Chapter 12: The Iodine 131 Experiment in Alaska In 1956 and 1957 the U.S. Air Force's Arctic Aeromedical Laboratory conducted a study of the role of the thyroid gland in acclimatizating humans to cold, using iodine 131. Like the case of the Marshallese, this study is another instance in which research conducted on populations that were unfamiliar at the time with modern American medicine posed special ethical problems and was therefore of interest to the Advisory Committee. The study involved 200 administrations of I-131 to 120 subjects: 19 Caucasians, 84 Eskimos, and 17 Indians,[227]Charts appearing in the report indicate slightly different subject numbers with some subjects participating more than once. Animal studies had suggested the thyroid gland might play a crucial role in adaptation to extreme cold. This experiment was part of the laboratory's larger research mission to examine ways of improving the operational capability of Air Force personnel in arctic regions. The results of the study were published in 1957 as an Air Force technical report by the principal investigator, Dr. Kaare Rodahl, M.D., a Norwegian scientist hired by the U.S. Air Force for his expertise--rare at the time--in arctic medicine.[228] Many observational studies of Alaska Natives were carried out by a variety of researchers in the 1950s and 1960s; most of these did not administer radiation to the natives, but only measured what had already accumulated in their bodies from fallout.[229] The thyroid study discussed here, however, differed in that it actively administered radionuclides to natives, raising more direct questions of consent, risk, and subject selection. The Alaskan I-131 experiment also offered subjects no prospect of medical benefit. This study is the subject of a review by a committee of the Institute of Medicine and the National Research Council. The IOM/NRC committee was mandated by legislation passed by Congress in 1993 and began operation in June 1994, including an on-site investigation of the experiments.[230] To the extent possible, the IOM/NRC committee has provided the Advisory Committee with information but, in accordance with its own procedures, has kept its own deliberations confidential. The IOM/NRC report was not available to the Advisory Committee, as it had not been completed by the time the Committee had concluded its deliberations. We did not conduct our own on-site investigation of the Alaskan experiments. Instead, we have relied on published materials (primarily Rodahl's 1957 report on the study, "Thyroid Activity in Man Exposed to Cold") and those observations presented to the Committee in testimony by representatives of the IOM/NRC committee, as well as by representatives of the Inupiat villages of the North Slope of Alaska where the research was conducted. More detailed study may always, of course, lead to different factual conclusions. The Advisory Committee was concerned with understanding the experiments well enough to develop general remedial principles to be applied to more detailed factual findings completed by others. According to Dr. Chester Pierce of Harvard Medical School, chair of the IOM/NRC committee, in 1994 Dr. Rodahl recalled that the base commander at the Artic Aero-medical Laboratory approved the study, and headquarters in Washington knew of the experiment.[231] Participants in the study were asked to swallow a capsule containing a tracer dose of radioiodine. Measurements were then made of thyroid activity, using a scintillation counter, and samples taken of blood, urine, and saliva.[232] The study's overall conclusion was that "the thyroid does not play any significant role in human acclimatization to the arctic environment when the cold stress is no greater than what is normally encountered by soldiers engaged in usual arctic service or by Alaskan Eskimos or Indians in the course of their normal life or activities."[233] One minor consequence of the experiment was to have the noniodized salt in the local stores replaced with iodized salt. Follow-up, Dr. Rodahl told the IOM/NRC Committee, was left to the Alaska Native Service, which was already aware of a goiter problem in these communities.[234] Alaska natives testifying in 1994 before the IOM/NRC committee could not recall any follow-up visits by physicians, according to Dr. Pierce.[235] Risk The Advisory Committee did not undertake a detailed dose reconstruction or assessment of the scientific quality of the research, since these tasks were already being undertaken by the IOM/NRC committee. The actual capsules of iodine 131 were prepared in continental U.S. laboratories. As was common at the time, the principal investigator, Dr. Rodahl, took a one-week course on the proper handling and administration to humans of iodine 131.[236] He then instructed the other physicians who would be working in the field. Doses were officially reported to range from 9 to 65 microcuries of iodine 131, with most being approximately 50 microcuries. The doses below 50 microcuries were due to the natural reduction in the radioactivity of the ready-made capsules during the long trip to remote regions.[237] (To compensate for the low doses, longer scanning times were used in the field, but in the 1957 report these results were judged to be unreliable.)[238] According to Dr. Pierce, Dr. Rodahl stated in 1994 that the dosage was standard at the time for tracer studies. This was the dose he had been taught in his training course; the dosage was approved by the AEC.[239] In terms of dosage and risk, the experiment was not significantly different from tracer studies conducted in the continental United States with two exceptions. First, some subjects were used more than once; several Alaska Native subjects reported they received as many as three doses.[240] Second, the subjects included women who were pregnant or lactating. Dr. Pierce reported that testimony at the IOM/NRC hearings in Alaska indicated that at least one subject may have been pregnant at the time; technical reports, he said, state that two female subjects may have been lactating at the time.[241] Although the AEC discouraged the nontherapeutic use of radioisotopes in pregnant women, such research was sometimes conducted. What sets the Alaska experiment apart from other studies conducted on pregnant and lactating women is that this experiment was not investigating a research question about an aspect of pregnancy or lactation. As discussed in detail in chapter 6, from its mid-1940s inception the AEC's radioisotope distribution program required prior review of "human uses" of radioisotopes to ensure that risks were minimized and safety precautions were followed. (In 1952 the Air Force issued a rule that required prior review for experiments, but the rule was limited to research conducted at Air Force medical facilities.[242]) As discussed in chapter 6, in 1949 the AEC's Human Use Subcommittee expressly discouraged the use of radioisotopes for research with children or pregnant women. Disclosure and Consent This experiment offered no prospect of medical benefit to subjects. If the subjects in this experiment did not understand and agree to this instrumental use of their bodies, then they were used as mere means to the ends of the investigators and the Air Force. It was at this time conventional for investigators to obtain the consent of "normal" (healthy) subjects or "volunteers" in nontherapeutic research. This tradition was particularly strong in the military services (see part I). It was also recognized by the AEC at least by February 1956 when the AEC's radioisotopes distribution program explicitly stated that where normal subjects are to be used they must be "volunteers to whom the intent of the study and the effects of radiation have been outlined."[243] The Committee is not aware of any documents from the time of the experiment that bear on what, if anything, the subjects were told and whether consent was obtained. There are also no documents bearing on whether the Air Force provided the researchers with guidelines on the use of human subjects or requirements for obtaining consent. However, documents available to the Committee indicate that the radioisotopes used by the Arctic Aeromedical Laboratory and Dr. Rodahl were obtained by the Air Force under license from the AEC.[244] The AEC's provision for healthy volunteers, as just quoted, was included in the AEC's publicly available materials and presumably should have been known to--and abided by--those conducting government research programs involving AEC provided radioisotopes.[245] The only available evidence comes from personal recollections of the principal investigator and a few of the former subjects. Dr. Rodahl recalled in 1994 that he obtained white volunteers through their military commanders and Indian and Eskimo volunteers through the village elders.[246] When a military volunteer came before him, he explained, in the subject's native tongue (English), the purpose of the study and what a subject would do and gave the person the opportunity to decline to participate.[247] When visiting the villages, the physicians could not communicate directly in the native language. They would find an English-speaking village elder and explain the purpose of the study. The elder would then find people to serve as subjects. What communication occurred between the village elder and the prospective subjects is not known. According to members of the IOM/NRC committee, Dr. Rodahl recalled that, although all potential subjects were given the opportunity not to participate, all of the Indians and Eskimos who reported did participate in the experiment.[248] Dr. Rodahl also reported that he did not use the term radiation in his explanation to the English-speaking village elders who then communicated with others in the villages. Interviews in 1994 by the IOM/NRC committee indicated that there is no word for radiation in the native languages. One Alaska Native subject, interviewed by the IOM/NRC committee in 1994, recalled that at the time he worked in a hospital, spoke English, and did know about "radiation." He could not recall any use of the term in the study.[249] In at least one village--Arctic Village--there were no English speakers. Subjects from this village testified in 1994 to the IOM/NRC that they thought they were taking a substance that would improve their own health and that they would not have participated in the study if they had known it required them to take a radioactive tracer.[250] These accounts raise difficult ethical questions about authorization and consent, questions made the more difficult by an incomplete historical record. It is, for example, unclear whether the village elders were employed solely as translators who were asked to transmit individual requests for permission to potential subjects, or whether Dr. Rodahl was responding to the perceived authority of the village elder who then "volunteered" members of his community. Thus we do not know what the individual subjects were told or whether their individual permission was sought. Today we continue to debate whether, when human research is conducted in cultures where tribal or family leaders have considerable authority over members of their communities, it is ever appropriate to substitute the permission of these leaders for first-person consent.[251] Even if the procedure used for securing authorization through the tribal leaders was appropriate, the available evidence suggests that the leaders may not have understood, and thus were not in a position to communicate to the subjects, that the experiment was nontherapeutic, that it had a military purpose, or that it involved exposure to low doses of radiation. The ethical difficulties posed by the language barrier were exacerbated by a significant cultural barrier. The Indian and Eskimo villages had little exposure to modern medicine. One village--Point Lay--is described in Rodahl's 1957 report as "relatively little affected" by the modern world.[252] There is a strong likelihood that there was no appreciation for the difference between treatment of a patient and research unrelated to any illness of the subject. The danger of exploitation was further heightened by the trusting relationship that developed between the native Alaskans and the field researchers. In part, this trust was the customary welcome given to visitors; in part it was due to the desire for medical care. In at least one village, harsh conditions may have increased the need for outside assistance. Rodahl's report states that Point Lay had suffered from semistarvation the previous year.[253] Dr. Pierce testified to the Advisory Committee that "in the mid-1950s, doctor visits to native villages were quite scarce." Dr. Rodahl said when his plane landed, the villagers would come running to meet him and the other physicians who came with him, and the villagers would immediately want their ailments treated. He said the physicians treated them because they were medical men. He also said "the natives trusted them, and they trusted the natives."[254] Testimony before the IOM/NRC committee included the recollection of one participant that he had been paid $10 for the study; in other testimony it appears some subjects may have believed there was an implicit quid pro quo, trading medical treatment for participation.[255] The testimony suggests that at least some subjects understood that part of what was being done to them was not medical care. Subject Selection The selection of Alaskan Indians and Eskimos as subjects for this research was not arbitrary. In order to better understand acclimatization and human performance under conditions of extreme cold, it was reasonable and potentially important to study people who lived under such conditions. At the same time, however, the population chosen was not one familiar with modern medicine, but rather a population for whom the treatments of modern physicians were a strange but valued innovation, and the research activities of modern medicine were totally unknown. As a consequence, the potential for misunderstanding and exploitation was significant. The Committee does not know whether there were at the time other populations also acclimated to cold weather who were better positioned than Alaskan Indians or Eskimos to be genuine volunteers for this nontherapeutic experiment. There has been no evidence that any attempt was made to explain the military purpose of the study to the Indians or Eskimos. Thus, in general, there was no oversight--or even knowledge--of how the village elders recruited participants and explained the nature of the experiment.