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 G DRAFT FOR DISCUSSION PURPOSES ONLY MEMORANDUM TO: Members of the Advisory Committee on Human Radiation Experiments FROM: Advisory Committee Staff DATE: November 8, 1994 RE: Use of External Radiation on Patients: Analysis of Total-Body Irradiation Research on Radioresistant Cancers, 1940-74 The staff work on the use of external radiation on patients is currently focusing on experiments involving clinical treatments involving total-body, partial-body, and localized radiation from which data were collected and analyzed for secondary purposes. This memo analyzes research involving total-body irradiation (TBI) that was conducted on behalf of the Department of Defense. Staff is continuing to collect and analyze data on this subject. Introduction During the period of 1940-74, total-body irradiation was recognized as effective for treatment of so-called "radiosensitive" malignancies that are widely disseminated throughout the body, such as leukemia and lymphoma, as well as Ewing's sarcoma. TBI was also beginning to be used to effect bone marrow transplantations, by first killing the cancerous cells in the marrow prior to infusion of clean marrow. In addition, TBI was explored on a number of occasions as treatment for so-called "radioresistant," solid body tumors on patients with advanced, metastatic carcinomas.1 [The terms "radiosensitive" and "radioresistant" are relative terms that appear to have little meaning in current medical parlance, but were widely used at least into the 1970s to distinguish leukemias and lymphomas and some of the childhood cancers from adult carcinomas such as of the breast, lung, or colon.] To date, staff has identified and reviewed articles and reports dated from 1940-74 describing the clinical use of TBI on patients at 20 U.S. institutions (and one Canadian). Nine of these institutions treated patients with radioresistant cancers; eight of these were associated with or funded by either the Manhattan Project or the Department of Defense.2 [See Attachment 1 for a list of these institutions. Most of the institutions that treated radioresistant cancers also treated radiosensitive cancers as part of the same study. Staff has no information that the Manhattan Project or the DOD funded institutions that used TBI exclusively on radiosensitive diseases with TBI. ] This data does not include all of the treatments that were undertaken during this time period.3 [A 1969 tabulation of the diagnoses of 1594 patients who received TBI under the Oak Ridge/NASA Retrospective Study lists 1160 with radiosensitive diseases (133 with acute leukemia, 320 with chronic lymphocytic leukemia, 175 with chronic granulocytic leukemia, 231 with lymphosarcoma, 168 with Hodgkin's disease, 96 with polycythemia rubra vera, 32 with thrombocythemia, and 5 with undefined blood diseases) and 434 with radioresistant diseases (331 with carcinoma, 17 with melanoma, 35 with sarcoma, 16 with renal disease, and 35 with arthritis and musculoskeletal disorders). Reprinted in Hearing 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 368 [Gore Hearing]. It does not cross-reference the patients with the institutions. Dr. Eugene L. Saenger of the University of Cincinnati has informed staff that he has identified approximately 23 articles describing TBI treatments on radioresistant tumors. Staff is awaiting that list and will update the data where relevant.] Staff is continuing to search for records on the TBI activities of other institutions, including the 46 listed as having contributed data to the Oak Ridge/NASA Retrospective Study. [Nineteen of those institutions are listed as performing less than twelve TBI exposures, and are not the subject of primary scrutiny. Preliminary responses from selected institutions indicates that several no longer have any records describing these activities. Some of the institutions have informed the staff orally that they did "non-experimental" TBI treatments on patients with leukemia during the 1950s, and therefore would have no protocols or review documents of that work -- e.g., Penrose Cancer Center, Colorado Springs, CO; University of Michigan; Charity Hospital, New Orleans, LA (after 1969); University of California, Los Angeles Hospital (not on Oak Ridge List).] This memo describes what is known at present about the group of studies involving radioresistant cancers with respect to such issues as the purpose of research, dose, [There is no consistent method of reporting dose; earlier researchers tended to report air dose in roentgens ("r"), and later researchers reported body dose in "rads." A given air dose of TBI is generally equivalent to a lesser body dose -- e.g., 325 r was reported as equivalent to approximately 200 rads by the University of Cincinnati. See text accompanying note 89.] type of disease, survival times, funding sources, informed consent, and patient composition. It will also discuss the interest and known activities of the DOD in this area. THE MILITARY INTEREST IN TOTAL-BODY IRRADIATION From the time production of the first atomic bomb began in 1942, the U.S. military has utilized medical practitioners of total-body irradiation for its own research purposes. The military interest has been largely two-fold: (1) to determine dose limits and the acute effects on troops, pilots, and workers exposed to radiation through nuclear warfare, nuclear powered aircraft, and weapons plants; and (2) to find a biological radiation dosimeter that could be used to determine the exposure dose based on analysis of human body fluids. Accordingly, the Manhattan Project sponsored three experiments during World War II involving patients, and in one case "three normal volunteers," exposed to TBI to understand the effects of radiation on the laborers and scientists working on the bomb. [These three experiments were previously discussed in Briefing Book 5, Tab H.] Following the war, the military again turned to TBI practitioners to answer questions about the effect that radiation from a proposed nuclear powered airplane would have on the pilots. As discussed in Briefing Book 5, a debate ensued in early 1950 within the DOD Committee on Medical Sciences on how to obtain such information. [See Briefing Book 5, Tab G, and the article by Gil Whittemore contained in Briefing Book 4, Tab E-2.] The Committee was considering a recommendation from the Nuclear Energy for the Propulsion of Aircraft (NEPA) Medical Advisory Committee to conduct human experiments on prisoners, patients, and healthy volunteers. Robert Stone, who wrote the NEPA recommendation, suggested that certain data could be obtained from patients at a large center such as Memorial Hospital in New York suffering from "carcinomas (you can't pick lymphomas, but carcinomous types of metastases) [who] live in varied states of health from a period of six to eight months and x-ray therapy was indicated in epilating measures." [Committee on Medical Sciences, Transcript of Meeting held on May 23, 1950, at 10. The AEC's Division of Biology and Medicine had stated that "that human experimentation at the present time is not indicated, that it would have serious repercussions from a public relations standpoint, particularly if undertaken by an agency that has to do a portion of its work in secret; and finally that adequate data can be obtained from animal experimentation, from the Los Alamos accidents, from certain observations which have been made by clinical radiologists, and from the studies at Hiroshima and Nagasaki." Quoted in 1951 annual report of the Armed Forces Medical Policy Council (AFMPC).] The debate was apparently resolved by the conclusion that human experimentation should not proceed, at least in the context of NEPA. Upon this decision, the Air Force turned to medical centers that were treating patients with radiation. Accordingly, the Air Force contracted with the University of Texas and M.D. Anderson Hospital in Houston, TX to conduct performance tests on patients receiving TBI. The contract document notes the following: It is clear that before attempting to operate its proposed nuclear powered aircraft, the U.S. Air Force must evaluate its radiation hazards. There are no scientific data with which to assess these dangers of the NEPA aircraft in terms of their probable effects upon crew performance and well-being. The most direct approach to this information would be by human experiments in specifically designed radiation studies; however, for several important reasons, this has been forbidden by top military authority. Since the need is pressing, it would appear mandatory to take advantage of investigation opportunities that exist in certain radiology centers by conducting special examinations and measures of patients who are undergoing radiation treatment for disease. While the flexibility of experimental design in a radiological clinic will necessarily be limited, the information that may be gained from studies of patients is considered potentially invaluable; furthermore, this is currently the sole source of human data. [ US Air Force, School of Aviation Medicine, SAM-3J, "Negotiation of Cost Reimbursement Contract, Project Specifications, Requirement and Justification" (May 16, 1950). In 1960, the Air Force contracted with the UCLA Medical School "To Study in Man the Effect of 250 to 300 r Total-Body Irradiation," and helped pay for the purchase of a linear accelerator to conduct the study. DASA Semiannual Progress Summary, Oct. 1, 1962, at 217 [HRE-111]. However, according to a retired UCLA Medical School professor who was in the radiology department at that time, the study never materialized because they never received any patients who warranted treatment with such high doses. He recalled that the Air Force eventually asked that its payment for the linear accelerator be refunded.] The Army followed suit shortly thereafter by contracting with Baylor University in 1953 for research on a biological radiation dosimeter and the effects of radiation based on data from patients receiving TBI. A similar contract with the Sloan-Kettering Institute for Cancer Research began in 1954, followed by a contract with the University of Cincinnati that began in 1960. A 1959 "Weekly Bulletin" from the Defense Atomic Support Agency (DASA) states: "It is hoped to make this work [by Sloan-Kettering] as well as the work of Baylor University College of Medicine and University of Cincinnati a complete program to provide us with answers on the human whole body radiation effects."[DASA document FCC/AG 319.14 (Nov. 16, 1959), at 2. [DOD/HRE-215]] Also in 1959, the Navy began doing TBI research at the Naval Hospital in Bethesda. Staff has little information on the extent to which the DOD reviewed these contracts in the context of other TBI work being done at the time in order to assess the efficacy of the underlying medical therapy, aside from what was presented in the proposals. One reviewer of the Cincinnati proposal noted that there are "so few radiobiologists in the country willing to do total body radiation that those that are should be encouraged." For this reason, he supported the proposal even though he had "very little hope that [this study] will result in practical data. As is pointed out in the proposal, a number of people have looked at the problem and the levels vary widely and there appears to be no consistency. A great deal of work has been done in animals, again without consistent findings." Rather, he hoped that the doctor "will soon decide that some other phase of the radiation program should be investigated and switch to this."[ Lt. Col. James B. Hartgering, Nov. 7, 1958.] THE USE OF TBI FOR "RADIORESISTANT" TUMORS Memorial Hospital (New York, NY): 1931-44 In 1942, Drs. Medinger and Craver reported treatment by total-body irradiation of 235 patients with "lymphomatoid" diseases and 35 patients with advanced carcinoma or sarcoma with generalized metastases (including 13 breast, 5 lung, 4 generalized melanoma, 3 teratoma of the testis, 2 prostate) at Memorial Hospital in New York. [Fred G. Medinger & Lloyd F. Craver, "Total Body Irradiation, with review of cases," Am. J. Roent., Vol. 48, at 651-671. This work was done with kilovoltage units before the advent of cobalt-60 and linear accelerator machines. All other TBI discussed in this report were generally done with a cobalt-60 machine, unless otherwise specified. ] Most of those in the miscellaneous group of 35 were treated when the radiation method was first being evaluated (1931-33). In contrast to the patients with lymphomatoid tumors who responded favorably to TBI, they noted that "[e]xcept for transient relief of pain in a few cases, the results in [the 35] generalized carcinoma cases were discouraging. The reason for this is quickly apparent. Carcinomas are much more radioresistant than the lymphomatoid tumors, and by total body irradiation the dose cannot be nearly large enough to alter these tumors appreciably." The authors expressed the concern that "a cancer-lethal dose of the material [discussing radioactive phosphorous as well at TBI] will produce deleterious reactions in the bone marrow and general metabolism which may prove lethal to the patient." [Id. at 668.] The article did not discuss the treatment doses for this group of patients; nor does it make any reference to the source of funding or informed consent. From 1942-44, Dr. Craver performed TBI on eight patients with radioresistant metastatic cancers in an experiment done for the Manhattan Project. Craver's report on this second 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."[ L.F. Craver, "Tolerance to Whole-Body Irradiation of Patients with Advanced Cancer," 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), at 486.] The study concluded that because there appeared to be "no ill effects other than those apparently caused by the progress of the disease, such doses of radiation should be well tolerated by healthy persons."[Id. at 498.] University of California Hospital (San Francisco, CA): 1942-46 From 1942-46, the University of California Hospital treated 29 patients with TBI as part of an experiment done for the Manhattan Project 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.[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 338-418.] The patients, who were considered "hematologically normal," were treated with total dosages ranging from 100 to 300 r between October 1942 to June 1946. Apparently, some of these patients suffered only from severe rheumatoid arthritis. [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." See Briefing Book 5, Tab H.] The report notes that the patients were selected by doctors who had no connection with the Manhattan Project. [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."[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," although no written consent was required or obtained. [Stone letter of Nov. 4, 1948, at 2.] Chicago Tumor Clinic (Chicago, IL): 1943-44 From 1943-44, the Chicago Tumor Clinic performed TBI on 14 persons in a study done for the Manhattan Project. [See J.J. Nickson, "Blood Changes in Human Beings Following Total-Body Irradiation," in Industrial Medicine, at 308-37. Dr. Nickson was the principal investigator of the Sloan-Kettering study described below.] Unlike the previous two, it was designed solely as a scientific experiment without treatment aims, and included the use of healthy volunteers 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. [Id. at 309. The irradiation of healthy persons for whom there was no prospect of therapeutic treatment appears unprecedented in any known TBI study.] The report notes that because there were no known treatments for the people in groups 1 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." [Id. at 309.] When no effect on the blood was observed in group 1 at 60 r, the dose was doubled; still no effect was found. [Id. at 335.] The "normals" were each subjected to three doses of 7 r. [The "tolerance dose" limit at that time was 36 r. See Briefing Book V, Tab M.] M.D. Anderson Hospital (Houston, TX): 1951-56 From 1951-1956, Drs. Miller, Fletcher, and Gerstner administered TBI to 263 cancer patients at M.D. Anderson Hospital in a study that was supported by the Air Force. [The results were published both as an Air Force School of Aviation Medicine (SAM) report -- Lowell S. Miller, Gilbert H. Fletcher, and Herbert B. Gerstner, "Systemic and Clinical Effects Induced in 263 Cancer Patients by Whole Body X-Irradiation with Nominal Air Doses of 15 to 200 R," No. 57-92, USAF, SAM (May 1957) ["SAM Report"] -- and in the literature -- "Radiobiologic Observations on Cancer Patients Treated with Whole-Body X-Irradiation," Radiation Research, Vol. 4, at 150-65 (1958). This memo will quote from the SAM Report. Unlike TBI research done for the Army by Baylor, Memorial Sloan- Kettering, and University of Cincinnati, M.D. Anderson does not appear to have submitted on-going progress reports to the Air Force. Accordingly, the only record of this study is from the subsequent SAM reports and the public literature.] The Air Force contracted with M.D. Anderson in order to determine whether exposure to total-body irradiation from a nuclear powered aircraft engine, as part of the NEPA program, would affect the flying capabilities of pilots. Accordingly, in addition to the TBI treatment, a number of patients were given a series of psychomotor tests to perform before and after receiving specified doses of TBI. These patients participated "by their own consent and judgment of the hospital staff." [Col. Robert B. Payne, "Effects of Acute Radiation Exposure on Human Performance," Review 3-63, USAF School of Aerospace Medicine, Aerospace Medical Division, Feb. 1963, at 10.] The SAM Report describes the Phase I effort to determine toxicity of TBI, which started with relatively low doses (reported as air doses in roentgens) of 15 to 75 r and then explored doses from 100 to 200 r. Finally, 30 patients, who had a variety of advanced diseases (mostly carcinomas) with no possible cure, were exposed to 200 r. [SAM Report, at 2 ("All patients showed such an advanced state of disease [accompanying photos show widely disseminated tumors] that cure by conventional means was regarded as completely hopeless." The report also states that "[a]t the time of irradiation, these patients were still able to walk and perform light physical tasks."). See page 4 for a list of diseases.] With respect to consent, the authors noted that the patients "knew about the advanced state of their disease and the experimental nature and possible risks of the proposed radiotherapy." [SAM Report, at 2.] No information is available on what types of risks were understood and described by the researchers, and there is no record of written consent. The M.D. Anderson researchers reported their findings only on the final group of 30 patients. Of these 30, 13 died within two months (nine of those died within one month). The mean survival time was 4.4 months, and all died within 20 months. The authors compared 12 lung cancer patients with two other studies, one that involved local radiotherapy and reported a life expectancy of 5 months and one that went untreated resulting in a mean survival time of 3.1 months. Based on this analysis, the paper concluded that "200-r whole-body x-irradiation either did not affect at all the life span of the patients, or might have caused a slight prolongation."[SAM Report, at 16.] Their analysis of hematologic effects concluded that "200-r whole-body x-irradiation seemed to increase the bleeding tendency in some of the patients, however, it did not cause alarming accidents." They also reported that infection caused complications in only one patient. [SAM Report, at 15.] As to short term effects, they reported that "anorexia, nausea, and vomiting only occasionally reached such a degree as to compromise satisfactory nutrition of the patients." [SAM Report, at 6.] The M.D. Anderson researchers noted in their report that their paper deals only with "those aspects of the problem which are of general radiobiological interest; a strictly clinicotherapeutic evaluation will be given elsewhere." [SAM Report, at 1. It is not known if such a therapeutic evaluation was ever completed, and none has been located to date.] However, the M.D. Anderson researchers did note that TBI had an overall effect on the disease in only three of the 30 cases -- "200 r whole-body x-irradiation produced a definite transitory amelioration of the disease in 3 cases, and a questionable improvement in several additional patients." [SAM Report, at 7. The report states that 30 percent claimed subjective improvement, but that this was possibly due to psychological rather than clinical factors. Id.] They concluded their Phase I analysis of therapeutic TBI by noting that "the threshold dose, beyond which in a small percentage of patients severe complications begin to appear, lies somewhere between 150 and 200 r." [SAM Report, at 20. They cautioned, however, that the condition of terminally ill patients may increase their sensitivity to both acute and longer term radiation symptoms. Id.] Baylor University (Houston, TX): 1954-63 From 1954-1963, Baylor University College of Medicine performed TBI on 112 patients under a contract with the Department of the Army for research on a biological dosimeter and on the acute effects of radiation. [The original contract was for a "Study of the Effects of Total and Partial Body Radiation on Iron Metabolism and Hematopoiesis"; by the end it was to study "The Effect of Total Body Irradiation on Immunologic Tolerance of Bone Marrow and Homografts of Other Living Tissue." Armed Forces Special Weapons Project (AFSWP) contract no. DA-49-007-MD-428; DASA contract DA-49-146-XZ-032. (The Committee has twelve reports.)] (For the first two years, a 250 kilovolt (KV) unit was used; in 1956, that was replaced with a 2 megavolt (MeV) Van de Graff machine.) In 1957, the principal investigators, Drs. Collins and Loeffler, published preliminary findings of their research to that date. This article, which was based on five cases of 150-200 r TBI on patients with radiosensitive cancers (lymphoma, chronic myelogenous leukemia, and multiple myeloma), concluded that single dose TBI has "therapeutic possibilities." But it cautioned that such treatment is not offered "with intent to cure. Even increased survival as a result of therapy is difficult to confirm. Under these circumstances the principal benefit of treatment is early relief of signs and symptoms," with TBI considered to cause less side effects than the chemotherapy in use at that time. [Vincent P. Collins and R. Kenneth Loeffler, "The Therapeutic Use of Single Doses of Total Body Radiation," Am. J. Roent., Vol. 75, at 546 (1956).] A 1962 DASA progress report states that despite its demonstrated advantages, TBI has not been widely used "because the therapeutic armamentarium for advanced cancer has been saturated with an ever-increasing number of chemotherapeutic agents made available through the therapeutic trials program." [Baylor DASA Report, Feb. 1, 1961 - Jan. 31, 1962, at 1.] In their 1964 DASA final report, the Baylor researchers reported that 71 of the patients received single doses between 25 and 250 r (the remaining received protracted doses over several days). Of those 71, 31 received doses of 150 or more r (7 at 150, 22 at 200, 1 each at 215 and 250). Among all 112 patients, there were 30 different cancers -- 54 had radioresistant cancers (e.g., lung, testicular, breast, G.I. tract, liver, kidney, prostate); the remaining had radiosensitive (leukemia, lymphosarcoma, Hodgkin's, multiple myeloma, Ewing's sarcoma). 47 patients died within 3 months, and an additional 21 within six months. The 1964 Baylor Final Report states that the majority of patients who received TBI were those who either failed to respond or were refused chemotherapy because of anemia and poor general condition. The report also notes the problems with giving "last-resort" treatment: When patients are referred as a "last resort," the radiotherapist does not wish to withhold treatment that may offer possible benefit but he cannot be certain that the benefit will outweigh the risk The risk is not that the patient will die but that the undesirable effects of radiation [i.e., bone marrow suppression] will appear more severe in the terminal cancer patient and that the time of death may be destined to coincide with the undesirable effects of radiation. Supportive treatment, even though it may not influence the course of the disease, must be included in the plan of treatment for such patients. . . . Although 68 patients died within 6 months following therapeutic total body irradiation, many of these experienced temporary remission and contributed valuable information to the study. [Baylor DASA Report, Feb. 1, 1963 - Jan. 31, 1964, at 7-8 [Baylor Final Report].] The report went on to discuss research that was done to counter the problem of bone marrow depression. "Following single exposures of therapeutic total body irradiation, the time of greatest depression occurs 25 to 30 days post treatment. Thus, if calculations are correct and bone marrow replacement is an effective treatment, severe bone marrow depression might be avoided if transplantation is carried out prior to the 10th day post irradiation." [Baylor DASA Final Report, at 16-17.] A chart predicting the effect of TBI at various air doses on healthy persons suggested that 100r would cause a 25% drop in blood count and 200r would cause a 50% drop [Baylor DASA Final Report, at 40.]; an earlier report stated that "age of patient does influence the recovery of leucocyte count following radiation." [Baylor DASA Report, Feb. 1, 1956 - Sept. 1, 1957, at 3. Presumably, the health of a person would also have an influence.] In evaluating the acute symptoms, the Baylor Final Report noted that "for levels up to 200r in single or protracted exposures, radiation sickness may be avoided by proper management." It also suggested that nausea and/or vomiting for some patients may have been caused by the power of suggestion. [Baylor DASA Final Report, at 5-6.] Sloan-Kettering Institute for Cancer Research (Memorial Hospital) (New York, NY): 1954-61 From 1954-61, Dr. James J. Nickson of the Sloan-Kettering Institute for Cancer Research performed TBI on over 20 patients as part of study for the Department of Defense on "Post-Irradiation Syndrome in Humans." [U.S. Army contracts DA-49-007-MD-533 and DA-49-007-MD-669; AFSWP contract no. DA-49-146-XZ-037. Because the Committee has not received all of the progress reports on this study, the total number of patients cannot be determined.] This study does not appear to have been reported on in the medical literature, nor is a final report available summarizing the complete study. The various annual reports indicate that dose rates ranged from 20-150 r, with the higher doses usually fractionated. Participants were excluded from the study if they showed signs of renal or hepatic dysfunction, bone marrow impairment, or had received x-ray therapy or chemotherapy in the previous six weeks; an effort was also made to find patients in generally good condition with "no complaints referable to their disease process." [Sloan-Kettering AFSWP Reports, Apr. 1, 1954 - Mar. 31, 1955, at 2, and Apr. 1, 1955 - Mar. 31, 1956, at 3.] It is not possible to determine whether and to what extent these patients were a subset of a greater number of patients who were treated with TBI. Early in the study, the researchers warned that [p]revious radiation insult to the bone marrow, even in the presence of a normal hematological picture, is a real hazard to the individual exposed to total body radiation. . . . This danger cannot be too strongly emphasized since we have no objective criterion to date by means of which we can predict the degree of hematological response in patients who have received previous irradiation. [Sloan-Kettering AFSWP Report, Apr. 1, 1954 - Mar. 31, 1955, at 4-5. The report went on to assess the importance of this concern "in the military setting," stating that persons who have received one exposure in the range of 100 r should not be re-exposed within at least 6-8 weeks." Id. at 16. See also History of the Armed Forces Special Weapons Project (AFSWP), 1955-58 [HRE-0836], ch. 7.4, at 34-35 ("Research at the Sloan-Kettering Institute showed that a second dose of ionizing radiation in humans provoked a much more severe response than a first dose of comparable amount. . . . This fact was of considerable importance to the military.").] There is no record regarding consent. Naval Medical Research Institute: 1959-60 Over a two-year period, the Navy employed total-body irradiation on 17 patients as a form of treatment for advanced cancer on a variety of radioresistant and radiosensitive disorders, to evaluate the use of bone marrow transplants, and to study the postradiation clinical effects. [Capt. E. Richard King, "Use of Total-Body Radiation in the Treatment of Far Advanced Malignancies," J.A.M.A., Vol 177, at 86-89 (Sept. 2, 1961). (The Navy has not been able to locate any additional records on this study.) ] This study included efforts to identify a reliable biological radiation dosimeter. [Ralph R. Cavalieri, Milton Van Metre, F.W. Chambers, & R. Richard King, "Taurine Excretion in Humans Treated by Total-Body Radiation," J. Nuc. Med. Vol. 1, at 186 (1960). A 1962 report from the Navy Bureau of Medicine and Surgery proposes to continue the biological dosimeter project through 1967 by collecting "daily urine specimens from patients exposed to total body irradiation for therapeutic purposes." Doc. WEB-03.087 (June 1, 1962).] Eleven patients received single doses, and six were treated with multiple doses. [In an effort encourage uniformity and consistency in measuring doses, King reported only the "air dose," which ranged from 150 to 900 r; one patient received 1500 r air dose in preparation for a kidney transplant. Of the first eleven, four had acute leukemia, one Ewing's sarcoma, one neuroblastoma, one undifferentiated sarcoma, one metastatic embryonal cell carcinoma of testis, two metastatic or inoperable bronchogenic carcinoma, and one person without a kidney. The diseases of the remaining six were reticulum cell carcinoma, lymphosarcoma, mesothelioma, wilm's tumor, Hodgkin's, and acute leukemia.] The report concluded that "[t]otal-body radiation therapy in a dose range of 100-400 r [air dose] appears to offer relatively safe and reasonably effective palliative therapy for advanced radiosensitive disease. . . . Good palliative responses were achieved by 6 patients with small repeated doses. The results of 11 patients treated with a single dose varied." [King, "Use of Total-Body Radiation," at 89.] City of Hope Medical Center (Duarte, CA), 1960-64 Researchers at the City of Hope Medical Center used TBI on 52 patients. [Melville, L. Jacobs & Fred J. Marasso, "A Four-Year Experience with Total-Body Irradiation," Radiology, vol. 84, at 452-56 (Mar. 1965).] Thirty -six had radiosensitive diseases (chronic leukemia, acute leukemia, lymphoma, polycythemia vera) and the remaining 16 had far-advanced widely disseminated cancers, with life expectancies of less than one month. This latter group of 16 received doses ranging from 170 to 800 rads (four received marrow transplants); eleven died within one month, two within two months, and one each in four and nine months. Due to a concern about possible nausea and vomiting, all patients who received 40 or more rads were given anti-nauseant medications within one hour prior to being irradiated; twelve patients still suffered some symptoms. The researchers concluded that "total-body irradiation has some usefulness, but it is limited. A more complete evaluation would seem indicted, and this study will be continued." [Id. at 456. The 1972 Ad Hoc Review Committee of the University of Cincinnati (Suskind Report) commented that "[t]he statement in this paper suggesting the need for further evaluation of this form of treatment refers most probably to the radiosensitive, widespread neoplasms rather than the results in the 16 patients with radioresistant cancers." (P. 11.)] The article makes no mention of military, or any other government, funding for this study, nor does it discuss consent. [In response to a request from the Advisory Committee, City of Hope Hospital is currently searching for records on these activities.] Oak Ridge Institute of Nuclear Studies (Oak Ridge, TN): 1958-74 From 1957 to 1974, the Oak Ridge Institute of Nuclear Studies (ORINS), which became the Oak Ridge Associated Universities (ORAU) in 1966, treated 194 patients with TBI in the course of research for the Atomic Energy Commission and the National Aeronautics and Space Administration (NASA). All of these patients had radiosensitive diseases. This program is being investigated by the staff as part of the institutional case study and a more detailed report will be made later. In 1966, the AEC's Medical Program Review Committee reviewed ORAU's TBI program. It recommended that ORAU use TBI to "compare the results of treatment by these modalities of a variety of neoplastic diseases to the results of treatment with chemotherapy. It would be very useful see what the effect of this type of therapy is compared to chemotherapy for a variety of other solid tumors such as carcinoma of the breast, carcinoma of the gastroenteric tract, the urogenital tract, etc., as well as for lymphomas." [Reprinted in 1981 Gore Hearing, at 249.] The staff of the Medical Division of ORAU responded that they had carefully considered treating such diseases, but had declined to do so "because we believe there is so little chance of benefit to make it questionable ethically to treat them. Lesions that require moderate or high doses of local therapy for benefit, or that are actually resistant (gastroenteric tract) are not helped enough by total body radiation to justify the bone marrow depression that is induced." The ORAU staff went on to note that "[o]f course, in one way these patients would make good subjects for research because their hematologic responses are more nearly like those of normals than are the responses of patients with hematologic disorders." [Reprinted in 1981 Gore Hearing, at 252.] University of Cincinnati (Cincinnati, OH): 1960-71 From 1960-71, Dr. Eugene L. Saenger and a team of medical researchers from the University of Cincinnati (UC) (referred collectively as the UC doctors [Over the course of the eleven year DOD study, a total of ten researchers participated in the project and contributed to the DASA reports: Eugene L. Saenger, M.D.; Ben L. Friedman, M.D.; James G. Kereiakes, Ph.D.; Harold Perry, M.D.; Harry Horwitz, M.D.; Bernard S. Aron, M.D.; I-Wen Chen, Ph.D.; Carolyn Winget, M.A.; and Goldine C. Gleser, Ph.D. Dr. Saenger was the principal investigator of the study, but not the attending physician or the administering radiologist for any of the patients.]) conducted total- body irradiation and partial-body irradiation (PBI) on 88 cancer patients at the then university affiliated Cincinnati General Hospital. Partial funding for this research was provided by the Department of Defense. The University of Cincinnati experiments first came to public attention in the summer of 1971 through references in a book by Roger Rapoport entitled The Great American Bomb Machine. Subsequent reports led to a story in the Washington Post on October 8, 1971, which quoted Dr. Saenger in defense of the program and Dr. Seymour Hopfam, a radiologist who specialized in the treatment of cancer patients at Memorial Sloan-Kettering, as saying that "nobody to my knowledge is using this (whole body radiation) as a therapeutic treatment. It approaches what happens in an atomic accident." [Stuart Auerbach & Thomas O'Toole, "Pentagon Has Contract to Test Radiation Effects in Humans," Wash. Post, Oct. 8, 1971, at A1.] That story prompted the University of Cincinnati to hold a news conference three days later to explain the program. The New York Times covered the briefing and reported that Senator Edward Kennedy had threatened to investigate the program through his Senate Health Subcommittee. ["Medical Center in Cincinnati Defends Whole-Body Radiation in Cancer Care," N.Y. Times, Oct. 12, 1971, at 24.] As a result of this controversy, the President of the University of Cincinnati refused to renew the DASA contract in the spring of 1972. No further patients were treated after that time, and the study was ended. As a result of this attention, three reviews of the UC experiments reported their findings in January 1972 -- 1) the January 3, 1972 American College of Radiology report in response to a request by Senator Mike Gravel (ACR Report); 2) the January 1972 Ad Hoc Review Committee of the University of Cincinnati Report to the Dean of the College of Medicine on "The Whole Body Radiation Study at the University of Cincinnati" (Suskind Report); and 3) the January 25, 1972 "Report to the Campus Community" of the Junior Faculty Association of the University of Cincinnati (JFA Report). [All three reports are found at Attachment 2. Martha Stephens, an English Professor at UC and the principal author of the JFA Report, has maintained a continuing interest in this issue and has provided the Committee additional information, including "An annotated record of certain short survivors of the U.C. radiation experiments" (Sept. 7, 1994) (Attachment 3). An attachment to the JFA report by the JFA Vice-President states: "The JFA has not had an opportunity to read and to vote on the report as currently worded. The JFA has not authorized in principle a report with the type of conclusions or judgments included in this report." When asked about this, Martha Stephens explained that the JFA "had a meeting after Christmas where I described my findings in considerable detail. I had my document that I read from that day. And it matched almost exactly what came out in the final report. And we voted to release these findings. We didn't vote on the final version, the exact wording of the final version, we didn't take back to the group. It differed hardly at all. That was [the JFA Vice-President's] pretext for saying the group didn't agree on this. Of course, it wouldn't have mattered if it had been the work of one person or 100. If it's accurate, it's accurate." 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Two of the three patients who received 150 rads TBI died in 32 and 30 days. Eight patients were irradiated between the 1967 and 1969 infusion attempts -- one with 200 rads TBI (for Ewing's Sarcoma), one with 150 rads and four with 100 rads TBI, one with 200 rads PBI, and one with 300 rads PBI and 100 rads TBI. The patient who received 150 rads died in seven days; three of the four patients with 100 rads died in 92, 24, and 20 days; and the patient who received 200 PBI died in 16 days. The first successful marrow infusion occurred at the next attempt in March 1969, after which subsequent marrow infusions were generally successful. At this time, all patients receiving 150 or more rads TBI were given autologous infusions. Of these eight patients, one died in six days following a stroke, one who received 230 rads had an unsuccessful marrow infusion, and one who received 200 rads with a "doubtful" take died in 89 days. Nine additional patients received 150 to 300 rads PBI, and four received 100 rads TBI. [See Table at Attachment 5 for results.] Institutional Review The University of Cincinnati established an institutional review board, known as the University of Cincinnati Faculty Committee on Research (FCR), in 1964. In March 1966, Drs. Eugene L. Saenger and Ben L. Friedman submitted a protocol entitled "Protection of Humans with Stored Autologous Marrow" to the FCR; this proposal was as an adjunct to the TBI study, which was still on-going and not itself the subject of review. (Dr. Saenger informed staff that he did not believe that he was required to submit this proposal to the FCR, but elected to do so on his own. [Saenger Interview, Oct. 20, 1994.]) The FCR, which consisted of eleven doctors at that time, raised a number of concerns, including whether the patients are advised that "no specific benefit will derive to him," the need for a more detailed description of the potential hazards, and whether the irradiation would "influence the morbidity or the mortality in these patients?" [Letter dated May 6, 1966 from Dr. Edward A. Gall, FCR Chairman, to Dr. Clifford G. Grulee, Dean of the College of Medicine. The review correspondence is attached at Attachment 7. Dr. Harvey Knowles approved the 1966 protocol on April 27, 1966.] The proposal was revised and resubmitted on March 1967 under the title "The Therapeutic Effect of Total Body Irradiation Followed by Infusion of Stored Autologous Marrow in Humans." A five person FCR subcommittee reviewed the proposal. Dr. George Shields recommended that the study be disapproved because "the radiation proposed has been documented in the author's own series to cause a 25% mortality. . . . I believe a 25% mortality is too high, (25% of 36 patients is 9 deaths) but this is of course merely an opinion." [Letter from Dr. George Shields to Dr. Edward A. Gall, Mar. 13, 1967. Shields also indicated that he was withdrawing from the subcommittee "for reasons of close professional and personal contact with the investigators and with some of the laboratory phases of this project." Shields added that if the study is approved, then his concern could be addressed by informed consent -- i.e., if "all patients are informed that a 1 in 4 chance of death within a few weeks due to treatment exists, etc."] Dr. Thomas E. Gaffney initially recommended disapproval for several reasons, including the "considerable morbidity associated with this high dose radiation." [Letter from Thomas E. Gaffney to Edward A. Gall, Apr. 17, 1967. A subsequent letter dated May 18, 1967 indicates approval subject to a proviso.] Drs. Harvey Knowles and Edward Radford, and R.L. Witt recommended approval with a number of provisos. The proposal was given "provisional approval" on May 23, 1967 based on a number of requirements, including "a delineation of the danger inherent in the method and the steps intended to protect the patient." [Letter from Dean Clifford Grulee to Dr. Ben L. Friedman, May 23, 1967. The review correspondence is attached at Attachment 7. Staff does not have records on whether the FCR reviewed and approved the consent form. See pp. 27-29 for further discussion of this review process as it relates to informed consent.] There is no indication that the FCR actually reviewed and approved the consent forms in light of this review. In 1970, the FCR re-reviewed the bone marrow protocol due to its 1967 provisional approval. Following a number of revisions based on numerous concerns, the protocol was approved in July 1971. In April 1972, Dr. Edward Silberstein submitted a protocol to the FCR entitled "Evaluation of the therapeutic effectiveness of total and partial body irradiation as compared to chemotherapy in humans with carcinoma of the lung and colon." [See Attachment 7 for correspondence. ] This was to be a Phase III study of the ongoing TBI work, for which an NIH grant was also contemplated. The UC President had refused to renew DOD funding that same month following public attention to the study. Patient treatment was suspended pending FCR review. The protocol was approved in August 1972 as a grant application to the National Cancer Institute. In February 1973, the NIH elected not to fund the proposal. Survival/Mortality In 1994 Dr. Saenger wrote: It is important to realize that in any given patient it is not possible to determine objectively whether death occurred too soon or was prolonged as a consequence of treatment. The only way that an estimate can be made is to compare the length of survival of a group of patients with the same tumor and extent of tumor treated by radiation to a group of patients with the same tumor and extent of tumor treated by different methods. [Memo of E.L. Saenger, M.D., dated Oct. 20, 1994 on "How can the Quality of Life and the Length of Life of a Cancer Patient be Determined?" (Attachment 4);] The Cincinnati doctors' 1973 article attempts such a comparison. It reported that the median survival time for the three cancers for which there was a statistically large enough group -- colon, cancer, breast -- was longer than comparable groups receiving no treatment, and almost as long as for patient groups receiving chemotherapy. (Survival time was based on date of diagnosis, not date of irradiation, so as to compare with other published studies.) [Radiotherapy for Advanced Cancer, at 672-76.] The article also compares the survival rates of 82 [The remaining six patients were still living at that time. TBI and PBI treated patients with the 24 patients who were accepted into the study group but then not treated because they were considered too weak to tolerate the radiation. [The Suskind Report (p. 26) states that of those 24, three patients elected another treatment, two refused treatment, and "in 19 patients either the pretreatment evaluation revealed a significant risk of radiation therapy (e.g., poor bone marrow reserve due to previous chemotherapy or radiation therapy), or advanced stage of malignancy, or treatment was not considered to be helpful."] Of the 24 untreated patients, four died within the 20-60 day time period (16%); of the 82 treated patients, 19 died within the same time frame (23%). [Radiotherapy for Advanced Cancer, at 678. The article states that "there is no difference between the 2 groups." A total of 25 of 88 patients died within the first 61 days (27%); 38 patients died within the first 95 days (43%).] (In addition, 11 of 32 patients who received 150 rads or more died within 20-61 days (34 %). [At total of 14 of 32 high dose patients died within the first 61 days (44%); 16 of 32 died within 91 days (50%).]) The article also identified "8 cases in which there is a possibility of the therapy contributing to mortality." [Radiotherapy of Advanced Cancer, at 677 (all eight had received localized radiation or chemotherapy before or after TBI). Dr. Saenger has reconsidered this analysis and now asserts that these deaths were due to the disease, not radiation. Saenger Interview, Sept. 15, 1994.] These eight were among 19 who died within 20-60 days; the remaining eleven "showed clear evidence of well functioning marrow with steady or rising white blood cell counts and absence of bleeding and infection at the time of death." [Radiotherapy of Advanced Cancer, at 678.] The 1972 ACR Report had also associated the death of eight patients to the fact that "the bone marrow function was subnormal and thus relatable to radiation syndrome." [ACR Report, at 8. The report also noted that "[i]t is not possible to determine positively that those patients who died within 60 days of the treatment would not have succumbed to their disease within that period, even though the clinical assessment had been that their disease was stable enough to justify their inclusion in the study." Autopsies were performed on only eight patients, so bone marrow biopsies were used for this evaluation.] Similarly, the Suskind Report stated that "19 died within 20-60 days and possibly could have died from radiation alone." [Suskind Report, at 65; it noted as well that in only eight (8) cases was the bone marrow found to be acellular or hypocellular near death or at autopsy." This report also stated that "[t]here is absolutely no evidence that whole body radiation shortened the period of survival of the treated patients," referring, apparently, to the statistical "survival rate" of the entire group of patients.] The Suskind Report also analyzed the design of the survival study, noting that "[i]t is uncertain whether this study and similar studies reported in the medical literature are truly comparable in all major factors that influence survival, such as selection of patients and ancillary medical management. Therefore, the significance of comparisons of survival rates is doubtful, unless marked differences are found. However, matched populations are not an essential element for a Phase II study in this type of illness." [Suskind Report, at 59.] As noted above, two reviewers on the 1967 UC FCR also expressed concerns about the mortality rate as of 1967. Study of Acute Effects The Cincinnati study included an effort to analyze acute effects of radiation exposure, such as nausea and vomiting. In order not to induce psychological reactions, information concerning these potential side effects was intentionally withheld from the patients for the first three days after irradiation. Explicit instructions not to inform the patients for this time period were put in their charts, and patients were kept segregated so as not to discuss their symptoms with one another. [This approach seems to follow upon the experience at Baylor, which complained of the subjective influence, and is in contrast with the City of Hope, which gave all patients medication in advance of irradiation. ] No mention was made of nausea or vomiting in the consent forms that were used beginning in 1965. Patients who experienced symptoms were given medication on request. [Saenger Interview, Sept. 15, 1994.] When asked whether information on these side effects would have been withheld in the absence of the DOD funding, Dr. Saenger replied in the first interview that it probably would not have been withheld, and in the second interview that it probably would still have been withheld. [Saenger Interview, Sept. 15, 1994 & Oct. 20, 1994.] The 1973 article also concluded that some palliation -- described as "relief of pain, decrease in tumor size, increase in activity, increase in well being (weight gain, appetite improvement, subjective statement by patient)" -- "was achieved in 51 per cent and that 31 per cent were made neither better nor worse." [Radiotherapy of Advance Cancer, at 679.] The Suskind Report states that by 1966 the design of the study to measure palliative effects was "unstructured and not uniformly applied, particularly as regards uniform definitions and methods of reporting." [Suskind Report, at 59.] Informed Consent According to the 1973 article, all patients gave informed consent in accordance with the UC Faculty Committee on Research and the National Institutes of Health. The use of written consent forms began in 1965, two years before they were required by the FCR and NIH; the form was revised twice thereafter. [The forms appear at Attachment 8.] There is no record that the DOD issued instructions or informed the University of Cincinnati about its policies relating to consent in the general context of human experimentation; Dr. Saenger has stated that he received no such information from the DOD. [Dr. Saenger stated that he was prompted to begin the use of written consent at this time when he received a letter from the DASA requiring all DOD components and contractors to obtain written consent for the use of "investigational drugs in any manner, including research programs." Saenger said he reasoned that there was little difference between drugs and radiation in this context and therefore applied the same standard. Saenger Interview, Sept. 15, 1994.] The first form, dated May 1, 1965, is entitled "Consent for Special Study and Treatment." It states that the "nature and purpose of this therapy, possible alternative methods of treatment, the risks involved, the possibility of complications, and prognosis have been fully explained to me. The special study and research nature of this treatment has been discussed with me and understood by me." [A second form went into effect at the same time for bone marrow aspiration and storage, and is basically the same as the above.] It is not known exactly what risks were described. [Because Dr. Saenger was not responsible for recruiting or treating patients, he could not speak to what was actually said to the patients. Staff has requested interviews with other physicians who had such contact. In 1981, Dr. Robert Heyssel, Director of Johns Hopkins Hospital, discussed the ethical climate prior to the mid-1960s: "I should say that in the climate of those times . . . that many things were done with human subjects, including the investigator himself, which would no longer be condoned. . . . None of these activities had to be reviewed by anyone else in any formal sense within the institutions. I think this was the situation probably up to and around 1966 in most institutions. I am not suggesting that that was the proper thing; I am simply saying that was the case. In terms of experimental therapeutics, I think an honest effort was made by most investigators to explain to families, to patients, that what was being done was in the range of the untried or experimental, but there were certainly no informed-consent rules that anyone was operating under during that period of time up to the midsixties." Gore Hearing, at 35-36.] As noted previously, there was intentionally no discussion of the acute effects of nausea and vomiting. A second consent form went into effect in 1967, following the 1967 FCR review of the bone marrow protocol discussed above. This form lists the risks as: "The chance of infection or mild bleeding to be treated with marrow transplant, drugs, or transfusion as needed." It also states that consent is for "a scientific investigation which is not directed specically [sic] to my own benefit, but in consideration for the expected advancement of medical knowledge, which may result for the benefit of mankind." There is no mention of the possible risk of death from bone marrow suppression. As noted above, Dr. Shields suggested in 1967 that the consent form should inform the patient of a 1 in 4 risk of death. The requirements of the provisional approval of the 1967 protocol did not explicitly require this type of notice, but only "the danger inherent in the method and the steps intended to protect the patient." Beginning in 1968, consent was solicited over a two-day time period. Dr. Saenger described this process: "Dr. Silberstein was the person who did all this, in that phase. He would explain to somebody the first day what the problems were, what was going to happen, what the risks were, etc. or what the benefits were. Then he had the patient and a representative come back the next day, the representative could have been the patient's mother or cousin, or some family person, or it could have been the patient's minister. And you go through the whole thing with the minister, and the patient and family were all happy with this desperate situation, and the signature was affixed." [Saenger Interview, Oct. 20, 1994.] In 1971, a third form came into use, following the second FCR review of the bone marrow protocol. This form expanded on the previous form by explaining that "[t]he bone marrow's ability to make [white] cells will be decreased for four or five weeks after you receive your radiation. If you receive a dose of radiation of 200 rads or more, which your doctor will tell you, your blood counts will fall to levels where infection or bleeding could be a problem." It also refined the previous form by stating it is "a scientific investigation which is not only directed specifically to my own benefit, but also in consideration for the expected advancement of medical knowledge, which may result for the benefit of mankind." Patients were generally not informed about the source of the funding. The Suskind Report added that "[t]his information was not withheld if the patient asked about this matter. The procedure follows the custom of every other research project in this University." [Suskind Report, at 50.] The ACR Report states that "[i]n the last few years they were told that the information might have military as well as clinical significance." [ACR Report, at 7.] Family members of patients testified to the Committee that neither the patients or their families were fully informed about the nature of the radiation. Some told of consistent lack of communication from physicians regarding the purpose and procedure of the radiation treatments. This occurred despite multiple and persistent requests by family members to meet and discuss these concerns with the doctors involved in administering these treatments. Selection of Subjects All but five of the patients were referred into the study from either the wards of the Cincinnati General Hospital or from its Out-Patient Tumor Clinic. The remaining five were private patients, three of whom were children treated for Ewing's sarcoma. The Suskind Report notes that 51 of 82 patients were black (62%), most were indigent, and many had relatively low intelligent quotients. It states that "[t]his distribution reflects the patient population of the Cincinnati General Hospital." [Suskind Report at 28-29. It also notes approximately 2% of all patients (both in-and out-patient) at the Hospital were private patients. Id. at 29.] ATTACHMENTS Attachment 1 A List of Institutions Performing TBI from 1970-1974 Attachment 2 A Report to the Dean of the College of Medicine at the University of Cincinnati by the Ad Hoc Review Committee of the University of Cincinnati, January 1972 Attachment 3 A Report to the Honorable Mike Gravel by the American College of Radiology Attachment 4 "A Report to the Campus Community," by the Junior Faculty Association. Attachment 5 "An Annotated Record of Certain Short Survivors of the ..U.C. Radiation Experiments," by Martha Stephens, September 1994 Attachment 6 "How Can the Quality of Life and the Length of Life of a Cancer Patient be Determined?," by Eugene Saenger, October 1994 Attachment 7 A List of University of Cincinnati Tbi/Pbi Patients Delineating the Date, Dose, and Post-Radiation Survival Time for Each Patient Attachment 8 Table of Patients with Bone Marrow Transplants Attachment 9 Correspondence of UC Faculty Committee on Research Attachment 10 Copies of Written Consent Forms used by UC TBI Study