The uranium extraction process helped make it possible for the Manhattan Project to build the first atomic bombs.

At Gomberg's suggestion, Spedding applied to the University of California, Berkeley, to study for his doctorate under Gilbert N. Lewis.

[3] Under Lewis's supervision, Spedding earned his Doctor of Philosophy (Ph.D.) in 1929,[4] writing his thesis on "Line absorption spectra in solids at low temperatures in the visible and ultraviolet regions of the spectrum".

[5] Spedding's graduation coincided with the onset of the Great Depression, and jobs became hard to find.

His benefactor was Herbert Newby McCoy, a retired chemistry professor from the University of Chicago, who had obtained a supply of these elements from the Lindsay Light and Chemical Company, where they were a byproduct of thorium production.

[13] When Spedding returned to the United States in 1935, the country was still in the grip of the Great Depression, and the job market had not improved.

[14][15] At one point he drove out to Ohio State University hoping to find a tenure track position.

"[15] Spedding took up the position as assistant professor and head of the department of physical chemistry at Iowa State College in 1937.

[4] By February 1942, the United States had entered World War II, and the Manhattan Project was building up.

[16] For advice on assembling the laboratory's Chemistry Division, Compton, a physicist, turned to Herbert McCoy,[17] who had considerable experience with isotopes and radioactive elements.

McCoy recommended Spedding as an expert on the rare earth elements, which were chemically similar to the actinide series that included uranium and plutonium.

[19] Due to lack of space at the University of Chicago, Spedding proposed to organise part of the Chemistry Division at Iowa State College in Ames, where he had colleagues who were willing to help.

[20] The first problem on the agenda was to find uranium for the nuclear reactor that Enrico Fermi was proposing to build.

Edward Creutz, the head of the group responsible for fabricating the uranium, wanted a metal sphere the size of an orange for his experiments.

Scaling this process up for industrial production was a dangerous proposition; ether was explosive, and a factory using large quantities was likely to blow up or burn down.

Spedding went over the details with Mallinckrodt's chemical engineers, Henry V. Farr and John R. Ruhoff, on 17 April 1942.

They were able to reproduce Goggin's results in August 1942, and by September, the Ames Project had produced a 4.980-kilogram (10.98 lb) ingot.

Fears that world supplies of uranium were limited led to experiments with thorium, which could be irradiated to produce fissile uranium-233.

[30] Spedding was "universally acknowledged as one of the world’s foremost experts on the identification and separation of rare earths".

[31][32] He later used ion exchange to separate isotopes of individual elements, including hundreds of grams of almost pure nitrogen-15.

[6] He received the William H. Nichols Award from the American Chemical Society in 1952, the James Douglas Gold Medal from the American Institute of Mining, Metallurgical, and Petroleum Engineers in 1961 and the Francis J. Clamer Medal from the Franklin Institute in 1969.