INTRODUCTION CHARGE AND MANDATE The Advisory Committee on Human Radiation Experiments was created by President Clinton to advise the Human Radiation Interagency Working Group [1] (the "Interagency Working Group") on the ethical and scientific criteria applicable to human radiation experiments carried out or sponsored by the U.S. Government. (See Appendices A and B for Executive Order and Charter.) The Committee is composed of 14 members, including a citizen representative and 13 nationally recognized experts in bioethics, radiation oncology and biology, history of science and medicine, epidemiology, nuclear medicine, and law. (A list of Committee members is attached as Appendix C.) Human radiation experiments are defined by the Committee's Charter to include "(1) experiments on individuals involving intentional exposure to ionizing radiation. This category does not include common and routine clinical practices . . . . (2) experiments involving intentional environmental releases of radiation that (A) were designed to test human health effects of ionizing radiation; or (B) were designed to test the extent of human exposure to ionizing radiation." [2] The Committee is mandated to review experiments conducted between 1944 and May 1974, the date the Department of Health, Education, and Welfare issued regulations for the protection of human subjects. Experiments done after May 30, 1974, may be sampled to determine if further inquiry into experiments is warranted. The Committee is also mandated to determine the ethical and scientific standards and criteria by which to evaluate the pre- May 1974 experiments, and the extent to which the experiments were consistent with such standards. The Committee "shall consider whether (A) there was a clear medical or scientific purpose for the experiments; (B) appropriate medical followup was conducted; and (C) the experiments' design and administration adequately met the ethical and scientific criteria, including standards of informed consent, that prevailed at the time of the experiments and that exist today." [3] Upon completing its review, the Committee may recommend that subjects (or families) be notified of potential health risks and the need for medical followup, and it "may recommend further policies, as needed, to ensure compliance with recommended ethical and scientific standards for human radiation experiments." [4] HOW THE COMMITTEE FUNCTIONS The Committee, as a Federal advisory committee, is an exercise in open government. Basic decisionmaking is conducted in open public meetings. The Committee has scheduled 13 (generally two-day) full Committee meetings over the course of its one-year term. In addition to a full Committee meeting in San Francisco, the Committee has scheduled at least three other public comment sessions in different regions of the country, as discussed below. Each meeting is announced in the Federal Register. (Dates and locations of meetings can be found in Appendix D.) At each meeting, staff and Committee members provide progress reports on the range of ongoing and anticipated tasks and projects. These have included the investigation and retrieval of documents related to agency searches, experiments and the world in which they were set, institutions of interest, past and present ethics policies, and contemporary research practices. Each meeting includes a public comment period. Committee meetings also include self-education presentations on the relevant aspects of radiation, ethics, law, history of experimentation, and Federal regulation. All meetings are transcribed, and the transcripts and meeting minutes are available to the public. The Committee has been extremely fortunate to assemble a multidisciplinary staff of substantial talent. The staff currently includes 34 full- and part-time members, supplemented by several expert consultants. The staff includes individuals with backgrounds in internal medicine, nuclear medicine, bioethics, physics, epidemiology, molecular biology, history (e.g., radiation science, human experimentation, the Cold War), law, health policy, communications, archival creation and management, and information systems development. The staff works at the direction of the Committee, and subcommittees have been formed to oversee staff work between meetings. The staff also consults with experts in dose reconstruction and other relevant technical areas. As discussed in Part III of this report, outreach is an essential component of the Committee's activities. Staff routinely meets with individuals and groups who are interested in learning about the Committee and from whom the Committee can learn. A public reading room at the Committee's offices contains basic Committee materials (such as Committee meeting briefing books and transcripts) and key collections of historical documents assembled by the Committee. The Committee expects that indices to document collections and its experiment database will shortly be available on Internet. THE COMMITTEE'S APPROACH The Committee seeks to answer several fundamental questions: (1) What ethics criteria should be used to evaluate human radiation experiments? (2) What was the Federal Government's role in human radiation experiments? (3) What are the criteria for determining appropriate Federal responses where wrongs or harms have occurred? (4) What lessons learned from studying past and present research standards and practices should be applied to the future? The Committee has been gathering vast amounts of information and working to render it orderly and accessible. Its members are currently engaged in the complex task of analyzing the scientific and ethical standards and procedures by which experiments on human subjects should be judged, both retrospectively and in the present. Once this task is completed, the Committee will draft a final report answering the above questions in the form of recommendations to the Interagency Working Group. Created in tandem with a Presidential directive that the executive branch be open to searching inquiry, the Committee began its work with few records, a huge task, and a short time frame. The work began with an examination of a largely untold part of the history of the Cold War. The examination entails digging into warehouses full of public and private records and probing the memories of numerous individuals. The Committee's work involves integrating ideas and information relating to big science and microdoses of radioactive isotopes, global policy and knotty ethical dilemmas, and the pain and fear of ordinary individuals. But this represents only half the job. The Committee is convinced that an important determinant of its success will be its ability to understand the present as well as, if not better than, it understands the past. Therefore, it has taken on the task of sampling and evaluating the ethical practices and standards governing human radiation research today, in order to determine whether change is needed. Among the obstacles the Committee must overcome in meeting its mandate is the lack of a common language to address the technically complex, often highly emotional issues related to human radiation experimentation. The voices to which the Committee must listen speak in the languages of medicine, a multiplicity of sciences, the military, sick patients, healthy subjects, policymakers, philosophers, and individuals in a variety of other roles. The Committee is seeking out and paying careful attention to everyone it can find who can contribute to its understanding, and it is working hard to bridge the linguistic and cultural gaps that can hinder its progress. [5] Together with the documentary evidence that the staff has unearthed and is continuing to gather, the Committee is drawing on these disparate voices to articulate the vital themes that will give structure and substance to its final report. To date the Committee has identified nine such themes, italicized in the paragraphs that follow, but other themes may come to light as the work shifts to analysis and normative judgment. It was obvious to the Committee from the language in its charter that a primary theme would be consent standards and procedures. A cornerstone of modern research ethics is the requirement that research proceed only with the informed consent of a competent subject or with adequate safeguards to protect the interests of a subject who cannot give consent. It now appears that, as it relates to government-conducted or government- sponsored research, this requirement and its application have evolved over time. It is important to understand when these policies and practices were adopted; when, if ever, the requirement was disregarded; and why. Similarly, it was clear that the Committee would have to make assessments of the potential harms and benefits of the experiments it is charged with studying. It is in the nature of most research that subjects may be exposed to risks in order to obtain desired information. It is therefore important to understand (to the extent possible) the level of risk to which subjects were exposed, as well as researchers' perceptions of the risk. It is also important to assess whether the potential benefits to the subject or to society were sufficient to justify the risk to which subjects were exposed. The Committee is aware that, within and outside the scientific community, there is study and debate regarding the effects of low doses of radiation. The Committee must be sensitive to all viewpoints. At the same time, the Committee and the public must understand the relation between this discussion and the Committee's charge. For example, the doses in historical experiments evaluated by the Committee may not differ from those in use today in routine and accepted diagnostic procedures. It is not the Committee's charge to go beyond presently accepted radiation standards. By the same token, it is not the Committee's view that contemporaneously accepted practices are risk free, and can have no health effects; accepted practices often may well involve risks. It is the Committee's charge to assess whether the risk, however low, was justified. For example, were subjects informed of the risk and the purpose(s) for its being undertaken? Was their consent obtained? Where consent was obtained, were some populations (e.g., indigent persons) chosen as subjects to the exclusion of others? Another theme the Committee noted early in its work concerns the selection of research subjects. The ethics of research turn as much on considerations of justice in the selection of subjects as they do on questions of consent or acceptable risk. The Committee deems it essential that it examine whether particular populations were targeted for participation as research subjects because of their relative lack of economic, social, or political power. For instance, fetuses, infants, children, prisoners, soldiers, minorities, the poor, the terminally ill, persons with cognitive disabilities, and the institutionalized may have been chosen as subjects because of their relative powerlessness. The Committee also recognizes the importance of understanding the organizational and structural context in which experiments were carried out. This theme includes the way in which (and by which) agency experiments were funded, the evolution of the institutions involved in the experimentation, and the way in which decisions were made. This area also addresses questions such as who decided which experiments and research programs were carried out and which were not, and by what authority these decisions were made. Along with the institutional factors, the Committee recognizes the human elements that must be taken into account if it is to fulfill its mandate. For example, what were the attitudes of researchers about the experiments they were conducting? How did researchers reason about whether to use animal or human subjects for their experiments? What were researchers' personal views about what constituted an acceptable consent from a subject? What did the word "informed" mean to the researchers in the context of consent? Although the Committee was appointed in response to potential abuses, it was evident to members from the outset that the medical and other scientific benefits of radiation was a theme that deserved attention. A great many diagnostic, therapeutic, and basic science applications have been developed as a result of government-sponsored research involving radiation. The story of human radiation experiments would be incomplete if it did not include an account of the benefits derived from this research. Because radiation experimentation evolved in tandem with the development of nuclear weapons, it seemed inevitable to the Committee that national security considerations would become part of the radiation experimentation story. Therefore, the relationship of experimentation, secrecy, and national security forms an important theme for the Committee to consider. One key question is the extent to which national security may have been invoked to justify the bypassing of ethics policies or the intentional exposure of populations to releases of radioactive materials. Underlying all of these themes is a central question for the Committee: what was the role of the U.S. Government where harms or wrongs were done to citizens who took part in radiation research? Information about the knowledge or ignorance of Federal agencies and officials relating to harms or wrongs to research subjects, and the extent to which relevant policies were followed or violated, will inform the Committee's conclusions and recommendations. Finally, the over-arching context for the Committee's retrospective judgments is that during the historical period specified by its charter (1944-1974), the United States was not only in the throes of the Cold War, but it was also living through the early stages of a profound scientific and social revolution. It was the dawn of the Atomic Age. The power of the atom was seen as a source of great promise--it would cure cancer and provide limitless cheap energy. But it was also the source of the most destructive force ever created by humanity and unleashed on the earth. A complete understanding of human radiation experiments must situate the research in this complex cultural context. TASKS AND STRATEGIES: AN OVERVIEW OF THE FIRST SIX MONTHS AND THE INTERIM REPORT In order to begin its task of evaluation, the Committee had to obtain basic information about the experiments it had identified and the worlds in which they were set. Relevant information might be located in any of hundreds of libraries or warehouses throughout the country, and in the memories of thousands of citizens. Time was short. The Committee had to develop a strategy to address the simultaneous undertaking of three basic tasks--information gathering, information organization, and information analysis-- each of which was fraught with uncertainty. The strategy had to be sufficiently disciplined to meet the Committee's time frame, yet sufficiently ambitious to understand and address the details of experiments with ionizing radiation, ethics policies governing them, and organizational charts of long-lost governmental organizations and agencies. At the same time, the strategy had to be sufficiently flexible to accommodate the possibility of dead ends, incomplete information, and most importantly, new discoveries leading to new avenues of research. Phase I: Gathering Information - "Big Picture" Mapping, Targeted Document Searches, and the Creation of Data Management Infrastructure The first phase of the strategy involved three components, the first of which was the development of a framework for all the information-the "big picture" into which the pieces of the puzzle could be fit. As discussed below, the components of this framework included: o An experimental database, to provide a single locale for cataloguing experiments as they are identified and storing basic information as it is retrieved; o An ethics timeline, to chart the evolution of Federal and private sector policies and practices pertaining to research ethics; o A scientific and medical standards timeline, to chart the evolution of these standards; and o Institutional maps, to plot the network of public and private institutions that planned, funded, managed, and performed the experiments and used the resulting data. The second component of this phase was an effort to identify the world of potential sources of information, and the most efficient methods to mine these sources. As discussed in Parts II - III below, for example, this strategy involved: o Refocusing agency document searches on headquarter level collections, in order to gain an overview of the forest in which individual experiments were set and identify data trails that might be followed; o Surveying private archives and library sources; o Initiating oral history, interview, and outreach projects to tap individual memories; and o Planning several research projects to assess and evaluate human experimentation that is ongoing today. The third component of this first phase of the strategy was the development of the technical infrastructure needed to house and make accessible the increasingly large body of information being received by the Committee. As discussed in Part IV, this component includes the creation of electronic databases available to both the Committee and the public. Phase II: Information Organization - Gathering the Threads, Focusing on Experiments While Phase I is still in progress, the Committee's brief tenure requires that it simultaneously focus on particular experiments (or groups of them) in order to begin the evaluative process. But on which experiments should energies be focused? The elements of the strategic problem include the following: (l) the number of pre-1975 experiments and intentional releases may well be in the thousands, and the number of post-1975 experiments even larger; (2) data gathering will remain incomplete even as evaluation begins; and (3) the Committee may be able to collect only fragments of data about many (and probably most) experiments. The need, therefore, was for a strategy that (l) made use of available data; (2) was likely to address particular experiments and releases of clear public concern; (3) would not neglect experiments and releases simply because applicable data were not readily available; (4) addressed experiments and releases that involved basic issues of concern to the public and the Committee; and (5) was sufficiently flexible so as not to be derailed by information roadblocks. The working solution for the pre-1975 world of experiments, as discussed in Part I, is a two-part strategy that combines (1) a focus on groups of experiments, with each group anchored by one or more well-publicized, widely discussed experiments; and (2) a focus on the institutions that conducted experiments, with each institution offering the opportunity to examine responsibility for decisionmaking about undertaking, funding, and performing experiments. The hope and expectation is that this strategy will permit an understanding of both important individual experiments (or groups of them) and the systems and contexts in which they were set. The working solution for the intentional releases is to determine (1) whether, at this late date, the public can learn who planned the releases, why, and what precautions, if any were taken; and (2) whether intentional releases, which were often shrouded in secrecy, could take place today in the absence of meaningful public notice. The working solution for the contemporary world of research involves three activities: 1. a review of a sample of recently funded research proposals (including radiation and non-radiation treatments), with the ethical evaluation focusing upon the processes of subject selection, harm/benefit, and informed consent and disclosure of information; 2. interviews with subjects of current research, attempting to assess their attitudes and beliefs related to research participation; and 3. collection of current agency policies related to the oversight of research on human subjects. The details of the components and activities of Phase II are discussed in the body of this interim report. Phase III: Information Analysis - Evaluation and Recommendations While Phase I continues, and Phase II has just begun, the Committee must simultaneously turn to the Phase III tasks of evaluating past and present experiments, recommending policy changes, and developing criteria for a range of remedies that may be appropriate where wrongs or harms have occurred. The development of a strategy for this effort is the immediate priority of the Committee as the first six months of its tenure come to an end. Specifically, the Committee currently is focusing on the development of ethical standards for judging past and present experiments and releases, as well as the above mentioned criteria. In Part V of this interim report, the Committee takes stock of where it has been; in Part VI the Committee summarizes the work to be done in the next six months. ********** 1 The members of the Interagency Working Group include the Secretaries of Defense, Energy, Health and Human Services, and Veterans Affairs; the Attorney General; the Administrator of the National Aeronautics and Space Administration; the Director of the Central Intelligence Agency; and the Director of the Office of Management and Budget. 2 Charter, section 3, Appendix B. 3 Charter, section 4.a, Appendix B. 4 Charter, sections 4.c and 4.d, Appendix B. 5 At the end of this report is a sampling of the bureaucratic terms and acronyms that punctuate the Committee's reading material, and to some extent this interim report. Interim Report of the Advisory Committee on Human Radiation Experiments, October 21, 1994