Just as the most basic political relationships between agency, Congress, and interest groups had to be constructed after the AEC's inception, health and safety regulation – usually sharply demarcated from development – was also constructed within the AEC. Contemporaries were quick to point out the unusual nature of this arrangement. But few challenged self-regulation in the early years. National security is the factor most commonly cited. One need look no farther than today's Department of Energy and the degree to which it continues to regulate its own weapons production plants to recognize how influential national security can be in distorting traditional patterns of oversight and review. Expertise and the way it was organized, however, were also central to the political evolution of safety review as it related to the development of commercial nuclear power.

Because nuclear power was not far removed from the laboratory, only a handful of experts understood the complexities of nuclear power: those who designed reactors were also the leading authorities on their safety. The AEC's initial approach to safety was modeled on the Manhattan Project's techniques. There, reactor designers were nothing less than jacks of all trades. As Enrico Fermi's assistant noted, Fermi “eagerly participated in constructing the ‘piles,’ in making measurements, in repairing instruments, etc.” Fermi was also in charge of safety. He was prophetic about the nature of reactor problems. After a lengthy brainstorming session with his assistants and Du Pont one day, Fermi was asked which of the many problems discussed might prove most troublesome.