Lisa Meitner had recognized that extra neutrons could produce a chain reaction that would produce a very large amount of energy. In early 1939 physicists from many countries attempted to create such chain reactions by slowing down the released neutrons. Among these were Enrico Fermi and a Hungarian-born physicist Leó Szilárd. They saw signs that such a reaction had occurred.

In August 1939 Szilárd drafted a letter to President Franklin D. Roosevelt (1882-1945) that the German results could lead to in an extremely powerful new weapon. To give his letter more weight he convinced Einstein to sign the letter. It worked. Roosevelt directed the government to support fission research and created the Uranium Committee. While there were several important studies during the next three years, it was the British who made the breakthrough finding that the rare isotope uranium-235 could be used in a weapon. The Americans were informed but ignored the results until a personal visit by one of the British team members convinced the Uranium Committee of the need for action. The United States then established a new office that could authorize large-scale engineering projects.

In 1942 the “Manhattan Project” was started to produce nuclear weapons. It was named after the Manhattan Engineering District in New York City from which it was run. The chief was U.S. Army General Leslie Groves who appointed physicist J. Robert Oppenheimer (1904-1967) as scientific director. Its first success was at the University of Chicago where, in December 1942, Enrico Fermi’s uranium reactor created the first self-sustained nuclear chain reaction.

The British discovery that naturally occurring uranium, a mixture of uranium-238 and only 0.7% uranium-235, would have to be highly enriched in uranium-235 created a need for enrichment plants. One method chosen had been developed in California. Uranium metal would be evaporated in a vacuum. The atoms went through a narrow slit and then into a region with a strong magnetic field. Because of their mass difference the two isotopes followed slightly different paths. The atoms condensed on the surfaces of separate containers. Dozens of giant machines, called calutrons, were built in a plant in Oak Ridge, Tennessee, chosen because abundant electricity was available from the nearby hydroelectric plants. Not enough copper was available to wind the coils for the magnets so 70,000,000 pounds of silver bullion were borrowed from the U.S. Treasury to be formed into wires for the machines.

Somewhat enriched uranium from the calutrons was then combined with fluorine to produce the gas U₆. Because of the mass difference of the two isotopes ²³⁵U₆ would diffuse through porous membranes slightly faster (about 0.5%) than its more massive counterpart. Thousands of separations were needed to produce weapons-grade uranium (85 to 90% ²³⁵U). The plant at Oak Ridge built to accomplish this gaseous diffusion had an area of 2 million square feet, employed 12,000 workers, and cost the equivalent of $6.2 billion in 1999 dollars. At one time it consumed 17% of all the electricity produced in the United States—more than New York City!