DOE Openness: Human Radiation Experiments: Roadmap to the Project
Origins of the AEC Radioisotope Distribution Program in the Manhattan Project
Chapter 6: Origins of the AEC Radioisotope Distribution Program in the Manhattan ProjectThe medical importance of radioisotopes was recognized before World War II, but distribution was unregulated by government. The postwar program for distributing radioisotopes grew out of the part of the Manhattan Project that had developed the greatest technical expertise during the war: the Isotopes Division of the Research Division at Oak Ridge. Production of useful radioisotopes required extensive planning for both their physical creation and their chemical separation from other materials. Plans to distribute radioisotopes to medical researchers outside the Manhattan Project were developed in the final year of the Project.
In June 1946, the Manhattan Project publicly announced its program for distributing radioactive isotopes. The new world of radioisotope research was to be shared with all. Most research would be unclassified. An enthusiastic Science magazine reported: "Production of tracer and therapeutic radioisotopes has been heralded as one of the great peacetime contributions of the uranium chain- reacting pile. This use of the pile will unquestionably be rich in scientific, medical, and technological applications." An article in the New York Times Magazine told readers that "properly chosen atoms can become a powerful and highly selective weapon for the destruction of certain types of cancer." Until now, "the doctors and biologists have had to plea for samples of isotope material from their brothers in the cyclotron laboratories. . . . Now the picture has changed in a revolutionary way. The Government has adapted one of the Oak Ridge uranium piles to the mass production of radioactive 'by- product material.'"
Extensive planning led up to this public announcement. Although the initial expectations were that basic research would precede extensive medical applications, from the very beginning officials planned for "clinical investigation" with humans. In doing so, they recognized that the "administration to humans places extreme demands, both moral and legal, upon the specifications and timing of the radioisotope material supplied." The recognition of special moral and legal aspects of human experimentation and reliance on the professional competency of those administering radioisotopes formed the cornerstones of the radioisotope distribution system's oversight of experiments. Significantly, however, the system was not designed to oversee consent from subjects prior to the administration of radioisotopes.
Radioisotopes could not simply be ordered from the Manhattan Engineer District; each purchase had to be reviewed and approved. For human applications, each application was reviewed by a special group of experts: the Advisory Subcommittee on Human Applications of the Interim Advisory Committee on Isotope Distribution Policy of the Manhattan Project. According to one of the initial planners, "The chief reason for setting this group up as a separate entity from the Research group [another subcommittee] is that of medico- legal responsibility involved in the use or treatment of humans, experimentally or otherwise." (When the AEC began its work, this subcommittee continued but was renamed the "Subcommittee on Human Applications of the Committee on Isotope Distribution of the AEC." In 1959 it was absorbed into the "Advisory Committee on Medical Uses of Isotopes." In 1974, the AEC's responsibilities were transferred to the Nuclear Regulatory Commission.) Coupled with this review was a requirement that those wishing to purchase radioisotopes demonstrate the special competence required for working with radioactive materials. This mechanism for centralized, nationwide review was unusual at the time it was begun.
The breadth of the subcommittee's purview can be seen in the range of proposals examined. Although the Advisory Committee is concerned primarily with medical research, the AEC subcommittee review extended well beyond this realm. Apparently, the subcommittee reviewed all proposed uses for radioisotopes that might result in the exposure of humans to radiation. These included, for example, using cobalt 60 in nails in wooden survey stakes (probably to assist in later locating them), sulfur 35 in firing underground coal mines, and yttrium 90 as a tracer in gasoline in simulated airplane crashes. (Its jurisdiction was limited to by-product material, however, and did not extend to fissionable materials such as plutonium and uranium.)
Soon after the Manhattan Project's public announcement, both the radioisotope distribution system and its oversight structure began operation. On June 28, 1946, the Subcommittee on Human Applications held its first meeting. Attending as members were Dr. Andrew Dowdy, chairman, and biophysicist Gioacchino Failla. Dowdy was director of the University of Rochester's Manhattan Project division, while Failla was a professor at Columbia University and consultant to the Metallurgical Laboratory in Chicago. Not attending was the third member of the subcommittee, Dr. Hymer Friedell, executive officer of the Manhattan Project's Medical Section. Attending as nonvoting secretary was Paul Aebersold, in charge of the production of radioisotopes at Oak Ridge (later to head the AEC's Isotopes Division). His efforts to promote the use of radioisotopes later earned him the nickname "Mr. Isotope." Also attending as advisers from Oak Ridge were W. E. Cohn, the author of the original memorandum proposing a system for distributing radioisotopes, and Karl Morgan, director of Health Physics at Oak Ridge, who would, over the years, become a leading figure in the establishment of occupational exposure limits for radioisotopes.
Although the primary task of the subcommittee was to oversee safety, at the time, many expected a shortage of radioisotopes. Thus, much of this first meeting was taken up with a discussion of priorities for allocation. (As it happened, supply exceeded demand within one year.) It was in the context of this discussion of allocation, not a discussion of safety or ethics, that a system of local committees was suggested. Each local committee (also called "local isotope committee" at this meeting) would include "(a) a physician well versed in the physiology and pathology of the blood forming organs; (b) a physician well versed in metabolism and metabolic disorders; (c) a competent biophysicist, radiologist, or radiation physiologist qualified in the techniques of radioisotopes." The main advantages of a system of local committees were administrative efficiency and delegation of prioritization for scarce isotopes. The primary functions of each local isotope committee were coordination, allocation, and safety. Evidently no mention was made of overseeing subject consent.
At this first meeting, the subcommittee had before it no actual requests to evaluate. Even so, members did agree on the general principles on which they would deny a request:
a. The requestors are not sufficiently qualified to guarantee a safe and trustworthy investigation.
There was no elaboration of crucial terms such as qualified, safe and trustworthy, insufficient knowledge, and safe application. Although no standards of adequate consent were mentioned, this degree of oversight was unusual in medical research during this time and even later.
Although it had no specific requests before it, the subcommittee did consider the anticipated uses of some isotopes. The uses of some isotopes were apparently rejected, not only because of the hazards of radiation, but also because of chemical toxicity and the availability of less-hazardous alternatives. For others, specific limits were set. For example, the subcommittee was especially cautious concerning isotopes of strontium because it concentrated in bone, as did radium, which was known to be hazardous from the prewar experience of the dial painters. The subcommittee set a specific exposure limit: "the Sr 90 (and Y 90 daughter) should not contribute in excess of 1% to the total rate of beta disintegration."
Such general guidelines have little effect unless a procedure is established for their implementation. At its first meeting, the subcommittee set out in detail the mechanism for its own future operation. What the subcommittee would be reviewing were requests to purchase isotopes for any use in human beings. Only after the subcommittee approved a request would the isotope be sold and shipped to the researcher. The need for speed in responding to requests for human uses was recognized.
Details of the procedure for purchasing isotopes were disseminated to potential users through a brochure issued in October 1946 by the Isotopes Branch at Oak Ridge. Most of the brochure concerned the paperwork, which, among other things, ensured that the Subcommittee on Human Applications would actually be notified of all applications for human use.
The last stage of the purchase procedure indicates the underlying concern with legal liability. Although Manhattan Project approval was required, the actual purchase was from the private contractor-operator of the Clinton Laboratories (later designated the Oak Ridge National Laboratory) in Oak Ridge, at that time Monsanto Chemical Company. The final purchase agreement contained a clause relieving both the government and the private contractor from any responsibility for "injury to persons or other living material or for any damage to property in the handling or application of this material. . . ." The Manhattan Project also required the purchaser to file with the Isotopes Office a statement required by section 505(i) of the Federal Food, Drug, and Cosmetic Act. However, the Advisory Committee found no evidence of direct involvement by the FDA at that time in the planning or operation of the radioisotope distribution program.
By October 1946, the distribution program was well under way: 217 requests had been received. Of these, 211 had been approved. Human use requests totaled 94, of which 90 had been approved.