DOE Openness: Human Radiation Experiments: Roadmap to the Project
Local Oversight: Radioisotope Committees
Chapter 6: Local Oversight: Radioisotope CommitteesFrom its inception, the AEC distribution system required each local institution to establish a "local radioisotope committee," later termed a "medical isotopes committee." Initially, the primary purpose was to simplify the allocation process by having local institutions establish their own priorities before applying to the AEC. Soon after the program began, supply increased and no dramatic new uses developed, so allocation was no longer a major issue. These local committees also took on responsibilities for physical safety, usually working closely with radiation safety offices. By October 1949 this requirement also applied to the AEC's national labs. When "general authorizations" were issued in 1951, granting broader discretion to qualifying local institutions, local isotope committees assumed greater responsibility.
By 1956, the functions of the local radioisotope committees included reviewing applications, prescribing any special precautions, reviewing reports from their radiological safety officers, recommending remedial action when safety rules were not observed, and keeping records of their own activities. The basic focus on radiological safety remained, although in reviewing applications a local medical isotopes committee could also consider "other factors which the [local medical isotopes] Committee may wish to establish for medical use of these materials." Exactly what these "other factors" might be was not specified.
These local committees together reviewed thousands of applications over the next decades. Although not federal agencies, they were required by the AEC, and their proper functioning was an important part of the oversight system envisioned by the AEC. To fully assess whether this system fulfilled its goals would be an enormous task, requiring the retrieval and examination of thousands of local records. However, to make a preliminary assessment of whether the system as a whole generally appeared to function as planned, the Advisory Committee did examine the records of several public and private institutions: the Veterans Administration (VA), the University of Chicago, the University of Michigan, and Massachusetts General Hospital (MGH). Doing so provided us with an understanding of the techniques of risk management used at the local level on a day-to-day basis. We specifically examined whether local radioisotope committees in fact were established as directed and what techniques they developed to monitor consent and ensure safety.
Establishment of Local Isotope CommitteesOverall, the federal requirement seems to have been an effective means of instituting a reasonably uniform structure across the nation for local radioisotope committees. The AEC's requirements for local committees were followed in all the institutions studied, and there is no reason for believing they were exceptional. One local radioisotope committee, that of Massachusetts General Hospital, was established in May 1946, prior to the AEC requirement. The other institutions established a local radioisotope committee when required to do so by the AEC.
Local committees also could have broader tasks than those required by the AEC. For example, the Radiation Policy Committee at the University of Michigan regulated all radioactive substances used on campus, not just those purchased from the AEC. These included reactor products, transuranic elements, and external sources of radiation.
The Veterans Administration added another level of oversight in the form of a systemwide Central Advisory Committee. In 1947 the VA embarked on a radioisotope research program that would take place within newly established radiation units in the hospitals that would be the recipients of AEC-supplied isotopes. Among early research projects were the treatment of toxic goiter and hyperthyroidism with iodine 131 and treatment of polycythemia rubra vera (overproduction of red blood cells) with phosphorus 32 at Los Angeles, radioactive iron tracers of erythrocytes at Framingham, and sodium 24 circulatory tracers in Minneapolis. By the end of 1948, radioisotope units had been established in eight VA hospitals. Each of the eight was asked to establish a radioisotope committee (as required by the AEC) to be appointed by the Dean's Committee of each hospital, while representatives from affiliated universities agreed to serve as consultants in the various units.
Local Monitoring of ConsentGenerally, although local institutions created clear procedures to monitor safety, these local radioisotope committees did not establish procedures to monitor or require consent. (See part I for discussion of the broader historical context of consent in medical research.) The standard application form to the Massachusetts General Hospital committee, as of 1953, had no place to describe an informed consent procedure. This does not, of course, resolve the question of whether consent was given. According to one prominent neurosurgeon interviewed by the Advisory Committee staff, William Sweet, at that time, in the case of brain tumor patients, oral consent was obtained from both the patient and, since mental competency could later be an issue, the next of kin.
Similarly, no mention of the 1947 AEC requirements stated in General Manager Wilson's letters is contained in the advice Shields Warren gave in 1948 to the VA, even though Warren, as director of the AEC's Division of Biology and Medicine, must have known of discussions about consent requirements. An issue that arose before the VA Central Advisory Committee was whether patient-subjects should sign release slips. This issue posed the question of whether the radioisotope units in the VA hospitals were treatment wards or clinical research laboratories. If wards, patients need not sign consent forms, for they were simply being treated in the normal course of an illness. Shields Warren agreed with this presumption and felt that there was no need for the patients to sign release slips: "The proper use of radioisotopes in medical practice is encompassed in the normal responsibilities of the individual and of the institution or hospital." In addition, he felt that the practice would draw "undue and unwholesome attention to the use of radioisotopes."
Movement toward more formal consent requirements gradually arose at the local level. In 1956 the University of Michigan's own Human Use Subcommittee directed that in an experiment using sodium 22 and potassium 42, each "volunteer would be required to sign a release indicating that he has full knowledge of his being subjected to a radiation exposure." Since the local committee was concerned about what it termed "unnecessary" radiation, the volunteers presumably were healthy subjects not otherwise receiving radiation for treatment or diagnosis. The committee appended a recommended "release" form to its minutes:
I, the undersigned, hereby assert that I am voluntarily taking an injection of _______ at a dose level which I understand to be considered within accepted permissible dose limits by the University of Michigan Radio-isotope Human Use Sub-Committee.
By 1967, the Michigan subcommittee also required that the subject explain the experiment to the researcher to clarify any doubts or misunderstandings. The following statement was incorporated into all applications to the university's Human Use Subcommittee:
The opinion of the Committee is that INFORMED CONSENT is the legal way of describing a "meeting of the minds" in a contract. In this situation it means that the subject clearly understands what the experiment is, what the potential risks are, and has agreed, and without pressure of any kind, elected to participate. The best way to ascertain that the consent is informed, is to have the subject explain back fully to the interviewer, exactly what he thinks he is submitting to and what he believes the risks might be. This facilitates clarification of any doubts, spoken or unspoken. The content of this discussion will be recorded in detail below.
During the 1960s, as explained in chapter 3, concern was growing over the adequacy of consent from subjects. Although not intended by the AEC to monitor the obtaining of consent from subjects, over the years the local radioisotope committees may have come to take on this task. By requiring such local committees, the AEC had, probably unwittingly, provided an institutional structure that allowed later concern for informed consent to be implemented at the local level.
Local Monitoring of RiskThis local and informal approach to consent is in sharp contrast to the detail and documentation with which risk was assessed. As discussed earlier, monitoring risk was the major task of the AEC's Subcommittee on Human Applications. The local committees mirrored this task, examining in detail the various experiments presented to them. As with the AEC subcommittee, local committees developed a variety of methods, none especially surprising, to ensure what they believed was adequate safety.
The basic dilemma facing local committees was to allow exploration of new territory while attempting to guard against hazards that, precisely because new territory was being explored, were not totally predictable. This dilemma was apparent at the local level, as well as at the level of the AEC's Subcommittee on Human Applications. For example, in the minutes of the Massachusetts General Hospital local radioisotope committee in 1955, during a discussion of new and experimental radiotherapies for patients, one member of the committee declared that the safety of the patient was of "paramount importance." Yet, other members suggested that a risk-benefit analysis needed to be an integral component of such a policy decision. The committee as a whole concluded merely that it was a complicated issue and that "it is not wise in any way to inhibit investigators with ideas, and yet the safety of the patient must come first."
Requiring prior animal studies was a basic method of assessing risk. For example, the twenty-two studies reviewed by the University of Chicago's local committee in 1953 included multiple therapeutic and tracer studies involving brain tumors, the thyroid gland, metastatic masses, and tissue differentiation. Those the Chicago committee viewed as involving any risk to the patient were preceded by extensive animal studies.
Animal studies were usually tailored to each project and also raised the question of the differences between how humans and animals might respond to a particular radioisotope. A more uniform standard directly applicable to humans was the system of dose limits established by the National Committee on Radiation Protection for occupational purposes: the maximum permissible dose for each isotope. In addition, although no national system existed for reporting their decisions, local committees drew upon their knowledge of what had been approved at other institutions. At least one local committee issued its own dose limits. The Massachusetts General Hospital local committee in 1949 issued a seven-point policy on human use of beta- and gamma-emitting radioisotopes. By 1956, the Michigan committee provided explicit limits for exposure of volunteers.
At other times, the condition of subjects who were patients was accepted as justification for higher doses. For example, in 1953 the Chicago committee approved a tracer study using mercury 203 "to study uptake by malignant renal tissue." Although admitted to be unusual, it was approved as potentially efficacious in patients suffering hypernephroma (a kidney cancer). Total dose would not exceed 10 milligrams of ionic mercury, a high dose for most tracer studies, which was approved as reasonable given the illness of the patients. Similarly, the Harvard Medical School committee in 1956 stipulated that "the risk of incurring any type of deleterious effect due to the radiation received should be comparable to the normal everyday risks of accidental injury." For seriously ill patients receiving experimental treatment, however, the committee stated, "the estimated deleterious effect from radiation should be offset by the expected beneficial effects of the procedure."
In addition to setting limits, local committees encouraged the use of technical methods to reduce risk. Use of different detection techniques could reduce the dose required. In 1955, for example, the Michigan committee considered an application to administer to normal volunteers up to 30 microcuries of sodium 22 and up to 350 microcuries of potassium 42, resulting in internal radiation doses of up to 300 millirem per week. (The purpose was to study sodium-potassium exchanges.) The committee asked itself: "Is it justifiable to subject the volunteers to an exposure in excess of the maximum permissible? This Committee did not resolve this question but came forward with the suggestion that more-sensitive counting techniques might permit this investigation at lower dose levels."
Another method of reducing risk was to restrict the type of subjects to those whose life expectancy was too short for long-term effects to appear. This has already been seen regarding terminal patients. Another variation of the same technique was to restrict the use of volunteers to those over a certain age. At Michigan, age restrictions on who would be acceptable as a volunteer began appearing in the 1960s.
When a worthwhile experiment also involved novel risks, another method to control risk was to require additional monitoring by the local committee as the experiment proceeded. At times, the Michigan committee required preliminary reports before allowing experiments to proceed further. In another instance, the Michigan committee required the researcher to obtain long-term excretion data because of concern that "the usual biologic half-life data might not be sufficient." Similar additional oversight was required at the University of Chicago in 1953. A proposal was made to use tritium-labeled cholesterol to study steroid-estrogen metabolism in women. The question of the distribution of estrogenic hormones in humans was unexplored at the time and deemed worthy of research. While the risk appeared low, the committee ultimately approved the study for the first round of the experiment only for nonpregnant women who were sterile or pregnant women who planned to be sterilized postabortion. If data from the first round suggested minimal risk to the women and the fetuses, the program could be expanded.
Thus, in establishing a system of local radioisotope committees, the AEC effectively increased the detail with which each proposed experiment was reviewed. Often, it appears, experimental protocols were revised at the local level before being approved and sent on to the AEC. Thus, the system created by the AEC did some of its most effective risk management out of sight of direct federal oversight.