DISCLAIMER The following is a staff memorandum or other working document prepared for the members of the Advisory Committee on Human Radiation Experiments. It should not be construed as representing the final conclusions of fact or interpretation of the issues. All staff memoranda are subject to revision based on further information and analysis. For conclusions and recommendations of the Advisory Committee, readers are advised to consult the Final Report to be published in 1995. Tab H Staff memorandum--Total Body Irradiation: A Preliminary Narrative * * * * * * *STAFF MEMORANDUM* * * * * * TO: Advisory Committee on Human Radiation Experiments FROM: Advisory Committee Staff DATE: July 20, 1994 RE: Total-Body Irradiation: A Preliminary Narrative Introduction Total-body irradiation (TBI) research appears to have begun in the United States in the early 1930s, when A.C. Heublein designed a room at New York's Memorial Hospital and treated 20 patients suffering from lymphoma, leukemia, and cancer with doses from 37.5 to 225 rads. Although he noted some progress, Heublein died before he could do effective followup. This research followed upon earlier work done in Europe in the 1920s.1 {1 See Melville L. Jacobs & Fred J. Marasso, "A Four-Year Experience with Total-Body Irradiation," 84 Radiobiology No. 3, 452-56 (Mar. 1965), citing A.C. Heublein, "A Preliminary Report on Continuous Irradiation of the Entire Body," 18 Radiobiology 1051-60 (June 1932) and Krause, "Diskussion," Rontgenkongress, Weisbaden, Germany, 1927.} By 1975, at least 42 U.S. institutions had performed TBI.2 {2 "Studies Relative to the Radiosensitivity of Man: Based on the Retrospective, Evaluations of Therapeutic- and Accidental Total-Body Irradiation -- Final Report" (Oak Ridge Associated Universities, Sep. 1, 1975) ("Oak Ridge TBI Final Report"), at 213 ("Cooperating Institutions in [the Oak Ridge] Retrospective Studies") (Attachment A).} The government began sponsoring TBI research in 1942 in connection with the Manhattan Project. At least eight of the 42 institutions performed their research with government contracts; an additional three were VA hospitals and one is the Los Alamos Hospital. Staff does not have funding source information on the numerous other institutions, some of significant prominence, that conducted TBI research. The following is a chronological description of the major government sponsored TBI studies with which the staff is currently familiar. II Manhattan Project The U.S. government first took an interest in TBI during the Manhattan Project when large numbers of people began working with ionizing radiation in the design and production of the first atomic weapons: "radiations from the fission process and from the fission products introduced the possibility of accidental or necessary exposure of the entire body of persons to x-rays, gamma rays, and neutrons to an extent never before thought possible."3 {3 B.V.A. Low-Beer & R- S. Stone, "Hematological Studies on Patients Treated by Total-Body Exposure to X-Rays," in Robert S. Stone, ed., Industrial Medicine on the Plutonium Project.- Survey and Collected Papers 338(1951)(National Nuclear Energy Series(NNES),Div. IV, Vol. 20) (hereafter Industrial Medicine). The NNES is the official history of the Manhattan Project.} 1 Accordingly, the Health Division of the "Metallurgical Project, (the component responsible for producing the weapons grade uranium and plutonium at Oak Ridge and Hanford) engaged in research on radiation effects. The NNES volume on Industrial Medicine on the Plutonium Project notes that in the early 1940s, "[m]any institutions in the country were treating patients with x-rays to the entire body. Three institutions were asked to cooperate by studying in greater detail and over prolonged periods of time the blood picture of individuals so treated. These institutions were the Memorial Hospital in New York (Heublein unit), the Chicago Tumor Institute (400 kv unit), and the University of California Hospital (100, 200, and 1,00 kv units)."4 { 4 Industrial Medicine, at 7.}Thus did the government begin its foray into TBI research. The first experiment was carried out at the University of California Hospital (San Francisco) to test the theory that exposure to radiation levels above the tolerance dose would result in a "rapid and radical change" in the blood picture.5 {5 A full report of this study, including charts and graphs on 16 of 29 patients, was prepared by Low-Beer and Stone in Industrial Medicine, at 338-41 S.} Accordingly, twenty-nine patients who required therapeutic irradiation, but were "hematologically normal," were treated with total dosages ranging from 100 to 300 r from October 1942 to June 1946. Apparently, some of these patients suffered from severe rheumatoid arthritis.6 {6 This study came under severe criticism in an October 20, 1948 letter from Dr. Alan Gregg, Chairman of the AEC Advisory Committee on Biology and Medicine to Dr. Robert S. Stone at the University of California Hospital which states that "we agree with those who believe the x-ray treatment of arthritic patients you have been giving patients (sic] is not justified." Stone responded in a November 4, 1948 letter that while the work was influenced by the need for data, "there was a reasonable expectation that the method utilized might be of therapeutic value to the subject." Stone also opposed the implication that the AEC should be able to deny funding to researchers whose methods it disapproved of Moreover, Gregg had noted that "[t]he secrecy with which some of the work of the Atomic Energy Commission has to be conducted creates special considerations for the clinical aspects of its work in that the public is aware of this necessity for secrecy and of the consequent difficulty of probing into it." Stone responded that although the interest of the Manhattan Project in the effects of TBI was kept secret during the war, no secret was made of the fact of the TBI or the continued blood counts. (Both letters are attached at Attachment B.)} The report notes that the patients were selected by doctors 2 who had no connection with the Manhattan Project.7 {7 Note, however, that the Associate Director of the Health Division, Dr. Robert S. Stone, had come from the Radiology Department of the University of California.} Although noting that the "treatments were administered as part of the normal therapy of these patients," the report states that "[a]dvantage was taken of the fact that patients were receiving such treatment by making numerous blood studies for the Manhattan Project."8 {8 Industrial Medicine, at 338-39.} According to a Nov. 4, 1948 letter by Dr. Stone, each patient accepted the treatment "with full knowledge of the facts," even though no written consent was obtained.9{9 Stone letter, note 6, at 2.} The second experiment was performed from December 1942 to August 1944 on eight patients at the Memorial Hospital in New York.10 { 10 See report by L.F. Craver, "Tolerance to Whole-Body Irradiation of Patients with Advanced Cancer," in Industrial Medicine, at 485 -98.} Each patient received a total of 300 r, at various rates, in order "to yield some detectable effects on the blood count and to serve as a guide to the clinical tolerance for whole body irradiation."11 {11 Id. at 485.} The report on this experiment makes clear that the primary purpose of the irradiation was to obtain experimental data, and that the prospect, of actual medical benefits to the patients. was hopeful at best because of past failures using the same procedure: "The hope that, despite the negative results obtained in 1931 in cases of radioresistant metastatic cancer by use of doses up to 450 r in the Heublein unit there might nevertheless on further trial be found some beneficial clinical effect, offered justification, in addition to the primary purpose, for undertaking the project."12 {12 Id. at 486.} The report on this experiment described the selection of patients "the most difficult part of the project," because the patients had to have "metastatic cancer of such an extent and distribution as to render their cases totally unsuitable for any accepted method of surgical or radiological treatment, yet ... be in good enough general condition so that they might be expected not only to tolerate the exposure to 3 00 r of total-body irradiation in a period of 10 to 30 days, but also to survive the combined effects of their disease and the irradiation for at least six months in order that some conclusions might be drawn as to the later effects of the irradiation."13 {13 Id at 486} Only three of the patients were monitored six months after irradiation, and treatment was discontinued for two patients after only half the dose because of failing health. The study concluded that because 3 there appeared to be "no HI effects other than those apparently caused by the progress of the disease, such doses of radiation should be well tolerated by healthy persons."14 {14 Id at 498.} The third study during the Manhattan Project was described as a reinvestigation of the previous two."15 {15 See J.J. Nickson, "Blood Changes in Human Beings Following Total-Body Irradiation," in Industrial Medicine, at 308-37. Dr. Nickson continued to engage in TBI research at Sloan- Kettering. See below at 7.} This study involved 14 persons from March 1943 to November 1944, and was performed at the Chicago Tumor Clinic. Unlike the previous two, It was designed as a scientific experiment and included the use of healthy volunteers seemingly as controls. The persons who were subjected to radiation during this study were divided into three general groups. The first group consisted of eight persons who had neoplasms that could not be cured but still were not extensive enough to influence general health.... The second group consisted of three persons who had illnesses that were generalized and chronic in nature [two had arthritis].... The third group consisted of three normal volunteers from among the personnel of the Metallurgical Laboratory."16 {16 Id at 309.} The report notes that because there were no known treatments for the people in groups I and 2, "x-ray exposures that were given were as likely to benefit the patient as any other known type of treatment, or perhaps even more likely than any other."17 {17 Id at 309.} When no effect on the blood was observed in group 1 at 60 r, the dose was doubled; stiff no effect was found."18 { 18 Id at 335.} The "normals" were each subjected to three doses of 7 r. This group was of particular interest to the researchers because the results "indicated that acute exposure to far more than the permissible level of 0. I r per working day could not be expected to produce diagnostic changes in the elements of the peripheral blood which were studied."19 {19 Id at 336.} The irradiation of healthy persons for whom there was no prospect of therapeutic treatment appears unprecedented in any known TBI study. 4 III Department of Defense After World War II, the Department of Defense continued to explore TBI to understand the effects of radiation in various military applications. A. Air Force The earliest dated study that staff is currently aware of was sponsored by the Air Force beginning in 1951. From 1951 through 1956, the School of Aviation Medicine, Randolph Air Force Base, Texas, sponsored TBI research that was run by the University of Texas and the M.D. Anderson Hospital and Tumor Institute in Houston. Limited results of the study were reported in an article by Drs. Lowell Miller, Gilbert Fletcher, and Herbert Gerstner on "Systemic and Clinical Effects Induced in 263 Cancer Patients by Whole-Body X-Irradiation with Nominal Air Does of 15 to 200 R."20 {20 School of Aviation Medicine, USA.F, No. 57-92 (May 1957).} That the study, which "originat[ed] from therapeutic considerations alone, attempts to contribute such additional information" to the what is known about the effects of total-body irradiation on humans, suggests that its primary purpose was therapeutic. It sought to learn whether TBI was an effective palliative treatment of persons with incurable generalized tumors, and if so, how high a dose is required. In the final phase of the study, SO patients were given doses of 200 r. The article noted that a "[c]lose similarity seems to prevail between the systemic effects produced in cancer patients by whole-body x-irradiation and those caused in healthy human beings by nuclear explosions." The authors found that those effects -- which include the early prodromal response of fatigue, anorexia, nausea, and vomiting, and later effects of bone marrow depression resulting in bleeding, infection, and pancytopenia - began to appear at low levels in about 50 percent of cases between 125 and 175 r, and are "clearly recognizable in about 80 percent of cases" at 200 r. They concluded that "the threshold dose, beyond which in a small percentage of patients serious complications begin to appear, lies somewhere between 150 and 200 r."21 { 21 Miller, Fletcher, and Gerstner, at 193-94.} The M.D. Anderson study included a second focus, concerning the effect of radiation on human performance. This part of the study appears to have been motivated by Air Force consideration of a nuclear powered airplane (formerly known as nuclear energy propulsion for aircraft [NEPA]). A March 12, 1952 summary of a conference on "the Medical Aspects of Nuclear-Powered Aircraft" gives a review of medical-oriented projects in association with the NEPA project, and includes the M.D. Anderson study involving "tests on humans involv[ing] coordination and psychomotor responses before and after irradiation." The summary reports that no evidence of alteration was found in 50 patients who received 15-50 r.22 {22 Memo dated March 12, 1952 to Kenneth Kasschan, Acting Director, Office of Research and Medicine, from C. S. Shoup, Biology Division, on "Review of Conference, 'The Medical Aspects of Nuclear-Powered Aircraft,' Wright-Patterson Air Force Base, Dayton, Ohio, March 6, 1952," at 5-6.}Interestingly, the summary did not 5 consider this study an "experiment," because the first listed project states: "Human experimentation. This was not carried out, although desirable."23 {23 See Tab F, Attachment 2.} This part of the study is also discussed in a 1963 article by Col. Robert Payne on "Effects of Acute Radiation Exposure on Human Performance."24 {24 In Review, No. 3 -63 (USAF School of Aerospace Medicine, Feb. 1963); this article was based on a paper given to a 1962 NASA sponsored conference on Protection Against Radiation Hazards in Space at Oak Ridge National Laboratory.} This article notes that "ethical and moral considerations would necessitate compromises with some of the principles of experimental design. For example, medical considerations required that patients be assigned to treatment levels in accordance with professional judgment as to the severity of disease."25 {25 Id at 3.} Although the author concluded from the study that "there is no dependable evidence that exposure to ionizing radiation affected the variables involved," he emphasized that "the application of these results to operational problems should be made with cautious regard for the medical status of the subjects and the limited relevance of experimental criteria."26 {26 Id at 12.} B. Armed Forces Special Weapons Project (AFSWP) The Armed Forces Special Weapons Project (AFSWP) funded a number of research programs using TBL some of which were reviewed in conjunction with the Research and - Development Division of the Office of the Army Surgeon General. In 1959, AFSWP was changed to the Defense Atomic Support Agency (DASA - which became the Defense Nuclear Agency in 1971), which took over the AFSWP contracts. The following describes the work of the three major investigators funded by AFSWP/DASA. 1. Dr. Collins The first AFSWP TBI study that we know about dates from 1952, when Dr. Vincent P. Collins, at Columbia University, College of Physicians and Surgeons, was awarded $5090.00 to 6 correlate total body irradiation in humans with bone marrow depression as reflected in plasma iron turn over rate.27 {27 Committee on Medical Sciences, Research and Development Board, BAW II 3/1, at 2 (Dec. 12, 1952), AFSWP Proj. No. 6-59-08-013(6) ("Radiation Effects").} The following year, Dr. Collins moved to the Baylor University College of Medicine and the Texas Medical Center and received an AFSWP grant to conduct research on the Effect of Total-Body Irradiation on Immunologic Tolerance of Bone Marrow and Homografts of Other Living Tissue. Dr. Kenneth Loefler joined Collins as the principal investigators. From 1953- 1964 they treated a total of 112 cancer patients. A 1994 abstract prepared by the Armed Forces Radiobiology Research Institute (AFRRI) states that DOD was concerned about the radiation effects on troops in a wartime environment.28 {28 See 1994 abstract provided to staff by the Armed Forces Radiobiology Research Institute (AFRRI); annual reports by Collins.} We do not currently have enough information to draw evaluate the primary purpose of Collins's work. 2. Dr. Nickson From 1954 to 1961, AFSWP also sponsored research on Post-Irradiation Syndrome in Man by the Sloan Kettering Institute for Cancer Research, under the direction of Dr. James J. Nickson; this is the same doctor who conducted the Manhattan Project study at Chicago Tumor Clinic involving the three healthy persons. This program involved a total of 34 cancer patients: 22 received total-body irradiation, and 12 received radiation to the head. A 1994 abstract prepared by AFRRI states that "[s]ince the primary intent of the study was to treat cancer and provide a direct benefit to the subjects, apparently the Nuremberg Code and the Declaration of Helsinki were complied with." 3. Dr. Saenger From 1960 until 1971, the Defense Atomic Support Agency sponsored total and partial body irradiation research at the University of Cincinnati Hospital at the lab of Dr. Eugene L. Saenger. Over that time period, 85 adults and three children were exposed to 100 to 300 rads of total body irradiation from a cobalt-60 machine in two doses - one from each side. Saenger's work has received the most public attention, and is currently the subject of at least one lawsuit. It is also the TBI project about which staff currently has the most information. Saengees early concern on such issues as dosimetry indicators in the urine and psychomotor responses to radiation suggests that military application was a central focus of his work. This motive is discernable from a close reading of his annual reports. Saenger's initial report stipulated the purpose of the study as follows: "These studies are designed to obtain new information about the metabolic effects of total body and partial body 7 irradiation so as to have a better understanding of the acute and subacute effects of irradiation."29 {29 "Metabolic Changes in Humans Following TBI," report period 1960-61 (DASA No. DA-49-146-XZ-029), at 1. (Note that there were a total of ten reports, published roughly annually.)} In his 1964 write-up, Saenger stated his purpose as obtaining information "which is necessary to estimate combat effectiveness of troops and to develop methods of diagnosis, prognosis, prophylaxis, and treatment of radiation injury." Later in that same report he concluded that "[c]ombat effectiveness would be maintained relatively well with an exposure up to 200 rad. However a second exposure would probably result in significant troop ineffectiveness."30 {30 Id, report period 1963 -64, at 1 & 10. This conclusion seems to be at variance with the M.D. Anderson study done for the Air Force. See p. 5 above.} After about 1966, the reports began to delineate more explicitly the degree of informed consent obtained from the subjects, as well as the therapeutic purpose of the work. By the project's conclusion in 1971, Saenger noted that the experiments were preformed for the sole purpose of improving "the treatment and general clinical management and if possible the length of survival of patients with advanced cancer." He also stated that "[a]ll patients gave informed consent in accordance with directives of the Faculty Research Committee of the University of Cincinnati College of Medicine and those of the NIH."31 {31 "Radiation Effects in Man: Manifestations and Therapeutic Effects," 1971-72 (DASA No. 0 1-69-C-0 1 3 1), at I & 4.} In 1972, three reports were issued on the validity and morality of Saenger's research. The dean of the University of Cincinnati Medical School established an ad hoc committee to investigate the research, which concluded that it followed all standards of human experimentation of the time, and that its purpose need not be questioned: "The data provided to the Committee regarding the effectiveness of whole body radiation suggests that survival of the patents in this study does not appear to differ from survival with the use of chemotherapy as reported in the literature."32 {32 The Whole Body Radiation Study at the University of Cincinnati: A Report to the Dean of the College of Medicine by the Ad Hoc Review Committee, at 66 (Jan- 1972).} (It is notable that one of the members of the committee were members of Saengees research team.) Concurrently, a group of junior faculty members conducted their own study of the project, and concluded precisely the opposite. Martha Stevens, an Assistant English professor who authored the report, wrote: We can only conclude that the purpose of irradiating cancer patients at General Hospital was primarily to study radiation injury for the DOD and that incurable cancer patients were used 8 because (a) they were going to die anyway and (b) they "might" benefit from the radiation in terms of reducing pain or slowing the spread of cancer. Stevens also noted that the patients "paid severely for their participation and often without even knowing that they were part of an experiment."33 {33 Martha Stevens, Henry Anna, & David Logan, "A Report to the Campus Community," at 3 (Jan. 25, 1972).} The third report was written by three radiation specialists, Drs. Henry Kaplan (Stanford), Frank Hendrickson (Chicago Presbyterian-St. Lukes), and Samuel Taylor (also Presbyterian-St. Lukes), on behalf of the American College of Radiology (ACR) at the request of Senator Mike Gravel (D- AK). Gravel had become interested in the research in conjunction with Senator Edward Kennedy (D-MA), and had requested that the ACR provide the final word on the matter. The three physicians sided with the dean's committee in determining that no harm had been done. They opened their report with the following: "In the normal context of a clinical investigation, the project is validly conceived, stated, executed, controlled and followed up. The appropriate scientific and professional committees of the University of Cincinnati have preformed their functions during the course of the project."34 {34 Letter dated Jan. 3, 1972 from Robert McConnell (President of the ACR) to Senator Mike Gravel.} C. Navy In 1959, the Navy conducted. its own TBI research at the U.S. Naval Medical Research Institute. An article by Capt. Richard King on the "Use of Total-Body Radiation in the Treatment of Far-Advanced Malignancies,"35{35 J.A.M.A. Vol. 177, No. 9, at 86 (Sept. 2, 196 1).} describes TBI treatments. on 17 patients "to treat certain cases of far-advanced cancer and leukemia, and to evaluate the use of bone marrow transplants, as well as to study the postradiation clinical course of such patients." The article concludes that "[t]otal- body radiation therapy in a dose range of 100-400 r appears to offer relatively safe and reasonably effective palliative therapy for advanced radiosensitive malignant disease."36 {36 Id at 89.} The article makes no mention of any military or other non-medical interest in the research. 9 D. Secrecy and Consent The Department of Defense maintains that its medical research, including TBI, was not classified after World War H and was generally published in the medical literature. However, the policy within the Department relating to the research was generally secret.37 { 37 See, e.g., note 22, above (document discussing TBI research in relation to nuclear powered aircraft was classified Secret).} Some of the investigators (Dr. Saenger, for example) had security clearances and therefore may have been involved in related classified activities. We do not have a full accounting from the department of its records; because many documents have yet to be found or have been lost, we cannot tell whether non-public parts of investigations may have existed. The extent to which patients provided informed consent is unclear. We have no showing that DOD studies followed the requirements of Secretary of Defense Wilson's 1953 memorandum on human experimentation. We now know that in June 1953 the Army stated that the policy applies to contractors as well as the Military.38 {38 See Tab G, Attachment J.} Dr. Saenger, for example, did not begin to document patient consent until 1966. His initial proposal was made to the Army in 1958-59. 39{39 The reviews appear in Tab L of the May 18-19 Briefing Book.} IV. Atomic Energy Commission/NASA The Atomic Energy Commission conducted experimental research on the effects of total-body irradiation at the Medical Division of the then Oak Ridge Institute of Nuclear Studies (ORINS), which became the Oak Ridge Associated Universities (ORAU) in 1966. From 1957 to 1974, ORINS/ORAU treated a total of 194 patients, mostly in its medium exposure-rate total-body irradiator (METBI, built in 1960) and low exposure-rate total-body irradiator (LETBI built in 1967). ORINS/ORAU also used the TBI facilities to conduct research on bone marrow transplants.40 {40 The Medical Division was directed by Dr. Gould Andrews. In 1963, Dr. Clarence C. Lushbaugh came to ORINS from the Los Alamos Scientific Laboratory to work on the effects of total-body irradiation.} In 1974, the AEC conducted a program review of the Medical Division of ORAU. It recommended that the clinical TBI programs be closed, having found that the NETBI and LETBI 10 programs had "evolved without adequate planning, criticism or objectives, and have achieved less in substantial productivity than merits continued support." The review also stated: The marrow transplantation program came under severe criticism. In view of accepted therapeutic modalities, ethical questions were raised with respect to the protocols employed in these studies. The leadership of this program is not defined; the coordination with immunology is ineffective. The number of patients accessible to the study is small and argues against the continuation of transplant clinical investigation at ORAU."41 {41 AEC Program Review of the Medical Division of Oak Ridge Associated Universities (May 9, 1974), based on April 16, 1974 ORAU Review.} This program became the subject of a congressional hearing in 198 1, in response to an article in Mother Jones magazine that suggested that the procedures were not medically sound and were presumably non-therapeutic experiments for NASA.42 {42 On March 13, 1994, "60 Minutes" aired a story based on the Mother Jones article.} The hearings were before the Investigations and Oversight Subcommittee of the House Science and Technology Committee, and were chaired by then Representative Al Gore, At the end of the hearing, Gore noted that the subcommittee would issue a report with conclusions and recommendations.43 {43 Hearings on the Human Total Body Irradiation (TBI) Program at Oak Ridge before the Subcommittee on Investigations and Oversight of the House Science and Technology Committee, 97th Cong., 1st Sess. (Sept. 23, 1981), at 302, ["Gore Hearing"].} Although no formal report was issued, the full Committee issued a statement in its bi-annual "Summary of Activities": The Subcommittee testimony revealed that while many of the conditions at the (ORAU] were not satisfactory, particularly when judged by the routine institutional safeguards and medical knowledge of today, the more scandalous allegations could not be substantiated. Given the standards of informed consent at the time, and the state of nuclear medicine, the experiments were satisfactory, but not perfect.44 {44 Summary of Activities of the House Committee on Science and Technology, 97th Cong., 2d Sess., H. Rept. No. 97- 1 0 1 0, at 186 (Jan. 3, 1983). The Committee noted that a later hearing was held on the state of radiation epidemiology within DOE on May 19, 1982. 11 A. NASA As reported at the last Committee meeting in the staff memorandum on NASA, the AEC and NASA agreed in 1963 to, among other things, conduct a comprehensive review and analysis of all known data from clinical TBI cases (the "retrospective study") and to engage in prospective TBI research that would undertake measurements of use to NASA. NASA was concerned about the effects of cosmic rays on the health and performance of astronauts in long-range missions outside of the Van Allen belts. Both studies were performed at ORINS/ORAU. The NASA prospective study was essentially a continuation of the TBI work that ORINS had been conducting,45 {45 Approximately 100 were cases were performed before NASA's involvement.} with additional data being collected for NASA, and included the construction of the LETBI in 1967. Andrew J. Stofan, then Acting Associate Administrator for the Office of Space Science, testified at the Gore hearing that NASA had no involvement in the medical procedures at Oak Ridge, but simply provided funds and was interested only in the data that were collected.46 { 46 Gore Hearing, at 155-72.} NASA also says that it only paid for data collection and analysis (such as the LETBI patient monitoring equipment), not for actual experimentation.47 {47 NASA claims that it did not review the experimental protocol, but deferred to Oak Ridge and the AEC}. Although NASA destroyed its records on the Oak Ridge project in 1980, in accordance with its standard records retention schedules, staff has found some of NASA's financial records and other relevant information in the DOE files. The joint "Retrospective Study of Radiation Effects" was formalized in December 1963 and continued throughout the next decade. Some of the data were used in the National Academy of Science's 1967 report on "Radiobiological Factors in Manned Space Flight." A final report was prepared in 1975 by R.C. Ricks and C.C. Lushbaugh, and fists a total of 45 institutions and over 2500 cases. The University of Cincinnati (Dr. Saenger) and City of Hope Hospitals were commissioned to make contacts with other institutions in order to collect the data.48 {48 "Studies Relative to the Radiosensitivity of Man: Based on the Retrospective Evaluations of Therapeutic and Accidental Total-Body Irradiation -- Final Report," at 9 (Oak Ridge Associated Universities, Sep. 1, 1975) ("Oak Ridge TBI Final Report").} V. Conclusion This report is intended as a narrative description of government sponsored TBI studies through 1974. It does not attempt to address the complicated medical or ethical judgments that were made by the researchers conducting the studies. As noted in the TBI Overview in the last briefing book, staff is exploring the extent to which government funds and military and/or space 12 interests influenced the research, including: the initial development of TBI research at the various institutions; the balance between therapeutic research and military and/or space oriented research on radiation effects; and the evolving standards of practice that guided the practioners at each of the institutions. 13