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. TAB F-2 DRAFT - FOR DISCUSSION PURPOSES ONLY MEMORANDUM TO: Members of the Advisory Committee on Human Radiation Experiments FROM: Advisory Committee Staff DATE: January 18, 1995 RE: Application of Department of Defense (DOD) policies regarding research involving human subjects. The unifying theme of this memorandum is the "reach" of DOD research ethics policies as stipulated in the Wilson Memorandum 1 [ February 26, 1953. Memorandum from the Secretary of Defense Wilson to the Secretaries of the Army, Navy, and Air Force.] beyond human experiments on atomic, biological and chemical warfare (ABC), to experiments with multiple purposes, contractors, experiments not related to ABC warfare, and the uses of radioisotopes for diagnosis and treatment. 1. EXAMPLES OF ATOMIC, BIOLOGICAL, AND CHEMICAL WARFARE EXPERIMENTS TO WHICH THE 1953 WILSON MEMORANDUM APPLIED At the December meeting the Advisory Committee asked staff to identify DOD-sponsored human radiation experiments to which the 1953 Wilson Memorandum unambiguously should have applied. One category of such experiments would be Army, Navy, Air Force, and Defense Nuclear Agency (DNA) human experiments conducted in connection with atomic bomb tests and bomb test simulations. As presently understood, these included: a. Flashblindness experiments sponsored by the Air Force 2 [ The Atomic Energy Commission was in general jointly responsible with the DOD for nuclear weapons tests. The precise relationship of the AEC to human experimentation is a project of staff inquiry.]; b. Crawling over contaminated ground, sponsored by the Army and Navy; c. Riding in tanks through contaminated areas apparently sponsored by the Army; 1 d. Psychological and physiological testing of soldiers put in place at bomb sites, sponsored by the Army; e. Measurement of radiation to which humans would be exposed, using atomic cloud flythroughs, sponsored by the Air Force; f. The probable use of humans to test protective equipment, Army sponsored; g. The use of humans for "decontamination" testing, e.g. hand measurements of radiation on plane fuselage, Air Force sponsored; h. Sampling of radioactive isotopes in human body fluids to measure bomb test exposure, Army and probably other service sponsored; and i. Possible civil-defense related experiments at "bomb tests." A second category would be "laboratory" research with "atomic warfare" related purposes. One possible example of this research is burn testing, probably sponsored by a number of services. Assuming that multipurpose research should be interpreted as having been covered by the Wilson Memorandum, as urged in 2. below, then TBI and psychological testing of cancer patients would be other examples. 2. MULTIPURPOSE EXPERIMENTS At the December meeting, the Committee asked staff to consider whether or not the DOD policy stated in the 1953 Wilson Memorandum (Nuremberg Code) was applicable to experiments that were intended to address questions related to ABC warfare but that also addressed other research questions, (so-called "multiple purpose research," for example, the development of data regarding atomic bomb effects and the development of data on cancer diagnosis or treatment). Two examples of research that had multiple purposes in the relevant sense are the total body irradiation (TBI) studies conducted at the University of Cincinnati and the psychological studies of patients undergoing radiation treatment at the M.D. Anderson Cancer Center in Houston (done in conjunction with the School of Aviation Medicine). Evidence that such research (with multiple purposes) was intended to be excluded from the Wilson Memorandum might be expected to appear in the policy memoranda themselves, in documents executing the policies, in experiment proposals or approvals, or in interviews with medical scientists who were active at that time. Staff has found no indication that the 1953 policy was not intended to apply to DOD sponsored research with multiple purposes in any of these possible sources. Lacking evidence to the contrary, staff is prepared to conclude that experiments with multiple purposes were included within the reach of the 1953 policy. 2 3. CONTRACTORS The Advisory Committee has already agreed that, at least in the case of the Army, the "reach" of the Wilson policy extended to contractors, whenever contractors were conducting research that otherwise was covered by the policy. This judgment was originally supported by the Army Secretary's memorandum following the issuance of the Wilson memorandum in which it is explicitly stated that special care shall be taken to ensure that the policy applies to contractors.3 [November 5, 1953. Memorandum for the Chief of Staff, "Use of Volunteers in Research."] Staff can now provide further powerful evidence that this was the case for the Department of the Army. In a 1962 memorandum, 4[July 10, 1962. Memorandum for the Record from Donald L. Howie, Assistant Chief, Medical Research, regarding the "Use of Volunteers for Army Medical Research."] an Army official recorded that Army research -- including that done by contractors -- had been governed by the principles stated in the Nuremberg Code, as recast in the Wilson Memorandum and a 1954 Army Office of the Surgeon General memorandum. The 1962 Army memorandum stated: 1. Volunteers have been used by in-service and contract investigators for a great variety of research projects, since WWII. By and large research has been conducted in strict accordance with the Nuremberg Code of 10 rules drawn up following the Nuremberg trials. . . . 4. The Army, specifically, has conducted both in-service and contract research involving the use of volunteers under rules which have been derived from the Nuremberg Code, the Army Organizational Act of 1950 (Sect 101) and Chief of Staff Memorandum 385, 30 June 1953. On March 12, 1954, principles, policies and rules of the Office of the Surgeon General "Use of Human Volunteers in Medical Research" was published based on the foregoing. This has been the basic guide which has been followed since its publication. . . .5 [July 10, 1962. Memorandum for the Record by Donald L. Howie, Assistant Chief, Medical Research, regarding the "Use of Volunteers for Army Medical Research."] The 1962 memorandum cites a 1960 survey of 21 active contracts involving the participation of "approximately 3000 students, 250 patients, and 300 prisoners" in which the March 12, 1954 Surgeon General directive is said to have been used as a "guide." The 3 memorandum also discusses the problem of conveying and implementing instructions to contractors. 6[July 10, 1962. Memorandum for the Record by Donald L. Howie, Assistant Chief, Medical Research, regarding the "Use of Volunteers for Army Medical Research."] We have recently discovered a document that appears to be the March 1954 Army Surgeon General's policy. The preface of the document states: "To be used as far as applicable as a non-mandatory guide for planning and conducting contract research."7 [March 12, 1954. "Use of Human Volunteers in Medical Research, Principles, Policies, and Rules of the Office of the Surgeon General." Document found in the files of John Enders, Ph.D., Nobel Laureate in Medicine and Physiology in 1954, Yale University; in Yale University archives.] Thus, it is increasingly clear that the 1953 policy was intended to guide contract, as well as in-house research.8 [That this policy was applied to contractors appears evident from an exchange between the Armed Forces Epidemiological Board and a researcher at Tulane University. June 27, 1956, letter from John Fox, M.D., to Captain R.W. Babione, AFEB.] 4. APPLICATION OF POLICIES TO NON-ABC EXPERIMENTS THROUGHOUT THE DOD There is strong evidence that the 1954 Army Surgeon General guidance cited in 3. above was intended to apply to human experiments in areas other than atomic, biological, and chemical warfare. First, the 1954 guidance does not state that it is limited to ABC research. If, as appears to have been the case, the Wilson Memorandum itself was not transmitted, the possible limitation would not have been evident. Second, the 1960 survey, quoted in 3. above, further suggests the broad application of the 1954 memorandum and reports 21 active contracts involving the participation of "approximately 3000 students, 250 patients, and 300 prisoners;" it seems unlikely that all of these subjects were engaged as participants in ABC research. Third, in a June 27, 1956 letter to the Armed Forces Epidemiological Board (AFEB), 9 [June 27, 1956, letter from John Fox, M.D., to Captain R.W. Babione, AFEB.] a Tulane University public health researcher acknowledges that his vaccine experiments will comply with the Surgeon General's rules for the use of human volunteers. The AFEB served the medical departments of the three services for preventive medicine advice and for the conduct of investigations. Although the Administrative position of Executive Secretary of the Board rotated among the services, and at this time was occupied by a Navy colonel, the Army Surgeon General was the Executive Agent. As such, all AFEB contracts were funded and managed under Army regulations. The Tulane researcher indicated that with respect to his research: "I have held it up since Dr. Dingle indicated I be familiar with the statement of the Office of the Surgeon General re the use of human volunteers. . . . I have read it and believe that our past and future work have 4 [sic] and will comply with the rules stipulated."10 [June 27, 1956, letter from John Fox, M.D., to Captain R.W. Babione, AFEB.] Thus it begins to appear as early as 1954 that the Army and the AFEB had a uniform policy based on the Nuremberg Code for at least "non-therapeutic" experimentation on what were called "human volunteers." On a related point, the July 10, 1962 "memorandum for the record" mentioned in 3. above (by the Army's Assistant Chief for Medical Research), describes a file of correspondence relating to the formation of the Surgeon General's 1954 policy, including a statement by the AFEB executive secretary that this policy created a "mandatory requirement for projects in classified areas requiring approval of the Secretary of the Army, but a guide for other types of research." 11 [July 10, 1962. Memorandum for the Record by Donald L. Howie, Assistant Chief, Medical Research, regarding the "Use of Volunteers for Army Medical Research."] Interestingly, the Wilson policy on ABC research makes no such distinction between classified and non-classified work. 5. NAVY POLICY ON RESEARCH INVOLVING RADIOISOTOPES "MEDICAL DIAGNOSIS AND TREATMENT": POLICIES FOR SO-CALLED "THERAPEUTIC RESEARCH" Several documents in the possession of the Advisory Committee show that in 1951 there was concern in the Navy about "medico-legal problems arising from the use of radioactive isotopes in Naval medical installations." 12 [Dement, D.E., Chief Bureau of Medicine and Surgery "Memorandum to Commanding Officer U.S. Naval Hospital, San Diego, California, Re: Radioactive Isotopes Program; request for comments and recommendations, August 27, 1951."] In response to this concern the Navy developed a policy, dated October 18, 1951, that included a form to be signed by the patient or next of kin, and a form to be executed by the local "Isotope Committee" that would direct the laboratory staff to administer the dosage. A legal analysis noted that a signed statement: constitutes evidence, if properly completed, that the patient was aware of and accepted any possible risks involved whether because of the modernity of the treatment 5 or because of other circumstances such as the patients own condition (provided the patient knows the facts).13 [October 18, 1951. Memorandum from Loren B. Poush, Code 11 to Code 74, BUMED, regarding the "Legal comments relative to proposed means of proper authorization and safeguard in use of Radioisotopes."] This policy appears to apply to all uses of radioisotopes, including research and diagnostic or therapeutic. No similar policy has been found for the other uniformed services. Of special interest is the fact that this "consent" policy was directed at the use of isotopes in "diagnosis and treatment." So far, this is the only example of DOD policy in any department before the 1960s that refers to what we would today call "therapeutic research," or research intended to provide a prospect of medical benefit to the patient-subject. Indeed, the Army's 1962 regulation (AR 70-25) governing human experimentation that replaced the 1954 Surgeon General's guidance specifically excluded therapeutic research from the reach of the principles outlined in the 1953 Wilson Memorandum. 6. THE 1962 ARMY REGULATIONS: CODIFICATION OF EXISTING PRINCIPLES In 1962 the Army issued Army Regulation No. 70-25: Use of Volunteers as Subjects of Research which described requirements for informed consent of volunteer research subjects. The coverage of the regulation includes: the use of volunteers as subjects in Department of the Army research, including research in nuclear, biological, and chemical warfare, wherein human beings are deliberately exposed to unusual or potentially hazardous conditions. The text of the regulation, at "3" provides three "exemptions" to the regulation: a. Research and nonresearch programs, tasks, and tests which may involve inherent occupational hazards to health or exposure of personnel to potentially hazardous situations encountered as part of training or other normal duties, e.g., flight training, jump training, marksmanship training, ranger training, fire drills, gas drills, and handling of explosives. b. That portion of human factors research, which involves normal training or other military duties as part of an experiment, wherein disclosure of experimental conditions to participating personnel would reveal the artificial nature of such conditions and defeat the purpose of the investigation. 6 c. Ethical medical and clinical investigations involving the basic disease process or new treatment procedures conducted by the Army Medical Service for the benefit of patients." In a "Draft" Army document (the status of which remains unclear) regarding the implementation of AR 70-25, the exemptions are further explained including the following:14 [Undated. Draft Memorandum "Implementation of Army Regulation 70-25, March 26, 1962, 'Use of Volunteers as Subjects of Research."] 3.b. Exemptions: . . . Paragraph 3c applies not only to research conducted on patients where medical and clinical investigations may be expected to be of direct benefit, but also to research utilizing normal subjects, where benefit to actual or potential patients may be reasonably expected, providing no 'unusual or potentially hazardous conditions,' as defined in paragraphs 1 and 2, AR 70-25, exist or a re anticipated. . . . (7) The use of radioisotope tracers in accordance with AEC regulations is not considered unusual or hazardous, as such. However, all investigations involving radioisotope tracers must be in conformity with existing AEC and Army regulations. The 1962 regulations appear to exempt research involving occupational exposures, human factors research requiring deception, and research "for the benefit of patients." However, as discussed in the attached comments of Dr. Philip Russell (Appendix A), the exemptions to the regulation appear to relate to lines of authority and control in the military establishement rather than with the reach of ethical principles. 7 Tab F-2 APPENDIX A Dr. Philip K. Russell Comments on Tab F-2, Section 6 AR 70-25 in 1962 described both a code of ethics and an administrative procedure. The regulation placed the Army Surgeon General in the position of responsibility for reviewing and supervising research done or contracted for by Army Medical R&D including the AFEB. Noteworthy is the fact that the Surgeon General had the authority only to review (not supervise or control) research done by others in the Army e.g. Chemical Corps. This speaks to internal power issues and only directly to the ethics. The exemptions to the regulation also reflect power and authority issues internal to the Army staff and the Army Medical Department (Army Medical Service in 1962) rather than ethical considerations. Exemptions 3a. and 3b. leave all training and operational issues in the hands of operations and or personnel authorities of the Army without interference by the medics. These two exemptions were undoubtedly essential to gain Army Staff approval of the regulation. Exemption 3c. is more subtle and reflects the division between the Army's medical research organization and the Army's patient care / hospital system. It appears that the leadership of the hospital system (later called Health Services Command) did not approve of the research people overseeing or reviewing their protocols - an administrative/power issue. The use of the term ethical medical and clinical investigation seems to indicate that they saw an administrative process to oversee studies done in hospitals by the health care people as unnecessary as well as inappropriate. Some commanders of the large hospitals were quite powerful and very unwilling to have R&D people interfering in their system. Note that Army sponsored research is funded by Program 6 (research and development) funds and managed under the 70 series of regulations. "Clinical investigation" is a term used to describe studies done by the patient care system, funded by Program 8 (operations) funds or by outside funds e.g. NIH grants. At that time there was an intent to keep the two systems independent of each other. The exemptions reflected intent to limit the reach of power (of the medical R&D people) not necessarily to limit the reach of the principles. Later, of course, the lack of oversight caused serious problems and since 1975 the oversight and supervisory authority by the Surgeon General is comprehensive. 7