07/22/2004 07:00:00

Caltech Nobel Laureate Ed Lewis Dies

PASADENA—Edward Lewis, winner of the 1995 Nobel Prize for his groundbreaking studies of how genes regulate the development of specific regions of the body, died Wednesday, July 21, 2004, at Huntington Hospital in Pasadena after a long battle with cancer. He was 86.

A member of the California Institute of Technology faculty since 1946, Lewis spent his life working on the genetics of the fruit fly, with special attention to the fundamental ways in which the genes relate to embryonic development. The work had profound implications for a basic understanding of the genetic regulation of development in humans. At the time of his death he was the Morgan Professor of Biology, Emeritus, and until very recently maintained an active schedule in his campus laboratory.

In a book published on Lewis earlier this year, author and longtime collaborator Howard Lipshitz wrote that Lewis's scientific research was "the bridge linking experimental genetics as conducted in the first half of the 20th century, and the powerful molecular genetic approaches that revolutionized the field in its last quarter." Lipshitz also lauded Lewis's much less widely known work on the understanding of radiation and cancer, and the closely related issues concerning nuclear-weapons testing policy.

Born May 20, 1918, in Wilkes-Barre, Pennsylvania, Lewis as an adolescent became interested in the genetics of the fruit fly, Drosophila melanogaster, which was already being touted as an excellent animal for research by Caltech's Thomas Hunt Morgan. Lewis performed genetics experiments on Drosophila while just a freshman in high school, and after taking a bachelor's degree in 1939 at the University of Minnesota, came to Caltech for a doctorate and remained at the Institute for the rest of his life, save for four years in the U.S. Army Air Force during World War II, when he worked as a meteorologist.

Lewis published several research papers while still a college student, and soon after the war was a recognized expert in the field of fly genetics. Returning to Caltech in 1946 as an instructor, he was named an assistant professor in 1948, earned tenure the following year, and became a professor of biology in 1956. He was named the Thomas Hunt Morgan Professor of Biology in 1966 and retained the chair until his retirement from active faculty duties in 1988.

In a campus article appearing in 1957, Lewis described his success in causing the flies to mutate with four wings (they normally have two). "We now have a working model for picturing the genetic control of development," he said. His prognostication was indeed correct, and nearly four decades later the Nobel Committee, in awarding Lewis the Nobel Prize in physiology or medicine, cited his triumph in identifying and classifying "a small number of genes that are of key importance in determining the body plan and the formation of body segments." The Nobel Committee also lauded Lewis for his discovery of "how genes were arranged in the same order on the chromosomes as the body segments they controlled."

In the same article, Lewis discussed his good fortune in becoming an active geneticist at a revolutionary time in biology. After the war, the gene was still treated as an abstract entity because the techniques needed to ascertain its molecular nature were yet to be developed, he explained. "You could begin to try to see how a gene is constructed, even though DNA hadn't yet been determined to be the hereditary material. The laws of genetics had never depended upon knowing what the genes were chemically and would hold true even if they were made of green cheese."

Although the modern techniques of molecular biology were yet to be invented, Lewis was never reticent about using novel methods to better understand the genetics of the fly. He created his four-winged mutants by bombarding the flies with x-rays, thereby playing a key role in discovering and explaining the role of homeotic genes--that is, genes that influence how the undifferentiated cells in a fertilized embryo separate into a head and a tail end, and how the eyes, legs, antennae, and other organs all form in their correct positions. These genes are "highly conserved," as geneticists say, because the genes are similar in all organisms and play a role in the development of all animals, from fruit flies to mice to humans.

"Ed was the bridge between the pioneers of Drosophila work--Morgan, Bridges, and Sturtevant--to modern developmental biology," said David Baltimore, president of Caltech and also a Nobel Prize-winning biologist. "Ed saw that even a lowly fruit fly could be a key to understanding the mysterious process of how a fertilized egg turns into a fully developed organism."

Lewis became a legend on the Caltech campus, and when he returned home after his 1995 Nobel Prize was announced—he had been attending a scientific conference in Switzerland at the time—was celebrated for his 60 years of dedication to his work and his classical approach to individual research in an era when "big science" increasingly became the more prominent model.

Lewis is survived by his wife of 57 years, Pam Lewis; and two sons, Keith Lewis of Redwood City, California, and Hugh Lewis of Bellingham, Washington.

Written by Robert Tindol