Advisory Committee on Human Radiation Experiments Minutes of January 19-20, 1995 January 19, 1995 Attending: Ruth Faden, Kenneth Feinberg, Patricia King, Eli Glatstein, Jay Katz, Susan Lederer, Ruth Macklin, Lois Norris, Nancy Oleinick, Henry Royal, Philip Russell, Mary Ann Stevenson, Duncan Thomas, Reed Tuckson. Philip Caplan, Special Assistant to the President for Cabinet Affairs, opened the tenth meeting of the Advisory Committee on Human Radiation Experiments at 9 a.m. in the Empire Room of the Omni Shoreham Hotel, 2500 Calvert Avenue NW, Washington, D.C. Dr. Faden briefed members on the agenda for the meeting and noted that most of the time will be devoted to Committee discussion on issues of retrospective moral judgment and blameworthiness. Approval of Minutes Members approved without amendment the minutes of the December meeting. Update on Subject Interview Study: Jeremy Sugarman and Nancy Kass. Dr. Sugarman briefed members on progress of institutional review board (IRB) approvals for the subject interview study. If time permits, a fifth site in the Southwest will be added to the study to widen the sample size. Several Texas institutions have been contacted about being involved in the study. Four sites under way are Baltimore/Washington, Seattle/Tacoma, Raleigh/Durham, Ann Arbor. Instruments for the study are being revised with comments from focus groups and reviews by investigators and others. Training of interviewers will begin on January 30. Members made suggestions about development of the instrument for interviews, and questioned Dr. Sugarman and Dr. Kass about the work plan for the studies. Members expressed concern about finding sufficient detail about persons who are research subjects and are not aware of their participation. Dr. Sugarman noted the pressure of time, with Dr. Kass adding that disclosure to patients that they are subjects might require more extensive consultation with doctors and/or investigators, or IRBs. Members directed the staff to seek as much information as possible about consent by persons unaware of their status as a research subject. Update on Research Proposal Review Project: Sara Chandros and Gail Geller. Ms. Chandros briefed members on the status of the review project. She noted that 37 out of 40 research institutions had submitted materials requested by the Committee for the review, and the remaining institutions' materials are expected shortly. Members inquired about the differences in documents between intramural and extramural protocols. Ms. Geller said the differences are of interest and a discussion of the distinctions will be one of the research products of the project. Ms. Chandros reported that 20 studies have been reviewed out of a projected 225 goal. Dr. Faden said the information needs to be available by the middle of March to be of most value in the Committee s deliberations. Committee Discussion: Government Standards and Government Culpability. Jonathan Moreno, Allen Buchanan, Valerie Hurt. Dr. Moreno briefed members on the documents that underlie the staff s general conclusion that the Atomic Energy Commission had policies on consent in experimentation that evolved in the late 1940s and established philosophical standards should apply to judging government activities through Secretary of Defense Wilson's memorandum of 1953 and beyond. Important documents included the 1947 Carroll Wilson letter and resulting adumbrations from AEC officials. Carroll Wilson was general manager of the AEC. Dr. Moreno said staff believes AEC policies should have been expected to govern other agencies activities. The AEC was the primary sponsor of radiation research; AEC was the agency at the time to look to for guidance and reflection on these questions; AEC personnel were called upon by other government agencies to advise on radiation-related human research; and standards stated by AEC were in fact those subsequently developed by other agencies, e.g. Department of Defense and National Institutions of Health clinical agencies. Mr. Guttman added that the AEC aggressively promoted use of isotopes for medical purposes. Members discussed the process by which the requirements for consent listed in Carroll Wilson's letters were modified in their application by the AEC panel on human applications of radioisotopes. Members discussed the ethical implications of the AEC's role in light of its increased sensitivity to public relations and liability issues demonstrated in documents released in the December and January briefing books to the Committee. Members agreed that the AEC had policy standards to which it should have hewed, and moved to discussion of the question of whether the AEC standards should be held to apply to other government agencies. Mr. Guttman noted that the same AEC cast of characters tended to populate other policymaking committees. Members approved a staff memorandum outlining the view that AEC standards were applicable to radiation research in the other government agencies of the time. Committee Discussion: Government Standards and Government Culpability. Dr. Faden introduced a discussion of the Department of Defense standards and Dr. Moreno briefed members on ethics data collection, specifically the application of the 1953 Wilson memorandum setting the Nuremberg Code as Defense Department policy. Dr. Moreno reported that staff had found no reason to believe that the Wilson memorandum was not intended to apply to mixed-purpose research. New documentary evidence suggests that the Wilson standards were also applied to research not involving atomic, biological and chemical (ABC) warfare. Dr. Moreno reported that 1954 guidance from the Department to a researcher, found in the Yale University archives by Dr. Lederer, seemed to use the Wilson memorandum for guidance on research outside the ABC areas. Dr. Russell noted that policies in the military differ because of the requirements of military commands dealing with different subjects, such as the patient care doctors vis-a-vis researchers, and operational leadership vis-a-vis medical officers in general. Dr. Faden said the Committee staff had more work to do in researching the development of 1962 regulations and the subsequent empaneling of an Army committee in December 1963 to refine or interpret the regulations. Dr. Russell suggested that the staff consult medical regulations of the time to elaborate on these issues. Dr. Oleinick noted that even today there are no special regulations on research involving soldiers. Dr. Faden also noted that it is important to determine when the Department of Health, Education and Welfare's rulemaking began to play a leading role in human experimentation regulations involving military subjects. Report: Ethics Oral History Project. Susan Lederer, Gail Javitt and Jon Harkness. Dr. Lederer briefed members on the recording of recollections of investigators and medical administrators from the postwar period. She said that the oral histories will be an important supplement to other evidence about clinical research in the period. Ms. Javitt said that the staff have seen evidence to support several hypotheses: 1. American medical researchers appeared to have been aware of the Nuremberg Code, but did not see it as relevant to American research. American researchers recounted efforts to inform subjects in some fashion, although some examples cited do not appear to meet today s standards of informed consent. 2. The increase of funding in postwar research led to the combining of medical investigator and physician roles. 3. Research practices differed on sick patients and on healthy subjects. The latter seemed to have been more thoroughly informed of risks involved in research. Dr. Katz called members attention to a passionate statement from one researcher, which he paraphrased as Look what doctors are doing in clinical practice, they re doing more interventions and not talking to patients very much. Dr. Lederer said there seems to be more of a tradition of informed consent in infectious disease research, where in most cases healthy volunteers were used. Dr. Harkness suggested that with the exception of the NIH Clinical Center, there seemed to be little infrastructure to implement the standards created by policymakers. And even then, Clinical Center standards of the early 1950s apparently were not imposed on extramural grantees. Dr. Harkness said that recollections of Nuremberg varied from intense to indifferent, in terms of its relevance to American medicine. Dr. Tuckson asked that subsequent reports on the oral histories attempt to elaborate on the physicians views of the Hippocratic responsibility in this transitional period. Dr. Faden said that the staff should generate by February a set of stipulative definitions of terms such as therapeutic research, which was used in the discussion as defining procedures which hold out some hope of physical benefit to the patient. Drs. Glatstein and Stevenson explained their own training on consent issues, but Dr. Glatstein noted that his training at Stanford Medical School was in a department with many Jewish professors, who might have been more sensitive to the Nuremberg Code because of atrocities in the Nazi camps that fell disproportionately on Jewish populations. Committee Discussion: Individual and Professional Culpability. Allen Buchanan, Jon Harkness, Jonathan Moreno. Dr. Buchanan presented an extensive paper on the nature of judgments of individual or professional culpability. Members questioned Dr. Buchanan about the appropriateness of assessing blame in light of limited evidence or obscure institutional lines of authority. Dr. Buchanan suggested that those in authority had a responsibility to enforce some degree of compliance with stated policies. He suggested that it is important that individuals within the government should not escape censure through a more general judgment about institutional responsibility. Dr. Thomas likened the Committee's role to that of a grand jury, rather than a jury making a final judgment in a trial, but Dr. Russell added that the public may well see the Committee's judgments as final, and he noted the difficulties facing members in judging the institutional context of policies after many years. Members discussed the remedies prescribed by the Army's 1975 Inspector General report on human experimentation and the responsibilities of officials to see that their policies are carried out. Dr. Royal said that the Committee's evidence may suggest that officials were engaged in a long process, by fits and starts, of improving ethics policies. Mr. Feinberg said the assessment of individual blame may be less important than laying out all the facts. He quoted Justice Brandeis, that sunlight is the best disinfectant. Dr. Buchanan added that it's important that officials not be allowed to claim as a defense that others in the chain of command should have attended to compelling ethical responsibilities. Members discussed how to make judgments in light of the differing world-views of bureaucracies and the professions, but Dr. Macklin noted that medical professionals today work within bureaucratic structures. Dr. Macklin summarized the discussion as having reached a consensus that it is possible to make retrospective moral judgments, but that members remained concerned that lack of evidence may lead to wrongful assignments of culpability. She added that members seem to agree that one issue is the failure of officials to ensure that policies were implemented, but that members also are aware of the difficulty of assessing responsibility in bureaucracies. And, as explained by Dr. Russell, the time-honored military tradition of laying blame at the feet of the commander of an organization is not necessarily the best way out of the moral judgments facing the Committee. Mr. Feinberg added that much of the Committee's work will hinge on evidentiary problems, and he feared that often evidence may simply not be available to make authoritative judgments on some issues. January 20, 1995 Attending: Ruth Faden, Eli Glatstein, Jay Katz, Patricia King, Susan Lederer, Ruth Macklin, Lois Norris, Nancy Oleinick, Henry Royal, Philip Russell, Mary Ann Stevenson, Duncan Thomas, Reed Tuckson. Public Comment Joan McCarthy, widow of Tom McCarthy, a Navy navigator and veteran of Operation Wigwam. She said the blast at Operation Wigwam was a human radiation experiment, involving deep- underwater explosions and determining operational capacities. She said her husband was not warned of risks, and received no medical follow-up. Members questioned Mrs. McCarthy about her experiences and the records she had been able to obtain from the government. Charles McKay, Severna Park, Maryland. A deep-sea diver at Bikini, he said he received no briefing on radiation risks before participating in Operation Crossroads. As with Mrs. McCarthy, Mr. McKay said that he received a very low dose reconstruction report, and he believed it to be highly inaccurate because it did not take into account diving experiences on Crossroads wrecks. He noted that President Truman called Crossroads a laboratory experiment. In answer to members, Mr. McKay reported no prior training or warning about radiation exposure. He added that soldiers and sailors were given no opportunity to decline Crossroads duty. Pat Broudy, Monarch Beach, California. Mrs. Broudy, legislative director of the National Association of Atomic Veterans, spoke about genetic effects to families of subjects of experiments. She noted that Colonel Stafford Warren reported after Crossroads about the impact of genetic damage to the young sailors participating in the bomb tests. Committee Discussion: Individual Culpability and Professional Culpability. Allen Buchanan. Dr. Buchanan distributed a brief paper written overnight to respond to Committee questions about culpability of bureaucratic actors. Dr. Royal noted the great difficulties in assessing harms in terms of measuring professionals culpability, and Dr. Thomas added that the evidentiary problems make it critical that the Committee develop test cases for such findings. Dr. Thomas suggested that if the Committee can't make the case to find individuals culpable, then and only then should it decide to look to organizational culpability. Dr. Faden agreed that the Committee must seek to make tough calls, and several members reiterated that the calls must be made with a commitment to fairness and justice. Dr. Macklin noted that the doctor works within a bureaucratic setting; the obligations of professionals extend to following the bureaucratic rules and policies, e.g. documentation of informed consent. Dr. Royal said that the lack of documentation after 40 years may not be conclusive, and Dr. Russell noted that the military system has evolved such that military doctors today rarely are under the authority of nonmilitary superiors. Dr. Buchanan suggested that it would be useful to make clear in the final report the distinction between the narrative of events and the judgments and conclusions made. He said mitigating factors might well persuade the Committee to assess harms and responsibility, but to stop short of assessing culpability. Dr. Buchanan added that moral standards have evolved, sometimes in fits and starts, in the course of human events; however, some obligations to human beings cannot be overridden on grounds of national security. Mr. Guttman noted that the Wilson memorandum was issued at a time of national emergency, the Korean War of 1950-53. He suggested however that national security may not be an obvious mitigating factor, at least for biomedical work in clinical settings. Dr. Faden said national security issues are more subtle influences in the institutional settings for radiation experiments, but she also noted that even in World War II the Committee on Medical Sciences required that prisoners in experiments be volunteers and sign written consent forms. However, Dr. Lederer and Dr. Katz contrasted that consent standard with the ethically questionable decision, at about the same time, not to prosecute Japanese investigators into chemical and biological warfare. Dr. Glatstein said that there was little codification of the ethics of scientific investigation for physicians. The revolution of medical ethics in a single lifetime is an important element in making judgments; even today, he said, there are many Western countries where consent forms are not required for medical procedures. A different ethical standard should be applied to the mass exposures by intentional releases; military interest was short-term radiation effects, Dr. Glatstein said, citing the statements of Mr. McKay and other atomic veterans. Ethical standards were highly variable for different classes of subjects. Dr. Buchanan suggested that the role of private sector organizations should be mentioned in the final report, especially for prospective recommendations, in light of the growth of biomedical businesses in the 1980s and 1990s. Mr. Guttman said one of the profound philosophical cruxes of the Advisory Committee s work is the relative disinterestedness of medical/scientific and military professionals. Dr. Buchanan said that the issue of trust related to professional affiliation is important in cases of misplaced deference to medical professionals or soldiers responding to national security imperatives. Society tends not to trust the man in a business suit in the same way. Risks grow with the synergism of two groups deference. Dr. Russell said misplaced trust related to status is an important concept of great value to the Committee s work, and Dr. Tuckson asked that members be mindful that incentives include power and rank, so that issues may be similar to business organizations. He noted also that any large organizations can be accused of a myriad of wrong actions on the path toward any substantial goal or project. Dr. Katz questioned whether decisions taken to defer to other disciplines were quite as innocent as the status-trust concept might suggest. He said the challenge for the Committee includes ways to alert citizens to situations where the interest of human rights is falling between the stools of committees. Dr. Buchanan said that the lesson for recommendations is to make sure that it s clear that abdication of ethical responsibilities is unacceptable. Clear lines of authority and corporate cultures that accept self-criticism are critical issues. Dr. Oleinick asked that Dr. Buchanan and other ethicists provide thoughts on the role and responsibilities of advisory committees in the government. Staff Report: Contemporary Agency Oversight. Wilhelmine Miller. Ms. Miller briefed members on staff memoranda establishing Federal policies for protection of human research subjects. She noted that special attention has been paid to circumstances in which agency heads may allow exceptions to standards in the common rule. Dr. Faden noted the observation that 100 fulltime equivalents reflected actual staff time on protection of human subjects by the Department of Defense and its contractors. The Department of Health and Human Services reported 13 fulltime staff in the office that oversees human subject research at the National Institutes of Health. Dr. Faden directed that the staff get a practical number for those overseeing the estimated $6 billion in today s HHS human subject research. Dr. Russell noted that the extensive bureaucracy of procurement and the crossing of bureaucratic lines would make a completely reliable number difficult to determine. Ms. Miller said the agencies say it is difficult to estimate. Dr. Russell said that the number of people involved is relatively small compared to the volume and cost of research projects. Members discussed the exception exercised in connection with nerve gas pre-treatment agents in the Persian Gulf War. Dr. Faden asked that staff provide more information to members interested in those issues. Ms. Miller briefed members on review of human subject experimentation in classified research. There is no requirement that funding sources be disclosed to subjects, but there is no exemption from informed consent requirements in those cases. Informed consent requirements may only be waived by agency heads, but restrictions on the waivers are invoked automatically. Dr. Macklin questioned whether the exceptions might not be fully protective of subjects, so long as the IRB can argue that risk is minimal. Dr. Royal asked that the staff seek from agencies an example of once-classified research in the contemporary period to determine how the system worked. Committee Discussion: Total Body Irradiation. Ron Neumann, Gary Stern. Dr. Neumann gave members an overview of total body irradiation (TBI) experiments. He said that the variability of hospital patients in TBI protocols was an important problem that may have acted as an incentive for continuing TBI work over a period of years. Mr. Stern briefed members on the documentary evidence, including the correspondence of Dr. Alan Gregg of the Advisory Committee on Biology and Medicine, that the Atomic Energy Commission had a special responsibility for oversight of TBI projects. Members questioned staff about the evidence available to make judgments about the culpability of agencies or officials in TBI projects. Dr. Oleinick noted that the experiments were conducted over 30 years and at the end of the day there was very little new information generated by the experiments. Dr. Neumann observed that no agency was in overall charge, with oversight personnel changing even within agencies, and review of the experiments was primarily by advisory committees. Dr. Eugene Saenger of the University of Cincinnati told Advisory Committee staff in an interview that he was not given access to earlier literature summaries compiled by the Armed Forces Special Weapons Project, but had reviewed the published articles; Dr. Saenger said he disagreed with arguments at the time that TBI held no hope of treating solid tumors. Members questioned the Saenger experiments, including whether the decision to accept TBI was reasonable on the part of patients; the content of advice to patients, their diagnoses and alternative treatments; funding and goals for the studies; co- investigators who dealt with patients in Cincinnati General Hospital; application of the Wilson memorandum and subsequent restatements of the Nuremberg Code to the studies; lack of regulation of cobalt-60 exposures as research. Dr. Stevenson said the record suggests that the review process failed the patients, as objections by some reviewers at the time would be enough to cause rejection of the proposals today. Military funders sought data from the experiments and apparently did not concern themselves with the therapeutic application of radiation, Dr. Neumann said. Dr. Faden observed that the TBI experiments demonstrate the complexity of issues before the Committee, involving questions of information, treatment, alternatives and study goals. Dr. Neumann said the large question raised is why sick hospitalized patients were used in light of debate over TBI on healthy volunteers proposed by the AFSWP for the nuclear-engine project for aircraft (NEPA). Dr. Glatstein suggested that, if military funding had not been available, TBI experiments would likely have ended much sooner than they did, e.g. Cincinnati in 1971. Dr. Russell described the case as bad administrative judgment and bad science compounded by inadequate oversight by outside bodies; determining where critical culpability lies is almost impossible. And, Dr. Neumann added, the data produced did not answer questions sought at the beginning of the process. Dr. Royal said that military interest in a biological dosimeter was a legitimate goal, but Dr. Faden said the key question is whether human experimentation was necessary. Dr. Glatstein said that the Saenger experiments ethical assessment depends on whether patients were informed of the risks, and it may be impossible for the Advisory Committee to make that determination at this remove. Professor King said a long string of administrative bungling is just as damaging from the victim s point of view. The Advisory Committee can draw lessons and recommendations from the facts, without necessarily assigning culpability to agents, she said. The investigator and hospital failed to stop the process at an earlier date, and the Department of Defense took a narrow view of its responsibilities, almost benign neglect of what its contractors were doing, Dr. Stevenson said. Subcommittee Report: Outreach. Reed Tuckson. Dr. Tuckson said that the Outreach Subcommittee plans to meet by telephone conference to discuss upcoming site visits and how to incorporate late-breaking testimony into the work plans for the final report. Dr. Tuckson also said he would seek to discuss ways to have the public health community more closely consulted on some issues, and to discuss new concerns of the advocacy community. Committee Discussion: Final Report. Ruth Faden, Dan Guttman. Dr. Faden said future Committee meetings would include an additional half-day of meetings, and she asked members to hold dates in May in case an additional Committee meeting is necessary. The February meeting will be held Feb. 15-17 and will include a discussion of remedies, experiments of opportunity and intentional releases, and experiments on children and pregnant women. Mr. Guttman distributed a calendar indicating the general dates that draft chapters would be circulated to Committee members. As the designated federal official, Mr. Guttman closed the meeting at 4:15 p.m. ATTENDANCE Persons signing in at the meeting included R.E. Halperin, ESSi; Midge Gardner, Vanderbilt University; Dennis Nelson, Citizens Call; Rob deVesty, VHA, Environmental Medicine; Chris Kline, Senate Governmental Affairs Committee; Michael Yesley, Los Alamos National Laboratory; Allan Murray, ANSTO; Gwen Jackson, Janis Stoklosa, NASA; Ann Hopkins, Tom Smith, Denise Nelson, National Association of Radiation Survivors; Pat Broudy, Maury Silverman, National Association of Atomic Veterans; Kathy Hudson, Department of Health and Human Services; Jonathan M. Weisgall, attorney; Marina Volkov, National Institutes of Health; Rachel Kirsh, Embassy of the Republic of the Marshall Islands; Tim Gerrity, Veterans Affairs; Kevin M. Stone, University of Maryland; Ashish Buder, Physicians for Social Responsibility; Marcia and Gale Haggard, radium survivors; Lt. Col. Dan Brown, U.S. Air Force; Joe Hebert, The Associated Press; Karen MacPherson, Albuquerque Tribune; Bill Ferry, Huntsville News; Lee Davidson, Deseret News; Bill Straub, Scripps Howard News Service.