Edward B. Lewis

American geneticist

• Born: May 20, 1918; Wilkes-Barre, Pennsylvania
• Died: July 21, 2004; Pasadena, California

Twentieth-century American geneticist Edward B. Lewis shared the Nobel Prize in Medicine for discovering the genetic aspects of embryo development. His work laid the foundation for developmental genetics and demonstrated the relationship between radiation and cancer at the genetic level.

Primary field: Biology

Specialties: Genetics; evolutionary biology

Early Life

Edward B. Lewis was born on May 20, 1918, in Wilkes-Barre, Pennsylvania, the younger of two sons. His father was forced to close his jewelry store during the Great Depression. While the family struggled financially, Lewis’s parents were committed to making sure their sons stayed in school. By the time Lewis was ready to go to college, his older brother was able to provide financial help to the family so that he could attend school.

As a young man, Lewis had two passions: music and biology. He was so proficient at the flute that he played with the Wilkes-Barre Symphony while he was still in high school, earning a music scholarship to Bucknell University, which he attended for one year before transferring to the University of Minnesota. Lewis’s love of music continued throughout his life, and he continued to take music lessons while doing graduate work at the California Institute of Technology (Caltech).

During his youth, Lewis also developed a love of animals, and he kept snakes, toads, and fish as pets. While in high school, he became interested in working with Drosophila (fruit flies), and he and his friend Edward Novitski ordered cultures so that they could perform experiments on these insects. Novitski later became an award-winning geneticist. Following high school, Novitski attended Purdue University, while Lewis enrolled at Bucknell. In 1939, Lewis transferred to the University of Minnesota, partly to work in the laboratory of geneticist Clarence Paul Oliver on Drosophila melanogaster. He completed his work at Minnesota quickly and proceeded to Caltech to work with geneticist Alfred Sturtevant. Lewis graduated with a PhD from Caltech in 1942. Following his doctoral work, Lewis completed a master’s degree in meteorology and did additional work in oceanography.

Life’s Work

After spending four years in the US Army Air Corps, Lewis returned to Caltech as an instructor in 1946. Not long after his return, he met genetics student Pamela Harrah while working with Drosophila. Harrah discovered a mutant that would become important to the study of gene regulation. Lewis and Harrah married in 1946 and continued to collaborate in the lab. The couple had three sons. Lewis was named full professor at Caltech in 1956. He was appointed Thomas Hunt Morgan Professor of Biology in 1966, a post he held until his retirement in 1988.

Lewis’s work at Minnesota followed Oliver’s work closely. In his Drosophila experiments, Oliver discovered that a single gene might have two components or might actually be two genes. Lewis worked with Oliver on these experiments, setting the stage for decades of work on recombinant genes and demonstrating that several recognized genes could well be duplicates.

At Caltech, Lewis made his first major discoveries in his work with fruit flies. At the time, it was not believed that recombination could occur within one gene; such processes only occurred between genes. Through his experiments, Lewis found that the star-recessive component of the gene was actually a second locus within the gene. Thus, rather than this component being yet another allele in a series of genes, it turned out to be another group of genes within the same gene. Lewis used the word “pseudoalleles” to describe what was originally thought to be a single gene. Building on earlier experiments, he was also able to show that if pairs of genes come from one ancestral gene, then their functions will be similar and the genes will interact. Lewis’s theory builds on the notion that after duplication, one pair of genes can mutate and perform new functions, while the other can retain older functions. In this way, the number of genes increases and the acquisition of new functions occurs in heterozygotes.

Lewis also discovered a process he called transvection. Because of the rearrangement of chromosomes, chromosomes were sometimes prevented from working closely together. He experimented with these inhibited chromosomes to conclude that any chromosome break within a certain number of experiments could inhibit pairing enough to indicate this transvection phenotype. Lewis determined that such patterns can be recognized in the generation immediately succeeding the break, saving the amount of time needed to investigate the effects of chromosome breakage. Building upon this discovery, Lewis developed several technical methods that became standard for experimenting with fruit flies. He discovered that neutrons were much more effective than X-rays or gamma rays in producing chromosome breaks. He also developed a procedure for treating fruit flies with the potent mutagen EMS that soon became standard procedure. Lewis also developed a machine that aided scientists in counting large numbers of flies. The fruit flies were suspended in a liquid and passed through a narrow tube, enabling experimenters to count large numbers of flies more easily.

Lewis’s experiments demonstrated that a deeply ordered set of regulatory genes underlay the various segments of a fruit fly’s body. A skilled experimenter and an expert at introducing mutations, Lewis persistently introduced duplications into the flies as he attempted to map the structure of each body segment and to confirm that tandem genes were responsible for the structure of these segments. In later experiments, he made connections between these mutant flies and their evolutionary ancestors. In the early 1960s, Lewis produced a four-winged fly that looked like a dragonfly. His experiments demonstrated that mutations cause very simple changes in an insect’s body structure. Lewis was able to construct a triple-mutant chromosome (anterobithorax, bithorax, postbithorax) that provided a map of the complex structure of the fly’s body. Lewis was awarded the Nobel Prize in Physiology or Medicine in 1995 for his work on the bithorax function of Drosophila, and he is often credited with founding the field of developmental genetics.

After his retirement in 1988, he continued to work on issues related to developmental genetics and medicine. Lewis died in 2004 at the age of eighty-six.

Impact

Lewis’s work on mutations, developmental genetics, evolution, radiation, and cancer won him numerous prizes and awards, including the Thomas Hunt Morgan Medal (1983), the Gairdner Foundation International Award (1987), the Wolf Foundation Prize in Medicine (1989), the Rosenstiel Award (1990), the National Medal of Science (1990), the Albert Lasker Award for Basic Medical Research (1991), and the Louisa Gross Horwitz Prize (1992). For his groundbreaking work on Drosophila, he was a corecipient of the 1995 Nobel Prize in Physiology or Medicine, along with Christiane Nusslein-Volhard and Eric Wieschaus. Because of Lewis’s work with Drosophila and his expert experiments on mutations, decades of subsequent researchers have been able to build on his findings regarding specific genes or pairs of genes that influence various evolutionary changes in both wild and domestic Drosophila populations.

Lewis developed new laboratory methods for working with Drosophila populations, such as a device for counting large numbers of fruit flies in experiments, and he pioneered the use of EMS, a highly potent mutagen that became a standard tool for introducing mutations in populations. Moreover, his insights into the properties and functions of regulatory genes were soon embraced by geneticists and had a tremendous impact on the ways that scientists understood gene regulation and development and evolution.

Although Lewis’s writings and research about the relationship between levels of radiation and cancer are not well known, his writing in this area caused a shift in public policy regarding radiation protection. His studies indicated that the effect of either low or high doses of radiation could result not only in changes to genetic makeup but in changes to the body. Lewis was called several times to testify before the Atomic Energy Commission, and his writings about these matters can be found in Genes, Development, and Cancer (2004), a collection of his writings drawn from his lifelong work.

Lewis’s important work in developmental genetics changed the direction of a number of scientific fields and influenced a large number of scientists and their work.

Bibliography

Crow, James F., and Welcome Bender. “Edward B. Lewis, 1918–2004.” Genetics 168: 4 (Dec. 2004): 1773–83. Print. Presents an overview of Lewis’s life and work. Contains several remembrances of Lewis from colleagues and former students.

Lipshitz, H. D. Genes, Development, and Cancer: The Life and Work of Edward B. Lewis. Boston: Kluwer Academic, 2004. Print. Complete collection of Lewis’s papers divided into sections that reflect the many areas of research in which Lewis was engaged. Includes summaries.

Ruse, Michael, and Joseph Travis, ed. Evolution: The First Four Billion Years. Cambridge, MA: Harvard UP, 2009. Print. Presents an introduction to the theory of evolution that contains a small overview of Lewis and his work.