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: Advisory Committee Staff DATE: July 19, 1994 RE: Draft Outline for the Early History of Government Regulation and Control of Human Radiation Experiments, 1942-1951 This memorandum is a draft outline of the development of the regulatory structure in which decisionmaking on human radiation experiments was set. The outline takes the story through the early 1950's, and focuses on the Defense Department (DOD) and the Atomic Energy Commission (AEC). As will be seen, important questions regarding these agencies remain to be answered. Eventually, the Veterans Administration and Health and Human Services (HHS) predecessor agencies must be sketched into the picture as well. 1942-1947: Manhattan Project and Early AEC As the Manhattan Project evolved into the AEC,1{1 A portion of the Manhattan Project became the Armed Forces Special Weapons Project, precursor to today's DOD Defense Nuclear Agency.} a new set of institutions was created to award funding for biomedical research and to regulate the distribution of isotopes. These institutions dealt with such issues as who would be responsible for the new research tool (radioisotopes) and what rules would govern isotope allocation. The fragmentary documentation available to the Committee at present indicates that, in the nascent AEC, these themes were addressed continually, at multiple levels. In mid-1946 the Manhattan Project created a Committee on Isotope Distribution Policy, with subcommittees on Allocation and Distribution and on Human Applications. The June 1946 initial meetings focused on setting priorities for allocation based on the potential therapeutic uses of particular isotopes, with a recognition that animal experimentation should precede human use. (Attachment 9 at pages 8-9) The minutes show the delegation of administration to research institutions, who would form local committees "to pass upon all isotope requests originating from their institution."2 {2 Because of limited documentation, the scope of the isotope regulation remains unclear. For example, did it include institutions with the capability to produce their own isotopes? An October 5, 1949 memorandum from Paul C. Aebersold, Chief of the AEC Isotopes Division to A.H. Holland, Director of Research and Medicine on "Use of Radioisotopes in Human Subjects" records: "Dr. Warren instructed that such allocation would be made by the Isotopes Division only after review and approval by the Subcommittee on Human Applications of the Committee on Isotope Distribution. It should be emphasized that the instruction applies even though the radiomaterial is produced in the laboratory where it is to be used." (Attachment 10; emphasis added.)} (Attachment 9 at page 11) The Subcommittee, in turn, would be required to pass upon all requests "before allocation can be effected."3 {3 However, earlier in the minutes, (Attachment 9 at page 7) there is the statement that "[t]he Sub-Committee on Human Applications will not...have to decide priorities on individual cases and uses. Once the overall allocation is made to the institution the local isotope committee governs the applications."} (Attachment 9 at page 10) 1 The Committee on Isotope Distribution created by the Army became the Advisory Committee on Isotope Distribution under the AEC. The four-member Advisory Committee included those involved in Manhattan-era human experimentation. In the fall of 1947, the AEC established both a Division of Biology and Medicine (DBM) to oversee biomedical research and an Advisory Committee on Biology and Medicine (ACBM) to monitor the DBM. It is not yet clear what formal authority the Advisory Committee had vis-a-vis the DBM. Similarly, it is not clear what role and authority the DBM groups had in relation to the Isotope Distribution Branch's decisions on isotope allocation. In September and October 1947 memoranda (Attachments 11 and 3, respectively) Oak Ridge called on the AEC "Advisory Board on Medicine and Biology"4{4 We presume this referred to the ACBM.} for guidance. In these memoranda, Oak Ridge asked if it could initiate "fundamental" and "programmatic" research with universities?5 (5 While the memoranda did not address it, Oak Ridge was simultaneously entering into a Memorandum of Understanding for work with the Public Health Service.} If so, what would be the ground rules governing responsibility for the human administration of isotopes? The Oak Ridge memoranda laid out a rich picture of the institutional imperatives which drove an AEC policy on human experimentation. The October 8, 1947 Oak Ridge memorandum explained that the "question [of AEC responsibility] can be subdivided into two phases: (1) When the materials are administered by private physicians and institutions outside the Project and (2) when given by physicians and researchers within the Project. This latter category includes contractors' personnel employing Atomic Energy Commission funds (indirectly) to perform tracer research, some of which is of no immediate therapeutic value to the patient. It therefore becomes desirable to establish acceptable medico-legal criteria for future human tracer research." (Attachment 3 at page 3) Following a review of the pros and cons of human experimentation,6 {6 The initial advantage was "[t]racer research is fundamental to toxicity studies." The initial drawback was "[m]oral, ethical, and medico-legal objections to the administration of radioactive materials without the patient's knowledge or consent." (Attachment 3 at page 4)} the October 8, 1947 memorandum addressed the questions of public image and potential legal liability that attended public disclosure of research. The memorandum (at page 8) indicates that the AEC's Insurance Branch, as well as its Biology and Medicine Division, had a key role to play in biomedical research: 2 Declassification of medical and biological documents has become a considerable task. All researchers are anxious to have their work appear in the journals as soon as possible.... [T]here are a large number of papers which do not violate security, but do c ause considerable concern to the Atomic Energy Commission Insurance Branch and may well compromise the public prestige and best interests of the Commission. Papers referring to the levels of soil and water contamination surrounding Atomic Energy Commission installations, idle speculation on the future genetic effects of radiation and papers dealing with potential process hazards to employees are definitely prejudicial to the best interests of the government. Every such release is reflected in an increase in insurance claims, increased difficulty in labor relations and adverse public sentiment. Following consultation with the Atomic Energy Commission Insurance Branch, the following declassification criteria appears (sic) desirable. If specific locations or activities of the Atomic Energy Commission and/or its contractors are closely associated with statements and information which would invite or tend to encourage claims against the Atomic Energy Commission or its contractors, such portions of articles to be published should be reworded or deleted. The effective establishment of this policy necessitates review by the Atomic Energy Commission Insurance Branch, as well as by the Medical Division, prior to declassification. In sum, at its creation, the AEC had multiple institutions with some role in shaping policy for oversight/regulation of human experimentation: the Division of Biology and Medicine (and its Advisory Committee on Biology and Medicine), the Isotope Distribution Committee (and its Subcommittees), the Insurance Branch, and top AEC management (e.g., General Manager Wilson). The issue of the ethics of human experimentation was, in this context, intertwined with issues of resource allocation, scientific and legal risk, and the division of responsibility in a developing bureaucracy. The precise role and responsibilities of these institutions remain to be discovered. Many questions remain. For example: (l) What was the relation of the informed consent policy stated by General Manager Wilson in November 1947 7 {7 The policy is referenced in a 1951 letter from Shields Warren to Leslie Redman which appears as Attachment L to Tab L of Briefing Book No. 4.} (concerning what might be as interpreted as "therapeutic or at least "clinical" research) to the terms on which the Isotope 3 Distribution Committee reviewed proposals?8 {8 As discussed in more detail in the accompanying Staff Memorandum on the History of Ethics Policies at this Tab, the March 1949 minutes of the Subcommittee on Human Applications provided that, in "instances in which the disease from which a patient is suffering permits the administration of larger doses for investigative purposes.... Applications for such use of radioisotopes will be given special consideration...providing...[t]he subject has given his consent to the procedure." (See Attachment 1, pages 5- 6)} (2) Did the Isotope Distribution Committee review all proposals, or did it delegate responsibility for individual experiments to AEC laboratory and/or university/industrial contractor level review committees? (3) What formal review and/or approval role did the Advisory Committee on Biology and Medicine have? (4) Who regulated experimentation involving external radiation and how did the rules compare to those governing isotope use? (5) What role did the Insurance Branch have? 1947-early 1950's: AEC and DOD Engage As discussed further in the accompanying staff memorandum on "functional" history at this Tab, in the late 1940's, DOD, the AEC, and their civilian investigators were engaged in continued discussion over potential programs involving military personnel's physical tolerance for radiation. Parallel with the development of the AEC's Division of Biology and Medicine and its Committees, the new Defense Department developed groups or committees at the level of the Office of the Secretary of Defense (OSD) which also addressed questions of human experimentation. In 1949 the Joint Panel on the Medical Aspects of Atomic Warfare was created to oversee atomic warfare-related research on a DOD-wide basis. (The group's charter and further materials were included in the first subpart of Tab O in Briefing Book No. 4). The Joint Panel documents show that the Joint Panel included leading civilian investigators and associate member(s) from the Public Health Service, and that it engaged in routine liaison with the AEC as well. The documents also show that, at the level of the Joint Panel, and in exchanges between the OSD and the AEC groups, military-related human experimentation was a continued subject of discussion. In November 1950, for example, the ACBM of the AEC met with representatives of the Armed Forces Surgeons General. The questions presented included "permissible exposure data if and when nuclear energy is used to provide the power in submarines and other ships." (Attachment 12 at page 1) General Cooney " presented the Army viewpoint by stating the great discrepancy among recognized authorities on permissible dosages." (Attachment 12 at page 2) The Army therefore "proposed human experimentation on a group of 200 service volunteers to determine the effects of operational effectiveness to dosages of total body irradiation within presumably low safe zones." 4 (Attachment 12 at page 2) The ACBM, however, "felt that human experimentation was not justified and that sufficient information could be obtained from animal experimentation and interpolation from clinical data." (Attachment 12 at page 2) The minutes of the DOD Joint Panel show that the AEC proceeded to convene a panel, which opined that the questions raised by the military could, indeed, be addressed in the absence of human experimentation.(See Attachment 13, a January 1951 letter attached to the minutes of the seventh meeting of the Joint Panel.) The issues involved in military-related experimentation were likely addressed by other groups, in addition to the DOD Joint Panel and the AEC groups, but documentation on their role has yet to be obtained.9 {9 For example, a document obtained by Advisory Committee Staff from the National Archives shows that in 1950 the Navy sat on the following groups, in addition to the Joint Panel: a) An Office of the Secretary of Defense "Task Group on Medical Aspects of Atomic Energy"; b) A Joint AEC/DOD "Panel on Biological and Medical Aspects of Radiological Warfare"; c) An Armed Forces Special Weapons Project Panel on Radiological Instruments; and d) two National Research Council panels (on radiology and on atomic casualties).} Moreover, documents indicate that the individuals who played primary roles in the AEC and DOD panels and advisory groups also played important roles in counterpart PHS radiation groups. For example, several well-known doctors and researchers including Dr. Joseph Aub, Dr. Hymer Friedell, and Dr. H.L. Andrews sat on the DOD joint panel and pertinent NIH study sections. Dr. Aub also served as a member of the National Cancer Advisory Council in the early to mid 1950s. Dr. Joseph Hamilton chaired the Radiobiology Study Section for NIH from 1946-1949. Here, again, the data needed to establish whether, to what extent and in what respects there was a relationship between military experiments and the PHS remain to be discovered. Conclusion Bureaucratic and regulatory history is a key to understanding whether and how the ethics codes enunciated by high level officials (e.g., the AEC General Manager or the Secretary of Defense) percolated down to the level of investigators, as well as the extent to which such codes were obeyed or enforced. Within and among agencies, multiple institutions were involved (albeit the individuals involved often wore more than one hat). Depending on their mission, these institutions (or individuals) may have addressed ethics questions obliquely, through the door of legal liability, more directly, through the door of health and safety, or, straight on as a matter of "ethics." Finally, while the story of these institutions remains to be fleshed out, it already seems clear that it is a story that is more relevant to the understanding of today's world than might have been suspected. At its creation, the AEC not only had a review group to consider "human uses," but this review group, in turn, empaneled local review committees at individual research organizations. The question of the relationship between Federal agency branches and local grantees (and, indeed, the relationship between the Isotope Division and the rest of 5 the AEC) has clear contemporary overtones. Similarly, in 1947, fear of private litigants or bad press (as distinct from considerations of national security) motivated the development of rules on secrecy and experimentation; this also has a contemporary ring. Finally, as discussed more fully in the accompanying staff memorandum outlining the "functional" history, it appears that, in 1947, no less than today, officials and investigators may have sought to take advantage of differing regulators and rules in order to do in one way or place what could only be done with difficulty in another. 6