2 AMERICANS, GERMAN SHARE MEDICINE NOBEL
SCIENTISTS RECOGNIZED FOR GENETIC BREAKTHROUGH

Author: By Scott Allen, Globe Staff

Date: Tuesday, October 10, 1995
Page: 3
Section: NATIONAL/FOREIGN

The winners are Edward B. Lewis, 77, of the California Institute of Technology in Pasadena, Calif.; Eric F. Wieschaus, 48, of Princeton University; and Christiane Nuesslein-Volhard, 52, at the Max-Planck Institute for Developmental Biology in Tuebingen, Germany.

By raising and studying thousands of fruit flies, Wieschaus and Nuesslein- Volhard identified specific genes that determine a fly's body shape and organ arrangement. Earlier, Lewis had found that the disturbance of specific genes could cause strange mutations such as a fly with a leg where an antenna should be.

Their research helped spawn worldwide efforts to discover the genetic master plan for all life forms, including humans. Many of the genes that control development of fly embryos turn out to play a similar role in humans, raising hopes that the fruit fly could offer insights into problem pregnancies in humans.

"Together, these three scientists have achieved a breakthrough that will help explain congenital malformations in man," said the citation from Sweden's Karolinska Institute, which awards the prize for medicine.

"They let the genie out of the bottle. Their research has stimulated other research in many other fields," said a member of the award committee, Bjorn Vennstrom, a professor at the Karolinska Institute, at a Stockholm news conference.

Massachusetts Institute of Technology biologist Nancy Hopkins, a collaborator with Nuesslein-Volhard, said the Nobel winners have made a fundamental contribution to the understanding of how life begins.

Rudolf Jaenisch, who researches embryo mutations at the Whitehead Institute for Biomedical Research in Cambridge, said the researchers deserved the Nobel and its $1 million prize, adding that their work has influenced the entire field of genetics.

"These genes are not only important to Drosophila," said Jaenisch, using the Latin name for the fruit fly. "Evolution has used these genes over and over again to set up body plans for much more complex systems like humans."

In the early 1940s, Lewis, now an emeritus professor at the California Institute of Technology, began researching strange mutations in fruit flies, such as flies born with an extra set of wings. Lewis found that these flies were missing a gene that controls their balance, while other genes produced a duplicate body segment.

Eventually, Lewis was able to predict various mutations in the fruit flies based on flaws in specific genes. In people, flaws in such genes are probably responsible for some early miscarriages and some of the roughly 40 percent of birth defects for which no cause is known, according to the Nobel citation.

In the late 1970s, Wieschaus, the Squibb professor of molecular biology at Princeton, and Nuesslein-Volhard wanted to go far beyond Lewis' work, hoping to discover all the genes that determine embryo development in the fruit fly.

Even with the prolific fruit fly, which reproduces within 14 days, it was a tall order.

''Nobody knew how many genes there were that were significant to the development of the organism, or how research to identify these should work," said Wieschaus in a statement. "It seemed to us the only way was to knock out individual genes."

Working together at Nuesslein-Volhard's lab, the pair created 40,000 inbred families of fruit flies, each with a mutation in a particular gene. Most of the flies seemed no different, but 150 fly families had profound differences.

"There would be no muscles, or the skin would become comprised of nervous cells. That's how we learned which genes are essential to development," Wieschaus said.

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