By the spring of 1942, Pauling's participation in the oxygen meter project had waned. With Arnold Beckman in charge of producing the instruments and Wood and Sturdivant managing most of the daily details, much of the earlier strain from that project was gone. Pauling had focused so much of his time and energy on the oxygen meter that, with the project off his hands, he found himself relatively unoccupied. Then, shortly after the bombing of Pearl Harbor and the subsequent U.S. declaration of war, a call went out through the ranks of the OSRD. As America's role in the war began to escalate in earnest, it was clear that soldiers were going to be sustaining injuries and would be in need of blood transfusions. The demand for blood would soon outstrip the available supply and the government was looking to scientists for help. As it so happened, Pauling had an idea.

In 1941 Linus Pauling had begun a limited program of study on bovine and human gamma-globulin, a project stemming from his interest in the manufacture of antibodies. Pauling initiated experimentation with the preparation of antisera - blood sera containing defensive antibodies - and in the process quickly became an authority on the chemistry of human blood and hemoglobin. This experience had given him insight into a potential method for creating a blood substitute. By April 1942 Pauling had submitted a contract proposal to the Committee on Medical Research. Entitled "The Chemical Treatment of Protein Solutions in the Attempt to Find a Substitute for Human Serum for Transfusions," the proposal outlined a plan to develop a gelatin-based substance which could be used as a plasma substitute. The project, if successful, would produce a synthetic material that would take the place of donated human blood plasma in transfusions, aiding Allied soldiers when America's peacetime blood reserves ran low.

The CMR accepted Pauling's proposal and within two weeks Pauling had assembled a group of researchers, including doctors Joseph B. Koepfli and Dan H. Campbell. After securing materials from Edward Cohn and other American-based scientists, the team was ready to begin.