ADVISORY COMMITTEE ON HUMAN RADIATION EXPERIMENTS Minutes: Meeting of May 18-19. 1994 Attending: Ruth Faden, Duncan Thomas, Mary Ann Stevenson, Patricia King, Eli Glatstein, Lois Norris, Kenneth Feinberg, Susan Lederer, Henry Royal, Ruth Macklin, Nancy Oleinick, Reed Tuckson, Jay Katz. Mr. Philip Caplan, special assistant to the President for Cabinet Affairs, opened the meeting at 9 a.m., May 18, 1994, at the Ramada Plaza, 10 Thomas Circle, Washington, D.C. Dr. Faden in the chair announced that Frank Press resigned because of his concern that he could not devote sufficient time to the Committee's efforts. Dr. Faden will consult with the Administration to see if the Committee can or should fill the vacant slot. Dr. Philip Russell apologized through the chair for his absence, and she reported that he will attend the third meeting of the Committee. He has worked with staff between Committee meetings. Dr. Faden briefed members on the general goals of the May meeting: to hear presentations from staff about its progress, provide direction for the staff's work over the coming four weeks, hear presentations about case studies which will guide methodology for later searches, begin a process of mutual education among the specialists on the Committee, and hear public comment from concerned parties. The chair and Executive Director Dan Guttman introduced the staff and noted that the science staff is to be fleshed out in coming weeks. A number of staffers are coming on board after other assignments but have already begun working part-time. Briefing: Ethical Principles of Human Experimentation. Dr. Macklin Dr. Macklin traced the origins and implications of underlying ethical principles, particularly on informed consent. Members questioned the speaker on issues that included whether it is possible to do ethical experimentation on populations housed in institutions where some coercive element is implicit; the nature of severity of infringement of voluntary participation and what objective tests might elicit a standard; how precise were criteria for disclosure of risk and benefits to patients. Dr. Katz emphasized that he did not believe the Belmont Report clarified many of these issues. Briefing: Health Effects of Radiation. Dr. Royal. Dr. Royal briefed the Committee on the nature of radioactivity with particular emphasis on the types of emissions which damage human tissue, and the dose levels that constitute life-threatening exposure. Members questioned Dr. Royal on the difficulty of measuring dosage long after exposure; patient reactions to risks of biological diseases and to radiation; problems of measuring fatal dosages or carcinogenic or teratogenic effects from data derived from Hiroshima and Nagasaki. Dr. Thomas disagreed with Dr. Royal's use of the phrase ``middle of the road'' to describe the point of view of an article by Rosalind Yalow provided to members. Briefing: History of Human Experimentation in the United States. Dr. Lederer. Dr. Lederer's brief included background on human experimentation, with special emphasis on what Dr. Lederer described as a vast increase in human research experimentation in 1910-1940, rather than World War II, which is often described as the point of acceleration in the number of these experiments. Dr. Lederer also traced a significant public discussion, focused in large part around efforts of Anti-Vivisectionist societies, about the merits and ethical dimensions of human subject experimentation. Written consent forms date from yellow fever research ca. 1900, but debate about perceived abuses of human subjects resurfaced on a regular basis well before the 1932-72 Tuskegee studies and the 1974 revision of government standards. Members questioned Dr. Lederer on the legislative history of efforts to curb human subject experimentation at the turn of the century, and the opposition of professional societies to the proposed legislation; the circumstances in which practitioners used human subjects rather than animals. Staff Report: Review of Agency Ethical Standards. Jeffrey Kahn, Jeremy Sugarman. Drs. Kahn and Sugarman briefed members on the report listing documentation generated by initial searches by federal agencies. Beyond the agencies initially believed to be focuses of Committee efforts -- Departments of Energy, Health and Human Services, Defense, Veterans Affairs, and CIA and the National Aeronautics and Space Administration -- relevant documents appear also to be in possession of the Federal Emergency Management Agency. In 1991, federal agencies adopted ``common rule'' policies embodied in 45CFR46, Subpart A. Drs. Kahn and Sugarman summarized responses from various agencies, including those subsumed by newer departments:  HHS. A chronology of human research policies. A research report on HHS documents was to be presented later in the May meeting.  Department of Energy: An overview report found that human research policies existed as early as 1947, when Atomic Energy Commission contractors were asked to provide certification from doctors that patients consented to experimentation. A more detailed DOE report was to be presented later in the May meeting.  Department of Defense: Secretary of Defense Wilson and Secretary Stevens of the Army approved policies embodying the Nuremberg Code in memoranda of 1953 and 1954. The Army policies were mentioned in a secondary source, the 1975 Inspector General's report regarding chemical experiments involving human subjects.  Department of Veterans Affairs: The agency is working on document outlining what papers it has in its possession or that are retrievable.  Central Intelligence Agency: Staff will meet with CIA. Initial contact suggested documents to 1977 will be reviewed as part of the work with the agency.  NASA: Materials are being assembled. Committee staff noted that many documents appeared in different places than might be expected, e.g. a letter to another agency that contained new material not obtained by the authoring agency. While questions are raised about the utility of policies that were classified and thus limited in distribution, notably the 1953 memo from Secretary Wilson, policies tended to exist. An early example: Interagency communications by the Committee on Medical Research, which funded projects during World War II, indicated that the agency required in 1942 that informed volunteers be used and that consent forms be obtained. Dr. Katz noted that the 1975 Inspector General's report concluded that consent polices were not followed in chemical experiments. Dr. Macklin noted that the 1942 regulations of the Committee on Medical Research included an explicit waiver of future claims against the government. Mr. Guttman said the disclosures of high-level policies in the Defense Department, based on the 1953 memo and the 1975 report, required vigorous exploration of several issues: the level of debate in the agency said to have been necessary to produce the 1953-54 Army policies; the level of implementation of the policy; the discovery of relevant additional documents. Dr. Royal suggested that staff also include in the search for ethical codes a survey of those issued by medical societies at the time. Dr. Macklin added that the Committee's need for documentation included the penumbra of both official and nongovernmental rules affecting researchers. Methodological Case Study: Cincinnati Experiments. Ron Neumann. Dr. Neumann reported that additional documents beyond those already known in the extensive files on the Cincinnati experiments are needed to assess consent issues. Additional reviews of publications by Dr. Saenger are needed, and patient records so far available do not make clear how patients came into the study. Issues: NIH funding of patient wards in the hospital for the experiments; the cost of the total-body radiation program; documentation of AEC and other government consultancies and whether Dr. Saenger held security clearances. Members questioned Dr. Neumann about the existence of any records that would help assess the usefulness of the Saenger experiments; why and how psychological testing expanded as part of the program; the apparent absence of comprehensive listing of patients. Dr. Neumann and members discussed the study and its implications for additional work. The Cincinnati experiments have been extensively studied, so there were a large number of documents and sources available, but that litigation over the experiments is likely to inhibit further cooperation from litigants in possession of documents. It is not clear how much documentation, if any, is today classified. A fruitful line of investigation involves making connections across agency lines by following documents related to funding, administration and follow-up to the experiments. Dr. Herken added that the degree of military interest was a striking point about the experiments. Members discussed both an assessment of the experiments, and the methodological questions. Dr. Glatstein noted that the statistics on mortality from the experiments are difficult to assess as death rates were very high from leukemia in the period, and that the first-phase of such research typically attempted to derive toxicity of dosages, and thus control groups were not used. Dr. Katz and Ms. King noted that it is important to be able to establish what different treatments were used and how research was designed, and Dr. Macklin added that it is important to know what was considered appropriate research methodology at the time. Dr. Neumann said that current documents would not make those issues clearer. Dr. Faden said the primary information may no longer be available to allow the assessment, in context of the times, of the appropriateness of treatment and the likelihood of constructive results from the Cincinnati research program. Dr. Stevenson said that the documents may be found to demonstrate the incentive to conduct the experiments, especially the question of whether government funding was the driving force in doing experiments that may have had no therapeutic value. Statement by Dr. Oleinick. Dr. Oleinick stated for the record that she had a prior association with one individual connected with the plutonium injection experiments, Dr. Hymer Friedell, who was head of the Department of Radiology at Case Western Reserve University and had previously had a role as deputy to Stafford Warren. Dr. Oleinick was unaware of the connection until the staff reports arrived, and Dr. Friedell has since retired, but Dr. Oleinick said that she wished her colleagues to know of the former association before consideration of the presentation on the plutonium injection experiments. Dr. Faden expressed appreciation for Dr. Oleinick's candor in bringing the matter before the Committee. Dr. Faden said in her judgment the association did not represent a conflict of interest, and without objection the Committee moved to consideration of the case study. Methodological Case Study: Plutonium Injection Experiments. Dr. Herken. Dr. Herken reported on the 18 known plutonium injection experiments and said that documents found as part of the search suggested that the 1943-47 experiments were part of a larger scheme, probably not carried forward because public controversy over the experiments surfaced in 1946. There is no record to determine if any further experiments were performed, although it is probable that the larger program planned by the AEC Interim Medical Advisory Committee was not carried out. While the AEC originally proposed that signed consent forms be obtained from subjects of experiments, the documents indicate that this proposal was successfully resisted by contractors. In a compromise that was in effect for at least one set of experiments, in July 1947, two attending physicians were required to certify that patients understood and consented to the experiments. It was not clear from the documents available why AEC officials did not insist on signed consent forms. Members questioned Dr. Herken about informed consent issues; whether animals had been tried as subjects prior to the human experimentation; potential sources of information. Dr. Herken said that while a 1974 investigation did a creditable job, the current file includes only references to the primary files and an inventory. Some records are to be found in repositories of different agencies, suggesting some primary material may be found through a wider search. Public Comment Period. The following persons addressed the Committee during its public comment period: E. Cooper Brown, National Committee for Radiation Victims. Mr. Brown urged the Committee to investigate the exposure of Marshall Island inhabitants and Navajo uranium miners as part of its work. Wallace H. Cummins, Radiation Health Effects Public Law Group (RADLAW). Mr. Cummins urged the Committee to ensure the full cooperation of agencies with its document searches and asked that the Committee hear regularly from the community of persons affected by radiation exposure. Fred Allingham, National Association of Radiation Survivors. Mr. Allingham urged the Committee to interpret broadly its definition of what kind of radiation exposure constituted experimentation, and to include a representative of the survivor community on the Committee. Daryl Kimball, Physicians for Social Responsibility. Mr. Kimball said the Committee's investigations should be an open process with the widest possible outreach for interested parties. He urged the Committee to hold some of its meetings in cities outside Washington. Dr. Tuckson expressed the view of the Committee that its efforts are aimed at responsibility and accountability on the part of the government of the United States. Survivor groups in particular were urged to provide information to the Committee. Statement by Dr. Thomas. Dr. Thomas stated for the record that he had consulted with the Centers for Disease Control on the Hanford studies. The work was limited to review of a few draft protocols, and the White House counsel's office did not view that role as a conflict of interest. Dr. Faden expressed appreciation for Dr. Thomas' candor and said the consensus of the Committee is that his role does not constitute a conflict of interest. Methodological Case Studies: Green Run. Dr. Whittemore. Dr. Whittemore noted that the ``green run,'' the release of a radioisotope of iodine at Hanford, Washington, in December 1949 was not a clinical experiment, but radiation released into the environment to aid in the government's long-range detection program. At the highest levels, it may have been a reaction to the first atomic bomb explosion in the Soviet Union; at the most basic level it is difficult to re-create what physically happened at the site. Apparently, the magnitude of radiation released could not be regulated because instruments in the smokestack did not work; the biological impact is even more difficult to measure after the passage of more than 40 years. Members questioned Dr. Whittemore about the extensive gathering of animal and plant specimens by officials, and an apparent lack of inquiries about the impact of the Green Run on persons; the reasons that the experiments were discontinued; whether sufficient documents have been declassified to adequately understand the experiments. Dr. Stevenson stated that it is imperative that the Committee gain access to classified documents if it is to fulfill its mandate. Members asked if subpoena power were available to the Committee. Dr. Faden and Mr. Guttman said that if the Committee finds it needs additional authority to carry out its mission, then it would seek that authority from the Administration. Members discussed whether environmental releases are within the scope of the Committee's mandate. Dr. Royal questioned whether the Committee has time or resources to deal with environmental releases. Dr. Faden said the issue of Green Run was specifically included in the Committee's charge by Executive Order. Dr. Whittemore noted that ethical issues raised by the scope of planning for Green Run may be a subject for consideration, rather than the event, but Mr. Feinberg noted that it is difficult to separate the ethical and technical issues. Thursday, May 20 Kathleen Whalen and Drew Poole of the White House counsel's office spoke to members about conflict of interest rules. At the request of members, Ms. Whalen said the counsel's office would research concerns about fees for future expert witness testimony. Staff Report: Review of Agency Data Collection Efforts, Department of Energy. Mr. Guttman reported on what he characterized as a strong effort from archivists and historians in federal agencies to gain access to the many documents, some still classified, pertaining to human experimentation. He said that of the immense volume of documents, many of the potentially interesting ones already declassified, there are many that are missing or have not yet been targeted for search by agencies. Agencies have reported on the difficulties caused by quality of recordkeeping in the past, and identified the Committee's research as an opportunity to improve that situation. Resource issues include secrecy classifications, and pockets of resistance in some agencies to searches; the latter are most likely for budgetary reasons. Staff recommends continuation of effort despite large volume of boxes, and continuation of effort to work with agencies on behalf of openness of both government records and those of contractors, as ordered by DOE. Members questioned staff on how records would be disseminated to the public; on the critical importance of Committee staff targeting its searches; on the importance of cross-checking to ensure that appropriate documents are being made available; and on potential alternative sources, such as the materials compiled by advocates of Navajo uranium miners. Mr. Guttman entered into the record a memorandum from Glenn Podonsky of DOE expanding upon the Staff Report. DOE suggested changes in the data collection Staff Report to reflect the department's views about the status of the document search. The Committee discussed the advisability of obtaining security clearances for two or more members to gain access to classified documents, but several members expressed concern about inhibiting the Committee's discussion. Dr. Faden said that obtaining security clearances would be strictly voluntary, as security clearances were not required as a condition of joining the Committee. Members and staff historians expressed concern that declassification would be a slow process, and Dr. Faden said the Committee would send a memorandum to agencies urging that declassification of documents relevant to the Committee's work be expedited. Mr. Podonsky told the Committee that DOE is committed to aggressive declassification of documents. He added that obtaining security clearances across many agency jurisdictions may be timeconsuming, although officials are working on procedures to allow reciprocation of clearances. Staff Report: Review of Agency Data Collection Efforts, Health and Human Services. Mr. Guttman discussed HHS organizational structures and search operations. He noted that early extramural grant records from HHS research agencies are the most difficult to get; HHS records for that period constitute tens of thousands of noncomputerized capsule descriptions of grants. In many cases it is impossible to tell whether these records refer to human experimentation, although some may be identified through a parallel search of published studies. Radiation Section studies from the 1940s to 1960s indicate that human experimentation involved anywhere from 15 to 400 grants a year, but some records also may appear in other section files. Cross-references with radioisotope licensing records may identify many of these, and the staff proposes to work with X-ray research subsections through HHS officials. Joint sponsorship of research also complicates matters, as do projects that involved both classified and unclassified components, some of which might not be in published literature. Wendy Baldwin of the department told the Committee that grantees were told to preserve their records. She said Option One proposed by the staff would be to re-orient the department's search to policymaking documents, but that would be done as directed by the Committee. Members discussed focusing HHS searches on the policy level; additional resources such as universities; additional searches by cross-referencing pools of reviewers of experiments, who were allocated by areas of expertise. Without objection, members approved most options proposed in the HHS staff recommendations. Deferred to later in the afternoon were: Option Five: Interview knowledgeable individuals. Option Six: Written documentation from Helpline callers. Committee Discussion: Committee/Staff Working Relationships and Formation of Subcommittees. Dr. Faden summarized the directions to staff: That the Committee endorsed and wished to continue all three methodological case studies, with some special emphases. Cincinnati questions included whether there was an original medical protocol; how patients were selected; what was the incentive or driving force behind the experiments; and whether Dr. Saenger held security clearances. For the plutonium injection studies, agencies should be directed to contact the Universities of Chicago and Rochester for additional information. Other data may also be sought from other universities. Staff should follow leads for linkages with other experiments than those currently known, and should try to determine the scope of other planned studies in that area. For the Green Run studies, the staff should pursue policy- level documents to determine where Green Run experiment originated. Questions include whether anyone challenged the propriety of the experiment, who started and designed the project in the context of research, how was it viewed from an ethical standpoint and why was it suspended. AEC Memorandum Ms. King introduced into the record a 1947 Atomic Energy Commission memorandum in which an AEC official ordered that information on human experimentation be classified as secret because of potentially adverse public comment. The memorandum is Appendix B. Discussion of Subcommittees Members discussed in detail the responsibilities of standing and ad-hoc subcommittees that would meet regularly in person or by phone and direct activities of staff. Members had some difference of opinion about the focus of an initial list of subcommittees proposed by the chair. Several members noted that there would have to be considerable communication across the subcommittee lines. Dr. Katz emphasized the view that one subcommittee must be largely focused on recommendations for future ethical behavior, and argued that proposals placed too much emphasis on the 1974 adoption of IRB rules as a clear guiding line. Ms. King expressed concern that the subcommittee structure might inhibit consideration of subjects across subcommittee lines. Other members felt the subcommittees should first proceed to the descriptive task, as the chair phrased it, or to discovery, as Mr. Feinberg described it. Members agreed to establish several subcommittees: Outreach. Outreach to the radiation survivors, professional communities and the public. Drs. Tuckson, Macklin, Lederer, Royal and Ms. Norris. Scope. Examining the charter of the Committee and determining if other cases (the Navajo, Micronesia) should be taken up by the group. Drs. Thomas and Royal and Mr. Feinberg. Data/Cold War. Overseeing searches for government-sponsored research in the Cold War. Drs. Glatstein, Oleinick, Stevenson and Ms. King. Data/Ethics. Drs. Macklin, Glatstein, Lederer and Faden. Staff Report: Department of Energy. Members revisited the specific directions to staff contained in the Staff Report on the DOE document searches. All eight specific Options proposed were approved, as summarized in the following: Option 1. DOE should proceed with the strategy of developing, in the near future, a comprehensive guide which will identify pertinent collections of records at various sites. Option 2. DOE should immediately focus on collections of high-level documents which can be immediately retrieved and made available. Option 3. DOE should focus on defining categories of classified documents not previously addressed that may contain relevant documents. Option 4. Focus on documentation of AEC radioisotope licensing process. Option 5. Provide the Committee with ``work for others'' study performed for Secretary Watkins. Option 6. Provide documents supporting the 1974 Inspector General's report on plutonium injection experiments. Option 7. Provide the Hotline database to the Committee. Option 8. Identify the most efficient means of accessing data from the National Archives. Staff were also directed to seek information from other universities that may have been involved in human experimentation other than the universities of Rochester and Chicago. Members said that secondary sources, such as libraries or grant offices, might yield additional information beyond the information tracked through funding sources and government documents. Staff Report: Health and Human Services. Members revisited options five and six proposed in the HHS Staff Report regarding interviews. Ms. King emphasized the need for Committee direction to staff about who should be interviewed by agencies, and what information should be sought by what questions. Security Clearances Members discussed whether clearances needed to be required of all members or of none, and whether clearances could be obtained but not acted upon. The questions were to be referred to the subcommittees for discussion. Members agreed to meet in subcommittees briefly before the close of the regular meeting. Mr. Caplan of the White House adjourned the meeting at 2:54 p.m. APPENDIX A The following persons signed in to attend all or part of the Committee's meeting: Karen MacPherson, Scripps Howard News Service; Marina Volkov, Federation of Behavioral, Psychological and Cognitive Science; John W. Billett, Health Physics Society; Sharon Brown, Battelle/PNL; Ellyn Weiss, DOE; Amy McClair, University of Cincinnati; Virginia Johnson, Gene Yount, Vince Morantis, Hal Halpern, DOE; Susan Crandall, OASIL; David George, Katy Hawkins, U.S. Navy; Peter Stewart-Harry, NIH; Traci Watson, U.S. News and World Report; Herb Perrone, ABC News; Sid Shaw, VA; Stephanie Niemier, Fred Bonkovsky, NIH; Lynn Zanski; Rebecca Kupper, American College of Radiology; Charles Sherrill, Bonneville Broadcasting; Bob Hohler, Boston Globe; Paul Barton, Gannett News Service; Craig Cobdell, DOE; Philip Hilts, New York Times; Gary Sanders, Ken Groves, Los Alamos National Laboratory; Earl Lane, Newsday; A.K. Tyrin, E.R. Johnson Assoc.; Sarah Comley, International Observers; Tom Popa, DOD (RECC); Gary Lee, Washington Post; Dan Glick, Newsweek; Marty Hamed, OUSD (P&R); William L. Freeman, IHS: Fred Allingham, National Association of Radiation Survivors; Lantz Miller, Society of Nuclear Medicine; H.W. Cummins, RADLAW; Daryl Kimball, Physicians for Social Responsibility; Stacey Cunningham, American Psychology Association; Eliot Marshall, Science; Stan Cimmons, AAMC; Colin Macilwain, Nature; Gerald J. Merritt, USAF; Wendy J. Fibison, NIH; Stephanie Shenier, DOD (ROCC). Attending from the Committee staff were Faith Bulger, Kristin Crotty, James David, Jerry Garcia, Dan Guttman, Gregg Herken, Deborah Holland, Jeffrey Kahn, Lanny Keller, Jeanne Kepper, Stephen Klaidman, Anna Mastroianni, Ron Neumann, David Saumweber, Jeremy Sugarman, Gary Stern, Donald Weightman and Gilbert Whittemore.