DOE Openness: Human Radiation Experiments: Roadmap to the Project
Chapter 5: ConclusionFrom 1945 through 1947 Manhattan Project researchers injected eighteen human subjects with plutonium, five human subjects with polonium, and six human subjects with uranium to obtain metabolic data related to the safety of those working on the production of nuclear weapons. All of these subjects were patients hospitalized at facilities affiliated with the Universities of Rochester, California, and Chicago or at Oak Ridge. Another set of experiments took place between 1953 and 1957 at Massachusetts General Hospital, in which human subjects were injected with uranium. In no case was there any expectation that these patient-subjects would benefit medically from the injections.
At fifty years' remove, it is in some respects remarkable that so much information has survived that bears on the question of what the patient-subjects and their families were told. Particularly for the Manhattan Project plutonium experiments information is available, in large part because of the 1974 AEC inquiry in which interviews with principals of these experiments were conducted and records of these interviews maintained. At the same time, however, there are significant gaps in the record for all the experiments. Particularly where the evidence is skimpy, it is possible that some of the patient-subjects agreed to be used in nontherapeutic experiments. But the picture that emerges suggests otherwise. This picture is bolstered by the historical context. As we discussed in chapter 2, it was not uncommon in the 1940s and 1950s for physician-investigators to experiment on patients without their knowledge or consent, even where the patients could not benefit medically from the experimental procedures. This context is referenced in a 1946 letter about the University of California injections: "These doctors state that the injections would probably be made without the knowledge of the patient. . . . Such injections were not divergent from the normal experimental method in the hospital. . . ."
Here we present our conclusions about the ethics of these experiments, first for the set of experiments conducted between 1945 and 1947 and then for the experiment conducted from 1953 to 1957. Because the facts appear to be different in the different institutions at which these experiments took place, we summarize what we have learned about risk, disclosure, and consent at each location. We also analyze the ethical issues the experiments raise in common. In our analysis, we focus on whether the subjects consented to being used in experiments from which they could not benefit medically, and the extent to which the subjects were exposed to risk of harm. We also focus on the particular ethical considerations raised when research is conducted on patients at the end of their lives. All but one member of the Advisory Committee believe that what follows is the most plausible interpretation of the available evidence in light of the historical context.
With one exception, the historical record suggests that these patients-subjects were not told that they were to be used in experiments for which there was no expectation they would benefit medically, and as a consequence, it is unlikely they consented to this use of their person.
In the case of the plutonium experiments, there was no reason to think that the injections would cause any acute effects in the subjects. This was not true, however, in the case of the Rochester uranium experiments. Both the plutonium and the Rochester uranium experiments put the subjects at risk of developing cancer in ten or twenty years' time. In some cases, this risk was eliminated by the selection of subjects who were likely to die in the near future. The selection of subjects with chronic illnesses was also an apparent strategy to contain this long-term risk of cancer. However, some of these subjects lived for far longer than ten years, and some were misdiagnosed altogether. On the basis of available evidence, we could not conclude that any individual was or was not physically harmed as a result of the plutonium injections. There is some evidence that there were observable, subclinical bone changes of unclear significance in at least two surviving subjects who were followed up in 1953 and 1973 and in one deceased subject who was exhumed in 1973. The uranium injections at Rochester were designed to produce minimal detectable harm--that was the endpoint of the experiment. Such minimal damage is reported to have occurred in the sixth patient of the series.
In the case of Mr. Cade at Oak Ridge, a physician claiming to have injected Mr. Cade reported that his consent was not obtained. An apparently healthy man in his early fifties, Mr. Cade was put at some (probably small) risk of cancer by the plutonium injection.
At the University of Chicago, the only evidence that bears on disclosure and consent comes from an interview with a Chicago investigator conducted as part of the AEC's 1974 inquiry. The investigator was recorded as saying that in obtaining consent patients were told that the radioactive substance to be injected "was not necessarily for the benefit of the patients but might help other people." This statement is misleading. It suggests that there was some chance these patient-subjects might benefit when there was no such expectation. At the same time, however, this statement suggests that the subjects at Chicago were told something. These subjects also were all apparently terminally ill and thus at no risk of developing plutonium-induced cancer; at least two of the three were known to have died within one year of the injection.
Misleading language was purportedly also used with subjects at the University of California, where a secondhand account suggests that subjects were told they were to be injected with a new substance that "had some properties like other substances that had been used to control growth processes in patients." Language in a 1946 letter suggests that at least some of the injections at the University of California may have occurred altogether without the knowledge of the patients. In the case of Mr. Allen, one of the California subjects, two physicians attested that the experimental nature of the procedure had been explained to Mr. Allen and that he had consented. And yet Mr. Allen's physician was subsequently informed that the follow-up studies were in relation to treatment Mr. Allen had received at the University of California. This suggests that, while Mr. Allen may have been told the procedure was experimental, it is not likely that he was told that the procedure was part of an experiment in which there was no expectation that he would benefit medically. Both Mr. Allen and Mr. Stevens survived long enough after injection to be at risk of plutonium-induced cancer.
All the available evidence suggests that none of the subjects injected with either plutonium or uranium at Rochester knew or consented to their being used as subjects in experiments from which they could not benefit. This evidence comes from recollections of some of the individuals who were involved with the plutonium injections, as well as documents about seminars and follow-up studies in the early 1950s suggesting that information about the experiments should be concealed from the subjects. Most of the subjects at Rochester had serious chronic illnesses. It is unclear how likely it was at the time that these patients would not survive more than ten years. A few of these subjects were still alive more than twenty years after the injections. None of the plutonium subjects but all of the uranium subjects were put at risk of acute effects from the experiment.
The purpose of the 1973 follow-up studies was withheld from two surviving subjects. Also, both Elmer Allen's physician and family members of deceased subjects were misled by AEC officials about the purpose of the follow-up studies. They were told that the follow-up was in relation to past medical treatment, which was not true.
It is unlikely that AEC officials would have lied about or otherwise attempted to conceal the purpose of the follow-up studies if at the outset the subjects had known and agreed to their being used as subjects in nontherapeutic experiments. It is also relevant that when the Atomic Energy Commission succeeded the Manhattan Project on January 1, 1947, officials decided to keep the plutonium injections secret. It appears that this decision was based on concerns about legal liability and adverse public reaction, not national security. The documents show that the AEC responded to the possibility that consent was not obtained in the plutonium experiments, as well as their lack of therapeutic benefit, by stating requirements for informed consent and therapeutic benefit for future research, while still keeping the experiments secret. As a result of the decision to keep the injections secret, the subjects and their families, as well as the general public, were denied information about these experiments until the 1970s.
The one likely exception to this picture of patients not knowing that they were used as subjects in experiments that would not benefit them is the polonium experiment conducted at Rochester. This is the one instance in which the patient-subjects are said to have volunteered after being told about "the general problem." Although there is no direct evidence that these subjects were told that the experiment was not for their benefit, the language of volunteering suggests a more forthright disclosure was made, more in keeping with the conventions in nontherapeutic research with healthy subjects than in research with patients (see chapter 2). We cannot reconcile the account of the polonium experiment with the historical record on the other injections.
The Advisory Committee is persuaded that these experiments were motivated by a concern for national security and worker safety and that, particularly in the case of the plutonium injections, they produced results that continue to benefit workers in the nuclear industry today. However, with the possible exception of the polonium experiments, we believe that these experiments were unethical. In the conduct of these experiments, two basic moral principles were violated--that one ought not to use people as a mere means to the ends of others and that one ought not to deceive others--in the absence of any morally acceptable justification for such conduct. National security considerations may have required keeping secret the names of classified substances, but they would not have required using people as subjects in experiments without their knowledge or giving people the false impression that they or their family members had been given treatment when instead they had been given a substance that was not intended to be of benefit.
The egregiousness of the disrespectful way in which the subjects of the injection experiments and their families were treated is heightened by the fact that the subjects were hospitalized patients. Their being ill and institutionalized left them vulnerable to exploitation. As patients, it would have been reasonable for them to assume that their physicians were acting in their best interests, even if they were being given "experimental" interventions. Instead, the physicians violated their fiduciary responsibilities by giving the patients substances from which there was no expectation they would benefit and whose effects were uncertain. This is clearest at Rochester where at least the uranium subjects, and perhaps the plutonium subjects, were apparently the personal patients of the principal investigator.
Concern for minimizing risk of harm to subjects is evident in several of the planning documents relating to the experiments, an obligation that many of those involved apparently took seriously. At Chicago, for example, where the highest doses of plutonium were used, care was taken to ensure that all the subjects had terminal illnesses. In those cases where this concern for risk was less evident and subjects were exposed to more troubling risks, the moral wrong done in the experiments was greater. Where it was not reasonable to assume that subjects would be dead before a cancer risk had a chance to materialize, or in the case of the uranium injections at Rochester where acute effects were sought, the experiments are more morally offensive.
Consideration for the basic moral principle that people not be put at risk of harm is apparently what animated the decision to give higher doses to only "terminal" patients who could not survive long enough for harms to materialize. A person who is dying may have fewer interests in the future than a person who is not. This does not mean, however, that a dying person is owed less respect and may be used, like an object, as a mere means to the ends of others. There are many moral questions about research on patients who are dying; the desperation of their circumstances leaves them vulnerable to exploitation. At a minimum, nontherapeutic research on a dying patient without the patient's consent or the authorization of an appropriate family member is clearly unethical.
Uranium was also injected in eleven patients with terminal conditions at Massachusetts General Hospital in an experiment conducted jointly by the hospital and Oak Ridge National Laboratory from 1953 to 1957. ORNL's purpose was to obtain data for setting nuclear worker safety standards. A second purpose was to identify a radioisotope that would localize in brain tumors and destroy them when activated by a neutron beam. Although all but one of the patient-subjects had brain cancer, the limited purpose of the experiment--to establish whether uranium would localize sufficiently--meant that there was no expectation that patient-subjects might benefit medically from the uranium injections.
The uranium doses in the Boston experiment were comparable to or higher than the one that caused measurable physical harm in the Rochester subject. Boston subjects were apparently subjected to brain biopsies, presumably solely for scientific purposes. At least three Boston subjects showed kidney damage at the time of death. In one of these cases, a trauma victim who was found unconscious, the autopsy report recorded clinical evidence of some amount of kidney failure and pathological evidence of kidney damage due to the chemical toxicity of uranium.
The only evidence available about what the Boston subjects were told comes from 1995 testimony of one of the investigators, Dr. William Sweet, who said it was his practice to "give a patient all the information we had ourselves." Presumably this would have included that the injections had no prospect of benefiting the patient. The Boston Project was an instance in which high doses were given to dying patients. Some of these patients were comatose or otherwise suffering from severe, irreversible central nervous system disease. Unless these patients, or the families of comatose or incompetent patients, understood that the injections were not for their benefit and still agreed to the injections, this experiment also was unethical. There was no justification for using dying patients as mere means to the ends of the investigators and the AEC. In at least one case, this disrespectful treatment clearly occurred. The trauma victim who arrived at the hospital unconscious was used as a subject despite the fact that his identity was never known. Presumably he was not accompanied by any family or friends who might have authorized such a use of his body.
Only extraordinary circumstances can justify deception and the use of people as mere means by government officials and physicians in the conduct of research involving human subjects. In the case of the injection experiments, we see no reason that the laudable goals of the research could not have been pursued in a morally acceptable fashion. There is no reason to think that people would not have been willing to serve as subjects of radiation research for altruistic reasons, and indeed there is evidence of people writing to the AEC to volunteer themselves for just such efforts (see chapter 13).
That people are not likely to live long enough to be harmed does not justify failing to respect them as people. Concerns about adverse public relations and legal liability do not justify deceiving subjects, their families, and the public. Insofar as basic moral principles were violated in the conduct of the injection experiments, the Manhattan Engineer District, the AEC, the responsible officials of these agencies, and the medical professionals responsible for the injections are accountable for the moral wrongs that were done.