ADVISORY COMMITTEE ON HUMAN RADIATION EXPERIMENTS Minutes: September 12-13. September 12, 1994 Attending: Ruth Faden, Eli Glatstein, Jay Katz, Pat King, 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 and the designated federal official of the Advisory Committee, opened the meeting in the Federal Room of the Ramada Plaza Hotel, 10 Thomas Circle, Washington, D.C. Dr. Faden briefed members on the agenda for the meeting. Staff Report: Introductions and Current Assignments. Jeffrey Kahn. Dr. Kahn introduced new members of the staff: Robin Cochran, Gail Javitt, John Kruger, and newly retained consultant Suzanne White-Junod. Approval of Minutes Members approved the minutes of the meeting of July 25-26 without objection. Staff Report: Update on Ethics Policies and Procedures. Jonathan Moreno. Dr. Moreno briefed the Committee on the debate in the Department of Defense's Committee on Medical Sciences over informed consent rules. The staff outlined the discoveries of the debate prior to adoption of the 1953 Wilson memorandum establishing the Nuremberg Code as Department of Defense policy, and the process by which policies were developed following the Wilson memorandum. A significant addition to this history was the surgeon general's 1962 interpretation that testing and operation of prototype equipment was outside the normal duties of soldiers, and thus apparently fell under the Wilson rule. Dr. Moreno discussed efforts to fill out the documentary record on the context of debates within the government on informed consent issues, and the role of legal liability concerns in the debate. Implementation of the Wilson directive continues to be a focus of document searches, as does the explication of ethical issues with respect to intentional releases and experiments of opportunity. Members discussed questions of intent as guides to ethical judgements, and legal liability concerns as a motivating factor for keeping exposures secret. Dr. Russell observed that much that the military did in the postwar world involved trying new methods of organization, of tactics and of weaponry to adapt to changing times. He noted that different agencies of the Department of Defense were likely to define experimentation and maneuvers, such as those that took place at the Nevada Test Site, in sharply different ways. Dr. Royal noted that the Committee has a limited time frame for discovery and a wide range of experiments, therefore the Committee must make hard decisions about what to pursue in depth. He noted that bringing these issues to light in a public forum may be a significant contribution even where the Committee does not have the resources to exhaust the topic. Members questioned Dr. Moreno on the differences between experimentation and training of soldiers; on the moral issues raised in the Committee on Medical Sciences; and whether rules such as those contained in the Wilson memorandum were followed in day-to-day operations of armed services or research agencies. Professor King said the question of motivation for policies is of less interest than the acceptable outcomes of the policies. Staff Report: Human Experimentation in Connection with Atomic Bomb Tests. Gregg Herken and Dan Guttman. Dr. Herken summarized the history of atomic weapons tests within the continental United States, a total of more than 900 tests until 1963. He traced the differences between the military and the Atomic Energy Commission on troop exposure rules, leading to military agencies taking responsibility for radiological safety in the maneuvers. Mr. Guttman said that the Joint Panel on the Medical Aspects of Atomic Warfare appears to be increasingly central to the question of human subject experiments at weapons sites. Mr. Guttman said records indicate that vision tests were included in the biomedical component of the tests in 1951-53, and studies at Walter Reed Army Institute of Research were conducted in connection with the Teapot test series in 1955. The tests were discussed in Congressional testimony in 1959. Tests involving cloud fly-throughs grew out of a 1948 accidental exposure of an aircrew. Mr. Guttman said many questions remain about what procedures were used in the operations; what other ethical debates occurred; and, what group or groups inherited responsibility for the planning after the Joint Panel was discontinued in 1953. Members discussed how to define biomedical experimentation in the weapons testing program, including psychological testing in troop maneuvers. Dr. Macklin suggested that exemptions from the Wilson policy for occupational exposures may have allowed the Department of Defense to avoid acknowledging that it was conducting research. Dr. Oleinick noted the repeated exposures as part of the cloud fly-throughs, and suggested that a reasonable question is how many were necessary. Dr. Russell observed that the military was having parallel discussions about combat effectiveness at the time, and Dr. Royal said that measuring radiation dosages may suggest an appropriate concern for pilot safety. Staff Report: Management Theme/Pilot Case Study. Oak Ridge and Los Alamos. Donald Weightman and Barbara Berney. Mr. Weightman discussed goals of in-depth looks at key institutions involved in radiation research. Staff work in this area is intended to show how decisions were carried out in the field, why specific projects were undertaken or rejected, and get a range of perspectives on how work was actually done across a variety of types of work at the time. He traced findings about gallium 72 studies in 1950-53 at Oak Ridge Institute for Nuclear Studies. Oversight roles for the gallium studies were more difficult to assess in light of gaps in the records of various committees. Dr. Royal noted that a stable isotope of gallium is routinely used today in diagnostics, and Mr. Weightman said that point addresses the issue of knowledge -- the gallium 72 study didn't work out but may have expanded the base of knowledge that aided in development of subsequently successful interventions. Not enough information is available to determine the scope of toxicity studies. Dr. Macklin asked about the distinction between waivers and consent forms at Oak Ridge. Jonathan Harkness of the staff reported that a 1958 Irving Ladimer thesis explained that Oak Ridge brochures explicitly required a commitment to a period of research as a condition of hospital admission. Dr. Berney discussed Los Alamos research focusing on weapons development, the principal mission of the facility, and protection of the workforce of the weapons facilities. A number of intentional releases took place, but frequently with minimal exposures to human beings. A number of sets of experiments conducted in Los Alamos had wider implications: experiments with chelation agents and experiments with radioactive iodine were among the portfolio. There is currently no evidence of motivation other than basic science for extensive tracer experiments and metabolism studies. Many employees were used as experimental subjects, and some of them report that they were knowledgeable and consenting volunteers. When employee volunteers reached limits of permissible exposure, Los Alamos turned to outside institutions like the Kiwanis Club. Need for secrecy militated against use of outsiders at the weapons complex, but there is little information about how or whether indigent patients at the hospital or other subjects were informed of experimentation. A process was established to approve experimental proposals, but records are not clear on informed consent issues. Dr. Royal said that a CNN documentary aired this spring included interviews with experiment subjects who are children of researchers. Dr. Faden said the staff would seek a tape for the Committee. Staff Report: Update on Agency Data Collection Efforts. Ruth Faden. Dr. Faden reported on the status of agency record searches in the National Aeronautics and Space Administration, Departments of Veterans Affairs, Health and Human Services and Defense. Dr. Faden noted that Denise Holmes has found new information in the Stafford Warren papers in Los Angeles, and the material will be digested for the next meeting. Dr. Faden said the Defense Nuclear Agency in particular has found significant new records, and Health and Human Services has devoted more staff to records searches in the Cold War period. Charles McCarthy has joined the staff as a consultant to assist in the Health and Human Services research. The Department of Energy has begun contacting universities involved in plutonium injections, but also has reported that records of the AEC/Energy Intelligence Division are likely to have been destroyed. Energy and Defense have facilitated the flow of formerly declassified material. Mr. Stern reported on the data collection efforts at the Central Intelligence Agency. The CIA had previously reported to the Committee that it could find no records of CIA-sponsored experiments involving human experimentation with ionizing radiation, or records relating to experimentation by other agencies. New records from the Defense Department indicate that the CIA was an associate member of the Defense Department's Committee on Medical Sciences, and representatives of the CIA appear to have attended meetings of that Committee and the Joint Panel on the Medical Aspects of Atomic Warfare relating to human experimentation. The Committee has asked the CIA to pursue this new information by searching for relevant documents. Subcommittee Report: Oral History. Susan Lederer. Dr. Lederer briefed members on the questions for the oral history project, which is expected to gain IRB approval by the end of September. She emphasized the effort to gain perspectives from practitioners in different types of research, e.g., surgical research, infectious diseases, military medicine. Members made suggestions about phrasing of questions and suggested inquiring about experimentation with children of interviewees as subjects. Dr. Lederer said the questions may be revised after initial experiences with interviews, and Dr. Katz suggested that the first transcript be promptly circulated to members for feedback on additional questions that might be added. Subcommittee Report: Protocol Review. Ruth Macklin. Dr. Macklin said the subcommittee's report includes the addition of a review of journal articles on research involving more than minimal risk. Members agreed that the study ought to include review of comparable studies involving agents other than radiation. Dr. Kahn reported on the gathering of abstracts from agencies. Health and Human Services provided significant material. NASA has not sent the abstracts requested, the Department of Energy has provided abstracts, Veterans Affairs provided little information to date, and the Department of Defense reported that its abstracts will have been provided by September 13. Dr. Macklin outlined the considerations for selection of protocols to be surveyed and the criteria for assessing the protocols. The process will include the request of information from the IRBs involved in protocols of interest. She added that the study will allow for a comparison of radiation research with other human research. Members discussed motivations for patients to engage in studies or in control groups, in the case of those for whom treatment is not indicated; definitions of clinical practice, risk factors and disadvantaged populations. Professor King questioned the usefulness of a review of journal articles, and a decision on the issue was postponed until the next conference call of the Protocol Review Subcommittee, in which Dr. Thomas and Professor King would join. Professor King noted that time frames should be included with every subcommittee report because of the time pressures facing the Committee. Subcommittee Report: Outreach. Reed Tuckson. Dr. Tuckson reported on the Outreach subcommittee's plans for an extended public comment period at the October meeting in San Francisco. The first panel hearing was set for October 21 in Cincinnati, coinciding with the meeting of the Task Force on Radiation and Human Rights. Dr. Tuckson praised the assistance of the Task Force in the work of the Committee. The subcommittee will continue to look for ways to further collaborate with the Task Force and others. The subcommittee proposed panel hearings in Spokane, Washington, Monday, November 21; Santa Fe or Albuquerque, New Mexico, Monday, January 30; Nashville, Tennessee, Friday, March 24. Professor King emphasized that the public hearings be seen as open to all points of view, gathering information to generate a range of perspectives for the Committee. She suggested that the March 24 meeting may be late for input, and the subcommittee agreed. The staff will consider, after the interim report is released, whether a summary or fact sheet should be distributed after each Committee meeting to keep interested parties informed of Committee activities. Members agreed to contact Communications Director Stephen Klaidman with dates on which they can participate in panel hearings. Public Comment Ruth Blaz, Hollywood, Fla. Mrs. Blaz addressed the Committee about the medical problems her son has endured since a 1947 radiation treatment. She read into the record a statement by her son, Joel Blaz. Mrs. Blaz made copies of her son's medical records available to the Committee. Cliff Honicker, Environmental Health Studies Project, Knoxville, Tenn. Mr. Honicker presented a series of documents regarding postwar federally funded experiments at the Medical College of Virginia, which had been the subject of presentations at the July 25-26 meeting. Mr. Honicker said he would share copies of the documents with the Committee. Mrs. Frances Brown, Southwick, Mass. Mrs. Brown told the Committee of her late husband's experience as a navigator who flew through clouds at weapons tests. She said Colonel Brown was assigned the duty and was given no protective clothing; he died of cancer in 1983. Tod Ensign, Citizen Solder, New York, N.Y. He urged the Committee to pursue more information about groups of volunteer officers who were placed near atomic blasts. He said that volunteer officers were too near ground zero for other than physical-effects experimentation. Mr. Ensign said the Committee should recommend compensation for persons who can demonstrate radiogenic cancers as a consequence of federally funded exposures. Pat Broudy, National Legislative Director, National Association of Atomic Veterans. Mrs. Broudy presented to the Committee a set of documents relating to radiation exposures at Marshall Islands and Nevada atomic tests. September 13, 1994 Attending: Ruth Faden, Kenneth Feinberg, Eli Glatstein, Patricia King, Susan Lederer, Ruth Macklin, Lois Norris, Nancy Oleinick, Henry Royal, Philip Russell, Mary Ann Stevenson, Duncan Thomas. Subcommittee Report: Subject Interview. Ruth Faden. Dr. Faden said the subject interview program is under review by the Office of Management and Budget, as required by the Paperwork Reduction Act. The subcommittee will conduct three sessions with oncology specialists to solicit ideas about how to better conduct the project. The Committee agreed that in the interest of time minor changes in the project suggested by the specialists panels could be incorporated into the project without bringing the matter back to the full Committee. Subcommittee Report: Intentional Releases. Duncan Thomas and Nancy Oleinick. Dr. Oleinick reported that data gathering continues. The subcommittee is looking with special interest into following up documents relating to human experiments during atomic bomb tests, particularly what troops were told and how data from exposures were evaluated. Indoctrination materials and reports of what was learned are of interest. The subcommittee proposed using the 1965 KIWI nuclear rocket test at Los Alamos as a case study. The test provides considerable available information, involved a number of agencies, and included at least some surveying of exposure to pilots of airplanes flying through clouds. Dr. Thomas said the volunteer observer program at weapons tests deserves close study. Dr. Oleinick said the Committee's purposes require the targeting of its research as narrowly as possible to generate enough information to evaluate how biomedical tests were carried out and how the knowledge gained was used by government or scientists. Dr. Faden said the Committee's charge requires a focus on issues involved in human subject experimentation, rather than being drawn too far afield. Subcommittee Report: Biomedical Experiments. Mary Ann Stevenson and Henry Royal. The subcommittee reported that it has worked with analyses of dosimetry contributed by staff and members, but the subcommittee feels that the available dose information is generally insufficient to evaluate the level of risk in many experiments. Ethical evaluations of experiments, as a general rule, are not likely to be easily determined on the basis of clear examples of inappropriate dosages. The subcommittee proposed circulating a document which summarizes different points of view about the information available from case studies of total body irradiation and plutonium injection experiments. The Committee approved the proposal. Dr. Macklin questioned how researchers made ethical decisions in the 1940s and 1950s, if today's knowledge does not make clear what dosages are dangerous. She said that medical professionals should have acted with great caution and a more conservative approach to dose levels. Dr. Stevenson said that there was a much more substantial body of knowledge about high- dose effects soon after exposure, but much less sophisticated knowledge of radiogenic carcinogenesis, although some information was available to researchers and their government employers. Dr. Royal observed that the fundamental reason for research is to probe the unknown. Briefing: Radiation Dosages. Henry Royal. Dr. Royal briefed members on how doses are estimated, how radiation affects different organs, and how experimental exposures might be evaluated. He noted how difficult it is to do dose reconstruction, and listed areas of concern in the record of the Cincinnati and plutonium injection experiments before the Committee. Members questioned Dr. Royal about the determination of levels of risk in occupational exposures; harm and benefit ratios; medical uncertainty and its impact on research decisions. Committee Discussion: Harms and Risk. Members discussed how judgments could be rendered in cases where experimental subjects were exposed to little or no measurable risk of harm. Mr. Feinberg said that a lack of a clear dividing line on harms may make a difference in how Committee members approach their judgment about remedies. While risk is most often calculated in terms of excess deaths, Dr. Macklin said that remediable injury may be defined in other terms. Dr. Royal said that there are calculations that can be made about the detrimental effects of exposures other than fatal effects, but that the decrement is very small in the type of exposures common in medical research. Dr. Stevenson said the limited time available to the Committee for its work suggests that complex dose reconstructions must be limited to cases where there is good reason to believe such a study is necessary. Staff Report: Classification of Documents. Don Weightman. Mr. Weightman briefed members on plans to review classified material and decide whether to target specific documents or collections for agency declassification efforts. Only two staff and one Committee member have obtained security clearances so far. Members with clearances may be asked to participate in document reviews from time to time. Staff Report: Draft Interim Report Outline. Anna Mastroianni. Anna Mastroianni reported that a staff draft of the interim report will be circulated to members for review before the October meeting. Dr. Faden said that the report is a progress report and will not draw conclusions about issues before the Committee. Mr. Guttman said the report must include a projection of whether the Committee's work will be concluded on time. Professor King said the report should try to project a plan for completion of the project in April. Dr. Faden said that the Committee may need an additional few months to complete its final report. Members suggested a separate section in the outline that would describe the interaction with agencies; and members suggested the draft include categories that group Committee activities in relation to general subjects that may be reflected in the final report. Public Statement Dr. Faden noted, in the interest of openness, that three members of the Committee -- Drs. Glatstein, Royal and Stevenson - - are members of the American College of Radiology. She also noted that Dr. Royal is listed as a coauthor with Eugene Saenger of articles on Chernobyl exposures, but that Dr. Royal and Dr. Saenger worked independently as part of an International Atomic Energy Agency study project. Dr. Royal submitted a letter for the record outlining the circumstances of the Chernobyl study, and Dr. Faden said the instances do not represent a conflict of interest for the purposes of the Committee. Committee Discussion: Goals and Priorities. Ruth Faden. Members discussed outstanding issues remaining to be decided at this meeting, falling generally into contemporary and Cold War sampling methods. Contemporary period. Dr. Faden summarized the 1993 protocol review as the Committee's major study to meet the Committee's charge to review the ethics of a sample of existing human radiation research. She said the journal review proposal would remain open to decision by the subcommittee with input of other members. Members agreed without objection. 1942-74 period. Dr. Faden said the Committee's work to date suggested numerous potentially profitable lines of inquiry. These included: a case study of an institution or institutions, such as Oak Ridge; intensive study of controversial experiments and those intentional releases listed in the Committee charter; a sample of the extensive listing of biomedical experiments, e.g., learning everything possible about the total body irradiation experiments; sampling or selecting studies of subject groups of interest, e.g., children or pregnant women; sampling or selection of experimental groups by the source of funding. Members discussed strategies of how to generate useful information about the different categories of studies; the need to speak to issues raised in the public mind because of controversy surrounding some experiments; the need to link search priorities to prospective recommendations in the final report; and how to grapple with issues of management and funder influence in the direction of experiments. Dr. Faden said a consensus suggests doing one intensive study of a national laboratory and one intensive study of a veterans hospital/university site, such as the University of California at Los Angeles. Professor King asked that the staff be directed to develop a recommendation about whether to undertake a third study, either another national laboratory or a special institution like the School of Aviation Medicine. Dr. Faden said that, in the interest of saving time, there may be a fax-poll of members about appropriate institutions for in-depth study. Several members said that the role of children as subjects should be given major emphasis in the final report. Professor King and Dr. Stevenson were asked to work with Dr. Sandra Thomas of the staff to determine whether sufficient information will be available to support such a study. Dr. Faden asked members to rank their suggested priorities among the potential lines of inquiry discussed for the 1942-74 period. Members discussed the resources of time and staff available for various options, which were ranked as follows: 1. Well-publicized Studies/Charter-stipulated Releases. 2. Institutional Case Studies (2). 3. Sampling/Selection within Biomedical Groups (Total body irradiation; biodistribution; tracers; radiation therapy and diagnosis; experiments of opportunity); 4. Sampling/Selection by Subjects: Children. 5. Sampling/Selection by Agency: Funding. Dr. Faden summarized the discussion as authorizing the staff to proceed with a detailed proposal for two institutional case studies, with perhaps a third to be determined. The staff was directed to circulate a list of heavily publicized experiments which require detailed analysis. Members agreed to the need to address issues raised by intentional releases in the Committee charter. In cases where there are heavily publicized experiments to deal with, every effort will be made to provide as much background as possible to provide a context for judging the appropriateness of the activities. To be pulled together before the next meeting is a report on children as a special case study, and Dr. Thomas and Dr. Berney of the staff were asked to consider an appropriate way to sample the world of biomedical experiments provided by government agencies. Dr. Faden said that for the moment, subcommittees would continue in their present structure, in addition to the subcommittee on Subject Selection/Children, on which would serve Dr. Faden, Professor King, Dr. Stevenson and Dr. Lederer. Mr. Caplan closed the meeting at 3 p.m. Approval The above minutes represent an accurate summary of the September 12-13, 1994, meeting of the Advisory Committee on Human Radiation Experiments. Ruth R. Faden Chair