Lord of the Flies : Studying a Bug Put Caltech Biology Professor on Path to Nobel Prize
The million-dollar prize, much like a lottery jackpot, started with a $1 investment.
Edward B. Lewis and his buddy Eddie Novitski were sophomores at Meyers High School in Wilkes-Barre, Pa., in 1933 when they saw an ad in the back of Science magazine offering 100 fruit flies for $1.
Intrigued by “the idea of using an animal and learning something valuable,” Lewis said, they used the entire Meyers Biology Club treasury of $4 and sent off to Purdue University for their breeding stock.
With encouragement from a biology teacher, they began growing the flies in a lab at school, stopping by every day after class to sort through newly hatched generations with a magnifying glass to find the unusual and exotic specimens that are the bread and butter of biological research. They even found one, a mutant called “held-out,” that has since proved valuable in genetics research.
Thus began a lifelong obsession with fruit flies that launched both of them into careers in biology and led Lewis, now a 77-year-old emeritus professor of biology at Caltech, to a share of the 1995 Nobel Prize for medicine or physiology.
Fittingly, that early friendship played a major role in Lewis’ path to the Nobel. It was a mutant fly discovered by Novitski shortly after he left Wilkes-Barre for college that provided Lewis with the first insights into the genetic factors that cause different regions of the fly to form.
Ultimately, it led him to identify the genes that determine how one segment of a crude, wormlike fly embryo becomes a thorax with wings while another becomes an abdomen with legs.
To the great surprise of most other biologists--but not to Lewis--those same genetic control elements have since been found to govern the body shapes of all other animals, including humans.
“This is a great example of how basic research answering apparently esoteric questions about flies and other lower organisms has fundamental importance for understanding humans,” said Bruce Alperts, head of the National Academy of Sciences.
Lewis had to overcome his early environment to satisfy his inborn hunger for information about genetics. “We didn’t have many books around the house,” he said, and “the high school library had nothing at all on genetics.”
What was available was a flute, 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.
The biology club also was an outlet, and Lewis and Novitski raised more than flies. Periodically, they went into the mountains around Wilkes-Barre and trapped rattlesnakes with a forked stick, and kept them in cages in the biology lab. “Every Saturday morning, the biology teacher would come in with us and we would force-feed them,” said Novitski, who is retired and lives in Eugene, Ore. “It makes your adrenaline run a little high . . . it’s not to be recommended. We were lucky we didn’t get hurt.”
Despite the fact that it cost him his scholarship, Lewis transferred after a year to the University of Minnesota, which, unlike Bucknell, offered genetics courses. His older brother--who subsequently became a career diplomat--had to help him out with the $25 a year out-of-state tuition charge.
Completing his degree in another two years, Lewis followed Novitski--who had graduated from Purdue in two years--to Caltech.
Except for short stints as a visiting professor at the University of Copenhagen and Cambridge University, as well as an interlude as a weatherman in the Army during World War II, Lewis has had Pasadena as his base of operations ever since.
Most students entering graduate school are assigned a research project by their principal professor, one that usually reflects the professor’s interests more than the student’s. But Lewis had already begun a promising fruit-fly research project as an undergraduate and his new mentor, eminent Caltech biologist Calvin Bridges, allowed him to continue.
In many ways, fruit flies are an ideal research tool. They don’t take up much space in the laboratory, their upkeep is cheap and their short lives and high reproductive rate mean that researchers can study the properties of hundreds of thousands of them in a relatively short period.
When Lewis began his work, scientists knew that genes controlled individual traits in living organisms and that these genes were carried by chromosomes, but little more than that. The discovery of the double-helix nature 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 provide the blueprint for a fruit fly (humans have 23 pairs) and put them under a microscope, they could see a definite structure--a series of black and white bands that did not vary from healthy fly to healthy fly. Mutations showed up as visible changes in the banding.
Lewis’ key discoveries began shortly after the war 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 by a duplicate of the segment just in front of it. Because these changes occur in the embryo, it was clear to Lewis that the gene he was looking at 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 the 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 nearly every biologist, he determined that these control genes were lined up on the chromosome in the same order that the segments appear in the body, a principle that has subsequently been found to hold for all other animals as well. It was this achievement for which he won the Nobel.
Even more surprising, geneticists have since found that the structure of these key control sequences is almost identical in all species. The control genes that cause the formation of a head in the fly are the same genes that cause the formation of a head in humans, even though the genes they turn on in each case are substantially different.
Significantly, Alperts notes, this work probably could have been done only with flies. Scores of researchers have attempted to produce similar mutations in mice and other animals without success. They have failed, it is now known, because mice--and humans--have multiple copies of these control regions and it is extremely difficult to produce the same mutation in each copy.
“You can’t knock out a single gene [in mice] and have the same effect you do in flies,” Alperts said. “This is one of the many examples where the shortest distance between two points is actually the long way around.”
Lewis has given up his interest in rattlesnakes. He and his wife of 50 years, Pam, instead raise tortoises at their San Marino home.
Pam, whom he met in the laboratory at Caltech, is an artist whose work has been used to illustrate meeting announcement posters.
The pair have two sons, Hugh, 48, a lawyer in Bellingham, Wash., and Keith, 36, a geneticist at UC Berkeley. A third son, Glenn, died at the age of 13 in a climbing accident on Christmas Eve in 1963. Glenn, Lewis said, was “a mathematical genius” and the family has established a prize in his memory at San Marino High School.
Lewis’ schedule has changed little in recent years. He is in his office at 8 a.m. and practices the flute for 10 to 30 minutes before taking a short swim at the Caltech pool. He then works until midnight, pausing only for a one- to two-hour nap in the late afternoon on a couch in his office.
The night before a recent interview, he was at work until 2 a.m. According to USC biologist Henry Sukov, who was a graduate student at Caltech, flute music often resonates through the entire building late at night when Lewis takes a few minutes to play and think.
Lewis plans to spend another seven years on the same schedule before cutting back.
Weekends are a different matter. He and his wife love opera and have a box at the San Francisco Opera. When they go north for the weekend, he also takes the opportunity for a flute lesson with professionals in the opera’s orchestra. Other weekends, he plays in an informal chamber music group in La Jolla.
Lewis professes no great interest in the fiscal side of the Nobel, noting that he and his wife have no real needs. “We’ll give away a lot of it--to the opera, among other places--and put the rest in a trust for my boys,” he said.
But he is emphatic about one aspect. “I’m very, very unhappy that the prize is taxed [by the U.S. government], and so is the award committee in Sweden,” he said.
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A Prizewinner
Edward B. Lewis received the 1995 Nobel Prize for physiology or medicine for his work demonstrating how a simple, wormlike embryo is converted into a complex fly with distinct body parts.
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The Gene Rule
One key aspect of his work was the discovery that the genes that orchestrate the formation of the head, thorax, abdomen and other parts of the fly are sited on a chromosome in the same order in which the parts occur in the embryo. (The order changes somewhat as the adult fly develops.) This rule has since been found to hold true for all species, including humans.
Source: Science magazine
