 CHAPTER XVIII. The Advisory Committee recommends to the Human Radiation Interagency Working Group that the IRB component of the Federal System for the Protection of Human Subjects be changed in at least the five critical areas described below. 1. Mechanisms for ensuring that IRBs appropriately allocate their time so they can adequately review studies that pose more than minimal risks to human subjects. This may include the creation of alternative mechanisms for review and approval of minimal risk studies. The majority of the Advisory Committee's concerns in its research proposal review project centered on research that exposed subjects to greater than minimal risk of harm. If human subjects are to be adequately protected, such research must be carefully scrutinized. However, higher risk research is often complex and careful review is time-consuming and difficult. The Advisory Committee heard from several chairs of IRBs who underscored the difficulties their committees experience in finding the time to adequately review such research. Members of IRBs have only so many hours they can devote to review of proposals. This problem of inadequate time appears to have worsened in recent years. Institutional review boards are required to review research proposals prior to their review for funding by the National Institutes of Health. As the probability that a proposal will be approved for funding has decreased over time due to increasing competition for limited research monies, the number of proposals being submitted to NIH from many institutions has significantly increased. This has resulted in a substantial increase in the workload of some IRBs whose members are spending considerable time reviewing proposals that are never implemented. Without guidance from the federal government and perhaps regulatory relief, IRBs may not have the flexibility necessary to concentrate their efforts where subjects are in greatest need of protection on the proposals that pose the greatest risks to subjects and that are actually implemented. 2. Mechanisms for ensuring that the information provided to potential subjects, 1. Clearly distinguishes research from treatment, 2. Realistically portrays the likelihood that subjects may benefit medically from their participation and the nature of the potential benefit, and 3. Clearly explains the potential for discomfort and pain that may accompany participation in the research. The advisory committee's empirical studies and public testimony suggests that there may be considerable confusion in the minds of many members of the public concerning what is research or experimentation and what is simply an application of a new technology or even standard medical care. There is reason to worry that participants in research may have unrealistic expectations both about the possibility that they will personally benefit from participation and about the discomfort, pain, and suffering that sometimes accompanies some research. This seemed particularly to be the case in Phase 1 and Phase 2 drug trials. It is important that in the informed consent process it is clearly communicated to the potential subject, particularly the potential patient subject, that the primary intent of research is to advance medical knowledge and not to advance the welfare of particular subjects. Inadequate and potentially misleading information about potential benefits and harms and about the trade-offs between enrollment and research and standard or conventional treatment was one of the major problems identified by the advisory committee in our research proposal review project. 3. Mechanisms for ensuring that the information provided to potential subjects clearly identifies the federal agency or agencies sponsoring or supporting the research project in whole or in part and all purposes for which the research is being conducted or supported. A morally complicating factor in several of the human radiation experiments the advisory committee has studied is the tendency to disclose to subjects only the medical purpose of the research, if that, and not those purposes of the research that advance interests other than medical science or the sponsorship of agencies other than DHEW, DHHS. For example, in the case of the total body irradiation experiments the data gathered from the research had a military purpose, quite distinct from questions of cancer therapy. The purpose and funding source may be relevant to a person's decision to participate in human subject research and should be disclosed. 4. Mechanisms for ensuring that the information provided to potential subjects clearly identifies the financial implications of deciding to consent to or refuse participation in research. Many of the consent forms that the committee reviewed as part of the research proposal review project were silent on the subject of financial costs. However, knowing whether being in research costs or saves the money may be necessary for potential subjects to make an informed decision about whether to participate. Potential subjects need to know whether the interventions that are part of the research are free or must be paid for, and, if there are any financial costs, what they are, the likelihood that third-party payers will pay for these research-related medical services, and the extent to which the research institution will assist patient subjects in securing third-party payment or reimbursement. 5. Recognition that if IRBs are to adequately protect the interests of human subjects, they must have the responsibility to determine that the science is of a quality to warrant the imposition of risk or inconvenience on human subjects. And, in the case of research that purports to offer a prospect of medical benefit to the subjects, to determine that participating in the research affords patient subjects at least as good an opportunity of securing this medical benefit as would be available to them without participating in research. In research involving human subjects, good ethics begins with good science. In our research proposal review project, the advisory committee was unable to evaluate the scientific merit of a significant number of proposals based on the documents provided by institutions. We suspect that this occurred in part because there is ambiguity about the role that IRBs should play with respect to evaluation of scientific merit, and, thus, that documents submitted to IRBs may be inadequate in this area. The advisory committee also heard dissatisfaction with this ambiguity in our interviews and oral histories of researchers and from chairs of IRBs. If the science is poor, it is unethical to impose even minimal risk or inconvenience on human subjects. Although the fine points of the relative merit of research proposals are best left to study sections and other review mechanisms specially constituted to make such judgments, IRBs must be situated to assure themselves that the science they approve to go forward with human subjects satisfies some minimal threshold of scientific merit. In some cases, the IRB may be the only opportunity for this kind of scientific review. In our subject interview study interviews with patient subjects, we confirmed that patient subjects often base their decisions to participate in research on the belief that physicians and research institutions generally would not ask them to enter research projects if becoming a research subject was not in their medical best interests. For these patients, even the most candid, clearly written consent form affords little protection for both the consent form and the consent process are of little interest to them. For patient subjects whose decisions to participate in research are based on trust and not on an assessment of disclosed information, the IRB review is of special importance. It is the only source of protection in the federal system for regulating human research positioned to ensure that their participation in research does not compromise their medical interests. Such a determination, however, often requires more specialized clinical expertise than any one IRB can possess. Federal policy must make it clear that IRBs have the responsibility to make this determination, but it must also allow mechanisms to be devised at the local level that permit this responsibility to be satisfied in an efficient and effective manner. Recommendation 11 The advisory committee recommends to the Human Radiation Interagency Working Group that a mechanism be established to provide for the continuing interpretation and application of ethics, rules and principles for the conduct of human subject research in an open and public forum. This mechanism is not provided for in the common rule. Issues in research ethics are no more static than issues in science. Advances in biomedical research bring new twists to old questions in ethics and sometimes raise new questions altogether. No structure is currently in place for interpreting and elaborating the rules of research ethics. A process that is essential if research involving human subjects is to have an ethical framework responsive to changing times. Also, for this framework to be effective any changes or refinements to it must be debated and adopted in public. Otherwise, the framework will fail to have the respect and support of the scientific community and the American people, so necessary to its success. Three examples of outstanding policy issues in need of public resolution that the advisory committee confronted in our work are presented below. 1. Clarification of the meaning of minimal risk in research with healthy children, including, but not limited to, exposure to radiation. 2. Regulations to cover the conduct of research with institutionalized children. 3. Guidelines for research with adults of questionable competence. Of particular concern is more than minimal risk research that offers adults of questionable competence no prospect of offsetting medical benefit. Current regulations permit the involvement of children as subjects in research that offers no prospect of medical benefit to participants when the research poses no more than minimal risk. An important question that has come to the advisory committee's attention both in the literature and in our research proposal review project is whether research proposing to expose healthy children to tracer doses of radiation constitutes minimal risk. The uncertainty surrounding this issue calls into question the adequacy of the federal regulations, as currently formulated, in providing guidance for this category of research. This is a policy question that ought to be discussed and resolved in a public forum at the national level, not left to the deliberations of individual IRBs. Current regulations do not provide any special protections for children who are institutionalized, unless they are also wards of the state. Thus, researchers and IRBs have no more guidance from the federal government on the ethics of conducting such research than was available at the time of the Fernald and Rentham experiments decades ago. The advisory committee also confronted, in its research proposal review project, another issue of research policy deserving public debate and resolution in a public forum. This is the issue of whether and under what conditions adults of questionable capacity can be used as subjects in research that puts them at more than minimal risk of harm and from which they cannot realize direct medical benefit. It is important that the nation decide together whether or under what conditions it is ever permissible to use a person toward a valued social end in an activity that puts him or her at risk but from which the person cannot possibly benefit medically. Recommendation 12 The advisory committee recommends to the Human Radiation Interagency Working Group that at least the following four steps be taken to improve existing protection of the rights and interests of military personnel with respect to human subject research. 1. Review of policies and procedures Policies and procedures governing research involving human subjects should be reviewed to ensure that they, one, clearly state that participation in research subjects by members of the armed services is voluntary and without repercussions for those who choose not to participate. And, two, clearly distinguish those activities that are research and therefore discretionary on the part of members of the armed services from other activities that are obligatory such as training maneuvers and medical interventions intended to protect the troops. 2. Appreciation of regulations Education in applicable human subjects regulations should be a component of the training of all officers and investigators who may be involved in decisions regarding research on human subjects. Mechanisms are needed to ensure that officers expected to have command responsibilities and all officers engaged in research, development, testing, and evaluation have an adequate appreciation of the regulations, including DOD regulations and directives and service regulations, that bear on the conduct of research involving human subjects, including an appreciation of the conditions under which such regulations apply, the role of officers in interpreting such regulations, and how such regulations are to be implemented. 3. Maximizing voluntariness The service secretary should consider the situations under which it would be appropriate to make obligatory two practices for maximizing voluntariness that have been employed on an ad hoc basis in some military research. First, that unit officers and senior non-commissioned officers, NCOs, who are not essential as volunteers in the research, be excluded from recruitment sessions in which members of units are informed of the opportunity and asked to participate in research by investigators. And second, that an ombudsman, not connected in any way with the proposed research, be present at all such recruitment sessions to monitor that the voluntariness of participation is adequately stressed and that the information provided about the research is adequate and accurate. The advisory committee recommends consideration of steps one through three above in light of our examination of history that makes plain how difficult it often is, in a military context, to distinguish an order from a request for voluntary participation and to distinguish research from training. These tensions are similar in many respects to tensions in the clinical context between research and treatment. Although the military has a long tradition of commitment to the use of volunteers in research and has introduced significant advances in the military system of protection for human subjects since the 1940s and 1950s, without constant attention to these inherent tensions, the potential for confusion and inappropriate practice continues. The military setting, with its strict hierarchical authority structure and pervasive presence in the lives of its members, poses special problems for ensuring the voluntariness of participation in research activities. Thus, although the DOD has adopted and implemented the consent requirements of the common rule, additional procedural safeguards and educational activities for officers may be warranted to counteract the generalized deference to authority inherent in military culture. Also, because the opportunity to serve the nation as subjects in defense-oriented research projects is closely akin to the demands placed on members of the military in their routine duties, it is desirable to emphasize the distinction between research and course of duty risks, both in consent procedures and in officer training programs. The advisory committee recognizes that additional procedural requirements in soliciting research volunteers and augmenting already demanding training curricula would have administrative costs and, to a limited extent, would shift organizational priorities. It is the advisory committee's understanding that the DOD is preparing to revise its directive, implementing the common rule, and that the advisory committee's recommendations, with respect to steps one through three above, are a timely contribution to the department's deliberations. Military personnel are exposed to both short and long-term risks in the course of training and regular duty activities, as well as when they participate in biomedical or behavioral experiments. The demarcation of those activities that are researched in contrast with those that constitute routine duty assignments and medical care in the military context is not always easy to discern from the standpoint of the potential subject member of the military. Indeed, except in medical settings where research studies are regularly performed and military testing sites that conduct weapons, materiel, and performance trials routinely, officers as well as their troops may be uncertain as to whether the status of particular exercises is research or training. Greater clarity in communications to potential subjects about the genuinely voluntary nature of participation in research projects and procedural safeguards in recruiting volunteers could improve their understanding of what they are being asked rather than required to do. Likewise, educating officers throughout the military services who may be in a position to solicit volunteers for research studies as to the distinctive rights of research subjects and the particular duties to protect subjects of research from both harm and violation of rights would make the common rule protections of subjects more effective. Four. Maintenance of a Registry. The secretaries of the Navy and the Air Force should be directed to adopt the policy of the Army as detailed in Army Regulation 70-25 to maintain a registry of all volunteers in human studies and experiments conducted under research and development programs. Such registries make it easier to confirm participation in research by subjects and facilitate their long-term follow-up. In analyzing the record of atomic bomb testing, the advisory committee has found that military personnel were exposed to radiation and non-radiation risks as participants in experiments that were conducted in conjunction with the tests and as participants in other activities connected to the testing. While these activities were not intended to measure biological effects of ionizing radiation, the exposure to radiation risk was incurred without adequate provision for the maintenance of records to document exposures or in order to allow for monitoring and follow-up of those who were exposed. Army regulations now provide for a registry of participants in experiments conducted under the authority of the Army's Research and Development Program. This tool for long-term monitoring and follow-up, in the case of exposures to risks unknown at the time of participation, should be employed by the other services as well. Recommendation 13. The advisory committee recommends that the Human Radiation Interagency Working Group takes steps to improve three elements of the current federal system for the protection of the rights and interests of human subjects. Oversight, Sanctions, and Scope. One. Oversight mechanisms to examine outcomes and performance. In most federal agencies, current mechanisms of oversight of research involving human subjects are limited to audits for cause and a review of paperwork requirements. These strategies do not provide a sufficient basis for ensuring that the current system is working properly. The adequate protection of human subjects requires that the system be subjected to regular periodic evaluations that are based on an examination of outcomes and performance and then include the perspective and experiences of subjects of research as well as the research community. The committee recommends that the Human Radiation Interagency Working Group consider new methods of oversight that focus on outcomes and performance of the system of protection of human subjects. The committee's subject interview study and research proposal review project, for example, yielded important and, here to fore, unavailable information about the current status of human subjects protections that could never be obtained from either an oversight policy that audits only for cause or a review that determines only whether paperwork requirements have been satisfied. We realize that resources available for oversight are limited and that there may be real constraints on what, practically, can be achieved. At the very least, we urge that in the setting of priorities for limited oversight dollars a premium be placed on methods that permit an examination of what the system is actually producing with respect to the outcome of human subjects protections in contrast to methods that focus on process. Two. Appropriateness of sanctions for violation of human subjects protections. The committee recommends that the Human Radiation Interagency Working Group review and evaluate the options available to the government when it is determined that there has been a violation of the common rule in the conduct of federally sponsored research involving human subjects. The object of this review is to determine whether the current structure of sanctions that can be imposed on investigators and grantee institutions is appropriate to the seriousness with which the nation takes violation of the rights and interests of human subjects. This structure includes mechanisms for detecting violations including issues of oversight discussed above, severity of sanctions, and dissemination of policy on sanctions to investigators and institutions. We are particularly concerned that, even in the absence of research-related injury, there be clear and severe penalties for investigators who use human subjects without their consent. Although at least one state authorizes civil and criminal penalties for failure to obtain a subject's consent, in most jurisdictions civil litigation is unlikely to result in penalties to investigators for failing to obtain consent from subjects if the subjects have not been physically injured. The committee is aware that the common rule provides for sanctions of violations of its provisions including the withdrawal of multiple project assurances and, with that action, research funding. It is not clear, however, that this system of sanctions functions well, nor is it clear that it adequately addresses the public's concerns that those who abuse the trust of research subjects be dealt with accordingly. 3. Extension of human subjects protections to non-federally funded research While some non-federally funded research is performed voluntarily in accordance with the common rule, there is a need to assess the level of research performed outside its requirements and to consider action to ensure that all subjects are afforded the protections it offers. The committee was charged with reviewing only federally funded research, and we limited our inquiries accordingly. However, we are aware that important areas of research are conducted largely independently of federal funding, for example, some research on reproductive technologies. We recommend that the Human Radiation Interagency Working Group take steps to ensure that all human subjects are adequately protected. End of Section 86 Section 87, a final report of the Advisory Committee on Human Radiation Experiments. This is a LibriVox recording. All LibriVox recordings are in the public domain. For more information or to volunteer, please visit LibriVox.org. Final report of the Advisory Committee on Human Radiation Experiments. Coming to terms with the past, looking ahead to the future. Chapter 18, Part 4 Recommendation 14 The Advisory Committee recommends that the Human Radiation Interagency Working Group review the area of compensation for research injuries of future subjects of federally funded research, particularly reimbursement for medical costs incurred as a result of injuries attributable to a subject's participation in such research, and create a mechanism for the satisfactory resolution of this long-standing social issue. A system of compensation for research injuries has been contemplated since at least the late 1940s, when the Army debated, but ultimately rejected, suggestions to establish a uniform program for compensating prisoner volunteers who were injured during experiments involving malaria and hepatitis. Beginning in the 1970s, a number of government-sponsored ethics panels endorsed the provision of compensation for research injuries, culminating with the President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research, President's Commission, in 1982. Since then, experts and commentators have continued to support this position. In our deliberations concerning retrospective remedies for injured research subjects, the Advisory Committee was unable to reference a federal policy or guide for a fair system of compensation of research subjects, as no policy exists even today. So that years from now others do not have to revisit and struggle with this issue, the federal government must take steps now to address the issue of compensation for injured research subjects. These steps should include consideration of the approach recommended by the President's Commission in its report, Compensating for Research Injuries, the Ethical and Legal Implications of Programs to Redress Injured Subjects. The President's Commission summarized the basic argument for compensation as follows. Medical and scientific experimentation, even if carefully and cautiously conducted, carries certain inherent dangers. Experimentation has its victims, people who would not have suffered injury and disability, were it not for society's desire for the fruits of research. Society does not have the privilege of asking whether this price should be paid. It is being paid. In the absence of a program of compensation of subjects, those who are injured bear both the physical burdens and the associated financial costs. The question of justice is why it should be these persons, rather than others, who are to be expected to absorb the financial as well as the unavoidable human costs of the societal research enterprise which benefits everyone. The Advisory Committee urges not only the consideration of a compensation policy for physical injuries attributable to research, but also that that consideration be given to appropriate remedies for subjects who have suffered dignitary harms, even in the absence of physical injury. Subjects so wronged have little recourse in the current system. Litigation in the absence of physical injury is unlikely to provide relief to people who have been used as subjects without their adequate consent. If it is determined that financial compensation is not generally an appropriate remedy in the absence of physical injury, consideration should be given to other remedies that would be fitting. Recommendations for balancing national security interests and the rights of the public. Recommendation 15. 15A. The Advisory Committee recommends to the Human Radiation Interagency Working Group the adoption of a federal policy requiring the informed consent of all human subjects of classified research, and that this requirement not be subject to exemption or waiver. In all cases, potential subjects should be informed of the identity of the sponsoring federal agency and that the project involves classified information. 15B. The Advisory Committee recommends to the Human Radiation Interagency Working Group the adoption of a federal policy requiring that classified research involving human subjects be permitted only after the review and approval of an independent panel with appropriate non-governmental experts and citizen representatives, all with the necessary security clearances. This panel should be charged with determining, one, that the proposed experiment has scientific merit, two, that risks to subjects are acceptable and that the balance of risk and potential benefit is appropriate, three, that the disclosure to prospective subjects is sufficiently informational and that the consent solicited from subjects is sufficiently voluntary, and four, whether potential subjects must have security clearances in order to be sufficiently informed to make a valid consent decision, and if so, how this can be achieved without compromising the privacy and voluntariness of potential subjects. Complete documentation of the panel's deliberations and of the informed consent documents and process should be maintained permanently. These records should be made public as soon as the national security concern justifying secrecy no longer applies. Although the Advisory Committee believes that the interests of both science and potential subjects are best served when research involving human subjects is conducted in the open, public policy prohibiting the conduct of human subject research in secret is unwise. Important national security goals may suffer if human subjects research projects making unique and irreplaceable contributions were foreclosed. More citizens may suffer harms for lack of such information than would be harmed if adequately safeguarded human subjects research was conducted in secret. It also is possible that a prohibition on classified human subjects research would be circumvented through redefinition of activities or disregarded outright. If this were to occur, the participants in such activities could end up less well protected than if they were bona fide research subjects. The Advisory Committee believes, however, that the classification of human subject research ought properly to be a rare event and that the subjects of such research, as well as the interests of the public in openness in science and in government, deserve special protections. The Advisory Committee does not believe that continuing with the current federal policy governing the protection of human subjects, which does not provide any special safeguards or procedures for classified research, is adequate. In the current political context, classified human subjects research occurs relatively rarely. Existing policy may prove an inadequate safeguard of individual rights and welfare, however, if in the future national security crises occur that generate a perceived need for classified research. The history of human experimentation conducted in the interests of strengthening and protecting national security that the Advisory Committee has examined demonstrates how the rights and interests of citizens can be violated in secret research. The convergence of elements of secrecy, urgent national purposes, and the essential vulnerability of research subjects, owing to differentials in information and power between those conducting research and those serving as subjects, could again lead to abuses of individual rights and, upon subsequent revelation, the erosion of public distrust in government. The Advisory Committee is particularly concerned about two aspects of current policy, exceptions to informed consent requirements and the absence of any special review and approval process for human research that is to be classified. The current requirements for the informed consent of research participants is not absolute, leaving open the possibility that subjects may serve as mere tools of the state in the interests of national security if consent is waived. A strengthened requirement for the informed consent of research subjects in classified research should safeguard against the merely instrumental use of individual people to serve national purposes. Institutional review boards of government agencies are not sufficiently independent of the interests of the organizations of which they are a part to set aside considerations of organizational mission when considering research construed as having the greatest national priority. Thus, determination by an agency IRB that a waiver of informed consent is warranted, or that sufficient information about a study remains in a censored protocol description for a potential subjects review, inadequately protects subjects' interests and rights, and does not adequately safeguard the public's trust. By contrast, an independent panel should be less subject to unintended bias than that of an IRB of a federal agency whose mission is to protect and promote national security. Although the Advisory Committee acknowledges that both the formation of an independent review panel and an absolute informed consent requirement create opportunities for information leaks or security breaches and delays in the progress of urgent research, these disadvantages are surmountable and are more than balanced by the increased vigilance afforded the rights and interests of citizens and the safeguarding of the public's trust in government. Recommendation 16. The Advisory Committee recommends to the Human Radiation Interagency Working Group that improvements be made in the protection of the public's rights and interests with respect to intentional releases. 16a. The Advisory Committee recommends to the Human Radiation Interagency Working Group that an independent review panel review any planned or intended environmental releases of substances in cases where the release is proposed to take place in secret or in circumstances where any aspect of the environmental review process required by law is conducted in secret. In conducting its review, the independent panel should ensure that, one, secrecy is limited to that required for reasons of national security. Two, records will be kept on the nature and purpose of the release, the rationale for not informing the public, including workers and service personnel as well as affected citizens, and alternative means of gathering data that were considered. Three, actions to mitigate risk were considered and will be taken. And four, actions will be taken to measure the actual effect of the release on the environment and human health and safety, to the extent that measurements are deemed needed and feasible. The panel should also review the conditions on which any information kept secret should be made public, with a view toward ensuring the release of information as soon as practicable, consistent with any legitimate national security restrictions. The panel should report to Congress periodically on the number and nature of releases it has reviewed. The advisory committee does not conclude that intentional releases can never be conducted in secret. It does conclude that, to the extent that the government proposes to conduct an intentional release that involves elements of secrecy, there must be independent review to ensure that the action is needed, that risk is minimized, and that records be kept to make sure a proper accounting is made to the public at the earliest date consistent with legitimate national security concerns. The advisory committee found that the government has sponsored numerous intentional environmental releases of radiation for research purposes. In many cases these releases were conducted in secret, without warning to the surrounding populations. While the risks posed by these releases appears to have been relatively small, in many cases little data remain on the precise measure of these risks, or on actions taken to minimize risk and to ensure that unknowing citizens did not inadvertently expose themselves to greater risks than necessary. In addition, the committee found that the risks and concerns posed by intentional releases for research purposes, in terms of both the magnitude of radiation exposure and the consequences of secret keeping, sometimes did not differ qualitatively from those posed by routine operational releases of radiation. Most notably, the radiation risk posed by the green run, a relatively large intentional release, was a fraction of that radiation released in the normal course of operation of Hanford in the mid-1940s. This recommendation is intended to apply to all secret releases of substances into the environment, not merely to substances determined to be hazardous. The committee believes that the operative concern is secrecy. Even if the substance released is entirely harmless, the backdrop of secrecy is sufficient to create a climate of distrust. The committee did not have the expertise, however, to determine whether so broad a sweep was feasible. At minimum, the committee recommends that any secret release of a substance that would necessitate an environmental impact statement be required to have a review by an independent panel. Today, federal environmental laws and rules provide for environmental impact statements, which are subject to review, in instances in which the federal government proposes actions with a substantial effect on the environment. However, the rules also provide that part, or even all, of such reviews may be conducted in secret. In fact, reviews that are secret in whole or part do take place. The Environmental Protection Agency has the authority and responsibility to oversee all environmental impact reviews, including those conducted in secret. However, the advisory committee's inquiries indicate that EPA's role in the review of secret impact statements has been limited. Moreover, the decades of secret keeping regarding intentional releases have created a basis for distrust, particularly among those living in potentially affected communities. Even today, there is little practical means by which the public can know the full extent, whether or not great, of environmental decision making and action that is being kept secret. The location of responsibility for review of these activities in a single panel that is itself accountable and that is independent of agencies that conduct releases should be a means to restoring lost trust. 16b. The advisory committee recommends to the Human Radiation Interagency Working Group that an appropriate government agency, currently the Environmental Protection Agency, maintain a program directed at the oversight of classified programs with suitably cleared personnel. This program should maintain critical records, such as environmental impact statements and environmental permits, permanently. The agency subject to regulation should ensure the timely consideration of environmental impacts and oversight and the timely provision of all necessary clearances. EPA should provide regular unclassified reports to Congress, describing the extent of its activities as well as any significant problems. The requirements of environmental law apply to activities of the federal government, regardless of whether those activities are classified. However, classification complicates the process of regulatory oversight by the EPA or any other regulatory agency and limits the ability to report to the public and for the public to express its own concerns. Furthermore, secrecy has been used to shield activities that raise public health concerns. For these reasons, the responsibility for environmental oversight is magnified for secret programs. There is no fundamental barrier to effective oversight. At least some regulators can be given the necessary clearances. However, ensuring timely and effective oversight requires cooperation between the regulated agency and the regulatory agency to establish the necessary oversight procedures. These mechanisms are not fully in place. For example, the EPA office with the statutory responsibility to review environmental impact statements maintains no records of classified environmental impact statements and has not historically had individuals cleared to review the most highly classified defense programs. The EPA office responsible for overseeing federal compliance with environmental regulations has just begun to establish mechanisms for overseeing secret programs. End of Section 87. Section 88, a final report of the Advisory Committee on Human Radiation Experiments. This is a LibriVox recording. All LibriVox recordings are in the public domain. For more information or to volunteer, please visit LibriVox.org. Final report of the Advisory Committee on Human Radiation Experiments. Coming to terms with the past, looking ahead to the future. Chapter 18, Part 5. Recommendations on Openness. Recommendation 17. The Advisory Committee recommends that the Human Radiation Interagency Working Group take steps to ensure the continued application of the lessons learned from the Human Radiation Interagency Working Group's efforts to organize and make accessible to the public and the government itself, the nation's historical records. The Committee's experience confirms that with the Presidential Directive and the strong and continued support of a multi-agency record search team, substantial amounts of the nation's documentary heritage can be located and retrieved. Through the research process, important lessons were learned about ways in which to improve the accessibility and usefulness of this documentary record to both the public and the government. We are aware that government resources are stretched thin and may well be diminishing. However, the nation's records are a precious asset that the government created and holds in trust for its citizens. This asset, and the commitment made to the public through the enactment of the Freedom of Information Act, is of limited value if the government itself cannot access its records as citizens rightfully expect it should. The Committee's experience confirms that there is an intense public interest in using these records, a public willingness to volunteer time and intelligence needed to help organize and research them, and great opportunity to make them available in ways that will permit citizens to do so. The Committee recommends that the Human Radiation Interagency Working Group effect the following five steps to increase both government and citizen access to information about the past. The implementation of these steps might be best accomplished by the designation of an individual or entity with responsibility and appropriate authority for their effectuation. 1. The most important historical collection should be entrusted to the National Archives. The agencies and the National Archives should review the extent to which this is now being done and develop policies to hasten the transfer of agency records to the National Archives. Federal law basically requires that permanent records be transferred to the National Archives when, one, they are more than 30 years old, or, two, earlier if the originating agency no longer needs to use the records for the purpose for which they were created, or in its regular current business, or if agency needs will be satisfied by use of the records at the National Archives. Nonetheless, many portions of older collections have been appraised as permanently valuable but are not at the National Archives. For example, the Committee found that a great number of AEC headquarters records of substantial interest to the Committee and the public are still held by the DOE, either at its headquarters or at the Washington National Records Center. These include the only collection of general manager files, the post-1958 Executive Secretariat files, virtually all the Division of Military Application files, and most of the files of the Division of Biology and Medicine. In the case of the Department of Defense, the records of the Office of the Secretary of Defense largely remain at the Washington National Records Center or with the Office of the Secretary of Defense. The public's ability to access records held by agencies is limited because, one, most agencies do not know in detail what records they still hold, and even if folder listings exist, they are not publicly available for the most part. Two, there's generally been little declassification review of these records. Three, there is no requirement that agencies permit access to even completely unclassified or declassified collections. And four, most agencies have very limited facilities to accommodate researchers. The public's ability to gain access to governments and federal records centers is also limited because, one, the task of examining the basic inventory forms, SF-135s, to determine what is in a record group is time consuming, and in many cases the SF-135s do not adequately describe the records. Two, there has generally been very little declassification review of these records. And three, permission must be obtained from the appropriate agencies to review even completely unclassified or declassified collections. This permission process can be time consuming, and agencies can impose restrictions, such as permitting review but not copying. Locating records at the National Archives has the following advantages. One, there is generally at least some type of finding aid, and in some cases folder listings prepared by the National Archives or the agencies when the records were sent. Two, archivists are able to assist researchers. Three, there is complete access to unclassified and declassified collections unless privacy act or similar restrictions apply. And four, many classified records at the National Archives, among the exceptions are restricted data records and records dealing with intelligence, are properly the subject of an informal and usually very quick in-house declassification review process called special declassification review. Under special declassification review, records are often reviewed within months, versus the years it takes under the Freedom of Information Act or mandatory declassification review. Two, agencies should make readily available all existing inventories, indices, folder listings, and other finding aids to record collections now under agency control. Classified finding aids should undergo declassification review, and declassified versions of these finding aids should also be made available. Finding aids or indices to federal government records holdings are an invaluable tool, without which it would be practically impossible to locate documents of interest from among the hundreds of thousands of boxes of records maintained by the government. Many collections of records still held by agencies have finding aids or indices that have been inaccessible to the public, either because they simply have never been made available or because they are classified. Finding aids should be made available to the public in a headquarters office, regional offices, including all field site reading rooms, and ultimately on the internet. This recommendation does not call for the creation of indices where they do not currently exist. For example, folder listings, which provide the titles of records files, exist for many of the AEC headquarters record collections that are still at DOE or at the Washington National Records Center. These include, among others, the only known collection of general managers files from 1947 through 1974, all of the division of military applications files from 1947 through 1974, all of the executive secretariat files from 1959 through 1974, and most of the division of biology and medicine files from 1947 through 1974. Without the folder listings it would have been difficult for the advisory committee to locate particular collections of interest, and, even if located, to determine the documents to be reviewed. The folder listings, however, have not been generally available to the public. Similarly, the DOE's Oak Ridge Operations Office vault contains more than 7,000 cubic feet of classified records. The committee found that the records holding task group, RHTG, collection in this vault, about 300 cubic feet, contained many documents of interest to the committee, which were typically readily declassifiable. This collection has an index, however, the index is classified. In the case of the National Archives, finding aids are generally available. However, there are 15 National Archives facilities around the country. Currently, the only means of determining exactly what records are at a particular branch is to contact that branch directly. This is a time-consuming process, and there are understandable limits on the number of pages of finding aids archivists can copy and send to any person. A single finding aid can total hundreds of pages. It would be much simpler and easier for the public to be able to review the finding aids from all 15 branches at any one of them. 3. The Human Radiation Interagency Working Group should ensure the development of policies to improve public access to records held by agencies or deposited in federal records centers. In the case of a vast amount of records, particularly those not yet transferred to the National Archives, the available descriptions are often too broad or incomplete to provide meaningful clues to the contents of boxes. Thus, a Freedom of Information Act request that seeks all information on a given topic may well receive a response that ignores information located in boxes or files that are not clearly labeled or indexed. Under these circumstances, searches may be more fruitfully conducted by citizens with an interest in, and understanding of, the subject of the search. However, because so many of the nation's records collections are off limits to the public, even citizens who are willing to help are often precluded from lending a hand. Many collections of interest to citizens contain no classified documents and can be made directly accessible to them. However, the committee reviewed collections, particularly those containing decades old records, where the entire collection was classified because it housed a small number of classified documents. For example, Record Group 326 at the College Park National Archives has approximately 160 feet of metallurgical laboratory, Argonne National Laboratory documentation that should be of significant historical interest. The collection itself is classified and currently inaccessible to citizens. The committee's examination of large portions of the collection found very few classified documents, and when found, these documents were immediately declassified. Executive Order 12958, issued by President Clinton on April 17, 1995, Classified National Security Information, provides broadly for the automatic declassification, with special exceptions, of all records that are more than 25 years old. In implementing the order, agencies should target collections that can be relatively quickly reviewed and made available to the public in their entirety. 4. Agencies should maintain complete records available to the public of document destruction. Government records management rules provide for the destruction at varying dates in the future of all records that are appraised as temporary, that is, non-permanent. They also provide that records be kept where certain collections, including classified records, are destroyed. But the committee found that records of destruction are themselves routinely destroyed. For example, upon committee inquiry, DOE investigation revealed that the files of the AEC's Intelligence Division had been substantially destroyed during the 1970s and as late as 1989. These files may have contained data on intentional releases, experimentation performed by the AEC for other agencies, and on the rules and practices of secret keeping regarding human data gathering. The DOE's inquiry found individuals who stated that they destroyed substantial records and that records of destruction were made. However, in accordance with DOE rules, the certificates of destruction were themselves later destroyed. As another example, documents provided by the Department of Veterans Affairs and the Department of Defense indicate that in 1947 the government contemplated the keeping of secret records in anticipation of potential liability claims from service personnel exposed to radiation, and that some such records were kept. However, despite substantial search efforts by the DOD and the VA, the specific identity of the records referred to has not yet been determined. The committee presumes that the vast majority of these records were destroyed in the routine course of business. Nonetheless, where records recording the destruction of important collections of records are themselves destroyed, the public cannot know whether important records have been destroyed, or merely are lost, and cannot be easily assured that destruction was in the routine course of business. 5. The Human Radiation Interagency Working Group should review and develop policies concerning public access to records generated or held by private contractors and institutions receiving federal funding. Since World War II, the government has relied on contractors and grantees to perform an increasing number of governmental activities, including government-sponsored biomedical research. When the advisory committee undertook to locate information on particular government-sponsored radiation experiments, it was often told by federal agencies that, if such information was created, it would have been maintained only by non-federal entities or investigators, and not the government itself. Where an activity is conducted by government employees, for example, researchers working in the facilities of the National Institute of Health's Clinical Center, citizens have a right to seek access to information relating to that activity under the Freedom of Information Act. A similar right of access often does not apply, however, where a similar or even identical activity is conducted, also on federal funds, at non-federal facilities. From the citizen's vantage point, the right to know about a government-funded activity should not depend on whether that activity is conducted directly by the government or by a government-funded private institution. At the same time, non-federal institutions are not governmental agencies, and there may be good reasons they should not be burdened with identical obligations to retain records and to provide information to the public. Rules are needed that accommodate both the citizen's right to know about the conduct of the government and the relevant differences between non-federal and federal institutions with respect to duties to create and maintain publicly accessible records. To ensure consistent and informed government-wide treatment of the question, the Human Radiation Interagency Working Group may wish to call on the Office of Management and Budget, OMB, and the Office of Federal Procurement Policy, OFPP, to review the current right of members of the public to gain access to the records of government grantees and contractors. Recommendation 18. 18A. The advisory committee recommends to the Human Radiation Interagency Working Group that the CIA's record-keeping system be reviewed to ensure that records maintained by that agency are accessible upon legitimate request from the public or governmental sources. This review could be performed by the CIA Inspector General or an oversight panel. 18B. The advisory committee recommends that all records of the CIA bearing on programs of secret human research such as MKUltra and the related CIA human behavior projects from the late 1940s through the early 1970s, including Bluebird, Artichoke, MK Search, MK Delta, Naomi, Chance, Often, and Chickwit become a top priority for declassification review with the expectation that most, if not all of these documents, can be declassified and made available to the public. These recommendations are intended to ensure that the public and the government have practical access to historical records of the CIA, where access is otherwise appropriate, and to address long-standing public interest and concerns regarding secret human experiments conducted or sponsored by the CIA. The framework of the records collections of all the Human Radiation Interagency Working Group agencies save the CIA is visible to the public. This is the case even in agencies such as the Defense Nuclear Agency, where historical research records are largely classified. While documents showing CIA participation in mid-century DOD-sponsored discussions of human experimentation were obtained from DOD, DOE, and the Public National Archives, the CIA was not able to locate such documents in its own files, and states that the CIA's role in these discussions was sufficiently minor that such records would not have been kept. The Advisory Committee also notes the recent report to the Attorney General of the BNL Task Force, which was investigating a bank-related scandal. While we benefited from extensive cooperation and assistance from the CIA's Office of General Counsel, the CIA's ability to retrieve information is limited. Records are compartmentalized to prevent unauthorized disclosure. Only some of those records are retrievable through computer databases. No database encompasses all records, and not all information is recorded. In the course of our work we learned of sensitive components of information not normally retrievable, and of specialized offices that previously were unknown to the CIA personnel assisting us. In addition, while the Advisory Committee has found no evidence to show that the CIA conducted or sponsored human radiation experiments, numerous documents, some of which remain partially classified, make reference to possible CIA interest in this area. Although Advisory Committee staff has reviewed all of the available classified information concerning human radiation experiments and requested that it be declassified, the public does not as yet have the benefit of such access. Twenty years after they were first revealed to the public, there continues to be a strong public interest in the CIA's mind control programs. The Advisory Committee received numerous queries about MKUltra and the other related programs from scholars, journalists, and citizens who have been unable to review the complete record. Although these CIA projects were the subject of significant governmental inquiry in the mid-to-late 1970s by the Senate and House committees and by the Presidentially Appointed Rockefeller Commission, and a substantial portion of the records have been declassified and released to the public, a number of documents remain classified, and many of the documents that have been released contain numerous redactions. This has made it extremely difficult to understand the full context of the activities or to clarify discrepancies or uncertainties in the record. A number of the declassified documents make reference to radiation experiments. However, because of the redactions, it is impossible for the public to determine from these documents whether there is additional secret information about radiation activities. Advisory Committee staff have reviewed the full text of these documents. For example, the 1963 CIA Inspector General report on the inspection of MKUltra, which was declassified in redacted form in 1975, stated that radiation was one of the avenues explored under MKUltra. But because so much of that document was redacted, the public reader might reasonably suspect that there is more information about radiation in the report. At the request of the Advisory Committee, the CIA re-released this document, and a handful of others, with minimal redactions. However, few other such documents have been re-reviewed for declassification in almost twenty years. Since most of the classified CIA documents concerning MKUltra and related programs, the Advisory Committee staff reviewed were declassified upon request. The Advisory Committee believes that if the rest of these records were reviewed for historical declassification, most, if not all, of the records could be declassified without harming the national security. So long as documents about secret human experiments are withheld from the public, it will be impossible to put to rest distrust with the conduct of government. The rapid public release of the remaining documents about MKUltra and other secret programs would be a fitting close to an unhappy chapter in the nation's history. End of Section 88 Section 89 of Final Report of the Advisory Committee on Human Radiation Experiments This is a LibriVox recording. All LibriVox recordings are in the public domain. For more information or to volunteer, please visit LibriVox.org. Final Report of the Advisory Committee on Human Radiation Experiments Coming to Terms with the Past Looking Ahead to the Future Chapter 18 Part 6 Addendum to Recommendation 4 Medical Notification and Follow-up The Advisory Committee's Charter requires that we consider the issue of notice to experimental subjects of potential health risk and the need for medical follow-up. If required to protect the health of individuals who were subjects of a human radiation experiment or their descendants, the Advisory Committee may recommend to the Human Radiation Interagency Working Group that an agency notify particular subjects of an experiment or their descendants of any potential health risk or the need for medical follow-up. Section 4C The basic intent of this provision is not directed at subjects who have already died or at subjects who have already become ill and been treated. It is primarily aimed at asymptomatic subjects who remain at significant risk for the development of radiation-induced cancers. Because at least two and as many as five decades have passed since the experiments took place, most of those who may eventually develop cancer as a result of the experiment will already have developed symptoms and sought treatment. However, some subjects may still be at risk and thus arguably might benefit from medical follow-up. The initial consideration in deciding whether to implement a program of active notification and medical follow-up is the identification of populations of subjects who have been put at significant risk for the development of radiogenic cancers. The magnitude and focus of these risk estimates are driven by the specific organs placed at highest risk from the particular radiation exposure. For example, thyroid being the organ at greatest risk in the iodine-131 experiments, testes in Oregon and Washington prisoner experiments, and the brain for the nasopharyngeal radium experiments. Risk estimates are calculated for each target organ according to a number of assumptions that may include adjustments for variables such as aged exposure, sex, or type of radiation, isotope versus external beam, and are generally expressed in terms of excess cancer incidence, mortality, for a given population over a specified period at a specified dose. The advisory committee adopted an excess site-specific cancer mortality, death, greater than one case in 1000 lifetime, as a criterion for determining that a subject had been placed at increased risk. However, because of the substantial passage of time since the initial exposure, the criteria for consideration of active notification were set at one in 1000 future or remaining lifetime risk and an excess relative risk of greater than 10% organ-specific. This level of risk was arbitrarily chosen by the advisory committee. When compared with the normal risk of developing cancer, 220 out of 1000, this level of risk is small. The advisory committee chose this small remaining lifetime risk as a reasonable initial criterion to decide if a more in-depth analysis of the effectiveness of screening and intervention was needed. Once a population has been determined to have an increased remaining lifetime risk for radiogenic cancer mortality, a second criterion must be satisfied before a government-funded medical follow-up program is recommended, namely, whether the exposed individuals would likely benefit from a program of early detection or early treatment of the malignancy. Effective screening procedures for the detection of an early-stage cancer exist only for a limited number of cancer sites. Moreover, the lack of specificity of all diagnostic screening tests results in a significant number of false positives, a positive test result in an individual who in truth is not affected, resulting in unnecessary and potentially hazardous medical procedures that may cause health problems in and of themselves. On the other hand, most diagnostic tests are also imperfectly sensitive, meaning that some individuals who actually have the disease will be falsely reassured that they are cancer-free and may thereby delay seeking attention when it becomes symptomatic. To this end, the advisory committee has adopted the following criteria for assessing the value of screening, preventative, or therapeutic measures for exposed subjects of biomedical experiments. 1. The condition must have a significant effect on the quality or length of life. 2. The condition must have an asymptomatic period during which it can be detected by available screening methods. 3. These screening methods must have high sensitivity and specificity. 4. Treatment in the asymptomatic phase must yield a therapeutic result superior to that obtained by delaying treatment until symptoms appear. 5. The medical benefits of screening in early treatment must outweigh any detrimental medical effects or risks. These criteria were applied to each exposed population at significant risk for development of a malignancy and evaluated according to the organs at risk from radiation exposure. In each case, the conditions enumerated above must be satisfied before a specific medical follow-up would be recommended. Details of the advisory committee's risk calculations can be found in chapters 7 and 9. To summarize, the advisory committee found no experiments involving iodine-131 administration to children that met our 1 in 1,000 criterion for remaining lifetime risk of dying of cancer. Even in the most highly exposed individuals, risks were estimated to be 1 in 2,000 remaining lifetime risk. In addition, the U.S. Preventative Services, USPS, Task Force concluded that routine screening for thyroid disorders is otherwise not warranted in asymptomatic adults or children. Though it has been suggested that people placed at risk for development of thyroid carcinoma following high-dose externally radiation to the upper body may benefit from regular physical examination of the thyroid, there are no data to support a similar risk or benefit for those who have been exposed to diagnostic or therapeutic doses of iodine-131. The advisory committee recognizes that in addition to the very small risk of a fatal thyroid cancer, individuals exposed as children to iodine-131 also have a larger risk of a non-fatal thyroid cancer or benign tumor. A lifetime risk that in many of the experiments we considered exceeded 1 in 1,000 and in a few individuals exceeded 1 in 100. We recognize that such conditions may require medical treatment and may be associated with considerable anxiety and discomfort. After considerable discussion, however, the committee concluded that notification was not warranted for the purpose of detecting such conditions early on several grounds. First, the prognosis for such conditions under standard clinical care is excellent and there is no evidence that early detection improves the outcome. Second, even among the subgroup of about 200 children exposed to this level of risk, the number of excess cancers expected is less than one whereas the normal prevalence in an unexposed population is about 20-30%. Third, many thyroid cancers that are detectable by screening may have no clinical significance. Finally, the most effective means of screening for thyroid cancer remains palpation, which has low sensitivity and low specificity. For the prisoners subjected to testicular irradiation, the advisory committee estimates that even the most heavily exposed individual, 600 rad to the testicles, would have a risk of only 0.4 in 1,000 of developing a fatal cancer, which does not attain our stated criterion. Furthermore, the USPS Task Force has concluded that there is insufficient evidence of clinical benefit or harm to recommend for or against routine screening of asymptomatic men, other than those with a history of crypto-organism, orcheopexy, or testicular atrophy, for testicular cancer. These considerations led the advisory committee to recommend against any program of active notification of these subjects. However, subjects who voluntarily request medical check-up or counseling should have such provided in a standard clinical setting. For the children who receive nasopharyngeal radium treatments, the advisory committee has estimated that the lifetime risk of tumors to the central nervous system, brain, head, and neck regions is approximately 4.35 in 1,000, and the excess relative risk is about 62%, both with considerable uncertainties. Although these experiments were conducted in the 1940s and much of the risk has probably already been expressed, it is still possible that the future risk is greater than, or equal to, our arbitrary 1 in 1,000 risk criterion. However, at greatest risk are the brain, head, and neck tissues, for which there is neither an accepted nor recommended screening procedure. Thus, while the subjects in these experiments meet the advisory committee's arbitrary 1 in 1,000 criterion for consideration for notification and medical follow-up, criterion 1 in recommendation 4, above, the utility of such a program has not been demonstrated, so criterion 2 of recommendation 4 is not satisfied. Adult military personnel who participated in trials of this procedure received significantly lower radiation exposures, did not attain our arbitrary 1 in 1,000 criterion for risk, and would similarly fail to meet the criteria in guideline 2. Therefore, the advisory committee does not recommend notification and medical follow-up of children or adults in this group of experiments. The advisory committee's charter also requires that we consider the need for notification of descendants of experimental subjects for purposes of health protection. The rationale for considering notification in this instance derived from the assumption that the offspring of former subjects might be at risk for disease or disability as a consequence of inherited mutations resulting from their parent's previous radiation exposure. The weight of evidence suggests that the risk of heritable genetic effects from the radiation exposures in the experiments we reviewed is very small, although it is possible that some offspring of exposed individuals might carry mutations that were caused by radiation. Moreover, in most medical experiments involving external sources of radiation, efforts are made to shield the gonads, ovaries, testes, as much as possible. With the exception of the testicular irradiation experiments where subjects agreed to undergo vasectomy to prevent transmission of any mutations that might have occurred, experiments involving external irradiation are likely to have produced relatively small gonadal doses, as would those experiments involving tracers. Even therapeutic studies involving internal radionuclides would generally involve only modest gonadal doses. Thus, in the vast majority of experiments it is likely that the risk of radiation-induced mutations is small in relation to natural rates. In addition to cancer and genetic effects, there are only a small number of well-established effects of radiation, including severe mental retardation among those exposed in utero, particularly between 8 and 15 weeks of gestation, sterility, cataracts, and hypothyroidism. Unlike cancer and genetic effects, however, these other endpoints appear to be deterministic effects that appear only after high doses that are unlikely to have been received by subjects in the experiments under consideration for notification. The advisory committee heard extensive public testimony about a range of other conditions that those testifying thought might be related to radiation exposures. However, the advisory committee believes that a program of active notification must be grounded on currently accepted scientific evidence concerning the conditions that are likely to be caused by radiation. End of Section 89 Recording by Elsie Selwyn Final Report of the Advisory Committee on Human Radiation Experiments Statement by Committee Member Jay Katz We were assigned two tasks. To examine the past and to examine the present, telling the full story of government-sponsored Cold War human radiation experiments serves many important purposes-rememberance, warning, healing. Ultimately, however, the value of knowing the past resides in the lesson it can teach us for the present and future. Thus, the central question is this. Do current regulations of human experimentation adequately protect patient subjects? Here I have the most serious reservations about our report. In summary, my conclusions are these. 1. In a quest to advance medical science, too many citizen patients continue to serve as they did during the Cold War as means for the sake of others. 2. The length to which physician investigators must go to seek informed consent remains sufficiently ambiguous so that patient subjects' understanding of the consequences of their participation in research is all too often compromised. 3. The resolution of the tensions inherent in the conduct of research, i.e. respect for citizen patients' rights to and interest in self-determination on the one hand and the imperative to advance medical science on the other, confronts government officials with policy choices that they were unwilling to address in any depth during the Cold War or for that matter in today's world. 4. Our recommendations only touch on these problems and at times make too much of the safeguards that have been introduced since 1974. The present regulatory process is flawed. It invites unsettled but real ways repetitions of the dignitary insults which unconsenting citizen patients suffer during the Cold War. 5. Medical research is a vital part of the American life. The federal government allocates billions of dollars to human research and the pharmaceutical industry spends many more billions to develop new drugs and medical devices. And research is by and large conducted with patients. Since all of us at one time or another will be patients, we are readily available subjects for research. Thus, the protection of the rights and interests of citizen research subjects in a democratic society is a major societal concern. Let me introduce my reservations by offering some preliminary remarks about the current regulatory scheme and the history of consent. The contemporary regulatory scheme provides insufficient guidance for addressing one basic question. When, if ever, should conflicts between advancing medical knowledge for our own benefit and protecting the inviability of citizen subjects of research be resolved in favor of the former? Enviability, unless patient subjects agree to invasions of mind and body, requires punctilious attention to disclosure and consent and in turn imposes considerable burdens on physician investigators, be it taking the necessary time to converse with patient subjects, or if necessary making discomforting disclosures. Moreover, taking informed consent seriously may slow the rate of medical progress with painful consequences to investigators' work into society. These dilemmas must be resolved forthrightly instead of allowing them to be resolved by a discretionary subterfuge. Neither the drafters of the 1974 federal regulations nor the members of the research community were willing to respond to the reality that taking informed consent seriously in this new age of informed consent confronted them with problems that required sustained and thoughtful exploration. Implementation would also turn out to be a most formidable task because of physicians' low regard for patient consent throughout medical history. The committee's analysis of the informed consent requirements in existence during the Cold War and earlier in the 20th century acknowledges, but not sufficiently so, that the millennia-long history of medical custom casts a dark shadow over what transpired during the Cold War. Patient consent until most recently has not been enshrined in the ethos of Hippocratic medicine. As I once put it, the idea of patient autonomy is not to be found in the lexicon of medicine. It is important to be aware of this history for it explains why our findings on contemporary research practices, which time prevented us from probing in sufficient depth, revealed deficiencies in the informed consent process both at the levels of physician-investigator interactions with their patient subjects and of IRB review. This is not surprising, for not only does it take time to change historical practices, it also requires more thoughtful rules and procedures than currently exist. My reading of the Cold War record suggests that government officials and concert with their medical advisors at best paid lip service to consent. Whenever they considered it, they worried mostly about legal liability and embarrassment. They were not worried or embarrassed about their willingness to conscript unconcenting patient subjects to serve as means in plutonium and whole-body radiation experiments. All this is a frightening example of how thoughtlessly human beings, including physicians, can treat human beings for noble purposes. Most references to consent with rare exceptions that we uncovered in government documents or in exchanges between officials and their medical consultants or meaningless words, which conveyed no appreciation of the nature and quality of disclosure that must be provided if patient subjects were truly to be given a choice to accept or decline participation in research. Form, not substance, punctuated most of the policies on consent during the Cold War period. The drafters of the federal regulations would eventually build their rules on this shaky historical foundation, disregarding in the process that the imprecision of their policies invited physician investigators not to alter decisively customary Hippocratic practices. The long-established tradition of obtaining consent from healthy subjects is a separate story. For this tradition did not extend to patients or patient subjects. Put another way, the latter were quarantined from disclosure and consent. In our finding 10, this was clearly stated. During the 1944-1974 period, physicians engaged in clinical research generally did not obtain consent from patient subjects for whom the research was intended to offer a prospect of medical benefit. Therefore, it should come as no surprise as noted in our report that when a decision was reached in 1951 not to pursue radiation research with prisoners or healthy subjects in connection with an important defense project, the military immediately contracted with the private hospital to study patients being irradiated for cancer treatment. Patients have always been the most vulnerable group for purposes of research. From the perspective of history, no significant conclusions can be drawn about ethical consent standards that should have existed for research with patients by drawing attention to consent requirements that existed for healthy volunteers. When persons became patients, the rules of consent changed. This observation also has relevance for the impact of the Nuremberg Code on the conduct of research. The code emerged from contexts not only of research with non-patients but also of sadistic and brutal disregard for the sanctity of human life unparalleled in the annals of Western research. American physician investigators therefore found it doubly easy to consider the pronouncements of the Allied military tribunal irrelevant to their practices. Let me interject here a few brief remarks about risks. Taking risks is inevitable in research. After all, research is by its nature a voyage into the unknown. To pierce uncertainty, to gain scientific knowledge requires risk taking. And, as our report makes clear, physician investigators and government officials as well have generally been attentive whenever physical risks needed to be taken to minimize them. But such care notwithstanding research requires taking risks. For example, research with highly toxic agents affects the quality and extent of remaining life. In our review of contemporary research, we identified many instances where patient subjects were knowingly exposed to such risks which have both physical and emotional dimensions. Scientific studies in today's world often involve patient subjects whose prognosis is dire, the most vulnerable of all disadvantaged groups and for whom no effective or curative treatments exist. And these situations hope can readily be exploited by intimating that research interventions may also benefit patient subjects, even though the experiment's objectives are in the service of gaining scientific knowledge. Embarking on this slippery slope begins with investigators' rationalizations which justify experimental interventions on grounds of possible therapeutic benefits. It continues with apprising patient subjects insufficiently of the slings and arrows of the experimental component, and it ends with feeding into patient subjects' own dispositions to deny the truth. In sum, by obliterating vital distinctions between therapy and research, investigators invite patients to collude with them in the hazy promise of therapeutic benefits. Put another way, the therapeutic illusion, as one commentator felicitously called it, can lead physician investigators to emphasize the possible, though unproven, therapeutic benefits of the intervention, and in turn to minimize its risks, particularly to the quality of remaining life. Such considerations played a role in the total body radiation experiments discussed in our report. In my reservations, I want to emphasize, however, the centrality of dignitary, not physical injuries in any appraisal of the ethics of research. This is the uncompromising message of the Nuremberg Code's first principle on voluntary consent, a message which during the Cold War period physician investigators found impossible to accept. But the problem goes deeper than that. The Code, without extensive exegesis, could not serve as a viable guide for the conduct of medical research. This made its disregard easy, and in the process, the central message which the judges tried to convey in their majestic first principle was also lost. Thus, too much can be made, as our report does, of Secretary of Defense Wilson's memorandum endorsing the Nuremberg Code. To hold him culpable for not implementing the Code makes little sense. If he is culpable of anything, it is for promulgating it without first having sought thoughtful advice about what needed to be explicated to make it a viable statement for research practices, merely embracing the Code invited, indeed guaranteed, neglect. Finally, from the perspective of history, I want to note that only since the early 1960s was the importance of consent given greater attention. Among the social forces that contributed to this development to stand out, judges' promulgation of a new legal doctrine of informed consent based on the Anglo-American premise of thoroughgoing self-determination in the explorations by a new breed of bioethicists, recruited from philosophy and theology of the relevance of such principles as autonomy, self-determination, beneficence, and justice to medical decision making. Their novel and powerful arguments so alien to the medical mind disturbed the sleep of the medical community. Physicians had a particularly hard time in coming to terms with the idea of patient autonomy. To this day, I believe this principle has only gained a foothold in the ethos of medical practice and research. In our report, we emphasize the primacy of patient-subject autonomy and research. It led us to conclude in our interim report that a cornerstone of modern research ethics is informed consent. I agree with the statement of principle from the 1963 beginnings of my work in human experimentation. I have championed the idea of respect for autonomy and self-determination in all interactions between physician investigators and patient subjects. But I introduced one major qualification when I wrote that only when the Nuremberg Code's first principle on voluntary consent is firmly put into practice can one address the claims of science and society to benefit from science. Only then can one avoid the dangers that accompany a balancing of one principle against the other that assigns equal weight to both. For only if one gives primacy to consent can one exercise the requisite caution and situations where one may wish to make an exception to this principle for clear and sufficient reasons. I mention this here because the final and most far-reaching recommendation for change that I shall soon propose is based on two premises. One, that any exception to the principle of individual autonomy, since it tampers with fundamental democratic values, must be rigorously justified by clear and sufficient reasons. And two, that such exception cannot be made by investigators or IRBs, but only by an authoritative and highly visible body. I now turn to our research proposal review project. The committee's review of contemporary research reveals that of the greater than minimal risk studies, which are the ones that raise complex informed consent issues. 23% were ethically unacceptable and 23% raised ethical concerns. My own independent review tells a grimmer story. 50% raised serious ethical concerns and an additional 24% raised ethical concerns that cannot be taken lightly. Since I focused exclusively on the informed consent process, the differences in our findings can perhaps in part be explained on that basis. My data, like the committees, were the protocols submitted to IRBs and the informed consent forms signed by patient subjects. I appreciate that the evidence available to us does not reflect what patient subjects might have been told during oral communications. But if the protocols in patient subject consent forms are flawed in significant ways, it is likely that the oral interactions are similarly flawed. Moreover, since IRBs are charged to pay particular attention to the informed consent process, I contend that IRBs should not have approved the problematic consent forms in the form they were submitted. The forms often seem to sow research rather than to convey a sense of caution that invites reflective thought. I had expected to discover problems, but I was stunned by their extent. Consider what we observed in Chapter 15 and what is described there in great detail. The obfuscation of treatment and research illustrated most strikingly in Phase 1 studies, but by no means limited to them the lack of disclosure and randomized clinical trials about the different consequences the patient subjects well-being if assigned to one research arm or the other, the administration of highly toxic agents in the scientific belief that only the knowledge gained from total therapy will eventually lead to cures, but without disclosure of the impact of such radical interventions on quality of life or longevity. I do not wish to minimize the impact of making total disclosure on patient subjects and physician investigators' hopes and fears, yet nagging questions remain. What are clear and sufficient reasons which permit tampering with disclosure and consent, and if permissible, who decides? Our recommendations do not go far enough to remedy the flawed nature of our current regulations which appear to rely so heavily on informed consent, but which in practice I contend to bypass true informed consent. Here I can only make a few comments about the changes required if we wish to protect adequately the rights and interests of subjects of research. 1. Informed consent is central to such protections. The drafters of the federal regulations have acknowledged that fact. They have failed, however, to take responsibility for making these requirements meaningful ones. Thus patient subjects now all too often give a spurious consent that can readily mislead physician investigators into believing that they have received the authority to proceed when in fact they have not. 2. The federal regulations imply that the principle of respect for patient subjects autonomy is central to the regulatory scheme. Leaving it at that is not enough, for the principle requires commentary so that physician investigators will have a more thorough going appreciation of the moral issues at stake whenever they ask human beings to serve as means for the ends of others. Only then will they learn, for example, that to take informed consent seriously requires them to spend considerable time with prospective patient subjects and to engage them in searching conversations. In these conversations, they must disclose A. that their subjects are not patients or, to the extent they are patients, that their therapeutic interests will be subordinated in specified ways to scientific interests, B. that it is problematic and in what ways, whether their welfare be better served by placing their medical fate in the hands of a practitioner rather than a physician investigator, C. that in opting for the care of a physician they may be better or worse off and for such and such reasons, D. that research is governed by a research protocol and a research question and therefore patient subjects interests and needs have to yield and to what extent to the claims of science, etc. Such disclosure obligations are formidable ones. They need to be fulfilled in a manner that will give patients subjects a clear appreciation of the difference between research and therapy, and in the spirit that disabuses them of the belief so widely held as our subject interview study demonstrates that everything the investigator proposes serves their best therapeutic interests. The Cold War experiments teach us that misplaced trust can deceive that trust must be earned by prior disclosures of what research participation entails. I agree as our recommendation 9 proposes that scientists should be educated to ensure the centrality of ethics in their conduct. To accomplish that educational task, however, requires policies that more clearly delineate the ambit of discretion which investigators can exercise in the conduct of research. B. Current criteria for informed consent encourage perhaps even mandate overwhelming patient subjects with information on every conceivable risk and benefit as well as on the scientific purpose of the study. Adherence to these mandates has led, and justifiably so, to concerns about the incomprehensibility of the informed consent forms that patient subjects must sign. Much thought and then guidance has to be given to IRBs and investigators as to essential information they must provide, e.g. alternatives, uncertainties, essential risks, realistic benefits as well as the impact of participation known and conjectured, on the quality of future or remaining lives. Many of the informed consent forms I have examined fail to emphasize the risks germane to the research protocol. Instead they go into numbing detail on risks that can be summarized. To put it bluntly, informed consent criteria in today's world, at least in the way they are communicated to patient subjects, often serve purposes of obscuring rather than clarifying what participation in research entails. 2. Though IRBs serve important functions, they do not have the capacity, if only by virtue of composition and lack of time, either to modify consent standards, including the ones I have just proposed, or more generally to make any other decisions that can affect the fundamental constitutional rights and personal interests of subjects of research. 3. IRBs should not have the authority to decide how to balance competing principles and situations where the competence of subjects' consent is in question, or where consent cannot be obtained because patient subjects suffer from a life-threatening condition, or where other complex issues need to be resolved, as illustrated in our chapter on the total body radiation experiments. Such fateful decisions are beyond their competence. Moreover, IRBs work in a climate of low visibility and other species of secrecy about which we express so much concern in chapter 13. These and other complex ethical problems should only be resolved by an accountable and highly visible national body. That body, then, can provide IRBs with guidelines that will better inform their deliberations. I would like to note here, but only in passing, that the body I envision will lighten IRB's tasks. For example, by fashioning policies for cursory review of the many minimal, slash no risk, studies, or by being available for advisory opinions whenever IRBs are confronted with new ethical problems, IRBs now spend an inordinate amount of time on such problems which they should not resolve in the first place. The national body should not review individual research projects except when investigators and IRBs disagree. Finally, a national body is needed for another reason as well, the considerable pressure for approval protocols to which IRBs are subjected by the scientists at their institutions. 3. Already in 1973, when I served on HEW's Tuskegee Syphilis Study ad hoc advisory panel, we proposed in our final report that Congress established a permanent body, we called it the National Human Investigation Board, with the authority to regulate at least all federally supported research involving human subjects. We recommended that this board should not only promulgate research policies, but also administer and review the human experimentation process. Constant interpretation and review by a body whose decisions, account by virtue of the authority invested in them, can protect both the claims of science and society's commitment to the inviolability of subjects of research. A more important task, which such a board would face in formulating research policies, is to delineate exceptions to the informed consent requirement when competing principles require it. For example, when might it be permissible for IRBs to defer consent, or more correctly to allow physician investigators to proceed without consent, with patient subjects suffering from acute head trauma. Conscripting citizen patients to anything they have not consented to is deeply offensive to democratic values, and if necessary requires public approval. Greater public participation in the formulation of research policies is vital, and the board must therefore establish procedures for the publication of all its major policy and advisory decisions, particularly those where compromises seem warranted between the advancement of science and the protection of subjects of research. Publication of such decisions would not only permit their intensive study both inside and outside the medical profession, but would also be an important step toward the case-by-case development of policies governing human experimentation. If we are truly concerned about the baneful effects of secrecy on public trust, what I propose here could restore trust. There is, of course, much more to consider, and I have written about it elsewhere. I hope, however, that I have said enough to suggest that the problems inherent in research with human subjects advancing science and protecting subjects of research are complex. Society can no longer afford to leave the balancing of individual rights against scientific progress to the low visibility decision-making of IRBs with regulations that are porous and invite abuse. The important work that our committee has done and its evaluation of the radiation experiments conducted by governmental agencies and the medical profession during the Cold War once again confronts us with the human and societal costs of too relentless a pursuit of knowledge. If this is a price worth paying, society should be forced to make these difficult moral choices and bright sunlight and through a regulatory process that constantly strives to articulate, confront, and delimit those costs. We have judged the past, and judgments of the past become most relevant when they teach us the lessons for the present and future, yet we did not judge the present with sufficient care. If the problem was time, I wanted to take the time to offer my judgments. I also took the time and took the road less traveled by, because much is at stake in the quest for advancing medical science that speaks not only to progress in the conquest of disease, but to other moral values as well. End of Section 90 End of Final Report of the Advisory Committee on Human Radiation Experiments