List of Attachments For Briefing Book Volume 2 Attachment 1: IG Report File No. 44-2-326, 44-2-330 Attachment 2: Statement of Gordon K. Soper, Principal Deputy Assistant to the Secretary of Defense For Atomic Energy Before the Subcommittee On Administrative Law and Government Relations Cincinnati, 4/11/94 Attachment 3: Informed Consent Attachment 4: Strong Memorial Hospital, Doctor's Orders, 1/2/45. Attachment 5: Abstract of Monthly Report for Section II-III, Metallurgical Laboratory Attachment 6: Memo to J. J. Nickson, From E. R. Russell, Regarding: Monthly Summary for Biochemical Survey Section, 5/20/46 Attachment 7: Distribution and Excretion of Plutonium in Two Human Subjects, E. R. Russell and J. J. Nickson. U.S. Department of Energy Office of Inspector General Office of Investigations Report of Investigation File No. 44-2-326 Report is the property of the Office of Investigation and is loaned to your agency. It and its contents may not be reproduced without written permission. The report is FOR OFFICIAL USE ONLY and its disclosure to unauthorized persons is prohibited. Public availability to be determined under 5 U.S. C. 552. OFFICIAL USE ONLY UNITED STATES ENERGY RESEARCH & DEVELOPMENT ADMINISTRATION OFFICE OF INTERNAL REVIEW INVESTIGATION REPORT OFFICIAL USE ONLY OFFICIAL USE ONLY UNITED STATES ATOMIC ENERGY COMMISSION DIVISION OF INSPECTION REPORT 44-2-326 By Giles L. Lofton Date August 16, 1994 Title: DIVISION OF BIOMEDICAL AND ENVIRONMENTAL RESEARCH, HEADQUARTERS - ACTIVITIES INVOLVING INJECTION OF INDIVIDUALS WITH PLUTONIUM BRIEF OF FINDINGS This inquiry was predicated on the request of Dr. James L. Liverman, Director, Division of Biomedical and Environmental Research and Assistant General Manager for Biomedical and Environmental Research and Safety Programs, Headquarters, to determine the involvement of AEC personnel in the injection of human subjects with plutonium, and followup studies, subsequent to the establishment of the AEC in 1946 and the takeover from the Manhattan District on January 1, 1947. This inquiry was part of the overall investigation authorized by the General Manager on April 17, 1974, in which representatives of the Division of Biomedical and Environmental Research (DBER) were designated as the lead interviewers and a joint DBER - Division of Inspection ------ --- issued on August 12, 1974. Dr. Liverman's request for an investigation by the Division of Inspection and the issuance of a separate report on this phase of the joint investigation was based upon conflict of interest considerations. The joint DBER-LVS report disclosed that during the period 1945- 1947, because of the concern over the exposure of many workers to the newly created element, 18 patients who were not Government employees and who were suffering from non job-related illnesses, were injected with quantities of plutonium at Oak Ridge, Chicago, San Francisco, and Rochester; that in 1967, after learning that one of those injected had lived for a period of 20 years, record searches were initiated by a radiobiologist at the Lawrence Berkeley Laboratory (LBL) to determine the whereabouts of other patients and discovered that four were still alive; that in 1973, additional followup studies were carried out on three of the four patients and on the remains of one exhumed patient in a project sponsored by the Center for Human Radiobiology (CHR) at the Argonne National Laboratory (ANL); that with respect to the 1943-1947 period, there was only one injection after the AEC came into existence. This inquiry disclosed that as early as December 1946, the Corps of Engineers, Manhattan District, became aware that certain radioactive substances were prepared for intravenous administration to human subjects and denied authority for such work under the contract: that in early March 1947, the AEC EXPRESSED the view that it was necessary that all clinical testing be carried out under a properly approved research program and that it was most important that it be susceptible of proof. Distributed to: 1 - General Manager 1 - Executive Asst. to the General Manager 1 - Division of Biomedical and Environmental Research Approved Period Inquiry: May 17 - July 17, 1974 OFFICIAL USE ONLY 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; that the patient express his willingness to receive the treatment, with written certification by at least two doctors as to the patient's state of mind, to the explanation furnished, and to this acceptance of the treatment; that this position was affirmed by the AEC General manager in April 1947; that the first director of the Division of Biology and Medicine (DBM), which assumed responsibility for the research program in AEC, became aware of the early injections in late 1947, agreed that rules should be established to preclude recurrence, but did not formally broach the matter based on the assumption that those injected were no longer living; that there were no injections, subsequently, to his knowledge; that about July 1973, he became aware that four patients were still and were being studied under the auspices of ANL-CHR. Relative to the followup studies, inquiry disclosed that while DBM- DBER representatives were knowledgeable of the record searches being done by LBL, mainly from published material, there was no evidence of formal approval for such studies; that the LBL budget documents dated May 1972 referred to the transfer of the followup studies to ANL-CHR, although the ANL budget documents for that same period do not specifically refer to the injected cases; that the consensus among DBER representatives was that a former Chief of the Medical Branch, DBM, and former employees under his direction probably were aware of the studies and consented; that the former Branch Chief stated that he had requested LBL to submit a formal proposal for the studies but knew nothing of what transpired after that ------------that DBER representatives stated that the plutonium work which was "folded in" with the ANL budget document on radium studies for 1972 and 1973 was not "flagged" for any particular attention and the fact that it was mentioned in the funded project constitutes at least tacit approval; that the work would probably have been approved and the assumption made that the contractor would follow that appropriate guidelines with respect to research involving human subjects; that ANL had made known to DBER in June 1973 that disclosure had not been made in the studies, although the ethics of the matter were not discussed, and no particular followup was made at that time. Relative to the matter of informed consent, inquiry disclosed that in May 1970, AEC formally adopted a publication of NIH entitled "Protection of the Individual As A Research Subject", which was subsequently supplanted by a similar DHEW document, and required its contractors to file an acceptable assurance of compliances with the procedures and to reaffirm that intent in all subsequent budget documents; that ANL agreed to comply and established a Review Committee for Research Projects Involving Human Subjects to review all proposals involving research on human subjects; that the plutonium studies were not presented to this Committee in 1973, and thus not considered by them, because the studies were considered to be covered by basic protocol of the radium studies which had been approved by the Committee in 1971; that this protocol also contains the requirement for informed consented; that the plutonium studies were not considered by the Committee until April 8, 1974, at which time instructions were given that informed consent must be obtained; that, prior to this time, in march 1973, a letter to the attending physician of one of the patients in the followup study made no mention of the true reasons for the followup, even though the patient had given consent for the injection in 1947; that in connection with the living patients and obtaining permission for exhumation from the next of kin of deceased patients, CHR gave specific instructions that the word plutonium was never to be used outside the CHR, and that if anything at all needed to be said to the next of kin, they were to be advised that the patients may have received a radioactive substance at some time. Inquiry disclosed that DBER representative attended the second meeting of the Advisory Committee at ANL in October 1973, at which time the plutonium studies were discussed; that the files relating to prior meeting of the Committee indicated that AEC had approved all positive action proposals; that DBER representatives recalled some informal discussions in which the CHR requested permission to study isotope other than radium, and that informal approval was given with the understanding that no on-going programs such as the -1a- Transuranium Registry would be transferred to CHR; that DBER representatives also attended a review of the CHR program in November 1973, at which time the injected plutonium cases were discussed at length; that the trip report prepared by one of the attendees, ostensibly as input for the formal divisional report, took significant issue with the CHR handling of the plutonium work and the potential serious problems which had resulted; that the ultimate formal report on the program review did not include these matters because they were not considered to be a programmatic issue; and that on April 4, 1974, a teletype was dispatched to the Manager, Chicago Operations office, citing specific instructions to be given ANL regard to human subjects, past present and future. -1b- DETAILS This inquiry was predicated on the request of Dr. James L. Liverman, Director, Division of Biomedical and Environmental Research and Assistant General manager for Biomedical and Environmental Research and Safety Programs, Headquarters, to determine the involvement of AEC personnel in the injection of human subjects with plutonium, and followup studies, subsequent to the establishment of the AEC in 1946 and the takeover from the Manhattan District on January 1, 1947. This inquiry was part of the overall investigation authorized by the General manager on April 17, 1974, in which representatives of the Division of Biomedical and Environmental Research (DBER) were designated as the lead interviewers and a joint DBER - Division of Inspection report was issued on August 12, 1974. Dr. Liverman's request for an investigation by the Division of Inspection and the issuance of a separate report on this phase of the joint investigation was based upon conflict of interest considerations. Attached as Exhibit A is a list showing the name and title of each person introduced in this report. BACKGROUND INFORMATION A study of the metabolism of plutonium in man was prompted during World War II because of the concern over the exposure of large numbers of workers to this newly-created element produced at Hanford Engineering Works in early 1944. The toxicity of the element was initially ---------- experiments with animals. Allowable limits for deposition in the human body were arrived at by utilizing information obtained from radium studies in man, the early results of the experimentation with animals, and the respective physical properties of plutonium and radium. Between 1945 and 1947, 18 patients, who were not Government employees nor their conditions job-related, were injected with quantities of plutonium at Oak Ridge, Chicago, San Francisco, and Rochester. In 1967, Dr. Patricia W. Curbin, Radiobiologist, Biology and Medicine Division, Lawrence Berkeley laboratory, formerly Lawrence Radiation Laboratory, upon learning that a patient injected in 1945 had lived for a period of 20 years, made record searches to determine the whereabouts of other patients and discovered that four were still living. In 1973, followup studies were carried out on three of the four patients and on the remains of one exhumed patient in a project sponsored by the Center for Human Radiobiology of the Argonne National Laboratory. Since the AEC staff did not know whether disclosure was initially made to or obtained from the patients, or whether the next of kin were properly informed, the AEC General manager, on April 17, 1974, authorized a joint inquiry by the Division of Biomedical and Environmental Research and the Division of Inspection with representatives of the Division of Biomedical and Environmental Research1 as lead interviewers. Dr. Liverman agreed that the Division of inspection would conduct the portion of the inquiry dealing with AEC involvement because of conflict of interest considerations. Examination of the charter for the overall inquiry disclosed that it states in part as follows: * * * * * "The purpose of the inquiry is to resolve the question of whether disclosure was made to or informed consent obtained from the patients. The primary thrust of the inquiry is directed to the recent studies conducted at Argonna National laboratory and the Strong Memorial Hospital of the University of Rochester. However, information regarding disclosure or informed consent at the time of the injections will also be sought when passible." 1 Hereafter referred to as DBER The final report containing the results of the inquiry was transmitted to the General manager on August 12, 1974. Examination of the report disclosed the following Summary of Disclosure and Informed Consent: * * * * * With respect to the 1945-1947 period, there was positive evidence of disclosure in one case. This was the only case injected with plutonium after the AEC came into existence and after its General Manager issued a directive is April 1947 that disclosure and consent, signed by witnesses but not necessarily by the subject, be made part of the official record. There were oral statements attesting to disclosure by a witness to the injections in three additional cases and by an informed employee in tow other cases. A witness attested orally to nondisclosure in another case. In the remaining case, persons regarded as potential witnesses to injections by personnel conducting the inquiry were either deceased or stated that they could not remember the events under consideration. The hospital record contained a signed and witnessed statement to the affect that disclosure and consent had occurred in the 1947 case. In one case, the patient record was lost; in another, the record had been destroyed in a fire; in the remaining 15 cases the records contained no notation with respect to injection of disclosure. Relative to the study undertaken in 1973, informed consent was --- obtained from living patients who were the subject of the study. However there is no reason to believe that the patients suffered harm or discomfort as a result of the studies. Consent, following improper disclosure, was obtained from the next of kin of an exhumed patient. Improper disclosure was made to the next of kin of additional deceased patients who have not been exhumed. * * * * * RESULTS OF INVESTIGATION Early AEC Involvement in Injection Program - Examination of correspondence disclosed that as early as December 1946, the Manhattan District, Corps of Engineers, predecessor to AEC, became aware from the review of a progress report from the Berkeley Area, that certain radioactive substances were being prepared for intravenous administration to human subjects as a part of the work under the contract; the Col. K. D. Nichols, U.S. Army Corps of Engineers, District Engineer, Manhattan District, advised the Area Engineer, Berkeley, on December 24, 1946, as follows: * * * * * "2. The first paragraph of this report indicates that certain radioactive substances are being prepared for intravenous administration to human subjects as a part of the work of the contract. After discussion with Colonel James P. Cooney, medical Director, 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 of the Manhattan contract. You will take immediate action to stop this work under this contract, and report to this office upon compliances." * * * * * -3- It was noted that while the AEC assumed responsibility for the Manhattan District contracts and facilities as of January 1, 1947, many of the latter staff remained with the AEC, the responsibility for the research program being assigned to the Division of Biology and medicine, now DBER. Examination of the record, subsequent to the above, disclosed that Col. Cooney visited the Berkeley Area, during which he discussed with Dr. Joseph G. Hamilton, former Assistant Professor of Medicine & Radiology, University of California (now deceased), his program for proposed human studies; that although Col. Cooney appeared to believe that the plan for conduction the research should be satisfactory to AEC, he made no firm statement with respect to Government support of such research. Examination of the archives disclosed an internal AEC memorandum, dated March 7, 1947, which states in part as follows: * * * * * "The Legal Division expressed the view that is 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. On Dr. Warren's recommendation, you authorized permission to obtain a written release but urge that in every case at least two doctors certify in writing to the patient's state of mind to the explanation furnished him and to his acceptance of the treatment." "It is contemplated that this memorandum will be initialed as a record of the interim authorization involved." * * * * * Examination of a memorandum, dated March 11, 1947, to the Interim Medical Advisory Committee of the University of California, from Dr. Stafford L. Warren, Emeritus Vice Chancellor of Health Science and Professor of Biophysics, UCLA, who was then Chairman of the Interim Medical Advisory Committee, AEC, disclosed that it states as follows: * * * * * "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. In the interim period, while and until the legal sector of the Atomic Energy Commission is formulating its policy on clinical testing in response to the Interim Medical Advisory Committee's recommendations, it is requested that no other clinical testing be performed by other contractors than has been already authorized. "This 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. This does not pertain to my clinical usage which is done by my qualified doctor upon his own and his university's responsibility and at costs not reimbursable by or not having any connection with the Atomic Energy Commission work." * * * * * Examination of a memorandum dated April 17, 1947, from Col. O. G. Haywood, Jr., U.S. Army Corps of Engineers, Manhattan District, to the AEC, Oak Ridge Tennessee, disclosed that it states in part as follows: * * * * * -4- "1. It is desired that no document be released which refers to experiments with humans and might have adverse effect upon public opinion or result in legal suits. Documents covering such work field should be classified 'secret'. Further work in this field in the future has been prohibited by the General Manager. It is understood that three documents in this field have been submitted for declassification and are now classified "restricted". It is desired that these documents be reclassified 'secret' and that a check be made to the Department of Commerce, or other off-Project personnel or agencies." * * * * * Examination of a letter dated April 30, 1947, from Mr. Carroll L. Wilson, former General Manager, AEC, to Dr. Stafford L. Warren, then Professor of Biophysics and Dean, School of Medicine, University of California, disclosed that it states in part: * * * * * "The Commission is entirely sympathetic with the view of your Committee that research personnel engaged in medical projects should be encouraged to exercise their own initiative and should be given an opportunity to devote part of their time to pursuing lines of research which appear fruitful to them, even though not immediately----------- specific items in the approved program for the particular project. Accordingly, the Commission is authorizing its Area managers to approve such research, up to twenty percent of the time of the research personnel engaged on such medical projects. When such approval is given, the Director of the medical project will be required to certify to the Commission (1) that the research is useful and is not outside the general scope of the Commission's research interests, and (2) that the research will not unduly interfere with the progress of the work on the approved program at the project. The Director also will required to indicate separately in his reports to the Commission what research has been done under this authorization." "It is understood that you 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 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. "The Commission does not intend to influence in any way the exercise of judgement by the doctor as to the administration of any particular treatment authorized under the approved program. Indeed, from the discussion at the meetings of April 3-5, it seemed evident to me that doctors would not allow their judgment on this matter to be influenced by anyone. "In any such clinical testing, the Commission continues to request that the same procedure be followed which was agreed upon early in march. That procedure contemplated that it should be susceptible of proof from official records that, prior to treatment, each individual patient, being in an understanding state of mind, was clearly informed of the nature of the treatment and its possible effects, and- expressed his willingness to receive the treatment. In view of your recommendation, the Commission does not request that written releases be obtained in such cases, but it does request that in every case at least two doctors should certify in writing (made part of an official record) to the patient's understanding state of mind, to the explanation furnished him, and to his willingness to accept the treatment." * * * * * -5- Dr. Shields Warren, Director, Cancer Research Institute, Boston, Massachusetts, first Director, Division of Biology and Medicine,* AEC, advised that he joined the DBM staff in November 1947 and remained until about June 1952; that he than became a member of the Advisory Committee on Biology and Medicine** for a five-year period and has remained a consultant up to the present time. Dr. Shields Warren stated that the Commission became acquainted with the fact that people had been injected with plutonium from an informal conversation he had with Dr. Hamilton about isotopic injection about Christmas of 1947; that Dr. Hamilton referred to "recent utilization of plutonium" in a scattering of cases of advanced disease who had been so injected because of the tremendous importance from the standpoint of the safety of many workers involved and the need to know, in addition to the data from experimental animals, some of the metabolic pathways in man, He said that Dr. Hamilton, during the course of the conversation,----- -------- like, "You know we have had something of a problem in this because there were very rigid restrictions on the use of the word plutonium and the handling of the material and letting anyone know that there was any such stuff." He said that it was his recollection that he talked with the Chairman of the ACBM at the time who stated that the problem was "sticky" to which he (Warren) expressed the need to learn more about the matter at some point in time. Dr. Shields Warren stated that from the time that he took over, and during his tenure, there were no injections made to the best of his knowledge and that he would have insisted that note be made had it been brought to his attention; that some time later, about 1931, they began to think of the plutonium studies in beagles at Salt Lake City; and that someone from the Salt lake group or possibly Dr. Durbin said, "Well, you remember there have been some injections of plutonium in man." He said that the subject was dropped right there and was not followed up because it was apart from the main thread of the conversation. Dr. Shields Warren stated that about a year ago, in July, Dr. Robert E. Rowland, Director, Radiological and Environmental Research Division, ANL, told him that some of the cases were still alive and that he was following up on them; and that Dr. Durbin discussed the same four cases with him in the fall of the same year. Dr. Shields Warren stated that there was no dialog within the Commission regarding these injected persons; that, as he recalls, he and the Chairman of the ACBM agreed that the best way to handle the matter was to set up rules, properly drawn up by the Human Applications Isotope Committee, which had then come into being, so that was without full safeguards could not occur; that they saw no point in bringing the matter up as long as they were certain that it could not happen again in the future; and that this was based upon their assumption that those patients were no longer living. * Hereinafter referred to as DBM ** Hereinafter referred to as ACBM -6- Dr. Shields Warren stated that there was some discussion regarding informed consent because they were reasonably sensitive on that subject at the time and that he always made it a point to explain to patients he had injected; that Dr. Hamilton told him that he had explained to the patients that they would receive an injection of a new substance that was too new to say what it might do but that it had some properties like those of other substances that had been used to help control growth processes in patients, or something of that general sort. He opined that one could not really call it informed consent because the patients did not know what it was, but only that it was a new and to them unknown substance. He added that there was not anywhere near the alertness to informed consent in those days as there is now. He said that he believed the foregoing statement to be accurate because Dr. Hamilton wad a very meticulous man with very high scientific and professional standards. As previously mentioned, the inquiry authorized by the General manager disclosed that only one individual was injected with plutonium subsequent to the takeover by AEC in 1947. Examination of the record disclosed that this individual is a 63-year old male, still living, who was injected on July 18, 1947, in his leg which was amputated four days after injection. Dr. Sidney Marks, Physician (Epidemiologist-Pathologist), Biomedical Programs, DBER, furnished notes transcribed by himself from the patient's medical record as maintained at the University of California Record Center in Richmond, California, examination of which disclosed the following entries: * * * * * "3/17/47* Xray scout films negative for any evidence of ------ --. Amputation postponed until Monday in order to have radioactive tracer substances prepared (Plutonium) and standardized. Pt. will have tumor uptake studies done." * * * * * "7-18-47 3:30 PM "The experimental nature of the intramuscular injection of the radioactive tracer sample was explained to the patient, who agreed on the procedure. The pat. was in fully oriented and in sane mind. Injection was given into the gastrocnemius muscle of left leg and the area marked with circle. Injection made at center of oracle. Needle depth -2cm. No blood appeared on aspiration and no bleeding after removal of needle. "At explanation of the procedure to the patient and assisting in procedure were "Miss Mary Wooton, R.N. "Dr. Donald J. Bellamy "Dr. Ray Mullens "Dr. B. V. Lov-Beer "/s/Miss Mary Wooton "/s/Dr. Donald J. Bellamy "/s/Dr. Ray Mullens "/s/Dr. B. V. Lov-Beer "7-18-47 10:30 PM. No pain or discomfort whatsoever following injection. "/s/R. Mullen "7-21-47 amputation" * * * * * *Date should have been 7/17/47. Record Searches and Followup Studies. Dr. Durbin, previously identified, stated that her interest in the patients who had been injected with plutonium was aroused in 1967 by Dr. William E. Lott, Technical Assistant, Safety and Quality Assurance Division, Richland -7- Operations Office, Richland, Washington, who at that time was a member of the AEC Division of Biology and Medicine, Headquarters, and who became concerned abut the toxicity of plutonium and americium in man after an accident at Rocky Flats. She advised that she corresponded with Dr. Lotz about such matters but that he did not respond. Examination of a letter dated September 13, 1968, from Dr. Durbin to Dr. Lotz, disclosed that she advised him that she had discovered that three of the patients who were injected were still living; and that she requested Dr. Lotz to discuss the matter of further followup, expressing a desire to obtain samples from those who were deceased; that she described the problem as "messy"; that she requested him to discuss the matter with the attorneys of offering something to the families of the deceased in order to get them to cooperate. Dr.Lotz advised that he assumed his present position in July 1968, and that prior to that time was assigned to the Division of Biology and Medicine at Headquarters, where one of his responsibilities was overseeing the "Internal Emitters Program" and pertinent research on the same by the various field laboratories. he said that, as he now recalls, he had responsibility for the studies at Argonne National Laboratory,* the Massachusetts Institute of Technology, and a private laboratory in new Jersey on the Radium Watchdial Research, and for the plutonium registry and related plutonium research conducted at the Hanford Works and the University of California at Los Alamos Scientific laboratory and the Lawrence Radiation laboratory, now Lawrence Berkeley Laboratory,** Berkeley. he said that he became acquainted with Dr. Durbin in this manner. He stated that he was almost-----------------when the aforenoted letter was written and recalled that Headquarters had relayed it to him. He said that, after reviewing the letter, he apparently did not answer it formally, but probably called Dr. Durbin and told her that he no longer had any responsibility in connection with the administration of the program in which she was interested. Dr. Lotz said that during the course of Dr. Durbin's research on internal emitter in animals, she apparently discovered that some people had been injected with plutonium and that she also wanted to help them out by paying the families at the time of death in exchange for the privilege of doing an autopsy, opining that this was the "messy" problem to which she alluded in her letter. Dr. Durbin stated that she also wrote to Dr David Bruner, now Special Assistant to Chairman Dixy Lee Ray, who at the time was in the Division of Biology and medicine, Headquarters, but received no reply. Examination of a letter dated August 25, 1969, from Dr. Durbin to Dr. Bruner, disclosed that she advised his of her correspondence to Dr. Lotz; that she described the followup work she was doing and the status and expressed the hope that someone would initiate a complete rethinking of the present attitude towards plutonium so that as much knowledge as possible could be gained from the early injections. Dr. Bruner advised that he was aware that there had been a series of patients who had been injected with plutonium in the early years, but that he was not aware that there were any still living until Dr. Durbin discovered them; that he had heard about the injections from Dr. Wright Langham of the Los Alamos Scientific laboratory; that in discussing the followup work with Dr. Durbin, he recognized the importance of data related to humans in that data from two or three human subjects would be worth more than that from a thousand animals; that he encouraged Dr. Durbin is that respect. He said that she did the work on her own, and as a scientist she had the right to do so. * Hereinafter referred to as ANL ** Hereinafter referred to as LBL -8- Dr. Durbin advised that her first encouragement from the Division of Biology and Medicine occurred in response to a letter dated December 10, 1971, to Dr. Joseph D. Goldstein, former Chief, Medical Research Branch, DBM, that this occurred after the unsuccessful attempts to correspond with Drs. Lotz and Bruner; that Dr. Goldstein responded by telephoning her and discussing the matter, stating that the studies would be important and encouraged her to go ahead with plans for such studies by submitting an AEC- 189, which she did the following spring. She said that Dr. Goldstein suggested that she propose the project to Dr. James L. Born, Associate Director, Biology and Medicine Division, LBL, which she did but funding was not available; that for a time there was some talk of having Dr. Rowland provide her funding to conduct the studies; that resistance developed in the laboratory administration regarding conducting such studies there, based upon Dr. Born's concern that the introduction of exhumed bodies into the politically charged Berkeley atmosphere night even results in picketing of the laboratory by students; and that because of the lack of support, she eventually turned her files over to Dr. Rowland, who then proceeded to conduct the studies. Examination of the referenced letter to Dr. Goldstein from Dr. Durbin disclosed that she transmitted a status report on the injected people which she had prepared for Dr. Born subsequent to a trip to Rochester, New York; that the letter states in part: * * * * * "Before any arrangements can be made I will have to make some sort of proposal for Dr. Born's approval (or disapproval a --- -------) and eventually we would want the permission of your office to proceed. Such a proposal should be forthcoming in the next few days. It is my belief that any information we can obtain about or from these people is of value beyond price. An opportunity such as this may not arise again for years, if ever." * * * * * It was observed that a handwritten note appeared at the bottom of this letter, was initialed "JDG" and dated December 17, 1971, which stated that Dr. Durbin would discuss the matter with Dr. Born and then submit an AEC-189 if agreeable to present organization. Dr. Goldstein stated that he discussed the matter with Dr. Durbin and advised her to discuss it with Dr. Born who had programmatic responsibilities for the Donner laboratory activity; that he did not consider it appropriate to discuss a program of this type with a subordinate employee unless such a program had the approval of the laboratory director and that he subsequently discussed it with Dr. Born. He said that he telephoned Dr. Born concerning this matter and to the reaction that he (Born) was not too interested in pursuing it and that it perhaps could have been done through other channels. He said that in talking to Dr. Durbin, he advised her that any program would require the approval of Dr. Born and also that if such activity were approved, the appropriate authorization should be secured through the submission of a Form 189. He stated that he heard no more on this matter and is not aware of the followup actions taken. Examination of Form 189, dated may 1, 1972, supporting the LBL 1974 budget submission, entitled "Metabolism and Toxicity of Transuranium Elements and Other Radioactive Bone-Seekers," identifying the person in charge as Dr. Durbin, disclosed that it contained the following: * * * * * "7. FY 1972 (Project Accomplishments)" * * * * * "239 - Plutonium in Man -9- "The review of the data from the 18 persons who were injected with 239-Pu in 1945-46 was completed and published in Ref. 1 and 2. A follow-up was started to learn(a) the identities of the individuals, (b) their subsequent medical histories, and (c) the place and time of death. The aim was eventually to obtain two valuable kinds of material - biological specimens from those that might still be living and a complete skeleton from which the internal distribution in the human skeleton could be determined. "The three California cases were completely traced. Two are dead; hospital and death records are on file. As of 1968 one was still living and his last known address is on file; hospital records are on file. "Eleven Rochester cases were traced. Seven are known dead, and one presumed dead (he was very ill with a long- standing heart condition and was transferred to a veteran's home), and three were still living as of December 1971. All hospital records and on file, and two death certificate are on file. "The Tennessee case was identified. His status as an employee of a local Oak Ridge contractor was established. His last know whereabouts was Atlanta, Ga. as of 1947. because of his age and illnesses, he is presumed dead. Hospital records are know to have been destroyed." * * * * * "8. FY 1973 (Planned Program)" * * * * * "239-Plutonium in Man "This project has been transferred to the Human Radiobiology Laboratory at the Argonna Laboratory>" * * * * * Dr. William W. Burr, Jr., Deputy Director, DBER, advised that the Form 189's are submitted to Headquarters for review during the budget process; that in the past the review process has varied from time to time in that a branch might review the entire effort of a Laboratory or other branches might review areas aligned with their expertise; that the Medical Research Branch under Dr. Goldstein would probably have reviewed the aforenoted 189 relating to the 1974 budget submission; and that Dr. Goldstein or Dr. Marvin Goldman, former Biophysicist (Physiologist), DBER, probably reviewed them personally. ----said that transferring the work to Dr. Rowland would have been up to Dr. Goldstein and would not have required any action on his (Burr's) part; and that Dr. Goldstein probably mentioned to him that he was recommending this transfer. Examination of a Form 189 for LBL, dated may 1, 1971, also concerning Dr. Durbin, and supporting the 1973 budget submission, disclosed that during FY 1971 the original data from 15 persons injected with plutonium in 1945-46 were reviewed using some different mathematical approaches and in the light of new knowledge from animal experiments of plutonium transports and long-term excretions; and that this review was prepared for a 20th anniversary book being published by the staff of the Radiobiology laboratory of the University of Utah. It was noted that there were no other comments relating to such work during FY 1973. -10- Examination of ANL Form 189, dated may, 1972, entitled "Exposure to External Radiation - Radium Studies," and supporting the 1974 budget submission, disclosed that it contained the following statements relating to plutonium: * * * * * "7. Description (Contd.) "D. Metabolism and Distribution of Bone-Seeking Isotopes in Man (R. B. Holtman, D. R. Kuchta, and H. F. Lucas, Jr.)" * * * * * "Anticipated Program FY 1973 and FY 1974. "...Bone and soft tissues from human with Thorotrast, plutonium or other internal emitters will be analyzed as samples become available." * * * * * "FY 1973 Incremental Requirements "Programmatic Activities Related to Radium Studies" * * * * * "Special projects also involving costs for patients or medical services are intercalibration studies between the Argonne and MIT laboratories for reading X-rays and for radioactivity studies, development of special diagnostic procedures, and pilot work on Thorotrast cases, uranium miners, plutonium cases and cases of accidental exposure." * * * * * Examination of a letter dated May 13, 1970, from Dr. John R. Totter, former Director, Division of Biology and Medicine, Headquarters, to Dr. R. B. Duffield, former Director, ANL, disclosed that it states in part: * * * * * "In order to standardize certain administrative procedures used in all studies involving the use of human subjects and supported by the AEC, the Division of Biology and Medicine has officially adopted the NIH Procedures described in the enclosed booklet entitled 'Protection of the Individual As a Research Subject." As the result of this adoption, the following action by your organization is requested. "1. That by July 1, 1970, you place on file with the Division of Biology and medicine an acceptable Assurance as described beginning on page 5 of the booklet. "2. That in all subsequent years, the 189's or contract renewal requests from your organization include a reiteration of this assurance, listing any changes in the advisory committee or procedures." * * * * * Examination of Dr. Duffield's reply dated June 18, 1970, to Dr. Totter, disclosed that it status that the Form 189's or contract renewal requests will include a reiteration of intent of compliance with the prescribed procedures. The aforenoted 189 did not contain such a statement of intent. -11- Examination of ANL Form 189, dated may 1973, relating to the aforenoted radium studies and supporting the 1975 budget submission, disclosed that it contains the following data relating to plutonium: * * * * * "7. Description (Contd.)" * * * * * "D. Metabolism and Distribution of (Bone-Seeking) Isotope in Man (J. Rundo and R. B. Holtman)" * * * * * "Blood and a complete 2-week sampling of excreta from a person with a long-term 239 PU burden were collected and as part of a cooperative study, the 239 PU will be determined by other groups, as well as by us." * * * * * "Anticipated Program FY 1974 and FY 1975. "...Bone and soft tissue from humans with Thorotrast, plutonium, protactinium or other internal emitters will be analyzed as samples become available. "E. Body Radioactivity Measurements (J. Rundo and E. A. May)" * * * * * "Subjects to be examined fall into three distinct categories. ...Initially, radiological protection of the individual is the principal reason for these measurements, to establish levels and hence dose rates. Subsequent measurements may be made to determine retention-time patterns so that integral does is trivial, to study the metabolism of the contaminant. These persons can then be considered as part of the their group, volunteers who ingest, inhale, or are injected with small amounts of radioactive materials for diagnostic or therapeutic reasons in a local hospital. Studies on such patients are possible in collaboration with a physician at the hospital." * * * * * It was noted that foregoing 189 did contain the following statements: * * * * * "All work with humans in the Radium Studies is done in conformity with DBEW policy on protection of human subjects. The protocol of procedures and practices was approved on September 17, 1971, by the Argonna Review Committee for Research Projects Involving Human Subjects, and a followup report for the period July 1, 1971 to December 31, 1972 was accepted by the Committee on February 5, 1973." -12- The aforenoted 189 did not make specific reference to the plutonium cases which were turned over to CHR by Dr. Durbin. Dr. Warren K. Sinclair, Associate laboratory Director, Biomedical and Environmental Research, ANL, advised that the study of the plutonium study was considered to be covered by the basic protocol of the Center for Human Radiobiology,* human radiation studies as approved by the ANL Human Use Committee in 1971. Examination of the Revised Research Proposal for Study of Radium Patients, attached to a memorandum dated August 27, 1971, from Dr. A. F. Stahney, Section Head, CHR, to Dr. R.J.M. Fry Chairman, Review Committee for Research Projects Involving Human Subjects, ANL, disclosed that the research objective is stated in part as follows: * * * * * "The research objective is to obtain quantitative relationships between radiation dosage and effects on humans by study of radium-dial painters and other people with body burdens of radioactive isotopes..." * * * * * Dr. Marks opined that the objective, as stated could be ---------- sufficiently to include the plutonium. As previously noted, the LBL Form 189, dated May 1, 1972, stated that the project for followup studies on the plutonium patients were transferred to the Human Radiobiology Laboratory (actually CHR) at ANL. Dr. Rowland stated that he visited Dr. Durbin in May 1972 to obtain her files on the patients after attending a meeting in Portland, Oregon; that she did not make the files available to him in May because they had not been xeroxed at the time; and that she finally turned copies of the files over to him in December 1972. He said that the Medical Branch of DBER was reluctant to fund studies for Dr. Durbin, but that Dr. Goldstein had suggested that the work be done at Argonne; that CHR pay part of the expenses incurred by Dr. Durbin during her last Eastern trip to track down records of the patients, which CHR did; that CHR also funded hospital costs for the patients admitted into Strong memorial Hospital in Rochester during 1973. He advised that the additional DBER contact was with Dr. Mark in 1973. Dr. Marks acknowledged that he had visited Dr. Rowland in June of 1973 since it appeared that he (Marks) would be the DBER technical representative for ANL activities; that Dr. Rowland discussed the plutonium studies with him advising that there had been no disclosure made; that there was no discussion advising that there had been no disclosure made; that there was no discussion of the ethics of the matter, but that Dr. Rowland asked for guidance in policy with regard to publishing the results of the work that had been done; that he (Marks) ultimately gave him verbal guidance on the publications question by requesting him to submit the data to Headquarters; and that while he advised Dr. Charles W. Edington, Associate Director for Research and development Programs, DBER, of the matter, he (Marks) made no particular followup at the time. Dr. Edington stated that he became aware of persons being injected with plutonium about a year ago from reading published material; that he was not aware that any of the laboratories were currently doing any work in this area until November 1973 when Dr. Rowland presented the CHR program during a visit in which he, Dr. Marks and others participated. He said that during this meeting, Dr. Rowland commented that there were three living patients and that they either had or were going to be brought in for study. He said that although he attended * Hereinafter referred to as CHR -13- the meeting, he did not prepare any write-up of the discussion; that while he wasn't overly concerned at this point, he did mention the matter to DR. Liverman. He advised that upon his return from the trip, he perused the ANL budget documents and found comments in a 189 that made reference to the plutonium work at the CHR. He said that he was not aware whether Dr. Goldstein knew that this work was included in the 189, but opined that since the technical staff was responsible for their review, it was an oversight that this matter wasn't "flagged." He added that he did not assure responsibility for Dr. Rowland's program until August 1973 when he was made Associate Director. Dr. Martin L. Minthorn, Deputy program Manager, Biomedical Programs, DBER, stated that he doesn't recall that the plutonium studies were flagged for any particular attention; that he believes that Dr. Lotz, Dr. Chester Richmond, former Biophysicist (Physiologist), DBM, and Dr. Goldman would have been primarily responsible for reviewing the intricate details of contractor proposals, and that Goldstein probably was well informed as to what was going on, adding that none of these individuals are currently in the division. he said that he first became aware of the injected patients while preparing a reply to a letter that had been written about the hazards of plutonium; that he learned about them from published material; that he was aware that the work has been transferred from Dr. Durbin to Dr. Rowland, but gave no other thoughts to the matter until it "broke" re-------- Dr. Marks stated that while he functioned generally as a technical representative from abut July until November 1973, no official appointment was ever made to that position; that he has not reviewed Forms 189 and that Dr. Goldstein tended not to use a "team" approach to such reviews; that Dr. Goldman would probably have reviewed the contractor proposal; and that he (Marks) did not get into the matters under review until June 1973, after the budget cycle. Dr. Bruce W. Wachholz, Radiation Biologist, Biomedical Programs, DBER, advised that he was not involved in review of contractor proposals or funding of any projects for the work in question; and that he believes that Dr. Goldstein and possibly Dr. Walter W. H. Weyren, Deputy Program Manager, Physical and Technical program, DBER, would have handled such matters. He said that he was aware that injections had been made, but that he as not familiar with the details and was not involved in the matter; that he first became aware of them in about October 1972; that some time subsequent to that, he was asked by Dr. Burr to put together some data on the injections, most of which he had gleaned from published literature; that in preparing the summary data, he did have occasion to talk to Dr. Durbin, who seemed quite disturbed that ANL had been given the responsibility for the work. Dr. Weyren advised that he learned of the injections from Dr. Goldstein during a site visit made to Berkeley; that Dr. Goldstein considered the matter an explosive situation; that he (Goldstein) probably would have handled the reviews of the 189's along with Drs. Richmond, Goldman, and possibly Wachholz; that each person generally had his own area of responsibility and usually it was all one could do to keep up with one's own responsibility. he said that he did not recall any detailed discussion of the plutonium matters in any of the budget meetings. Dr. Charles E. Carter, Program manager, Biomedical Programs, DBER, advised that he was hired effective November 19, 1973, and was not aware that the plutonium studies were included in an ANL 189 until Dr. Edington pointed it out to him. He said that such of the language in such documents is casual but that a 189, submitted and funded, is in his opinion tacit approval. Dr. Burr advised that the language included in the Form 189 is a matter of degree; that if the proposal contains new work, the language would highlight the work; that would appear that -14- the plutonium work was "folded in" with the radium studies, and thus was not "flagged" for any particular attention. He said that this does not mean that DBER would not have approved the work, however, nor would any questions have been raised regarding compliance with the adopted DREW guidelines, which supplanted document. he said that the latter would more appropriately be raised during a field review of a contractor's operations. Informed Consent. It will be recalled that as early as March 1947, AEC expressed the view that all clinical testing 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 was possible risk involved be explained very clearly and that the patient express his willingness to receive the treatment; that in lieu of a written release, at least two doctors in each case would certify in writing to the patient's state of mind, to the explanation furnished him and to his acceptance of the treatment; and that this position was reiterated in April 1947. It will also be recalled that May 1970, as a result of adoption of an NIH publication entitled "Protection of the Individual As A Research Subject," AEC required its contractors to file an acceptable assurance of compliance with the procedures and to reaffirm that intent in the budget documents or contract renewal requests, and that ANL agreed to comply. Examination of the ANL letter indicating there agreement ------- attachments, dated June 19, 1970, which are identified below and state as follows: * * * * * "Review Committee for Research Projects Involving Human Subjects "The Argonne National Laboratory has formally adopted the principles expressed in the Nuemberg Code as its guide in research which makes use of human subjects. "To implement these principles, and to verify that all such research is in compliance with the Nuemberg Code, a Review Committee for Research Projects Involving Human Subjects will be established at the Argonne National Laboratory. This Committee will receive all proposals involving research on human subjects. No research will be undertaken without the prior approval of the Review Committee. "The Review Committee will have the responsibility to verify that all human subjects clearly understand the nature of the research program in which they are involved, and to see that the voluntarily obtained informed consent of the subject has been obtained in writing. Further, the Committee will determine to its satisfaction that permanent records of the research carried out at the Laboratory are kept, and will have the right to inspect these records at any time. "No individual involved in the conduct of the research activity will participate in its review, except to provide information to the Review Committee." * * * * * "STATEMENT OF COMPLIANCE "The Argonne National Laboratory will comply with the principles of the Public Health Service with regard to research involving human subjects (as stated in the document entitled, 'Protection of the Individual as a Research'). The document recommends a review independent of the investigator to safeguard the rights and welfare of those subjects. -15- "I assure the Division of Biology and medicine of the USAEC that Argonne will establish advisory groups competent to review research plans involving human subjects, prior to the initiation of such research, in order to insure adequate safeguards. Group reviews and decisions will be carried out in reference to (1) the rights and welfare of the individuals involved, (2) the appropriateness of the methods used to obtain informed consent, and (3) the risks and potential benefits of the proposed research. "We shall be sure that there is a continuing exchange of information and advice between the review group and the investigator, particularly to deal with proposed changes in research design, and with emergent problems which may altar the investigational situation with regard to the criteria above. Argonne will be sure that the policies and the advice of its review groups are followed. It will also provide whatever professional attention or facilities are required to safeguard the rights and welfare of human subjects involved in research. Records of group review and decision on the use of human subjects and of informed consent will be developed and kept by the institution." * * * * * Examination of "The Institutional Guide to DHEW Policy On Protection Of human Subjects," dated December 1, 1971, and which supplanted the aforenoted NIH document, disclosed that it sets forth the policy as stated in DHEW Grant Administration Manual Chapter 1-40; and that with respected informed consent, it states as follows: * * * * * "c. The informed consent of subjects will be obtained by methods that are adequate and appropriate." * * * * * "Informed consent is the agreement obtained from a subject, or from his authorized representative, to the subject's participation in an activity. "The basic elements of informed consent are: "1. A fair explanation of the procedures to be followed, including an identification of those which are experimental; "2. A description of the attendant discomforts and risks; "3. A description of the benefits to be expected; "4. A disclosure of appropriate alternative procedures that would be advantageous for the subject; "5. An offer to answer any inquiries concerning the procedures; "6. An instruction that the subject is free to withdraw his consent and to discontinue participation in the project or activity at any time. "In addition, the agreement, written or oral, entered into by the subject, should include no exculpatory language through which the subject is made to waive, or to appear to waive, any of his legal rights, or to release the institution or its agents from liability for negligence.4" * * * * * -16- "Use of exculpatory clauses in consent documents is considered contrary to public policy. Tunkl vs. Regents of University of California, 60 Cal. 2d 92, 32 Cal. Rptr.33, P. 2d 441 (1963, Annot., 6 A.L.R. 3d 693 (1966." * * * * * It will be recalled that Dr. Sinclair, previously identified, stated that the plutonium studies were not presented for consideration by the Human Use Committee because they were considered to be covered by the basic protocol of the radium studies as approved by the Human Use Committee in 1971. Examination of that protocol disclosed that it contains instructions regarding informed consent and a consent form. Dr. Marks made available a memorandum dated April 8, 1974, prepared by the Chairman, Review Committee for Research Projects Involving Human Subjects which states in part as follows: * * * * * "Plutonium Cases "It is the Committee's understanding that one subject to whom it is believed 1/10th microcurie Pu-238 was given intramuscularly prior to amputation of a bone tumor, was examined at the Center for Human Radiobiology for the determination of radioactivity during -----------------. It is our understanding that the patient's physician was aware of the examination to be made. However, neither the patient nor the physician was informed that the patient had been injected with plutonium prior to the amputation of his leg." * * * * * "It is our opinion that the CHR should not be involved in examination of patients believed to have a body burden of plutonium, or excreta from such subject, unless the patients have been informed that the examination is to establish the presence or absence of residual radioactivity. stemming from the plutonium that they received many years ago. "This opinion is given in the belief that informed consent, when given by a patient, is based on full information about the reasons for the examinations to be carried out. Clearly, the protocol for obtaining informed consent from the radium cases is applicable to the plutonium cases and must be followed." * * * * * It will be recalled that the inquiry authorized by the General Manager disclosed the only one injection was made subsequent to the takeover by AEC; that in this instance there was documented evidence of oral consent to the procedure; that this individual subsequently had a leg amputated and is still living. Examination of a memorandum dated March 7, 1973, from Dr. Austin M. Brue, Medical Director, CHR, to this individual's attending physician, disclosed that it states in part as follows: * * * * * "We are trying to locate a patient of yours by the name of ... in order to do a follow-up study on treatment he received for a sarcoma in July, 1947. -17- "We are especially interested in cases of this sort, and his is of particular interest since he has this unusual malignant tumor and has shown such a long survival time. "If he is able and willing we would like him to participate in a metabolism study at Strong memorial Hospital in Rochester, New York for abut ten days. Please assure him it would only be for observation and collection of excreta. "We will take care of his transportation and hospital costs, and he will receive about $140.00 participation reimbursement for cooperating in this study. If it is necessary for him to have someone accompany him, we will take care of the transportation and lodging of that individual and allow them $13.00 a day for meals and other incidental expenses. "If Mr. ... is unable to come at this time, please advise us of his condition and convey to him our interest." * * * * * Dr. Rowland said that the CHR had contacted the local doctor who in turn contacted the patient; that the patient then corresponded with the CHR before coming for the studies; that the contact with the patient was made by letter, and that as far as he knew there had been no direct conversation; that to his knowledge, the patient's physician was informed that the patient was to be studied because of the Center's interest in the treatment of the patient's osteogenic sarcoma; and that the patient was enthusiastic about his trip. Dr. Brues implied that he was requested by Dr. Rowland to correspond with a physician to make arrangements to have the patient brought to Rochester for study; that the letter sent to that physician indicated the interest of the group in studying the patient in view no explicit statement about radioactivity in the communication although the letter was written on CHR stationary. Dr. Brues implied that he did considerable soul-searching in the preparation of the original contact letter to the physician and in the preparation of the follow-up letter after the patient's examination, the latter representing the customary communication of the results of a CHR to an attending physician. Dr. Stahney advised that this patient had not signed a consent form and attributed this failure to the unusual way of recruiting this man for the study; that the patient happened to be studied at the CHR because he was reluctant to fly to Rochester where samples were to be taken and instead took a bus; that the trip routed him through Chicago, and since he was there anyway, he was brought to ANL for such studies as the clinical history, radiological and laboratory examinations, but was not given a physical. He said that the CHR had intended to tell the man about his plutonium deposition when they fully confirmed that this was indeed the man with the deposition; that the amount the man had received was relatively small and was injected into a leg that was amputated shortly thereafter; that the plutonium was not demonstrated in whole body counting and the small amounts of urine that were examined originally failed to show evidence of plutonium; and that if was only when the analysts at CHR began to examine 24-hour samples in January or February 1974, that they conclusively demonstrated plutonium deposition in the man and, therefore, felt justified in making the disclosure to him. Examination of a memorandum dated May 31, 1974, from Dr. Brues to Dr. Rowland, disclosed that Dr. Brues accompanied Dr. Weyren, previously identified, on a visit to this patient's attending physician to inform him of the details ----- the early injection and suggest -18- that he convey this information to the patient; that the patient was also visited and advised that he should contact his physician about a discussion they had with him. Examination of latter dated June 6, 1974, to Dr. Weyren from Dr. Brues advised of the telephone conversation with the physician who stated that he had told the patient that he had received an injection of plutonium while in the hospital for the amputation; that the patient was aware of the injection, and wasn't much concerned although he did not know what it was that had been injected; and that he agreed to send a letter to AEC explaining what he had been told, what questions he may have asked and the answers and his attitude. The aforenoted memorandum dated April 8, 1974, from the Chairman, Review Committee, stated in part as follows: * * * * * "It is also noted that excreta from two further so-called plutonium cases were examined and that these cases are under the care of Dr. Waterhouse. It is our understanding that these patients have not been informed that they received injections of plutonium." * * * * * Dr. Rowland advised that he thought that Dr. Christine Waterhouse, Professor of Medicine, Strong Memorial Hospital, Rochester, New York, had not informed the patients of the early plutonium injections during the recent studies and believed that her attitude was that the patients are frail now and might be barred by such disclosure at the present time. He said that Dr. Waterhouse had not admitted the patients to Strong memorial Hospital for the metabolism studies, but had hospitalized then for other reasons. He said that the excreta samples were taken while the patients were hospitalized. Dr. Waterhouse stated that during the past year, she was approached by Dr. Rowland and was visited by Dr. M. S. Littman, Physician, Gottlieb Memorial Hospital, Case-Western Reserve university School of Medicine, Cleveland, Ohio, in regard to the surviving plutonium patients; that she agreed to cooperate in the venture since she felt that for scientific reasons it was important to collect the information , emphasizing that she only had the excrete collected and that the patients were admitted due to illness and not for the plutonium study. She emphasized that she is willing and planning to disclose to both of her patients as soon as possible the fact that they were injected with plutonium and has not done so yet in order not to interfere with any plans the AEC might have for disclosure to all of the people involved in the study. Examination of a memorandum dated December 21, 1972, from Dr. Rowland to Mr. H. A. Schultz, Senior Staff Assistant, Records and Data processing, CHR, disclosed that 18 case files were transmitted for his retention; that these were the plutonium cases; that he was instructed to acquire any missing information; that three cases were to be hospitalized in New York in the near future for excreta collections; that autopsies on some would be attempted; and that the following instruction was included: * * * * * "Please note that outside of CHR we will never use the word plutonium in regard to these cases. 'These individuals are of interest to us because they may have received a radioactive material at some time' is the kind of statement to be made, if we need to say anything at all." * * * * * Examination of a memorandum dated April 24, 1973, from Dr. Stahney to Mrs. M. M. Shanahan, Deputy Director, MIT Radioactivity Center, Southwest Field Office, Phoenix, -19- Arizona, disclosed that it transmitted ten folders containing copies of all CHR information on the cases for which death certificates had been received; that it instructed that the necessary steps to be taken to locate relatives and obtain permission to exhume any or all; and that it contained the following: * * * * * "... It should be noted we want to examine the remains in order to determine the microscopic distribution of residual radioactivity from past medical treatment." * * * * * Dr. Marks advised that he also found a memorandum from Dr. Stehney to Dr. Fry, dated December 14, 1973, which told of the status of the studies but did not address itself to the matter of informed consent. Relative to the exhumations, Dr. Rowland stated that they were handled by two groups of people, Dr. Jan Liaben, Physician, FMC Corporation, Philadelphia, Pennsylvania, on the one hand, and Mrs. Shanahan and Dr. Robley Evans, Consultant, MIT Radioactivity Center, Southwest Field Station, Phoenix, Arizona, together on the other; that the family in a typical case was told that the time; and that the purpose explained to them was that the current studies concerned the composition of the radioactive material by means of-- --------- the body and to study the effects of the materials. Dr. Evans and Mrs. Shananhan recalled that this program was an outgrowth of the activities at MIT; that when they transferred their principal locus of activity to Phoenix, they continued to obtain permission for exhumations for De. Rowland; that their principal contact was Dr. Liaben; that authorization to obtain permission for exhumation of the plutonium cases was contained in the aforenoted memorandum from Dr. Stahney; that the memorandum also provided guidance with respect to what would be told to the survivors; that they contacted the sister of the exhumed patient and obtained permission, the sister living in Phoenix area; that they told the sister that they wanted to study the composition of a mixture of radioactive isotopes and the attendant effects of the material which had been given to the deceased patient some time before her death; and that since the sister did not inquire as to the reason for the injections, the issue was not broached. Dr. Evans and Mrs. Shanahan said that the instruction from Dr. Stahney did not call for mentioning plutonium; that when the instructions were sent to Dr. Lisben, he refused to do anything about the matter until the mysterious nature of the project was explained to him; that Dr. Lisben obtained permission from the brother of the exhumed patient, which was the only one complete permission obtained at the time of interview. Dr. Lisben advised that he had been obtaining permissions for exhumation in the radius program for about 12 years; that his active pursuit of permission in the plutonium cases began in April 1973; that prior to that time, he received a request from Mrs. Shanahan to proceed with obtaining permission for exhumations on a list of individuals without indicating the nature of the isotope deposition that the decreased may have had; that there was also some indication of unusual secrecy regarding this particular group of cases which disturbed him; that he refused to go ahead without further information; that she advised him to contact Dr. Stahney for clarification, which he did; that after determining that the activity was proper and that the element was plutonium, but he was not to mention this fact, he and Dr. Stehney agreed that an appropriate approach would be today that the Center was investigating the composition of radioactive materials that had been injected at an earlier data in an -20- experimental type of treatment; and that since the composition of the mixture was not well know, there would be considerable scientific interest in investigating the nature of the isotope and the effects that it might have had. He said that this was the presentation he made to the various survivors that he contacted. He said that in the case of the already exhumed body, he interviewed a brother in addition to the sister who was contacted by Dr. Evans and Mrs. Shananhan. He added that he had obtained permission for only one other deceased when the program was stopped, which he turned over to Mrs. Shanahan. Dr. Stehney advised that his impression of the exhumations was that the families were told that there is residual radioactivity from treatments that were given to the deceased persons many years ago. Other Contacts with DBER personnel. Dr. Rowland advised Dr. Liverman by a latter dated November 1, 1973, that the CHR had located four individuals out of the group of 18 who were injected in 1945-57, and that the details of CHR involvement in the study could be obtained from Dr. Marks, the technical representative for the CHR, who was fully informed of CHR activities in this area during his visit to CHR on October 4-5, 1973. Dr. Marks reiterated that while he generally functioned as a technical representative from about July until November 1973, an official appointment to that position was never made; that this concept is no longer used, Dr. Carter now being the principal contact with the laboratories. He said that he did attend the Advisory Committee Meeting at CHR on October 4-5, 1973, during which Dr. Rowland discussed various programs, including the ------- -------- although not addressing himself to the matter of ethics. Dr. Marks furnished a copy of the minutes of this second meeting of the Committee, dated January 31, 1974, examination of which disclosed that it states in part as follows: * * * * * "The events of the past year have added to these three a fourth group, the exhumation and study of deceased individuals among a group of 18 persons who were injected with plutonium in 1945-1947. There was extensive discussion of these four groups, directed toward the ultimate recommendation of priorities. A very brief summary of each follows." * * * * * "The fourth and newest goal in the exhumation program relates to obtaining information concerning plutonium retention and toxicity, a top priority matter in the AEC Biomedical program. One of the 18 persons injected with plutonium i 1945-1947 has been exhumed recently and it is estimated that exhumation permissions may be obtained on perhaps mother half dozen cases, several of whom survived long enough so that invaluable skeletal retention data should be obtainable. The CHR now has an experienced plutonium chemist, Dr. Robert Larsen, and urine aliquots will be assayed at CHR/ANL and Los Alamos." * * * * * It was noted that page 2 of this record of minutes also stated in part: * * * * * "Evans has reported by letter to the ACCHR on his conversations relevant to the CHR on September 11, 1973 at AEC/Germantown with Jim Liverman and especially with Bill Burr and Sid Marks, seeking definitive AEC/DBER responses to the several questions which the ACCHR put to DBER in our report dated April 17,1973. Most important, our broad-brush statement of long-range objectives for the CHR on page 18 or our report, is accepted. Concerning our other and more specific recommendations -21- to DBER, the DBER response is that all the positive-action proposals are O.K., e.g., the study of human cases other than radium and nesothorium as described on page 21 of our report. The only restriction is that no on-going programs outside the radium and nesothorium area at other laboratories would be transferred bodily to the CHR in the immediate future." * * * * * Examination of the DBER files disclosed that the report referred to above, dated April 17, 1973, was the minutes of the first meeting of the Advisory Committee of the CHR which took place on November 16-17, 1972; that the "broad brush" statement, referred to above, was stated as follows: * * * * * "Long-range (30-yr) objectives. "A long range goal for the ongoing project (radium and nesothorium) should be data acquisition and the development of well-tested dose-response relationships which can be rationally extrapolated to low-dose effects in very large populations. "This cannot be overemphasized in view of the cornerstone position of the O.1 uCl values for other internal emitters, including plutonium and transplutonium elements. The effort should include systematic research on the mechanism(s) of the dose-response relations for radiogenic tumor occurrence and for other biological end points in human subjects." * * * * * Dr. Marks stated that the objective stated above only dealt with the relationships of various elements to each other and was not germane to the proposition of actual plutonium work with human subjects. He recalled the conversation with Dr. Evans as related to the discussion on page 21 of the referenced report which deals with the development of a long-term program relative to other internal emitters in man, including plutonium. He said that the discussion was informal and that Dr. Evans has asked if it would be permissible to study other isotopes; that he was told yes if the occasion arose, but that no ongoing programs would be established at the CHR. He said that there was nothing wrong with studying other isotopes; that he was told yes if the occasion arose, but that no ongoing progress would be established at the CHR. He said that there was nothing wrong with studying other isotopes, but that this did not mean that the guidelines established for human subjects could be violated, and that no inference or approval has been given by DBER to that effect. Dr. Burr concurred in Dr. Marks' comments, recalling that Dr. Evans had asked if the CHR could go beyond the radium studies and that he was told yes, except that no ongoing programs such as the Transuranium Registry at Hanford would be moved to that location. Dr. Burr concurred in Dr. Marks' comments, recalling that Dr. Evans had asked if the CHR could go beyond the radium studies and that he was told yes, except that no ongoing programs such as the Transuranium Registry at Hanford would be moved to that location. Dr. Marks advised that he participated in the AEC review of the CHR which took place on November 27-29, 1973, and furnished a copy of his memorandum to the files which he said that he prepared and submitted to Dr. Carter for his use in preparing the formal divisional memorandum on the review. Examination of this memorandum disclosed the following discussion on the subject of plutonium: * * * * * "Dr. Rowland discussed the intravenously injected plutonium cases. All the Durbin records were turned over to him in December 1972. He has established that there were 12 deaths in the 18 cases. Of the remaining, four are known to be alive -22- and three of these are under study. One was studied in the hospital at the University of Rochester in January 1973. A second was brought from Arizona to the University of Rochester in June 1973 for hospitalization, and the third was studied shortly thereafter. Urine bioassays for Pu-239 in these cases have been performed at the CHR. Pu was detectable in the urine in two of the three cases. Through the resources of the Southwest Field Station, permission for exhumation of dead intravenously injected individuals is being sought actively. The first exhumation in this group was performed in September 1973. Death occurred in this case 1.3 years after the injection. An autopsy with removal of the internal organs had been performed previously, but the skeleton was obtained during the exhumation. Dr. Rowland in interested in obtaining both urine and stool specimens on the remaining living patients. In his discussion John marshall mentioned that the body burden remains relatively constant from about 100 to 10,000 days after injection. Focal excretion is between 1/10 and 1/2 that of the daily urinary excretion. "Comments "The Center appears to have largely ignored the need for an epidemiologic design. Two relevant viewpoints by the administration emerged from the review. One was that the pursuit of a design is hopeless for this material; therefore, don't try. The other was that examination of patients for clinical disease and radium burdens is an unfortunate raison d'etre of the laboratory. If the scientific personnel ------ are bothered excessively with this mundane task, they will depart for greener pastures. "The administration of the Center seems to be so unimpressed with the human radiobiology in its midst that it is likely to communicate only disinterest in the radium study to its professional staff. This attitude toward the human study breeds a contradiction that undercuts much of the work of the Center. Bob Rowland is furiously promoting the Center as a source of information for setting permissible burdens for other radioisotopes such as Pu. However, the dose-response relationship in radium patients is a key item in his models for extrapolation from animal to man for any other radioisotope. Without adequate incidence values for radium- induced disease in man, reliable dose-response relationship cannot be formulated. In other words, the known relationship between animal and man For Ra is, in fact, unknown because human incidence data remain unavailable. This vital element in the extrapolation model is missing and, apparently, little is being done in an organized way to fill the gap. "Competent epidemiologist like George Hutchison and Edy Tompkins have urged Rowland to proceed to formulate and implement an epidemiologic study on the Ra populations. They obviously do not regard the effort as hopeless. As yet, the closest he has come to obtaining the services as a suitable person to provide guidance along three lines was the near acquisition of a postdoctoral fellow in biostatistics. If Rowland had succeeded in hiring that individual, he probably would not have had the background and maturity required to design this complex study. If Bob Rowland were to seek epidemiologic talent with a fraction of the vigor that he displays in acquiring such personnel as Pu chemists, he could easily repair this major defect in his program. "Much of the Canter's problems may be ascribed to faulty administration. Dr. Rowland has embarked on a course of expansion without consolidation. Until now, he has devoted his major effort to expanding the facilities, staff and budget of the Center. He boasted openly of the fact that his is the only division at Argonna that has undergone significant expansion in the past few years. During this survey talk, he -23- expressed his intention of promoting a similar expansion of the environmental side of his operation. In the meantime, he has filed in the task of consolidation in the CHR and exhibits a reluctance to delegate that responsibility to others. We gained the impression that Andy Stehney functions to implement Rowland policies and, probably, carry out his detailed orders but not create policy. I suspect that Stehney is more of a lieutenant than a chief, anyway. "My overall impression was that Rowland does not understand that the human radium study is a scientific study, can be carried out in accordance with a proper design (despite its difficulties), will reflect credit on his organization if done properly and will provide a basis for other work in this laboratory such a Marshall's. While denigrating the most relevant part of his operation, the human radium study, he imposes an excessive burden of relevance on his other research personnel such as Elizabeth Lloyd and Stanton Hoegerman. I had the impression from the outside reviewers that these workers are likely to be more productive if Rowland will allow them greater latitude than he has given them thus far. He may improve the quality of is organization if he will, on the one hand, consider the human radium study relevant, scientific and a potential source of important data and, on the other hand, his more basic research as only peripherally relevant but justifiable on the grounds of scientific merit. Finally, he is hell bent on making his operation relevant by dragging it into the plutonium age without regard for the consequences. He agrees---------- handling the plutonium work created enormous potential problems in several areas. "Recommendations "I would recommend that Dr. Rowland do the following: "1. Concern himself with consolidation of the CHR rather than further expansion of his Division and/or acquire the services of a strong, innovative deputy for the CHR. If the latter course is followed, Rowland should delegate a major share of responsibility to the deputy. "2. Reorient his philosophy and priorities such that he will: "a. treat the human radium study as a worthwhile scientific investigation, "b. assign to the human radium study top priority for relevance in his operation, "c. judge basic research in the CHR on the basis of merit rather than relevance, and "d. consider his plutonium research as a secondary activity and not a prerequisite to the continued existence of his Center. "3. Obtain the services of one or more epidemiologist on a consulting basis to develop an adequate epidemiologic design for the human radium study and to assist in its implementation. Implementation of a good design should be his highest priority and can justify diversion of resources from other activities to accelerate its pace. "4. If all else fails, he should use the ultimate option - replace the division director." * * * * * -24- Dr. Marks stated that the "division director" to whom he refereed was Dr. Rowland, himself; that the remark was intended to be facetious but, in retrospect, was probably too much so to be put in a formal memorandum to the files. Dr. Wachholx, previously identified, advised that he participated in the review of the CHR and prepared an informal trip report which he gave to Dr. Carter; that he presumed that a formal report would have been prepared to Dr. Liverman, using whatever information was included in the individual trip reports; that since Dr. Marks was handling the plutonium matters, he did not put any significant comments on this mater in his report, the latter being confirmed by a review of his trip reports by the writer. Dr. Carter advised that he prepared the consolidated report of the aforenoted review of the CHR and furnished a copy of the report which was transmitted to Dr. Robert G. Sache, Director, ANL, on June 14, 1974. Examination of this report disclosed that it states that due to the nature of the work conducted in the Division, the review encompassed the three program (radium studies, radiological physics and environmental research) separately, utilizing experts in each of the areas in an effort to obtain information on the scientific merit of the work conducted in those areas; that the review was successful in providing DBER with an overview of the status of the work being performed and, in addition, focussed attention on some specific problems, both research and management, which Argonne and DBER management should discuss with the intent of improving administration as well as scientific operation of the work supported in the Division. It was noted that the ------------ -----dressed to the CHR does not deal with the problems to which Dr. Marks referred and which were the basis for the inquiry authorized by the General manager and that requested by Dr. Liverman. Dr. Carter stated that Dr. Rowland did present considerable information regarding the intravenously injected plutonium cases during the aforenoted review, but that he (Carter) did not include such data in the final report since it was not programmatic issue. He said that he was aware that the problem might become "center stage" and that he suggested to Dr. Edington, in the vein of high priority, that the problem should be discussed internally, including the Office of the General Counsel, the latter being done in mid December with the idea of developing a method obtaining informed consent. He said that about Christmas, Dr. Rowland called to advise that he was submitting abstracts which would be used at the international conference in July 1974 and that they could contain analyses of specimens on those injected individuals; that he told Dr. Roland that the matter had been discussed with Counsel and that the plutonium matter would be dealt with by Dr. Liverman before the Commission, emphasizing to Dr. Rowland that he should recognize the dimensions of the problem to safeguard the interest of all concerned. He said that since the program for the conference was being developed at ANL, Dr. Liverman discussed the matter with Dr. Sachs, advising him that the formal abstract might be delayed, not withheld, until the problem could be solved, which he believed Dr. Sache accepted. Examination of a memorandum dated December 26, 1973, from Dr. Michael V. Nevitt, Deputy Laboratory Director, Research, ANL, to Dr. Liverman, disclosed that Dr. Nevitt advised that he and Dr. Carter agreed the previous week that the plutonium matters should be discussed by ANL and AEC soon after the first of the year. Examination of a teletype dated April 4, 1974, to Mr. Robert H. Bauer, Manager, Chicago Operations Office, from Dr. Liverman, disclosed that it stated as follows: * * * * * "Patients injected with plutonium "Please request the Director, ANL, to carry out the following: -25- "1. That ANL comply with DHEW guidelines for the protection of human subjects in any further investigations of patients injected with plutonium during 1945-47 (and in all studies on human subjects as previously required in letter from Dr. John R. Totter to Dr. R. B. Duffield of May 15, 1970); "2. That past, present, and future studies by ANL on the patients cited in 1. be referred to the ANL Institutional Review (Human Use) Committee for its review. It is hoped that this review will be completed and report of the Committee made available to you by April 26, 1974; "3. That copies of all available information on file at ANL on all injected patients cited in 1. be provided to the Director, DBER, within the next ten days; "4. That the following actions will be taken by ANL only after coordination with AEC personnel: arrangements are to be made for ANL and AEC physicians to jointly inform physicians attending certain surviving patients of the need for appropriate disclosure to the patients by the attending physicians. Coordination of arrangements will also be made for joint disclosure to the estate of the exhumed patient; "5. That ANL report promptly to AEC progress in implementing 1, 2 and 3 above. "Dr. Sidney marks, DBER, has staff responsibility for conduct of necessary investigations relative to this matter. He will make arrangements with ANL personnel and others as needed to obtain all available information for the Director, DBER. END" * * * * * -26- This report is the property of the Office of Investigations and is loaned to your agency. It and its contents may not be reproduced without written permission. The report is FOR OFFICIAL USE ONLY and it disclosure to unauthorized persons is prohibited. Public availability to be determined under 5 U.S.C. 552.