Trudi Schüpbach and Eric Wieschaus: A shared passion for nature’s truth
Life in nature makes us recognize the truth of these things, so look at it diligently, follow it, and do not turn away… For, verily, art is embedded in nature; whoever can draw her out, has her
It’s no surprise that Dürer is the favorite artist of developmental biologist Eric Wieschaus, Ph.D., Squibb Professor of Molecular Biology at Princeton University.
“I like the technical quality of his work,” says Wieschaus, who dreamed of becoming a painter as a boy in Alabama. “I was drawn to developmental biology because it’s visual. I had this intuitive understanding of where things are, where they should be. You get that from looking.”
Like Dürer, Wieschaus applied his talent for observation and perception to the mysteries of nature -- not on young hares, but on Drosophila melanogaster, the common fruit fly.
Using this tiny, hairless insect as a model, Wieschaus was able to identify the genes that determine cell size, shape and position during embryo development. Mutations in these genes alter the fruit fly’s normal body plan. These genes later proved to have similar or identical matches in humans, and their discovery has helped transform how scientists look at congenital birth defects.
While Wieschaus’ work may never hang in the Louvre, it did bring him the most prestigious award in the world. In 1995, at 48, he received the Nobel Prize in Physiology or Medicine with Edward B. Lewis, Ph.D., of Caltech and Christiane Nüsslein-Volhard, Ph.D., of the Max Planck Institute for discoveries about the genetic control of early embryonic development.
“The genetic screens carried out by Wieschaus and Nüsslein-Volhard were driven by pure curiosity, but their discoveries had a tremendous impact,” says Daniela Drummond-Barbosa, Ph.D., assistant professor of Cell and Developmental Biology at Vanderbilt University Medical Center. “Many of the genes they identified were later implicated in a variety of biological processes with high relevance to human health.”
“He is singularly prepared to tackle new questions and unconventional approaches,” she explains. “He is fun, he is unconventional, and he is charming. Several people completely misjudged his intellect, based on his extremely kind and humble behavior, but he is without doubt one of the smartest people I know. ”
Wieschaus met Nüsslein-Volhard at the University of Basel in 1974, while completing his Ph.D. thesis from Yale. The pair discovered a mutual interest in Drosophila embryology and started working together.
Nüsslein-Volhard recalls their times in the lab with fondness. “Eric was loved by the technicians,” she says. “Every Sunday he brought a hot meal he had cooked to the lab, walking the 15 minutes through the woods with his big bag. I usually brought in a cake. When we had dull repetitive work to do, we listened to (Mozart’s opera) ‘The Magic Flute.’”
Wieschaus, who became fluent in German and French during his time in Switzerland, soon left to complete postdoctoral work at the University of Zurich. But he often returned to Basel to finish experiments and plan future studies with Nüsslein-Volhard.
“She was the single most important influence in my work,” he recalls. “And she’s still a close friend.”
In Zurich, Wieschaus began performing experiments on Drosophila with a graduate student named Trudi Schüpbach, who was working on the genetics of sex determination in the fruit fly. After countless late nights in the lab, their scientific collaboration developed into a close friendship -- and then into something more.
“It was proximity,” Wieschaus explains, his eyes crinkling at the corners as he shares an impish smile with his wife of 25 years. “We started as colleagues.”
Wieschaus and Schüpbach married in 1983 after taking faculty positions at Princeton.
Schüpbach, who received her Ph.D. from the University of Zurich, is professor of Molecular Biology at Princeton, where she studies the genetic and molecular mechanisms that cause developmental asymmetries in the Drosophila egg. She and Wieschaus are Howard Hughes Medical Institute investigators and members of the National Academies of Science.
Over the dinner table
Eleanor Wieschaus paints a picture of growing up in an extraordinarily stable and loving family, where Schüpbach helped the kids with homework and Wieschaus cooked dinner. “We ate together every evening,” she says. “That was non-negotiable, even when I was a teenager and wanted to hang out with my friends. My dad’s a great cook -- he likes to make Italian.
“It was a great role model to have two parents who loved their work,” Eleanor continues. “They showed me that it’s possible to have a great career andto have kids who look up to you, respect you and love you.” She pauses, then laughs: “But they’re just normal people. Well, semi-normal. After all, they are scientists.”
Wieschaus and Schüpbach are characteristically modest about their parental achievements. They point out that juggling a science career and a family can work well -- as long as one accepts that the lab and the kids will be the only things in one’s life for awhile.
“You get up, get the kids to schools, get to the lab, work all day, then get home and make dinner,” say Wieschaus. “Then there are hours of work left to do when the kids have gone to bed. It would be horrible if you didn’t love both. If you’re happy with just career and family, you’ll make it. But if you need anything in your life beyond family and science to make you feel good, it’ll be hard.”
In the early years, Wieschaus and Schüpbach were too busy raising their girls to discuss research over the dinner table. But now the nest is empty and they talk science a lot more.
“We have side-by-side labs and we share a weekly lab meeting, so we know what’s going on with each other,” Wieschaus says. “I like the everyday activity that’s part of big science more than the great discovery. A lot of scientists have ambition keeping them in the lab. I’m there because I like what I do.”
While at university, however, Schüpbach found only two role models for a woman aiming at a career in science. “One woman was in botany and one was in physics,” she recalls. “They were workaholics and not married, so they didn’t really set an example that a woman could be a scientist and have a family. It was hard then, but it’s different now.”
Schüpbach has hastened that difference by advising woman graduate students and postdoctoral fellows who want a family and a career in science. “They come and talk to me about when is the best time to have kids, or whether to even have kids,” she says.
Role models of a geekier sort influenced Wieschaus’ career path. Neither of his parents was a scientist and he had never considered a science career, until he attended a summer science camp at the University of Kansas between his junior and senior years of high school. “It was perfect for a nerdy high school kid like me to hang out with other nerds,” he recalls with a laugh.
While a sophomore biology major at Notre Dame, Wieschaus earned much-needed money by washing bottles and fixing fly food in the Drosophila laboratory run by Professor Harvey Bender. There he encountered his first fruit flies and learned basic genetics.
“I like genetics – it’s solid,” Wieschaus asserts. “You do it and you learn something right there. And Harvey Bender showed me it was possible to have a good life as a scientist. I thought ‘Yes! This is life for me.’ It wouldn’t be weird, it would be perfect.”
Wieschaus completed his postdoctoral work in Zurich in 1978, then got his first taste of life as an independent scientist at the European Molecular Biology Laboratory (EMBL) in Heidelberg. Best of all, Nüsslein-Volhard was also working at EMBL. The pair at last could discover how the Drosophila egg developed into a segmented embryo.
Two sets of eyes
Newly laid Drosophila eggs develop in about 10 days, first to larvae, then pupae, then flies. Somewhere in that cycle, certain genes tell each larva to segment into sections that eventually make up the adult fly’s head, tail, back and belly. But which of the fly’s 20,000 genes controls the process?
Wieschaus and Nüsslein-Volhard decided to look at nature in a different way, just as Dürer had done nearly three centuries earlier. First, they fed the flies toxic substances. This created random mutations that knocked out the function of individual genes. They bred the defective flies, then studied the genetic mutations by peering through a microscope.
For a scientist with an artistic eye, there was much to see. “We sat opposite each other at a dual eyepiece microscope,” Wieschaus recalls, smiling at the memory. “We were very competitive. We’d look and one of us would say ‘interesting’ and the other would say ‘not.’ I’d say ‘mutant.’ She’d say ‘not.’ It helped to have two good sets of eyes. There was a better chance of seeing.”
The pair culled through more than half of the 20,000 fly genes, and identified 15 genes in three groups that control embryonic segmentation. The first group of genes, called gap, causes the fly embryo to segment along the head-tail axis. The second group, pair-rule, governs every second segment in the embryo. The third group, segment polarity, refines the individual segments so that the head and tail look different. They published their results in the journal Nature in 1980.
“It took us two years to figure out how to do it and one year to do the experiments,” Wieschaus recalls. “We knew it was working, but we didn’t appreciate what we had done until it was over. We didn’t realize the importance until others reacted to it.”
Most scientists probably fantasize about receiving the phone call, the one from the Nobel committee, but Wieschaus declares he was not among them when he answered the phone in the fall of 1995.
“It was very early in the morning when I got the call, so I really had no feelings at all,” he explains, face deadpan, eyes teasing. “Then I woke up my three daughters, who were mostly interested in going back to sleep.”
“I was excited,” says Eleanor Wieschaus, who recalls the event with more clarity than her now-famous father. “Princeton is a small town and it was front-page news. I was in eighth grade -- the typical attention-seeking middle child. It was fun when the news came out.
“People were saying ‘Wow! Your dad won a Nobel Prize!’ My dad doesn’t come across as the typical scientist. He’s brilliant, but to me, he’s just my goofy dad.”
Schüpbach’s happiness over her husband’s achievement came with an additional perk -- it drew attention to their shared discipline of developmental biology. “I was very proud his work was deemed worthy of the award,” she says. “It was very important -- not just for Eric but for all the scientists who work in this field.”
For Wieschaus, the best part of winning the prize was sharing his parents’ happiness and pride. “It meant everything that they could be there in Sweden for the award ceremony,” he says. “I couldn’t have done it without their support.” His mother and late father, who died in 2000, “were very accepting and encouraging of everything I did.”
“It was so cold in December, with only four hours of light,” Eleanor Wieschaus remembers. “We stayed in a beautiful hotel, and it was the St. Lucia Festival -- the festival of light. My sisters and I were so nervous during the ceremony. We were afraid that my dad would fall when he walked up to shake the king’s hand. He’s a bit of a klutz.”
Eleanor enjoyed the limelight in Stockholm, especially when she and her two sisters were interviewed by a Swedish children’s TV show. When the host asked if the girls wanted to follow their father’s footsteps into science, Eleanor declared, “No -- it’s too tedious!”
Think of Galileo
After winning the Nobel Prize, Wieschaus spoke at the United Nations and before Congress, then plunged into a river of lectures and appearances that could have inundated a less grounded man. “You become a public person,” he explains. “It can get overwhelming. Now I do a certain amount (of lectures) and no more. The good part is that the attention allows one to be an advocate for science.”
Wieschaus and Schüpbach are concerned about the public’s perception of science, whether it is human embryonic stem cell research or the theory of natural selection.
“I feel very strongly about this because oogenesis is my field,” says Schüpbach. “People don’t understand even the basics. When they talk about a certain point when life begins, they don’t understand that it’s all alive. The egg is alive, the sperm is alive, the mother is alive, the fertilized egg is alive.
“How much do people know about how the embryo is formed?” she continues. “Do people know what a blastocyst is and what it does? People need to know what they’re talking about before they start drawing conclusions.”
Wieschaus teaches a required undergraduate class for non-science majors at Princeton called “DNA to Human Complexity.” His students often challenge him when science conflicts with their religious beliefs, and he has learned to handle the issue philosophically.
Wieschaus tells his students that scientists argue constantly. They inch forward toward some facet of the truth by running experiments and gathering data. But arguing the truth of religion over science doesn’t strengthen one’s faith.
“You either believe it or you don’t,” Wieschaus says. “Religious faith is a gift -- you can’t argue people into it. Religion has always had to deal with new science, and it has always adapted.”
“Think of Galileo,” Schüpbach interjects. “The Catholic Church fought against his position at the time, but I don’t think you’ll find a Catholic today who thinks the earth is the center of the universe. I’ve never understood why the notion of evolution is considered anti-religious. There’s no reason why God could not have used evolution.”
Wieschaus and Schüpbach also worry about the political manipulation of scientific research.
“There is governmental support for science as an engine that drives military pursuits, but there’s no support for science as a whole,” Wieschaus asserts. “Scientific facts are being suppressed, especially with global warming. There’s no appreciation for the science behind it or the consequences of our actions.”
According to Wieschaus, the culprit is not a fear of science, but the belief that science is just another way to make a buck -- and that manipulating science can make even more bucks.
"We don’t mind different political opinions, but it’s emotional for us as scientists,” he says. “We see educated people who misuse science, who don’t value it. As rare as scientific truth is, it should remain pure.”
As pure, perhaps, as an artist’s devotion to illuminating the truth behind nature, whether in a fruit fly or a young hare.