He received a BA in Biostatistics from the University of Minnesota in 1939, where he worked on Drosophila melanogaster in the lab of C.P. Oliver. In 1942 Lewis received a PhD from California Institute of Technology (Caltech), working under the guidance of Alfred Sturtevant. In 1939, Edward B. Lewis arrived at Caltech and finished his PhD within three years. Lewis enrolled in the U.S. Army Air Corps training program in meteorology in 1942 and later received his masters in the area a year later. As he left for military service in 1943, he was told by the university president Robert A. Millikan that he had a position as an instructor at Caltech when he returned. He served working mostly as a weather forecaster in Hawaii and Okinawa for four years. Lewis returned in 1946 and took his position at Caltech where his duties included helping in the laboratory for an introductory genetics course. He was promoted in 1956 to a professor and became the Thomas Hunt Morgan Professor of Biology in 1966.

In 1946, Edward B. Lewis met Pamela Harrah (1925–2018). She was an accomplished artist, but also shared Lewis’ interests in animal life. She had went to Stanford and studied genetics and later discovered the mutant Polycomb, that now is important in the understanding of gene regulation. They married and had three sons named Glenn, Hugh, and Keith. Pam developed an infection that caused her to have a visual and physical, partial unilateral paralysis, which limited her mobility.

During the 1950s, Lewis studied the effects of radiation from X-rays, nuclear fallout and other sources as possible causes of cancer. He reviewed medical records from survivors of the atomic bombings of Hiroshima and Nagasaki, as well as radiologists and patients exposed to X-rays. Lewis concluded that “health risks from radiation had been underestimated”. Lewis published articles in Science and other journals and made a presentation to a Congressional committee on atomic energy in 1957.

The issue of linearity versus threshold re-entered the debate on nuclear fallout in 1962, when Ernest Sternglass, a Pittsburgh physicist, argued that the linearity thesis was confirmed by the research of Alice Stewart. (See also John Gofman )

Edward B. Lewis was a member of the National Academy of Sciences, the Genetics Society of America, the American Philosophical Society, and the American Academy of Arts and Sciences. He was a foreign member of the Royal Society (London) and an honorary member of the Genetical Society of Great Britain. He was a recipient of 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 Basic Medical Research Award (1991), and the Louisa Gross Horwitz prize (1992). He held honorary degrees from the University of Umeå, Umeå, Sweden and the University of Minnesota. Finally in 1995 he was awarded the Nobel Prize, which he shared with Christine Nüsslein-Volhard and Eric Wieschaus.

On November 20, 2001 Lewis was interviewed by Elliot Meyerowitz in the Kerckhoff Library at the California Institute of Technology, Pasadena, California. This interview was released on DVD in 2004 as “Conversations in Genetics: Volume 1, No. 3 – Edward B. Lewis; An Oral History of Our Intellectual Heritage in Genetics” 67 min; Producer Rochelle Easton Esposito; The Genetics Society of America.

His Nobel Prize–winning studies with Drosophila, (including the discovery of the Drosophila Bithorax complex of homeotic genes, and elucidation of its function), founded the field of evolutionary developmental biology and laid the groundwork for our current understanding of the universal, evolutionarily conserved strategies controlling animal development. He is credited with development of the complementation test. His key publications in the fields of genetics, developmental biology, radiation and cancer are presented in the book Genes, Development and Cancer, which was released in 2004.