In 1932 Hungarian scientist Leó Szilárd read H.G. Well's The World Set Free in which atomic bomb-like weapons were first described. Impressed by Well's story, Szilárd began to actively study nuclear reactions. In doing so, he was able to envision a device which could create a blast from a nuclear chain reaction. For several years the idea of an atomic bomb was largely ignored. Then in late January 1939, Niels Bohr, a Danish physicist, announced the discovery of nuclear fission. Several days later, American physicist J. Robert Oppenheimer was told of the discovery. He immediately realized that fission - the process by which the nucleus of an atom splits into smaller parts, resulting in a large release of energy - could be used to create controlled explosions much like the ones that Szilárd had suggested seven years earlier.

Through the summer and fall of that year, physicists in the U.S. and Europe continued to experiment with fission. An explosive device like the one that Oppenheimer and Szilárd had imagined was looking increasingly plausible. In October 1939 President Roosevelt received a letter from Szilárd and Albert Einstein warning of a German program to develop atomic energy. The physicists encouraged the president to begin a U.S. research program into nuclear weaponry. In response Roosevelt asked Lyman J. Briggs, the director of the National Bureau of Standards, to organize a committee to govern preliminary research. The Briggs Advisory Committee on Uranium consisted of a small group of scientists with a miniscule budget. Given the small work force, little progress was made in the U.S. during 1940. Scientists in the United Kingdom, however, had launched an effective program that led to the discovery of fast fission in Uranium-235.

In 1941, following the creation of the OSRD, the S-1 Uranium Committee was formed with Lyman Briggs as its director. Researchers from the U.S. and U.K. were brought in to begin work on a uranium-based bomb. It wasn't long, however, before the scope of the organization had pushed it beyond the committee limits. Worse than the administrative difficulties was the slow work pace. Vannevar Bush was becoming impatient. In order to increase project efficiency, Robert Oppenheimer was asked to conduct the program's complex neutron calculations. Despite his left-wing leanings and interest in radical politics, Oppenheimer agreed.