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Edward B. Lewis, 86; Nobel Winner Helped Unlock Secrets of Genetics

July 23, 2004|Thomas H. Maugh II and Rosie Mestel | Times Staff Writers

Edward B. Lewis, the Caltech Nobel laureate who was the first to explain how genes control the development of organs during the early growth of an embryo, died Wednesday at Huntington Memorial Hospital in Pasadena after a long battle with cancer. He was 86.

Lewis' studies explained how an essentially shapeless fertilized egg develops into an organism with a front and back, head and feet, and right and left sides. Although he performed his work with that ultimate laboratory tool, the fruit fly, researchers have subsequently shown that the same mechanisms operate in virtually all animals, including humans.

"Ed saw that even a lowly fruit fly could be the key to understanding the mysterious process of how a fertilized egg turns into a fully developed organism," said Caltech President David Baltimore.

His work served as a crucial bridge between the old school of biology that focused on the structures of organisms and the newer, more radical school, which attempted to understand how those larger structures were molded by simple pieces of DNA.

"He was one of the giants of genetics -- and such a nice man," said embryologist Eddy De Robertis of UCLA. "He was always very courteous and willing to talk to people and to encourage young people."

Lewis and a friend were sophomores at Meyers High School in Wilkes-Barre, Pa., in 1933 when they saw an ad in Science magazine offering 100 fruit flies for $1.

They used the entire Meyers Biology Club treasury of $4 to purchase a batch and began growing the flies in a lab at school, stopping by every day to sort through the newly hatched generations with a magnifying glass to find the rare and exotic mutants that are the bread-and-butter of biological research.

They even discovered one, a mutant called "held-out," that is still used in genetics research today. Their after-school activity began a lifelong obsession with fruit flies that led Lewis to share the 1995 Nobel Prize for Medicine or Physiology with Eric F. Wieschaus of Princeton and Christiane Nuesslein-Volhard of the Max Planck Institute for Developmental Biology in Tubingen, Germany.

When he began his research -- virtually all of it conducted at Caltech -- scientists knew that mysterious pieces of information called genes controlled individual traits in living organisms and that these genes were carried by chromosomes. But science did not know much more.

The discovery of the double-helix structure of DNA was still more than 20 years away, and identifying the structure of a single gene further still.

But when researchers took the eight pairs of chromosomes that make up the blueprint of a fruit fly and put them under a microscope, they could see a definite structure -- a series of black and white bands that did not vary in healthy flies. Mutations showed up as visible changes in the banding.

Lewis' breakthrough discoveries began after World War II, when he crossbred two mutant flies and got offspring with "a perfect wing" immediately behind the normal wing.

In this fly, an entire segment of thorax had been deleted and replaced with a duplicate of the segment just in front of it. Lewis recognized that the mutated gene that caused the change played a crucial role in development. And because one gene alone could not bring about such massive changes, it was clear that the mutated gene was orchestrating the activity of a much larger number of genes needed to produce the wing segment.

Over the decades, he collected and crossbred other mutants and identified the genes that control the development of each fly segment. To the surprise of virtually all biologists, he showed that these control genes were lined up on the chromosome in the exact same order that the segments appear in the fly's body, a principle that has subsequently been found to hold for other animals as well. It was for this achievement that he won the Nobel Prize.

His contribution, Baltimore said, "was enormous because, at that time, nobody had any idea that things worked that way. He really established a paradigm."

Lewis' achievements could only have been done in fruit flies, commented Bruce Alberts, head of the National Academy of Sciences, when Lewis received the Nobel Prize. "You can't knock out a single gene [in mice] and have the same effect you do in flies."

Lewis seemed to have an inborn hunger for information about genetics, but it was hard to satisfy when he was growing up in an impoverished family. "We didn't have many books around the house," he once told The Times. "And the high school library had nothing at all on genetics."

But there was a flute in the house, and Lewis practiced daily, becoming good enough to play with the Wilkes-Barre Symphony Orchestra while he was in high school. He subsequently won a flute scholarship to Bucknell University.

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