Plutonium Studies in Man

Page 1

PLUTONIUM STUDIES IN MAN The potential physiological hazards of working with plutonium were reoognized by its discoverer, Dr. Glenn T. Seaborg. of World War 11, thousands of people were handling plutonium and information During the later years was urgently needed for establishing realistic criteria for limiting their exposure to this hazardous material. A program to study the metabolism of plutonium in experimental animals was undertaken by the Manhattan Engineer District (MED) in 1944. important objective of these studies was to determine how plutonium body burdens could be estimated from urinary excretion data and to extrapolate this knowledge to man. However, as it became apparent that the metabolism of certain radionuclides differed in different animal species, it was recognized that reliable information pertaining to the deposition and excretion of plutonium in humans could only be obtained from persons to whom small but known amounts had been administered. Several planning meetings were held by the senior medical staff of MED before the decision bas made to initiate metabolic studies of plutonium in man. Between 1945 and 1947, tracer doses of soluble plutonium were administered to 18 hospital patients. 0.095 to 5 . 8 microcuries, equivalent to 2.4 to 145 occupational body burdens.* The quantities employed ranged from No adverse effects resulting from the injections were observed at any time. Eleven of the patients were injected at Strong Memorial Hospital in Rochester, one at Oak Ridge Hospital, three at Billings Hospital in Chicago, and three at the University of California Hospital in San Francisco. *The internationally accepted permissible occupational exposure limit (body burden) for plutonium is currently 0.040 microcuries.

Page 2

REPOSITORY: OFFICE OF HUMAN RADIATION COLLECTION: PLUTONIUM INJECTION INVESTIGATION FOLDER: PLUTONIUM INJECTIONS - GENERAL

Page 3

but one of the injections were given before the AEC was established on August 1, 1946. According to early documents, the criteria considered i n choosing subjects for the study were age, life expectancy, and relatively normal kidney and liver function. nose selected were generally over 45 years of age and suffered from malignant o r chronic disorders that made survival for ten years highly unlikely.In several instances, however, survival was longer than had been anticipated. Ten patients died of their diagnosed illnesses or related conditions within three years after injection, one each died within 15 and 21years,the fate of two i s unknown, and four area live today. Blood samples and excreta were collected from all subjects for varying periods of time (weeks t o months) after injection. These were analyzed for plutonium content, a s were any tissue specimens that became available on bippsy o r autopsy. Approximately five years after injection, two of the subjects were given follow-up examinations a t Strong Memorial Hospital and additional specimens were obtained for analysis. The analytical work was carried out initially by. MED personnel and later by AEC contractors. For more than 25 years, estimates of body burdens of plutonium i n humans have been based on the data collected from these patients. The scientific community has been aware of this study for many years. The findings have The most complete analysis of the data may be found inthe Durbin, of Lawrence Berkeley Laborabory, i n the monograph "Radiobiology

Page 4

I n December 1972, the accumulated records of the study, then i n the possession of I>r. Durbin,were transferred to the Director, Center for Human Radiobiology (CHR) a t Argonne National Laboratory (ANL). January and June 1973, he arranged for clinical examinations and excreta collections for three surviving patients at Strong Memorial Hospital i n One of these patients was also brought t o ANL fora physical examination and radioactivity measurements. plutonium content a t ANL and those from one patient also at Los Alamos ScPentific Laboratory. I n addition, the Director, CHR, obtained permission for the exhumation of the body of one injected patient. conducted B t CHR, provides information on the amount and distribution of residual plutonium i n bone. The data obtained from the patient specimens permit construction of a more accurate plutonium excretion curve for man. Two papers describing these findings will be presented a t the International Congress of Radiation Research t o be held in Seattle, Washington, in July P974. All specimens were analyzed for Analysis of t h e remains, The current inquiry.was undertaken to establish (1) whether the patients injected with plutonium dr their next of kin were informed about the nature and purpose of the injections at the time they were given, and (2) whether the living patients were told the reasons for the recent follow-up studies, and the families of the deceased the reasons for the exhumation requests. Interviews and document searches were conducted by personnel from t h e Division of Biomedical and Environmental Research and t h e Division of Inspection. The issues of disclosure and informed consent must be considered i n the light of the times. It was not customary then to obtain written consent from patients for any type of clinical experimentation; rather,oral consent

Page 5

It must also be recalled that plutonium was acf as s if i ed term and could not be mentioned publicly until after the end of the war. However, the human plutonium studies remained classified "secret" because, according t o 1947 documents, their publication might have adverse effects on public opinion o r result in legal entanglements. In April 1947, Mr.C. L. Wilson, General Manager of the newly formed AEC, experimental treatment was given inthe presence of witnesses. spelled out the agency's position pertaining to the participation of human subjects in clinical research programs. H e wrote a s follows in a letter to Dr. Stafford L. Warren, Chairman of AEC's Interim Medical Advisory Committee on Clinical Testing: "The Commission continues t o request that &he same procedure be followed which was agreed upon early in March. That procedure contemplated that it should be susceptible to proof from official records that,prior to treatment, each individual patient, being i n an understanding state of mind, was clearly informed of the nature of the treatment and its possible effects, and expressed his willingness t o receive the treatment. recommendation, the Commission does not request that written release be I n view of your obtained i n such cases, but it does request that in every case atleast two doctors should certify in writing (made part of an official record) t o the patient ' s understanding state of mind, tothe explanation furnished him, and to this willingness to accept the treatment." The recently completed inquiry has provided the following information relative to the status of disclosure at the various hospital locations involved. According tothe chemist who prepared the plutonium solutions for injection,the physician who made the injections obtained oral consent from each patient in the presence of the chemist and a nurse t o administer a radioactive substance that would not necessarily be of benefit to the

Page 6

subject, but might eventually help other people. However, this physician stated that he was not involved in injecting plutonium into patients and could not comment on the disclosure issue. b. Oak Ridge (1 patient) The physician ordered t o administer the injection of plutonium a t Oak Ridge Hospital stated that he made no disclosure to the patient at any time. The hospital record of each patient was examined either by a Rochester staff physician or by an AEC team. materials were found. deceased, and no source of direct information regarding disclosure to the patients was discovered. d. San Francisco (3 patients) No references to injections of radioactive The physician who presumably made the injections is The hospital records of the first two patients injected contained references to special studies involving radioactive materials, but none to disclosure or i n connection with the special studies,said that he could not remember the The physician yhose name appeared i n the hospital records, presumably The third patient, who is still living and was under study i n 1973, was injected intramuscularly ic to a leg affected by a malignant tumor and amputated a few days later. His hospital record shows that the experimental nature of the radioactive tracer sample was explained to the patient to the injection. and that he agreed The patient was stated to be fully oriented and of sane mind. The responsible physicfan, now deceased, signed his name. Two other physicians and a nurse witnessed the disclosure and also signed the patient ' s

Page 7

Since 1947, guidelines for conducting medical experiments on humans and the concept of informed consent have been c9early formulated. The AEC has adopted the Department of Health, Education and Welfare's policies for protection of human subjects (set forth in DREW Publication No. (NIH) 72-102, December 1, 1971) and requires adherence by its contractors. The most pertinent provisions are (1) review and approval of the research program by an appropriate institutional committee, and (2) documentation that the informed consent of each subject has been obtained. agreement to participate in an activity after having been given afair explanation of the procedures t o be followed (including identification of those that are experimental); a description of the expected discomforts, risks and benefits ; disclosure of Alternative procedures available ; offer t o answer all questions; and instruction that the subject is free to withdraw Informed consent is the subject ' s The recently conducted studies involving the surviving injected patients must be considered in the light of clinical research policies in force today. As a result of the AEC inquiry,the following has been established. When the Director, CHR, discussed plans for the follow-up studies with a member of his staff, he instructed him ina memo (dated 12/21/72) that plutonium was not t o be mentioned outside of CHR. Arrangements for the clinical examinations were made witha physician who has known about the plutonium injections for many years and who i s on the staff of Strong Memorial Hospital in Rochester. This physician admitted the patients to the Metabolic Ward of that hospital, assumed responsibility for their a are and collected

Page 8

patients were not told of the actual reasons for their hospitalizations and no consent forms were presented o r signed. The patients ' hospital costs were paid by CHR. The Two of the three surviving Rochester patients are under the care of this physician and have been hospitalized frequently because of chronic illnesses dating back t o the 1940's. connection with these conditions, and consequently, i n the opinion of t h e physician, did not present unusual situations for the patients. The third surviving patient of the Rochester series i s under the care of a private physician and did not participate in the recent follow-up studies. Their hospitalizations in 1973 were also in The surviving San Francisco pati en h who had given consent t o be injected and i s now living in Texas, was contacted through U s personal physician. The latter was advised that CHR wished t o do a follow-up study of treatment that the patient had received for his malignant tumor i n 1947. In addition to his admission t o Strong Memorial Hospital,this patient was also examined a t CHR where he did not sign the standard consent form used for other CHR Although the clinical study was initiated in January 1973, itwas only brought to the attention of the Human Use Committee of ANL in stages, beginning i n November 1973. The committee m e t on March 14, 1974, and on April5, 1974 issued a report recommending a course of action that would bring CHR into compliance with DHEW guidelines. One of the steps to be taken was t o inform the patients of the purpose of their examinations, namely t o

Page 9

establish the presence o r absence of residual radioactivity stemming from t h e plutonium they had received many years ago. Efforts to exhume the bodies of ten deceased persons injected with plutonium were initiated by the Director, CHR, i n 1973. He instructed the Southwest Field Station of the Massabhusetts Institute of Technology permission for exhumation and to tell the relatives that the purpose of examining the remains was t o determine the microscopic distribution of residual radioactivity from past medical treatment. In fact,the families of the deceased were told that the latter had received injections of mixtures of radioactive isotopes as part of an experimental treatment. I n one case, the family was given no reason for the injection. The exhumations were t o be performed to characterize the composition of the injected mixture and t o study the effects of the isotopes.