslein–Volhard began lecturing at universities in Germany and the United States. She was a Silliman lecturer at Yale and the Brooks lecturer at Harvard.

New Research on Fish

In 1981, Nüsslein–Volhard accepted an offer for a junior position at the Friedrich–Miescher–Laboratory (FML) at the Max–Planck Institute for Developmental Biology in Tübingen. In 1985, she became the institute's director. "The FML consists of four groups," she recalled in her Nobel autobiography. "The group leaders stay for not longer than six years, and are entirely free in their research topics. They have a generous budget, enough space and no teaching obligations."

At the institute, she conducted more research into fruit–fly genetics, then announced she would begin similar research on the basic patterns of genetic development in the common zebra fish. This announcement generated some surprise, despite Nüsslein–Volhard's track record in fruit–fly research. Some fellow scientists felt that the new project would be risky, even foolish.

But that didn't stop the enterprising Nüsslein–Volhard, who felt the zebra fish would be perfect for her continuing research. For one thing, a zebra fish has a rudimentary spinal cord, which makes it a more advanced species than a fruit fly. Also, it develops from a transparent embryo, which could have untold value in such research. Many technical problems had hampered prior research on vertebrates such as frogs, mice, or chickens, most notably the inability to see the embryo developing. The use of zebra fish would eliminate that barrier. The transparency of the zebra fish embryo makes it possible to view the embryo developing and easy to observe organ growth. Zebra fish provide other advantages as well: they are small, breed quickly, and the embryos develop outside the mother's body.

In 1986, Nüsslein–Volhard brought fish tanks into her laboratory, and she and her team developed tools for fish breeding and keeping stocks of fish. By 1993, she had a full fish house with 7,000 aquaria, and her team included 16 researchers. In 1996, the researchers published a 481–page paper on the genetic structure of a zebra fish. The work, described as "groundbreaking," provided a valuable tool for other researchers working to identify similar genetic mutations in humans.

So far, it has not been determined if experiments with zebra fish will yield any more significant genetic information. But Nüsslein–Volhard perseveres undaunted. "In my lab, we will continue working on the investigation of the molecular mechanisms involved in the establishment of polarity in the Drosophila embryo, as well as continue the exploration of the zebra fish as a model for the study of vertebrate specific features," she said in her Nobel autobiography. "We believe that the combination of several approaches and systems in one laboratory provides a powerful basis for further understanding of the development of complexity in the life of an animal."

A "National Treasure"

In her native Germany, the citizens regard her as a national treasure. Her professional colleagues describe her personality as both strong–willed and meek.

She lives near Tübingen, living in the millhouse of a monastery that was built around the fourteenth century. In this home, she even keeps some zebra fish as pets. Her hobby evokes memories of the artistic family environment of her childhood: she makes her own jigsaw puzzles by cutting apart reproductions of famous works of art.

Books

Newsmakers 1998, Issue 1. Gale Group, 1998.

Notable Scientists: From 1900 to the Present, Gale Group, 2001.

Online

"Christiane Nüsslein–Volhard—Autobiography, "NobelPrize.org,http://nobelprize.org/medicine/laureates/1995/nusslein-volhard-autobio.html (May 17, 2005).

Ellis, Peter, "Christiane Nüsslein–Volhard," Scientist of the Month, http://www.longman.co.uk/tt–secsci/resources/scimon/aug01/nuss.htm (January 6, 2005).