Lewis, Edward B.

(b. 20 May 1918 in Wilkes-Barre, Pennsylvania; d. 21 July 2004 in Pasadena, California), geneticist who won the Nobel Prize in Physiology or Medicine in 1995 for his discovery of a gene cluster crucial in controlling normal development in animals and whose findings helped alert the public to the dangers of radiation testing.

Lewis was born in Wilkes-Barre, Pennsylvania, in 1918. His father, Edward B. Lewis, was a jeweler and watchmaker who suffered hard times during the Depression; his mother, Laura (Histed) Lewis, was a homemaker. He had one older brother, who had a distinguished career in the foreign service. Lewis’s great uncle gave him a flute when he was ten years old, and this awakened the boy’s interest in music. He became an accomplished flute player and won a music scholarship to Bucknell University. Lewis also developed an early interest in nature, especially in toads and snakes. By the time he was in high school he was already experimenting with Drosophila melanogaster (fruit flies) along with his friend Edward Novitski, who also became a noted geneticist.

After a year at Bucknell University, Lewis transferred to the University of Minnesota and graduated with a BA in biostatistics two years later (1939). There he worked with Clarence P. Oliver, a Drosophila researcher, studying a mutation that Lewis would continue to study while doing graduate work at the California Institute of Technology (Caltech). He went to Caltech not only because Novitski was already studying there but also because of its strength in Drosophila genetics research. The Nobel Prize winner Thomas Hunt Morgan, father of Drosophila genetics, had set up the program at Caltech, and Lewis chose to work with one of Morgan’s students, Alfred H. Sturtevant.

After completing his PhD in 1942, Lewis plunged into war work, studying meteorology at Caltech and receiving an MS in this field in 1943. He served for four years as a captain in the U.S. Army Air Forces, primarily as a weather forecaster in Hawaii and then Okinawa. In 1946 he returned from the Pacific, left the service, and became a biology instructor at Caltech. He remained at Caltech, rose to the rank of professor in 1956 and was named Thomas Hunt Morgan Professor of Biology in 1966. He became a professor emeritus upon his formal retirement in 1988 but continued to do research until his death. While Lewis taught genetics courses throughout his years at Caltech, his real teaching went on with his graduate students in the laboratory. His work schedule was unusual. He did most of his research after midnight and would take breaks from his work to play the flute.

In 1946 the noted geneticist George Beadle was brought to Caltech as chair of the biology division and with him came a young graduate student, Pamela Harrah. She and Lewis married on 26 September 1946, just six weeks after they met. She worked in Lewis’s laboratory until their first child was born, and Lewis was particularly proud of the fact that she discovered a Drosophila mutant called Polycomb, which was to become significant in his research when it was discovered to have effects on other genes he was studying. She later pursued an interest in art and became an accomplished painter. Lewis and his wife had three sons, one of whom died while mountain climbing in 1965.

Lewis devoted his entire career to Drosophila genetics, a leading area of biological research in the first half of the twentieth century. Morgan and his coworkers were the first to work out genetic maps, that is, to find a correlation between particular traits and the location of the genes that controlled them on specific chromosomes—the protein and DNA structures in the cell nucleus. This approach lost favor by the 1950s because of the rise of molecular genetics using microorganisms such as viruses, bacteria, and yeast, which were all genetically simpler and easier to propagate in large numbers. Lewis, however, stuck with Drosophila and continued to investigate a small area on one of its chromosomes where he identified a number of genes that came to be called the Bithorax complex.

The Bithorax complex is a series of genes found aligned close to one another. They affect the structure of the fly’s thorax (middle section) and abdomen. Lewis found that these genes give each body segment they affect a unique set of instructions for development. If one of these genes mutates or changes so that it can no longer provide normal instructions, the segment then develops similarly to the one just posterior to it. For example, in one mutant, a leg is found on a segment where an antenna should be. These genes were called homeotic, meaning that they affected the placement of traits within the fly. At the time this phenomenon was discovered, it was unique, though researchers later found a similar gene sequence that controls the forward part of the fly: the head and the front of the thorax. In both these complexes, the positions of the genes on the chromosome correlate with the positions of the segments they influence, so those to the left on the chromosome control the more forward segments of the fly. Lewis hypothesized that this order arose from duplication of genes and that as the genes duplicated they took on different developmental roles. This theory brought his work into the area of evolutionary biology, and gene duplication has since been shown to be an important spur to evolutionary change.

As Lewis was pursuing this research in the 1950s, he also became involved in work on the health effects of radiation. He had used radiation to cause mutations in flies, and he had a background in biostatistics, so he could appreciate the mathematical arguments involved. While it was accepted that even low levels of radiation could cause mutations in sex cells, it was widely assumed—and touted by the government—that low-level radiation did not cause mutations in somatic cells, all the body’s cells apart from sex cells. This question was important both because aboveground testing of nuclear bombs was increasing the public’s radiation exposure and because evidence was mounting that cancer might be due to somatic cell mutations. Lewis analyzed statistics on leukemia and other cancers among survivors of the Hiroshima and Nagasaki bombings and came to the conclusion that there was no lower threshold for the dose-response curve. In other words, any radiation exposure would increase the chances of getting cancer, even if only slightly. This significant finding bolstered the case for the cessation of above ground testing and helped to create the political climate that led to the American-Soviet Limited Test Ban Treaty in 1963.

Throughout the 1960s and 1970s the mainstream of biological research focused on molecular biology—on working out the sequences of DNA in microorganisms—in part because the genetics of animals appeared too difficult to tackle. The genetic techniques of studying mutants by crossing flies with various combinations of traits seemed labored and imprecise. But Lewis still saw it as valuable and continued his work on the Bithorax complex, making a number of important discoveries, including the fact that the genes in the complex produce proteins that regulate genes farther down on the same sequence. His work was so detailed that when molecular biologists began to sequence animal genes, the Bithorax complex was an early target, with David Hogness of Stanford University beginning work on cloning the complex in 1978. This work led to deciphering the DNA sequences of the complexes.

When the DNA sequence of this complex was worked out, it was discovered that each gene in the complex had a 180-unit control segment, which came to be called the homeobox. It was also eventually discovered that the Bithorax complex is not peculiar to insects but is found in all animals, including humans, and is a fundamental control early in development. As the significance of the complex became appreciated in the 1980s and 1990s, there was renewed interest in Drosophila research and in Lewis’s work. In 1995 he was awarded the Nobel Prize in Physiology or Medicine, along with two molecular geneticists who had studied Drosophila mutants, Christiane Nüsslein-Volhard of the Max Planck Institute in Germany and Eric F. Wieschaus of Princeton University.

Before Lewis won the Nobel Prize he had received a number of other honors. In 1983 he was awarded the Thomas Hunt Morgan Medal from the Genetics Society of America, of which he had been president. He was elected to membership in several prestigious bodies, including the National Academy of Sciences, the American Academy of Arts and Sciences, and the Royal Society (London). He received the National Medal of Science in 1990 and the Albert Lasker Award for Basic Medical Research in 1991. Lewis died of cancer in Pasadena, California, in 2004 at the age of eighty-six.

By the 1990s Lewis’s Drosophila research was appreciated as groundbreaking. He had provided the genetic basis for an understanding of how genes relate to development, research that had significant implications for human health. Knowledge of how homeotic genes work provides clues about the molecular basis of developmental defects, a major cause of infant mortality and morbidity in the United States.

Lewis’s papers are in the archives of the California Institute of Technology, which is also the repository for oral history interviews of Lewis (conducted by Rachel Prud’homme in Pasadena, California, 31 July and 11 Oct. 1984). Biographical information is included in a collection of Lewis’s most important research papers: Howard D. Lipshitz, ed. and annot., Genes, Development, and Cancer: The Life and Work of Edward B. Lewis (2004). A concise biographical essay is James F. Crow and Welcome Bender, “Edward B. Lewis, 1918–2004,” Genetics 168 (Dec. 2004): 1173–1184. More on Lewis’s biography and work can be found in Ian Duncan and Geoffrey Montgomery, “E. B. Lewis and the Bithorax Complex” (parts I and II), Genetics 160, 161 (Apr., May 2002). Lewis’s Nobel Lecture is in Tore Frauml;ngsmyr, ed., The Nobel Prizes 1995 (1996). Obituaries are in the New York Times (26 July 2004) and Nature (9 Sept. 2004).

Maura C. Flannery