Advisory Committee on Human Radiation Experiments (Achre) Final Report: Chapter 17: Findings for the Period 1944-1974: Biomedical Experiments

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. RECOMMENDATIONS OF THE ADVISORY COMMITfEE ON HUMAN RADIATION EXPERIMENTS AND A R E SUBJECT TO REVlSlON BASED ON COMMITTEE REVIEW AND DISCUSSION. NOT FOR QUOTATION OR CITATION.1_ Finding for the Period 1944-1974 The Advisory Committee finds that from 1944 through 1974 the government sponsored (by providing funding, equipment, or radioisotopes) several thousand human radiation experiments. In the great majority of cases, the experiments were conducted to advance biomedica1 science; some experiments were conducted to advance nationaI interests in defense or space exploration; and some experiments served both biomedical and defense o r space esploration purposes. These experiments were conducted by researchers affiliated with government agencies, universities. hospitals. and other research institutions. Only fragmentary information survives about most experiments

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THIS IS A DRAFT-THE CONTENTS DO NOT REPRESENT FINAL CONCLUSIONS AND/OR ’ RECOMMENDATIONS OF THE ADVtSORY COMMITTEE ON HUMAN RADIATION EXPERIMENTS AND ARE SUBJECT 70 REVISION BASED ON COMMITTEE REVIEW AND DISCUSSION. NOT FOR QUOTATION OR CITATION. Findinys for the Period 1944-1974 The Advisory Committee finds that from 1944 through 1974 the government sponsored (by providing funding, equipment, or radioisotopes) several thousand human radiation experiments. In the great majority of cases, the experiments were conducted to advance biomedical science; some experiments were conducted to advance national interests in defense or space exploration; and some experiments served both biomedical and defense o r space exploration purposes. - - These experiments were conducted by researchers affiliated with government agencies, universities, hospitals. and other research institutions. Only fragmentary information survives about most experiments

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THIS IS A DRAFT-THE CONTENTS DO NOT REPRESENT FINAL CONCLUSIONS AND/OR RECOMMENDATIONS OF THE ADVISORY COMMITTEE ON HUMAN RADIATION EXPERIMENTS AND ARE SUBJECT TO REVISION BASED ON COMMITTEE REVIEW AND DISCUSSION. NOT FOR QUOTATION OR CITATION. The Advisory Committee finds that the majority of human radiation experiments in our database involved radioactive tracers administered in amounts that are likely to be similar to those used in research today. Most of these tracer studies involved adult subjects and are unlikely to have caused physical harm. However, in some nontherapeutic tracer studies involving children, radioisotope exposures were associated with increases in the potential lifetime risk for developing cancer that would be considered unacceptable today. The Advisory Committee also identified several studies in which patients died soon after _L receiving external radiation or radioisotope doses in the therapeutic range that were associated with acute radiation effects. Review of available information indicates that the majority of the approximately 4.000 human radiation experiments in the Advisory Committee database involved the use of radioisotopes as tracers in research designed to measure physiological processes in either normal or diseased states. These experiments were not typically aimed at measuring the biological effects of radiation itself. However, information on the majority of experiments in our database was fragmentary and thus did not allow for detailed estimates of dosimetry or examination of issues of experimental design and subject selection.

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THIS IS A DRAFT-THE CONTENTS DO NOT REPRESENT FINAL CONCLUSIONS AND/OR RECOMMENDATIONS OF THE ADVISORY COMMITTEE ON HUMAN RADIATION EXPERIMENTS AND ARE SUBJECT TO REVISION BASED ON COMMITTEE REVIEW AND DISCUSSION. NOT FOR QUOTATION OR CITATION. To supplement the information in our database and provide context to our analysis, we independently reviewed archival documents from AEC-mandated institutional local isotope committees. These local use committees were part of a larger AEC program that facilitated the distribution of radioisotopes for use in govemment-sponsored human subjects research in the 1947-1974 period and involved the review of experimental risk on an individual basis to ensure that human uses of isotopes were within accepted risk standards of the day. We thus used these materials as an indicator of isotope use and regulatory practices at that time. While we recognize the limitations of the data available to us, our evaluation suggests that most tracer studies conducted during the period 1944-1974 likely involved low doses that did not cause any acute or long-term effects. The Advisory Committee cannot rule out, however, the possibility that some people were or will be harmed as a consequence of their invoIvement in The Committee did identify some nontherapeutic tracer experiments involving the administration of iodine 131 to children, which may have raised the subsequent risk of developing thyroid cancer to levels that would be considered unacceptable today. Based on the average risk estimate for each experiment, approximatedly 500 individuals were exposed to greater than minimal risk. (The Committee used a threshold of greater than or equal to one excess case of cancer per 1,000 subjects for categorizing experiments as greater than minimal risk.) Combining the average risk estimates for each experiment, this translates into an expected

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THIS IS * DRAFT-THE CONTENTS DO NOT REPRESENT FINAL CONCLUSIONS AND/OR RECOMMENDATIONS Of THE ADVISORY COMMITTEE ON HUMAN RADIATION EXPERIMENTS AND A R E SUBJECT TO REVISION BASED ON COMMITTEE REVIEW AND DISCUSSION. NOT FOR QUOTATION OR CITATION. excess of 1.3 incident cases of thyroid cancer for the entire group. Fortunately, unlike many other cancers, thyroid cancer is curable in more than 90 percent of cases; therefore, it is unlikely that, even if cancers developed, these exposures caused any premature deaths. Furthermore, although there is strong scientific evidence that radiation doses delivered over a short period of time from external sources can result in increases in cancer incidence at specific sites, comparable data suggest that the carcinogenic effects of isotope exposures are less than those of external irradiation. The difference in carcinogenic effect is thought to be due to the relatively low dose rate of the isotope exposure, which allows for effective repair of radiation damage. One additional isotope study involving the administration of radioiron to pregnant - women has been linked to a possible increase in cancers in children who were exposed in utero. However, the small number of observed cancers as we11 as considerable uncertainties in the amount of radioisotope administered have made the determination of causality dificult. Finally, the Committee found some experiments where radioisotope exposures were associated with either acute or chronic physiologic changes of uncertain clinical significance, pathologic evidence of kidney damage secondary to chemical and radigion toxicity in some patients injected with uranium, and radiographic evidence of minimal bone changes in some long-term survivors of plutonium injections. Studies that involved radiation doses in the therapeutic range were for the most part performed on patient-subjects where there was, at least arguably, a prospect that the subjects

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THIS IS A DRAFT-THE CONTENTS DO NOT REPRESENT FINAL CONCLUSIONS AND/OR . RECOMMENDATIONS OF THE ADVISORY COMMITTEE ON HUMAN RADIATION EXPERIMENTS AND ARE SUBJECT TO REVISION BASED ON COMMITTEE REVIEW AND DISCUSSION. NOT FOR QUOTATION OR CITATION. might benefit medically fiom the exposure. However, the TBI and experimental gallium treatments, in which patients suffered symptoms of acute radiation sickness and died soon after treatment, raise the question of whether their deaths were hastened by the radiation treatments. Resolution of this issue requires review of individual medical histories, which the Advisory , Committee could not undertake. The Advisory Committee finds that human radiation experimentation during the period 1944 through 1974 contributed significantly to advances in medicine and thus to the health of the public. Human radiation research was essential to the development of new therapies such as the use of radioactive iodine to treat thyroid cancer; the use of phosphorus to treat blood diseases such as polycythemia vera; and the use of radioactive strontium- as a palliative in prostate and other cancers metastasized to the bone. Diagnostic uses of radionuclides developed during this period include scanning techniques to identify tumors and radiolabeling techniques that help evaluate a variety of cardiac diseases. The quality of images produced by external sources of

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THIS IS A DRAFT--THE CONTENTS DO NOT REPRESENT FINAL CONCLUSIONS AND/OR RECOMMENDATIONS OF THE ADVISORY COMMITTEE ON HUMAN RADIATION EXPERIMENTS AND ARE SUBJECT TO REVISION BASED ON COMMITTEE REVIEW AND DISCUSSION. NOT FOR QUOTATION OR CITATION. radiation also improved dramatically between 1944 and 1974, making possible, for example, techniques such as balloon angioplasty to open occluded arteries. The Advisory Committee finds that some government agencies required the consent of some research subjects well before 1944. These requirements generally did not stipulate what was meant by consent, however, nor did they generally indicate whether investigators were obligated to disclose specific information to potential subjects. The government did not have comprehensive policies requiring the consent of all subjects of research, including both healthy subjects and patient-subjects, until 1974. 4a. Research Involving Healthy Subjects: In the 1920s, the Army promulgated a regulation concerning the use of "volunteers" for medical research. In 1932, the secretary of the Navy required that subjects of a proposed experiment be "informed- volunteers." In 1942 the requirement that healthy subjects be informed volunteers was also articulated by the Committee on Medical Research, which oversaw war-related research for the Executive Ofice of the President. In 1953, the principle of consent articulated in the Nuremberg Code was adopted by the Department of Defense in a Top Secret memorandum from Secretary of Defense Charles

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THIS IS A DRAFT-THE CONTENTS DO NOT REPRESENT FINAL CONCLUSIONS AND/OR RECOMMENDATIONS OF THE ADVISORY COMMITTEE ON HUMAN RADIATION EXPERIMENTS AND ARE SUBJECT TO REVISION BASED ON COMMITTEE REVIEW AND DISCUSSION. NOT FOR QUOTATION OR CITATION. Wilson regarding human research related to atomic, biological. and chemical warfare (this document is known as the Wilson memorandum); in 1954, this application of the Nuremberg Code was expanded by the Army Office of the Surgeon General as an unclassified policy for all research with "human volunteers." A policy of requiring researchers to obtain consent was adopted by the Clinical Center, the research hospital of the National Institutes of Health, in 1953; by the Atomic Energy Commission in 1956; and by the Air Force in 1958. In the 1960s, all branches of the Department of Defense promulgated regulations requiring the consent of healthy subjects, and the Isotopes Distribution Division of the AEC included in its guide for researchers a requirement of consent from all subjects. In 1966, the surgeon general of the Public Health Service issued a policy requiring the consent of all subjects of research conducted or funded by PHS; ais0 in the late 1960s, the Veterans Administration codified in its operating manuaI a requirement of consent from all research subjects. In 1972, the National Aeronautics and Space Administration adopted similar consent requirements, although exceptions were made for certain subject populations, such as astronauts. In 1974, the Public Health Service policy was promulgated as a regulation for all contracts and grants of the- Department of Health, Education, and Welfare. The CIA did not formally adopt consent requirements until 1976, when an executive order mandated that it follow the 1974 regulations of DHEW concerning research involving human subjects.

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THIS IS A DRAFT-THE CONTENTS DO NOT REPRESENT FINAL CONCLUSIONS AND/OR AND ARE SUBJECT TO REVISION BASED ON COMMITTEE REVIEW AND DISCUSSION. NOT RECOMMENDATIONS OF THE ADVISORY COMMllTEE ON HUMAN RADIATION EXPERIMENTS €QR QUOTATION OR CITATION. 4b. Research lnvolving Patient-Subjects: In an April 1947 letter, the AEC general manager stated the AEC's understanding that AEC contract researchers would inform patientsubjects of the risks associated with a research intervention and that patient-subjects express a willingness to receive the intervention. In a second letter, written in November 1947, the general manager specifically stipulated that the AJX require researchers to obtain "informed consent in writing" from patient-subjects where "substances known to be or suspected of being poisonous or harmful" were given to human beings. In 1948, the AEC permitted the administration of "larger In 1953, the NIH Clinical Center required consent from all patient-subjects and specified that written consent was to be obtained from patient-subjects involved in high- or uncertain-risk experiments. In the early 1960s, several government agencies adopted consent provisions for investigational drugs; these requirements applied to some radioisotope experiments with patients. In 1965, the AEC required that consent be obtained from a11 subjects, including patientsubjects, who were administered radioisotopes for experimental purposes, except when it consent of all patient-subjects. As noted in Finding 4a above, in 1965 the AEC required that consent be obtained from all subjects administered radioisotopes for experimental or nonroutine uses. In 1966 the surgeon general of the Public Health Service issued a policy requiring the consent of all subjects of research conducted or funded by PHS, including patient-subjects.

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THIS IS A DRAFT-THE CONTENTS DO NOT REPRESENT FINAL CONCLUSIONS AND/OR RECOMMENDATIONS OF THE ADVISORY COMMIITEE ON HUMAN RADIATION EXPERIMENTS AND ARE SUBJECT TO REVISION BASED ON COMMITTEE REVIEW AND DISCUSSION, NOT FOR QUOTATION OR CITATION. Exceptions to this requirement were permitted for only certain kinds of social science research posing minimal risk. A 1972 NASA policy applied to all subjects of research, presumably including patient-subjects. By 1973, all the branches of the military had promulgated regulations requiring the consent of patient-subjects. In 1974, the PHS policy was promulgated as a regulation for all contracts and grants of DHEW. The Advisory Committee finds that government agencies did not generally take effective measures to implement their requirements and policies on consent to human Evidence of the implementation of the AEC's consent requirements stated in April and November 1947 letters from the general manager is slim. A document suggests that the April 1947 requirement for a signed statement fiom two physicians- testifying to consent was satisfied in at least one case. However, the Advisory Committee did not find evidence that this or other requirements stated in the 1947 letters were embodied as a provision of AEC contracts involving human subject research or otherwise routinely communicated to contract researchers. Further, there was no reference to the requirements stated in these letters or to the letters themselves in the

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THIS IS A DRAFT-THE CONTENTS DO NOT REPRESENT FINAL CONCLUSIONS AND/OR RECOMMENDATIONS OF THE ADVISORY COMMITTEE ON HUMAN RADIATION EXPERIMENTS AND ARE SUBJECT TO REVISION BASED ON COMMITTEE REVIEW AND DISCUSSION. NOT FOR QUOTATION OR CITATION. written material disseminated to researchers by the AEC's program for distributing radioisotopes for "human uses." Moreover, requests for guidance concerning human use policies from investigators at AEC-operated research facilities suggest that the 1947 requirements were not routinely disseminated. Subsequent requirements that healthy subjects be informed volunteers and that consent be obtained from seriously ill patients receiving higher doses of radioisotopes were more widely communicated; we have not been able to determine the extent to which they were actually implemented. Secretary of Defense Wilson's February 1953 Top Secret memorandum detailing requirements for research with human subjects was rewritten as an unclassified June 1953 directive from the secretary of the Army. It is difficult to determine why these requirements were applied to some activities and not to others. For example, elements of some of these requirements appear to have been implemented in some experiments conducted in conjunction with atomic bomb tests and not in others. In 1954, these requirements were adopted by the Army surgeon general as applicable to all research involving "human volunteers." This 1954 statement was transmitted to contractors as a "nonmandatory guide." However, there is some evidence that the A r m y sought to include this statement as a condition in at least some contracts. Evidence of …