During World War I, he served in the U.S. Army, where he worked on the development of poison gases, especially Lewisite. He became an assistant professor of chemistry at Harvard University in 1919 and the Sheldon Emery Professor of Organic Chemistry in 1929. He researched the physical structures of natural products, particularly chlorophyll, and he was one of the first to explore the sometimes complex relationship between chemical equilibrium and the reaction rate of chemical processes. He studied the biochemistry of oxyhemoglobin providing insight into the disease methemoglobinemia, helped to explain the structure of chlorophyll, and contributed important insights that underlie modern theories of acid-base chemistry.
In 1933, Conant became the President of Harvard University with a reformist agenda that involved dispensing with a number of customs, including class rankings and the requirement for Latin classes. He abolished athletic scholarships, and instituted an "up or out" policy, under which untenured faculty who were not promoted were terminated. His egalitarian vision of education required a diversified student body, and he promoted the adoption of the Scholastic Aptitude Test (SAT) and co-educational classes. During his presidency, women were admitted to Harvard Medical School and Harvard Law School for the first time.
Conant was appointed to the National Defense Research Committee (NDRC) in 1940, becoming its chairman in 1941. In this capacity, he oversaw vital wartime research projects, including the development of synthetic rubber and the Manhattan Project, which developed the first atomic bombs. On July 16, 1945, he was among the dignitaries present at the Alamogordo Bombing and Gunnery Range for the Trinity nuclear test, the first detonation of an atomic bomb, and was part of the Interim Committee that advised President Harry S. Truman to use atomic bombs on Japan. After the war, he served on the Joint Research and Development Board (JRDC) that was established to coordinate burgeoning defense research, and on the influential General Advisory Committee (GAC) of the Atomic Energy Commission (AEC); in the latter capacity he advised the president against starting a development program for the hydrogen bomb.
In his later years at Harvard, Conant taught undergraduate courses on the history and philosophy of science, and wrote books explaining the scientific method to laymen. In 1953, he retired as President of Harvard University and became the United States High Commissioner for Germany, overseeing the restoration of German sovereignty after World War II, and then was Ambassador to West Germany until 1957.
On returning to the United States, Conant criticized the education system in ''The American High School Today'' (1959), ''Slums and Suburbs'' (1961), and ''The Education of American Teachers'' (1963). Between 1965 and 1969, Conant authored his autobiography, ''My Several Lives'' (1970). He became increasingly infirm, had a series of strokes in 1977, and died in a nursing home in Hanover, New Hampshire, the following year.
