DISCLAIMER The following is a staff memorandum or other working document prepared for the members of the Advisory Committee on Human Radiation Experiments. It should not be construed as representing the final conclusions of fact or interpretation of the issues. All staff memoranda are subject to revision based on further information and analysis. For conclusions and recommendations of the Advisory Committee, readers are advised to consult the Final Report to be published in 1995. * * * * STAFF MEMORANDUM* * * * * TO: Members of the-Advisory Committee on Human Radiation Experiments FROM: Staff DATE: July 20, 1994 RE: Draft outline for a "functional" history of human radiation experiments, 1942-1954 The following is a working outline for a narrative history of human radiation experiments in the period 1942-1954 - organized according to-the purpose rather than the type of experiment and keyed to specific documents. Although informed by the evidence received to date, parts of the outline are necessarily speculative. Accordingly, it should be considered a "thought piece" for comment. Since institutions and the policy on informed consent evolved separately from, but roughly parallel to, the policy on human experiments, the "bureaucracy story" and the "consent story" are the subjects of separate accompanying staff memos. The Experiment Story 1942-1947 The series of human radiation experiments that were carried out in the period 1942-1947, under the sponsorship of the Army, were primarily aimed at finding out how radiation affected the people building the atomic bomb. The focus of concern was on the workers. The bomb builders faced two different types of hazards: external radiation from the materials being used in the bomb's manufacture and internal radiation from ingestion, injection, or inhalation of bomb materials. Concern with external radiation hazards became the impetus for the total body irradiation (TBI) experiments on human subjects conducted during the Second World War. Concern with internal radiation hazards inspired biodistribution experiments like the plutonium injections. Not surprisingly, the first materials used in the biodistribution experiments were the primary materials needed in the atomic bomb: polonium (used in the bomb's initiator), uranium (used in one type of bomb), and plutonium (used in the other type of bomb). By the time the Army turned over responsibility for the bomb project to the civilian AEC in early 1947, radiation experiments involving all three primary materials of the bomb had been carried out on human subjects, as injections or ingestions. A single inhalation experiment, involving a human subject and tracer amounts of zirconium, was conducted in the fall of 1945. 1 1947-1954 With the onset of the Cold War, the focus of concern with radiation shifted from the bomb workers to soldiers, and from materials in the weapon itself to fission by-products of a nuclear explosion. Accordingly, a new series of human radiation experiments were proposed, and tentatively approved by the interim leadership of the AEC, focusing on the hazards facing military personnel. These experiments included TBI exposures equivalent to the external radiation likely to be encountered by the crew of a nuclear-powered bomber to be developed by the Air Force's Nuclear Energy Propulsion for Aircraft (NEPA), as well as biodistribution experiments aimed at discovering the internal effects of fission products inhaled by infantrymen fighting on the Army's projected nuclear battlefield. Because of postwar objections to the Army's conduct of the wartime plutonium experiments, the civilian AEC decided to approach the subject of human experimentation more cautiously. In the fall of 1947, following an internal debate over human experiments, the AEC established a Division of Biology and Medicine (DBM) to oversee its sponsorship of future biomedical research, as well as an independent Advisory Committee on Biology and Medicine (ACBM) to serve as a watchdog over DBM. As a result of objections to human experimentation on the part of the leadership of both DBM and ACBM the large-scale, programmatic series of experiments originally inherited from the Army, and initially endorsed by the AEC, were indefinitely postponed.1 {1 Uncertain as to how the AEC's regulations of 30 April 1947 concerning consent might affect experiments at regional AEC facilities, an Oak Ridge official wrote ACBM in fall 1947 seeking guidance on questions of liability. See Memorandum to the Advisory Board on Medicine and Biology on 'Medical Policy" dated October 8, 1947 (Attachment 3).} Instead, the only biodistribution experiments known to have been carried out on human subjectsduring the period of internal AEC debate - in the spring and summer of 1947 - were isolated and apparently investigator rather than agency-initiated. These include a plutonium injection done in July 1947 under the interim guidelines concerning informed consent experiments and an americium injection in June 1947 that may have been done outside even the interim guidelines. Unclear lines of authority, and competing jurisdictions within the AEC, may also have meant that the Commission' s guidelines governing human experimentation were inconsistently applied in the approval process. By early-1949, DBM director Shields Warren and ACBM chairman Alan Gregg were denying permission for AEC-supplied isotopes to go to would-be grantees, on the grounds that some human experiments were "inadvisable."2 {2 However, researchers May have been able to circumvent Shields Warren and DBM by appealing directly to AEC's Isotopes Division, which was then actively promoting the medical use of radioactive isotopes. Thus, in January 1949, when Berkeley physician John Lawrence was denied permission by Shields Warren to use carbon-14 on human subjects, Lawrence apparently appealed the decision to the Human Applications subcommittee of the AECs Advisory Committee on Isotope Distribution. See Telegram from Warren to Lawrence, dated January 13 and letter dated January 22, 1949 (Attachment 4); and "Revised Tentative Minutes of March 13, 1949 Meeting..... (Attachment 5 at page 4). We do not know if this appeal was successful. By 1953, however, Lawrence was using carbon-14 in procedures involving human subjects at the county-run Laguna-Honda Home in San Francisco.} In July 1949, Shields Warren 2 admitted to "taking an increasingly dim view of human experimentation."3 {3 Letter from Shields Warren to Robert Stone dated July 11, 1949 (Attachment 6).} Yet, from the evidence, human experiments continued. A crucial battle was fought, and evidently won, by DBM and ACBM in 1949-50, when Warren and Gregg blocked repeated efforts by the Defense Department and the AEC's own Division of Military Application to initiate an extensive program of Total Body Irradiation (TBI) experiments, using healthy human subjects, related to the nuclear-powered airplane.4 {4 See Gil Whittemore's article, "A Crystal Ball in the Shadows of Nuremberg and Hiroshima," included in the briefing book for the July 5-6, 1994 meeting.} Since no evidence has yet surfaced in documents received by the Advisory Committee staff of human experiments in another area of particular interest to the military at this time-inhalation studies in connection with radiological warfare-it may be that Warren's and Gregg's efforts to discourage human biodistribution experiments had some success as well. In summary, it appears that by the late 1940's the issue of human experimentation was a government-wide concern. Once new AEC institutions were created to regulate radioisotope use, and AEC officials/advisors came to express doubt about human experimentation, the nature and scope of human experiments shifted. By late 1948, reasonably well-defined rules, procedures, and organizations were in place which theoretically allowed the AEC to monitor and oversee human experimentations involving Commission-produced isotopes or TBI. However, there were evident loopholes and inherent weaknesses in the oversight procedure. For example, TBI did not require isotope use and was not subject to the isotope distribution rules, yet was attractive to a military in search of answers to critical questions about combat effectiveness following atomic bomb blasts. In contrast to tracer experiments, moreover, TBI presented the opportunity for a physician-researcher under AEC contract to assert professional autonomy and declare a potential therapeutic benefit.5 {5 For example, UCSF radiologist Robert Stone, previously reprimanded by Shields Warren and Alan Gregg for questionable human experiments using TBI, countered that his decisions concerning the selection of patients and methods of treatment were his prerogative and could not be dictated by the AEC. See Letter from Robert Stone to Shields Warren dated July 26, 1948 (Attachment 7).} It may be significant, in this regard, that the Defense Department sponsored TBI at multiple locations in the 1950s, including Sloan-Kettering, Baylor, M.D. Anderson, and the University of Cincinnati. 3 In contrast to large-scale and programmatic research between 1942 and 1947, human radiation experiments conducted in the period 1947-1952 were apparently the result of proposals by individual and independent researchers who were, nonetheless, keenly aware of the AEC's and Defense Department's interest and priorities and who presumably tailored at least the description of their projects for that purpose. Researchers apparently used flaws in the system - including confusing lines of authority between competing agencies within the AEC, loopholes in the AEC's arrangement with contractors, and declarations of professional autonomy on the part of physician-researchers - to thwart the established approval process.6 {6 One early loophole, for example, allowed AEC contractors to "exercise their own initiative and be given an opportunity to devote part of their time to pursuing lines of research which appear fruitful to them..." See Letter from Carroll Wilson to Stafford Warren dated April 30, 1947 (Attachment 8). Another loophole seemed built in to the approval process. Logically enough, the members of the Human Applications subcommittee were those few individuals who at the time possessed knowledge about the experimental use of isotopes. For better or worse, this meant that the same group of individuals who had carried out human experiments for the Army during the war now advised the Civilian AEC on the same subject Finally, It is also possible that the definition given to the term "human experiment" itself provided a loophole Thus, NEPA researchers evidently defined experiments as procedures carried out on healthy human subjects. Under this definition, cancer patients receiving TBI exposures equivalent to those proposed in the NEPA program would not have been the subjects of an "experiment." See the ethics in Tab F.} 4