It researched plutonium's chemistry and metallurgy, designed the world's first nuclear reactors to produce it, and developed chemical processes to separate it from other elements.

Scientists who worked there included Enrico Fermi, James Franck, Eugene Wigner, Glenn Seaborg and Leo Szilard.

When it became certain that nuclear reactors would involve radioactive materials on a gigantic scale, there was considerable concern about the health and safety aspects, and the study of the biological effects of radiation assumed greater importance.

[2] In August 1939, Szilard drafted a confidential letter to the President of the United States, Franklin D. Roosevelt, warning of the possibility of a German nuclear weapon project, and convinced his old friend and collaborator Albert Einstein to co-sign it.

[4] In April 1941, the National Defense Research Committee (NDRC), asked Arthur Compton, a Nobel-Prize-winning physics professor at the University of Chicago, to report on the uranium program.

[6] Emilio Segrè and Glenn Seaborg at the University of California produced 28 μg of plutonium in the 60-inch cyclotron there in May 1941, and found that it had 1.7 times the thermal neutron capture cross section of uranium-235.

[8] On 20 December, soon after the Japanese attack on Pearl Harbor that brought the United States into the war, Compton was placed in charge of the plutonium project.

[14] Other factors contributing to the decision were Chicago's central location and the availability of scientists, technicians and facilities in the Midwest that had not yet been taken away by war work.

[24] From 17 February 1943, Compton reported to the director of the Manhattan Project, Brigadier General Leslie R. Groves, Jr., instead of the OSRD S-1 Section.

The health group took space in the Anatomy Building, Drexel House, Billings Hospital and the Killis Laboratory and the administrative offices went into Eckhart Hall.

[27] Szilard later wrote that "the morale of the scientists could almost be plotted in a graph by counting the number of lights burning after dinner in the offices at Eckhart Hall.

[27] The University of Chicago made a 0.73-acre (0.30 ha) site occupied by tennis courts available to the Manhattan District on a one dollar lease, for the construction of a new chemistry building with 20,000 square feet (1,900 m2) of space.

Construction of facilities including laboratories and service buildings and an access road was commenced in September 1942 and completed in early 1943.

[25] Between 15 September and 15 November 1942, groups under Herbert L. Anderson and Walter Zinn constructed sixteen experimental reactors (known at the time as "piles") under the Stagg Field stands.

[33] Construction at Argonne fell behind schedule due to Stone & Webster's difficulty recruiting enough skilled workers and obtaining the required building materials.

[50] This included tests to investigate the properties of isotopes such as tritium and determine the neutron capture cross section of elements and compounds that might be used to construct future reactors, or occur in impurities.

[55] In early 1943, Wigner and his Theoretical Group that included Alvin Weinberg, Katharine Way, Leo Ohlinger, Gale Young and Edward Creutz produced a design for a production reactor with water cooling.

Cylindrical uranium slugs with aluminum jackets would be pushed through channels through the reactor and drop out the other side into a cooling pond.

[61] The fuel slugs were given a jacket of aluminum to protect the uranium metal from corrosion that would occur if it came into contact with the water, and to prevent the venting of gaseous radioactive fission products that might be formed when they were irradiated.

[62] The aluminum canning process was given close attention, as ruptured slugs could jam or damage the channels in the reactor, and the smallest holes could vent radioactive gases.

Edward Creutz investigated it and discovered that at the right temperature range, uranium could be hammered and rolled, and drawn into the rods required by the production reactor design.

Working with Alcoa and General Electric, the Metallurgical Laboratory devised a method of soldering the aluminum jacket to the uranium slug.

[66] Under pressure to identify a source of processed uranium, in April 1942 Compton, Spedding and Hilberry met with Edward Mallinckrodt at his chemical company's headquarters in St. Louis, Missouri.

When it became certain that nuclear reactors would involve radioactive materials on a gigantic scale, there was considerable concern about the health and safety aspects.

Robert S. Stone, who had worked with Ernest Lawrence at the University of California, was recruited to head the Metallurgical Project's health and safety program.

Simeon Cutler, a radiologist, assumed responsibility for radiation safety in Chicago, before moving on to head the program at the Hanford Site.

The project set a limit of 5 micrograms (μg) in the body, and work practices and workplaces at Chicago and Clinton were modified to ensure that this standard was met.

Much of the chemistry division moved to Oak Ridge in October 1943,[49] and many personnel were transferred to other Manhattan Project sites in 1944, particularly Hanford and Los Alamos.

[77] Where possible, the University of Chicago attempted to re-employ workers who had been transferred from the Metallurgical Laboratory to other projects once their work had ended.

Testing in 1977, 1978 and 1987 indicated residual levels of radioactivity that exceeded Department of Energy guidelines, so decontamination was carried out in 1988 and 1989, after which the site was declared suitable for unrestricted use.