Personal Statement from Elizabeth Zitrin, Attorney at Law Public Member of the Ad Hoc Committee on Radiation Experiments 3 FINDING FIFTY YEAR OLD FACTS The task of this Committee was difficult for many reasons. One of the more frustrating was the spotty availability of documents. There were, of course, many documents available for review. Periodically, however, a new document would be unearthed, perhaps by an archivist at another institution of facility, from among the reported hundreds of thousands or archived pages, and delivered to the Committee as possibly relevant to its work. On occasion those documents contained revelations about critical aspects of this complicated scenario -- aspects that had been the subject of considerable discussion and speculation by the Committee. We have all relied, necessarily, on the information available to us. The conclusions drawn are based on that information, and may be modified at a later date when more is known. There may yet be - somewhere - documents which would shed more light on some of the puzzling aspects of these half-century old events. In spite of the difficulties, my fellow Committee members pursued their task with intelligence, dedication and integrity. The Chairman maintained a rigorous schedule of meetings, and encouraged full participation and comment from every member throughout the months of deliberation. He and the sub-committee chairs ably frame the complex issues and guided the many long and thoughtful discussions. FRAMEWORK OF THE PLUTONIUM EXPERIMENTS Concern dating from early 1944 about occupational exposure to plutonium of workers involved with the Manhattan Project led Dr. J. Robert Oppenheimer, in March of 1945, to write a letter requesting scientific investigation into the effects of plutonium on humans. (Appendix 6) Injections of plutonium into the 18 human subjects at the three institutions occurred between April 1945 and July 18, 1947 (CAL-3). CAL-1 was injected on May 14, 1945, and CAL-2 was injected on April 26, 1946. Prior to the injection of CAL-3 on July 18, 1947, the last subject injected was HP-10, a year earlier, on July 16, 1946. On August 1, 1946, the Atomic Energy Act of 1946 became law. The Act created the Atomic Energy Commission (AEC), and gave the Commission, on behalf of the federal government, a monopoly of ownership of all fissionable material, including plutonium, under the jurisdiction of the United States. The Act also 1 E. Zitrin recognized the necessity of research concerning these materials, and authorized the Commission to make arrangements for research and development. With the passage of the Act, authority and control over plutonium, and other fissionable materials, passed from the Manhattan Project (MED, the Manhattan Engineer District) to the civilian AEC. In late 1946 and early 1947, a series of memos and letters was written by the MED and the successor AEC concerning the injection of plutonium into humans. The change-over from the MED to the AEC changed the ground rules for human experimentation. The new regime and the new protocol for the use of human subjects came into effect after the first 17 of the 18 plutonium recipients, and before the injection of only CAL-3. THE PARAMETERS OF THE PLUTONIUM EXPERIMENTS The MED Project The broad purpose of this research was to evaluate the hazards of exposure plutonium. This was the concern expressed by J. Robert Oppenheimer, and was the impetus for the project. It appears that the details of conduct of the research were left to the expertise and discretion of the researches at the various institutions receiving plutonium for this purpose. The Committee has found no prospectively written protocol, and no evidence of a uniform, multi-institutional protocol or subject selection criteria. although it has been indicated, without confirmation, that a protocol was apparently reviewed in 1974 for the AEC's Division of Inspection report. (Appendix 21) The clearest statement of criteria for the research is found in Dr. Langham's report of the University of Rochester branch of the project. (Appendix 10) This is the report of the Rochester (HP) subjects only: "This report is the final presentation of the results of twelve plutonium tracer cases...." While reference is made to CAL-1 and to CHI-1, CHI-2, & CHI-3, this is the report on HP-1 through HP-12 only. The HP subjects, and only the HP subjects, received uniform doses of plutonium. Of the subjects at the other institutions, only CHI-1 received a dose 2 E. Zitrin conforming to the HP subjects. Langham also discusses the Rochester guidelines for subject inclusion: "The life expectancy of the individual was carefully considered as a basis of selection of subjects for study. As a rule, the subjects chosen were past forty-five years of age and suffering from chronic disorders such that survival for ten years was highly improbable." Despite these guidelines, two of the twelve Rochester subjects were under 45. One was a 41 year old woman, one was an 18 year old girl. While we looked to the Rochester report for guidance about the parameters of the MED research, it cannot be said that all of the institutions involved were required to conform to a single set of criteria or guidelines. The MED/AEC memos1 These memos are informative in a number of significant areas: 1. They provide a window on the concern within the agencies about human experimentation, and the development of criteria for injecting people with plutonium; 2. They set out requirements for documentation of disclosure to subject; 3. They set out requirements and limitations for AEC approved program researchers engaged in medical projects; 4. They clarify that the UC researchers were operating under AEC authority and that they sought and received approval for a clinical project; and 5. They set out the conditions under which that project could be pursued. On December 24, 1946, in anticipation of the transfer to the AEC, Colonel Nichols, the District Engineer of the MED advised the Berkeley Area Engineer that authority to inject humans with plutonium was terminated: "2. The first paragraph of this report indicated that certain radioactive substances are being prepared for intravenous [sic] adminstration to human subjects as a part of the work of the contract. After discussion with [deleted name], Manhattan Project, it is felt that such work does not come under the scope of the Manhattan District Program and should not be made a part of its research plan. "3. It is therefore deemed advisable by this office not only to recommend against work on human subjects but also to deny authority for such work under the terms 1 These memoranda and letters are quoted in Appendix 21, Atomic Energy Commission, Division of Inspection Report, 44-2- 326, August 16, 1974, pp. 3-6, and appended summaries. 3 E. Zitrin of the Manhattan contract. You will take immediate action to stop this work under this contract, and report to this office upon compliance." A January 8, 1947, draft memo from Colonel Kirkpatrick, Acting Manager, Field Operations of AEC, to the AEC Berkeley Area Engineer, puts the AEC stamp on termination of human testing: "Until the Atomic Energy Commission is able to consider sponsoring this type of experimentation, authorization cannot be given for the use of radioactive materials in human subjects under this contract." The "great uproar" over human subjects when the AEC took over was recalled by Patricia Durbin in a 1969 letter quoted below at pages 7-8. A March 7, 1947, internal AEC memo, following a proposal by Dr. Joseph Hamilton of the University of California for clinical research in humans, states the necessity of AEC approval and the disclosure requirements of the AEC's interim authorization: "The Legal Division expressed the view that in all clinical testing it would be necessary to make sure that the testing was being carried on in relation to a research program properly approved. We further expressed the view that it was most important that it be susceptible of proof that any individual patient, prior to treatment, was in an understanding state of mind and that the nature of the treatment and possible risk involved be explained very clearly and that the patient express his willingness to receive the treatment." A March 11, 1947, memo refers, as does the March 7 memo, to interim authorization for clinical testing at UC. "At present, clinical testing programs have been authorized as a part of the University of California at Berkeley and the University of Rochester contracts only." The evolving standards ar again referred to in this memo, which continues, "In the interim period, while and until the legal section of the Atomic Energy Commission is formulating its policy on clinical testing..., it is requested that no other clinical testing be performed by other contractors..." The March 11 memo "refers only to work done under the auspices of, at the expense of, or with equipment furnished by and under the responsibility of the Atomic Energy Commission." The AEC continued to work on developing its policy for these studies. In an April 30, 1947, letter from G.L. Wilson, General Manager of the AEC to Dr. Stafford L. Warren at the University of California School of Medicine, the AEC authorized 4 E. Zitrin its Area Managers to approve research conducted by personnel operating under AEC authority, where they were engaged in medical projects which appeared fruitful even if "not immediately related to specific items in the approved program..." If such approval were to be given, not more than twenty percent of the researcher's time could be so occupied, the research would need to be certified to be useful and "not outside the general scope of the Commission's research interests," and the research could "not unduly interfere with the progress of the work on the approved program..." Reporting to the Commission was also required. The April 30, 1947, AEC letter went on to detail the parameters of the UC research on humans it was approving: "It is understood that your Committee has recommended a program for obtaining medical data of interest to the Commission in the course of treatment of patients, which may involve clinical testing. The commission wishes to make clear to your Committee its understanding of the program which is being approved. The Commission understands that in the course of the approved program: "a. treatment (which may involve clinical testing) will be administered to a patient only when there is expectation that it may have therapeutic effect; "b. the decision as to the advisability of the treatment will be made by the doctor concerned." [emphasis added] The letter goes on to reiterate the disclosure requirements outlined in the March 7 memo, noting that in view of a recommendation of the University Committee, signed releases would not be required, but written certification, signed by at least two doctors, regarding the mandated disclosure, would be necessary. This is the disclosure procedure followed for CAL-3. WHAT EXPERIMENTS WERE THE CAL SUBJECTS IN? CAL-1 and CAL-2 were injected with plutonium under authority of the MED as part of the project which had its inception in the concern articulated in Dr. Oppenheimer's March 1945 letter about the safety of plutonium workers. CAL-3 was injected after human experimentation as part of that project was terminated. At the time of CAL-3's injection with plutonium, Dr. Hamilton had sought and obtained AEC authority to conduct clinical testing under the conditions detailed in the AEC's April 30, 1947, letter. CAL-3 did not meet those conditions 5 E. Zitrin because there was no exception of therapeutic effect. It is my conclusion that CAL-3 was injected pursuant to the authority granted by the AEC in the April 30, 1947, letter, and that his injection did not meet the requirements of that authorization. The two hypotheses The lack of a written, prospective protocol, and the lack of uniformity among the three institutions and among the subjects has led the Committee to consider two hypotheses about the nature of the experiment or experiments the three CAL plutonium subjects were a part of. The first hypothesis is that all three CAL subjects were part of the MED sponsored experiment; the second is that CAL-2 and CAL-3 were part of a separate therapeutic research project. The evidence we have seen more clearly points to a third, hybrid scenario - the MED project, the subsequent AEC therapeutic authority, plus Dr. Hamilton's own agenda. Hamilton received plutonium as part of the MED experiment. The purpose of evaluating the exposure of workers was clear, and led to the distribution of the product to the research centers. Hamilton was himself interested in finding out it plutonium -- or other radioactive materials -- might some day be useful in the treatment of bone cancers. He piggybacked this interest onto the MED and later AEC projects he was authorized to pursue. He wanted, under the umbrella of the MED project, to inject patients suffering from bone cancer. In the absence of rigid experimental protocol and subject inclusion criteria, he did this in his selection of CAL-2, who had bone cancer, and from whom he might begin to collect data of greater interest to him. He did it again with CAL-3 under the most restrictive, and therefore inapplicable, authority of the AEC. Hypothesis #2 The arguments presented in favor of Hypothesis #2 are not persuasive. To begin with, they rely in large measure on the "criteria" found in the Rochester report, where no uniform protocol or UC protocol or subject selection criteria have 6 E. Zitrin been found, and in spite of the fact that not even Rochester subjects all met those criteria. Even so, reliance on the Rochester age and dose criteria does not truly support Hypothesis #2. CAL-2 and CAL-3 were not the only subjects who were not over 45; two of the twelve HP subjects were under 45 as well. CAL-2, CAL-3 and CHI-1 were much closer in dose to the HP subjects than CAL-1 was; the dose variation is more consistent with the absence of clear or uniform criteria for al participating institutions. University-sponsored research While the possibility of clinical usage under individual and university responsibility, with no connection of any kind to the AEC, was allowed for in the memo of March 11, this did not apply to Dr. Hamilton, who was an AEC project researcher. Hamilton received research funding from the Federal Government, and operated under MED and AEC contracts and their restrictions -- in case of CAL-3 the limitations of the April 30 letter. After the March 11 memo was written, Hamilton pursued his proposal for clinical testing under AEC authority, and received approval. The next subject injected with plutonium -- the only other subject injected -- was CAL-3. Even so, there is no evidence of a separate University- sponsored bone cancer research protocol, design, or articulated purpose. No such research concerning CAL-2 or CAL-3 (or CAL-4, the americium subject, for that matter), was ever reported by Dr. Hamilton or described in any document we have seen. No one else has written, reported or noted that Hamilton was conducting such research, including Patricia Durbin in her extensive 1971 Plutonium in Man: A Twenty-Five Year Review. (Appendix 23) And Hamilton did not inject any humans with plutonium after CAL-3, while he pursued his work with animals. Therapeutic effect The MED/AEC memos and letter reflect a clear concern about human experimentation, and attention to the development of policy after having terminated the use of human subjects. Patricia Durbin, in an April 23, 1969, letter to John R. Howard at UCSF about getting access to subject records (document #0002316), notes that most patients were old, but some were misdiagnosed. 7 E. Zitrin "Because of this there was an understandable great uproar when the civilian AEC took over from the Manhattan Engineering District," and the human data were then designated as secret. The language of the AEC's restriction is quite clear: "treatment...will be administered to a patient only when there is expectation that it may have therapeutic effect..." It refers to a particular adminstration to a person having the expectation of therapeutic effect. If, as it is argued, there was no risk and no need for expectation of individual benefit, there would have been no reason for the authorization to expressly leave "the decision as to the advisability of the treatment" to "the doctor concerned." What then would have been left to decide about advisability? Reporting and not reporting CAL-2 and CAL-3's absence from early reports on the plutonium experiments does not necessarily support the assertion of Hypothesis #2 that there was another experiment. It is more compelling that they were not reported as a part of any other hypothesized experiment, and that, in fact, no other such experiment was reported at all. Hamilton may not have reported CAL-2 with CAL-1 because CAL-2 was a child, and an inappropriate subject to the MED's purpose. CAL-3 was not reported because his injection did not conform to any approved protocol. It is not insignificant that both Durbin, in 1971 (Appendix 23), and the AEC's own Division of Inspection Report in 1974 (Appendix 21) included all 18 subjects as a group. CAL-2 and the September 1945 report The September 1945 report by Dr. Hamilton (Appendix 27) referring to his intention to inject the next human subject with yttrium, strontium and cerium in addition to plutonium, provides further, and persuasive, evidence that CAL-2 was injected pursuant to MED authority for the first protocol. The Committee's citation of inconsistencies between this report and the actual injection of CAL-2 are not persuasive. CAL-2 was the only plutonium subject to have received a combination 8 E. Zitrin radioactive substances: plutonium, cerium and yttrium. The inconsistencies cited are relatively minor changes in plans. The documents the Committee has reviewed over the past year display an assortment of errors and inconsistencies. Patricia Durbin's 1971 Plutonium in Man includes in Appendix 3 a list of errors in the original Pu source materials. It is worth noting, by way of illustration of the difficulty of working with an incomplete record, that Dr. Hamilton's September 1945 report was discovered and forwarded to the Committee as the Committee's "final" draft was being circulated. THE SUBJECTS: DIAGNOSIS, PROGNOSIS AND THERAPEUTIC POTENTIAL There was no possibility or expectation of benefit to any of the three CAL subjects. Prior to the injection of any of these subjects, plutonium was known to be acutely toxic, and was known to be more toxic in the same amounts over a longer period of time. The investigators did not know that these subjects were dying. They may have believed that they were dying, but they knew that each diagnosis and each prognosis on which they based that belief, could well be wrong. And was, as often as not. While reliance on diagnosis and prognosis is necessary in terms of treatment, it is a high risk gamble in the context of research like this where there is no potential benefit to the subject who is bearing 100% of the risk. The investigators should have considered, and evidently did not, the possibility of inaccurate prognosis. CAL-1 Both the diagnosis and the prognosis for CAL-1 were inaccurate. CAL-2 CAL-2's inclusion is disturbing for a number of reasons: 1. He was 4 years old and an inappropriate subject in a study designed to evaluate he effects of plutonium on adult workers, although his bone cancer made him an interesting subject for Hamilton's work in that area. 2. There was no potential for therapeutic benefit. The absence of expectation 9 E. Zitrin of benefit is supported by Dr. Hamilton's September 1945 report, which refers to two specific research purposes, and makes no reference to any therapeutic potential. 3. The boy was flown to San Francisco, evidently under the auspices of the Red Cross, aboard U.S. military transport, at no cost to the family, apparently in the hope that some treatment would be available to him here. Reference has been made to a newspaper's description of the boy's "race against death." It turned out that there was no help for him, but the circumstances could indicate that his family was given false hope about the potential for benefit to the child from the plutonium "treatment." CAL-3 CAL-3's diagnosis would properly have led to the prognosis that he had an 80% likelihood of living 5 years, and a 75% likelihood of living 10 years. The absence of therapeutic potential for CAL-3 is of particular concern because, as has been discussed above, his injection with plutonium occurred at a time when the AEC required that "treatment...will be administered to a patient only when there is expectation that it may have therapeutic effect..." CONSENT The Committee on Medical Research While the scope of neither the authority nor the influence of the Committee on Medical Research in the 1940s is known to the Committee, it is worth noting its contribution to the evolution of standards for consent to research in some detail. A discussion and citations may be found in Appendix 29. The CMR distributed some $25 million to medical institutions and universities for research to benefit soldiers, and provided the model for the National Institute of Health. The 1942 CMR consent decision was not, as the Committee's report indicates, one individual's view on one research proposal. This is the language of a Federal medical oversight Committee decision on human experimentation in general: "Human experimentation is not only desirable, but necessary in the study of 10 many of problems of war medicine which confront us. When any risks are involved, volunteers only should be utilized as subjects, and these only after the risks have been fully explained and after signed statements have been obtained which shall prove that the volunteer offered his services with full knowledge and that claims for damages will be waived. An accurate record should be kept of the terms in which risks involved were described." [emphasis added] These standards were clearly in place during the war. Conclusions CAL-3 's chart reflects compliance with AEC's requirement for documentation of consent. It does not tell us whether the subject was in fact adequately informed. All three CAL subjects had treatment consents in their charts. It the absence of much of the documentation about consent procedures, particularly for CAL-1 and CAL-2, conclusions about consent necessarily depend upon what can be drawn from the overall circumstances as we know them. We know from the 1947 memos detailing consent requirements that the AEC considered the preexisting consent practices inadequate. That is persuasive evidence of their inadequacy. I cannot conclude that any of the CAL subjects were told that the researchers believed the injected product to be dangerous to humans, that they could not be certain (although it was their belief) that the injected doses would be safe, or the extent to which the actual risks were unknown. It is unlikely that subjects were told that, due to the anticipated long-term toxicity of plutonium, they were selected because of their presumed limited life expectancy. In view of the prevailing attitudes of the time, it is likely that any information the subjects were given about the injections was cursory and reassuring. HARM The Committee's Report states that the experiments "were consistent with accepted medical research practices at the time." That may be, but id does not make them ethical. And they were not consistent with the highest standards of the time articulated by the government, the profession or the pubic. These subjects were harmed by being deprived of their autonomy. They had 11 E. Zitrin the right to be told what the investigators wanted to do to them and why, to be told about the risks, and to be given the opportunity to freely volunteer or decline. The researchers undoubtedly believed that the risks were quite small, and well worth taking when weighed against the potential benefit to science and the national defense. But whether the risk, if any, is worth the benefit, if any, is not a scientific decision, and it is not the judgement of the science that matters. That is the province of the individual. Elizabeth A. Zitrin, JD Patient Advocate San Francisco, 3 February 1995 12