Just as Pauling was entering into new contracts with the NDRC and increasing the team's manufacturing efficiency, a major shift occurred. On June 28, 1941, the Office of Scientific Research and Development (OSRD) was brought into being, effectively taking over the NDRC's position of authority. Pauling's work, though still associated with the NDRC, now operated under the OSRD umbrella.

The National Defense Research Committee had been, in large part, a success. It had funded research groups across the country, developed several specialized laboratories, and managed a nation-wide research program of unparalleled scope. Nevertheless, the Committee wasn't operating at maximum efficiency. The budget was limited by the holdings set aside for the Council of National Defense and, as a division of the Executive Office, had no means of raising additional funds. On June 28, 1941, only one year after the formation of the NDRC, President Roosevelt signed into being the Office of Scientific Research and Development. Unlike the NDRC, the OSRD was able to request funding directly from the Congressional Appropriations Committee, vastly increasing the potential budget. Furthermore, the OSRD enjoyed an unprecedented level of autonomy in the creation of independent contracts. For the first time, scientists had access to the sort of funding and flexibility traditionally available only to the corporate sectors.

Nonetheless, alongside the benefits of the OSRD came a long series of complications. Rather than being completely disbanded, the NDRC was subsumed by the OSRD. In its new role, the NDRC became an advisory body with the power to form research contracts of its own. As a result, it was often unclear just which researchers should serve under the OSRD and which should remain with the NDRC as advisers.

The bill that created the OSRD also brought into being the Committee on Medical Research (CMR), a subdivision of the OSRD parallel to the restructured NDRC. The CMR was designed to investigate biomedical problems that had the potential for military application. Over the course of the war, this included research into water deprivation, tropical diseases, cold weather survival, dietary needs, physical stress and, most significantly, antibiotics like penicillin. The organization was led by one representative each from the Army, the Navy, and the Public Health Services, as well as four private citizens, all of whom reported to Bush. Similar to the newly reformed NDRC, the CMR created and managed contracts under the authority and funding of the OSRD. Likewise, the CMR received information and advice from the National Research Council, a part of the National Academy of Science.