Conclusion

Chapter 8: Footnotes

2 . A list was published in the 1967 National Academy of Sciences report on "Radiobiological Effects of Manned Space Flight" and is 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 [Gore Hearing], 97th Cong., 1st Sess. (23 September 1981), 355. The Advisory Committee requested information from most of these institutions (except for those performing five or fewer procedures) on their use of TBI. Virtually all of them informed the Advisory Committee that they no longer have any records describing these activities, besides what has been published in the literature; some of the institutions have informed the staff orally that they did "nonexperimental” TBI treatments on patients with leukemia during the 1950s and therefore would have no protocols or review documents of that work.

3 . Three were conducted during the Manhattan Project years, and five between 1951 and 1971.

4 . Renamed the Oak Ridge Associated Universities (ORAU) in 1966.

5 . City of Hope Hospital in Duarte, California. Melville L. Jacobs and Fred J. Marasso, "A Four-Year Experience with Total-Body Irradiation," Radiology 84 (1965): 452-456 (using a cobalt 60 teletherapy unit).

6 . 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.

7 . J. T. Chaffey et al., "Total Body Irradiation in the Treatment of Lymphocytic Lymphoma," Cancer Treatment Report 61 (1977): 1149-1152; M. H. Lynch et al., "Phase II Study of Busulfan, Cyclophosphamide, and Fractionated Total Body Irradiation as a Preparatory Regimen for Allogeneic Bone Marrow Transplantation in Patients with Advanced Myeloid Malignancies," Bone Marrow Transplant 15, no. 1 (January 1995): 59-64 (This study combines chemotherapy with doses of 1,200 rad of TBI).

8 . R. A. Clift, C. D. Buckner, and F. R. Appelbaum, "Allogeneic Marrow Transplantation in Patients with Chronic Myeloid Leukemia in the Chronic Phase: A Randomized Trial of Two Irradiation Regimes," Blood 77 (1991): 1660.

9 . The methods of reporting radiation doses have changed over the years. Throughout the 1950s, researchers tended to report the dose in roentgens ("R" or "r"), which represented the amount of radiation emanating from the source; from the 1960s through the present, researchers reported the dose in rad (also known as centigrays), which represent the amount of radiation absorbed by the body. For x rays, the rem--for roentgen equivalent man--is equivalent to a rad. A given air dose (roentgen) of radiation is generally equivalent to a lesser body dose (rad). For example, 325 R (air dose) was reported in one experiment as approximately equivalent to 200 rad (body dose).

10 . Fred A. Mettler, Jr., and Arthur C. Upton, Medical Effects of Ionizing Radiation, 2d ed. (Philadelphia: W. B. Saunders Co., 1995), 41, 278 (table adapted from J. T. Conklin).

11 . One of the difficulties in reporting the chance of death at a given dose is a confusion between the use of air (or skin) dose as opposed to body (or midline tissue) dose (the former is generally significantly higher than the latter), and whether or not medical care is provided. Many investigators fail to indicate clearly what type of dose they are using. Mettler and Upton report that "[i]t is probable that with appropriate medical treatment, the LD50 [lethal dose for 50 percent of recipients] skin dose may be in the range of 6 Gy (600 rad) or an MTD [midline tissue dose] of 3.96 Gy (396 rad)." Mettler and Upton, Medical Effects of Ionizing Radiation, 278.

12 . Fred G. Medinger and Lloyd F. Craver, "Total Body Irradiation, with review of cases," American Journal of Roentgenology 48 (1942): 651, 668. The investigators used a 250-kilovolt (KV) machine and doses up to 450 R. The dose that would cause severe bone marrow damage and be potentially lethal was considered to be between 200 and 400 roentgens. This figure can vary depending on the length, frequency, and intensity of the dose; for example, a single dose of 200 R will generally cause more severe reactions than five doses of 40 R spaced over one or two weeks.

13 . J. J. Nickson, "Blood Changes in Human Beings Following Total-Body Irradiation," in Industrial Medicine on the Plutonium Project: Survey and Collected Papers, ed. Robert S. Stone (New York: McGraw-Hill Book Co., 1951), 337.

14 . B. V. A. Low-Beer and Robert S. Stone, "Hematological Studies on Patients Treated by Total-Body Exposure to X-ray," in Stone, Industrial Medicine, 338.

15 . Ibid.

16 . Ibid., 338-39.

17 . Alan Gregg, M.D., Chairman of the AEC Advisory Committee on Biology and Medicine, to Dr. Stone, 20 October 1948 ("The secrecy with which some of the work . . .") (ACHRE No. UCLA-111094-A-24), 1.

18 . Robert Stone, M.D., to Allen Gregg, M.D., Chairman of the AEC Advisory Committee on Biology and Medicine, 4 November 1948 ("The candor of your letter of October 20th . . .") (ACHRE No. UCLA-111094-A-25), 3.

19 . Medinger and Craver, "Total Body Irradiation," 668.

20 . L. F. Craver, "Tolerance to Whole-Body Irradiation of Patients with Advanced Cancer," in Stone, Industrial Medicine, 485.

21 . Ibid., 486.

22 . Ibid.

23 . See Nickson, "Blood Changes in Human Beings Following Total-Body Irradiation," in Stone, Industrial Medicine. After World War II, Dr. Nickson continued to engage in TBI research at Sloan-Kettering.

24 . Ibid., 309. "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." Ibid.

25 . Robert Stone, M.D., to Shields Warren, M.D., 6 October 1948 ("I have recently been shown a letter from Mr. Keller . . .") (ACHRE No. DOE-120994-A-27), 1.

26 . Ibid.

27 . The chief of the AEC’s Insurance Branch supported declassification: "It is conceivable that if it became a matter of common knowledge that experiments on human beings such as those described in this document were being carried on by the Commission it might result in some adverse publicity and perhaps encourage litigation. However, we feel that this objection is outweighed by the advantages to be gained by making this information available to technically trained personnel." Clyde E. Wilson, Chief of the AEC Insurance Branch, to Anthony Vallado, Deputy Declassification Officer, AEC Declassification Branch, 10 September 1948 ("Review of Document") (ACHRE No. DOE-120894-E-42).

28 . Gregg to Stone, 20 October 1948, 1.

29 . For example, M. Soden et al., "Lymphoid Irradiation in Intractable Rheumatoid Arthritis: Long-term Follow-up of Patients Treated with 750 rad or 2,000 rad, . . ." Arthritis and Rheumatism 15, no. 3 (May 1989): 577-582.

30 . Ibid.

31 . 31 . Stone to Gregg, 4 November 1948, 2.

32 . NEPA stood for Nuclear Energy for the Propulsion of Aircraft.

33 . Other participants included Robley Evans, Hymer Friedell, Robert Stone, Shields Warren, and Stafford Warren, all of whom were often called on for other radiation research advice in the late 1940s and 1950s by the AEC, the DOD, and other agencies. NEPA Advisory Committee on Radiation Tolerance of Military Personnel, proceedings of 3 April 1949 (ACHRE No. DOE-120994-B-1).

34 . In a subsequent paper, Stone cited Jenner's experiments with smallpox, Walter Reed's experiments with yellow fever, and World War II experiments with malaria on prisoners as examples. Robert S. Stone, paper of 31 January 1950 for the NEPA project ("Irradiation of Human Subjects as a Medical Experiment") (ACHRE No. NARA-070794-A-9). Stone also sought to justify the use of normal humans on national security grounds: "The information desired is sufficiently important to the safety of the U.S.," and the doses would be "relatively low in relation to the lethal doses." The "safety of the U.S." language was later dropped by the full committee. NEPA Advisory Committee, 3 April 1949, 43-48.

35 . Advisory Committee for Biology and Medicine, transcript (partial) of proceedings of 10 November 1950 (ACHRE No. DOE-012795-C-1), 6.

36 . Ibid., 29.

37 . ACBM, transcript of proceedings of 3 April 1949.

38 . Ibid., 39-40. Stone noted that "volunteering exists when a person is able to say Yes or No without fear of being punished or of being deprived of privileges due him in the ordinary course of events." Ibid., 39.

39 . Ibid., 40.

40 . Ibid., 42.

41 . Ibid., 41.

42 . NEPA Medical Advisory Committee, 5 January 1950 ("Radiation Biology Relative to Nuclear Energy Powered Aircraft") (ACHRE No. DOE-060295-C-1), 4.

43 . Robert S. Stone, 31 January 1950, 3. "The extremely small hazard of undetectable genetic effect, undetectable effect on the life span and possibly slight effect on the blood picture are the extremely small hazards that must be weighed against the value of having actual experience with exposure of humans." Ibid., 4.

44 . See Committee on the Biological Effects of Ionizing Radiation, National Research Council, Health Effects of Exposure to Low Levels of Ionizing Radiation: BEIR V (Washington, D.C.: National Academy Press, 1990), 168-169, 171-175, 242-253. See also Donald A. Pierce and Michael Vaeth, "Cancer Risk Estimation from the A-Bomb Survivors: Extrapolation to Low Doses, Use of Relative Risk Models and Other Uncertainties," in Low Dose Radiation: Biological Bases of Risk Assessment, eds. K. F. Baverstock and J. W. Stather (London: Taylor & Francis, 1989), 54, 58-59. The BEIR V leukemia model includes both a linear and quadratic term in dose, the latter dominating the risk above 90 rad. For a single exposure to 10 rad, the BEIR report gives an estimated excess relative risk of 15 percent (lifetime, averaging over ages at exposure). Extrapolating this figure linearly to 150 rad would produce an excess relative risk of 2.25, but when the quadratic term is included, the total relative risk becomes 7. This estimate is in perfect agreement with the observed and fitted risks among the atomic bomb survivors at 150 rad, as plotted by Pierce and Vaeth. For exposures at particular ages and expressed at particular follow-up times, the relative increase can be either larger or smaller than this figure.

45 . Ibid., 3-4.

46 . W. A. Selle, Secretary, NEPA Medical Advisory Committee, to Dr. Richard Meiling, Director, Medical Services Division, 22 March 1950 ("As indicated to you in person on March 8 . . .") (ACHRE No. NARA-070794-A-9).

47 . DOD Research and Development Board, Committee on Medical Sciences, proceedings of 23 May 1950 (ACHRE No. DOD-042994-A-15), 10.

48 . Marion W. Boyer, AEC General Manager, to Robert LeBaron, Chairman, Military Liaison Committee, 10 January 1951 ("As you know, one of the important problems that would confront us . . .") (ACHRE No. DOE-040395-B-1), 3-4.

49 . Participants were Alan Gregg (ACBM chairman), Dr. Austin Brues of the Argonne National Laboratory (operated by the University of Chicago), Dr. Simon Cantril of Swedish Hospital in Seattle, Dr. Andrew Dowdy (who had chaired the NEPA Medical Advisory Committee), Dr. Louis Hempelmann of Rochester, Dr. Robert Loeb of Columbia, Dr. Curt Stern of the ACBM, and Dr. Shields Warren of the DBM. Ibid.

50 . Mettler and Upton, Medical Effects of Ionizing Radiation, 278.

51 . Marion W. Boyer, AEC General Manager, to Robert LeBaron, Chairman, Military Liaison Committee, 10 January 1951 ("As you know, one of the important problems that would confront us . . .") (ACHRE No. DOE-040395-B-1), 3-4.

52 . Joseph Hamilton to Shields Warren, 28 November 1950 ("Unfortunately, it will not be possible . . .") (ACHRE No. IND-071395-A-9).

53 . Armed Forces Medical Policy Council to the Secretary of Defense, 30 June 1951 ("Annual Report") (ACHRE No. DOD-091694-A-1), 158.

54 . Interview of Colonel John Pickering by Dr. John Harbert and Gilbert Whittemore (ACHRE staff), transcription of audio recording, 2 November 1994

55 . Wilson F. Humphreys, Colonel, USMC, Assistant Chief of Staff, to Commanding Officers, 16 November 1959 ("DASA Base Commanders' Weekly Bulletin") (ACHRE No. DOD-082694-A-1), 2.

56 . At least four of the five DOD institutions used the new, high-energy radiation sources--cobalt 60 or megavoltage x rays. (The available data did not make clear what type of unit Sloan-Kettering used.)

57 . John A. Isherwood, Chief, Army Radiological Service, to Assistant Chief, U.S. Army Medical Research and Development Command, 22 October 1958 ("1. Recommend approval . . .") (ACHRE No. DOD-042994-A-16).

58 . Executive Panel of the NEPA Medical Advisory Committee, proceedings of 8 July 1949 (ACHRE No. DOD-042994-A-17), 77 (emphasis added).

59 . Carroll Wilson, AEC General Manager, to Robert Stone, 5 November 1947 ("Your Letter of September 18 . . . ") (ACHRE No. DOE-052295-A-1).

60 . P.L. 82-557, sec. 5, 66 Stat. 725 (16 July 1952).

61 . Max Brown to Vice Chancellor, University of Pittsburgh, 12 March 1957 ("This in reply . . .") (ACHRE No. NARA-012395-A-6).

62 . Department of Defense, Defense Atomic Support Agency, Contract DA-49-146-XZ-029 (contract with the University of Cincinnati), Modification no. 1, ASPR. no. 7-203.22, 28 February 1961 (ACHRE No. DOD-042994-A-23).

63 . Lieutenant Lando Haddock, USAF, 19 October 1950 ("Negotiation of Cost-Reimbursement") (ACHRE No. DOD-062194-B-3).

64 . The results were published in Lowell S. Miller, Gilbert H. Fletcher, and Herbert B. Gerstner, to the School of Aviation Medicine, report of May 1957 ("Systemic and Clinical Effects Induced in 263 Cancer Patients by Whole Body X-Irradiation with Nominal Air Doses of 15 to 200 R") (ACHRE No. DOD-102594-A-1); and Lowell S. Miller, Gilbert H. Fletcher, and Herbert Gerstner, "Radiobiologic Observations on Cancer Patients Treated with Whole-Body X-Irradiation," Radiation Research 4 (1958): 150-165.

65 . Miller, Fletcher, and Gerstner, "Systemic and Clinical Effects," 1. "Colonel McGraw stated that he thought that the cases studied were terminal cases. He was answered in the negative." Air Force Research Council, proceedings of 14 January 1954 (ACHRE No. DOD-092894-A-1), 7.

66 . Miller, Fletcher, and Gerstner, "Systemic and Clinical Effects," 2.

67 . Ibid. The report also states that "[a]t the time of irradiation, these patients were still able to walk and perform light physical tasks."

68 . Ibid.

69 . Attachment, Lester J. Peters, Division of Radiotherapy, M. D. Anderson Cancer Center, to Steve Klaidman (ACHRE), 22 December 1994 (ACHRE No. CORP-010995-A-1).

70 . School of Aviation Medicine (SAM) Research Council, proceedings of 14 January 1954 (ACHRE No. DOD-092894-A-1), 6-7.

71 . Ibid.

72 . Robert B. Payne to the School of Aviation Medicine, report of February 1963 ("Effects of Acute Radiation Exposure on Human Performance") (ACHRE No. DOD-121994-C-1), 10.

73 . One Air Force reviewer stressed that "the patients cannot be considered as normal people." SAM Research Council, proceedings of 14 January 1954, 6. Even the study investigator warned 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." Payne, "Effects of Acute Radiation," 12.

74 . SAM Research Council, proceedings of 14 January 1954, 7.

75 . SAM Research Council, proceedings of 29 August 1955 (ACHRE No. DOD-092894-A-2), 6.

76 . Miller, Fletcher, and Gerstner, "Systemic and Clinical Effects," 20. The researchers noted 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." Ibid., 1. It is not known if such a therapeutic evaluation was ever completed, and none has been located to date.

77 . Ibid., 7. The report states that 30 percent claimed subjective improvement, but that this was possibly due to psychological rather than clinical factors. Ibid.

78 . Ibid., 20. They cautioned, however, that the condition of terminally ill patients may increase their sensitivity to both acute and longer-term radiation symptoms. Ibid.

79 . SAM Research Council, proceedings of 14 January 1954, 7.

80 . Colonel Robert B. Payne, "Effects of Acute Radiation Exposure on Human Performance," Review 3-63, USAF School of Aerospace Medicine, Aerospace Medical Division, February 1963, 3.

81 . William C. Levin, Martin Schneider, and Herbert B. Gerstner, paper of 1960 for Air University, School of Aviation Medicine ("Initial Clinical Reaction to Therapeutic Whole-Body X-Irradiation") (ACHRE No. DOD-072794-B-18).

82 . The original contract was for a "Study of the Effects of Total and Partial Body Radiation on Iron Metabolism and Hematopoiesis"; it was later known as "The Effect of Total Body Irradiation on Immunologic Tolerance of Bone Marrow and Homografts of Other Living Tissue." (The Advisory Committee has eight progress reports.) At least three of the patients had arthritis. Baylor University College of Medicine to the Armed Forces Special Weapons Project (AFSWP), report of 1 January 1954 (ACHRE No. BAY-101794-A-1). This condition was not among the diseases listed as having been treated in the Baylor University College of Medicine to Defense Atomic Support Agency (DASA), report of 1 February 1963-31 January 1964 (ACHRE No. BAY-101794-A-2), 6.

83 . The "fundamental problem has been to define effect of irradiation and quantitate effect with amount of radiation exposure." Baylor University College of Medicine to DASA, report of 1 February 1963-31 January 1964, 1. Collins and Loeffler published preliminary findings in 1956. Vincent P. Collins and R. Kenneth Loeffler, "The Therapeutic Use of Single Doses of Total Body Radiation," American Journal of Roentgenology 75 (1956): 546. Collins appears to have first conducted DOD-sponsored TBI research in 1953 while at Columbia University. See Joint Panel on the Medical Aspects of Atomic Warfare, proceedings of 7 January 1953 (ACHRE No. DOD-072294-B-1), item 10.

84 . Baylor University College of Medicine to AFSWP, report of 1 September 1955-31 January 1956 ("A Study of the Effects of Total and Partial Radiation on Iron Metabolism and Hematopoiesis") (ACHRE No. DOD-090994-D-2), 6.

85 . Baylor University College of Medicine to DASA, report of 1 February 1963-31 January 1964, 1; Baylor University College of Medicine to Defense Atomic Support Agency, report of 1 February 1961-31 January 1962 (ACHRE No. BAY-101794-A-3 ), 2.

86 . Baylor University College of Medicine to DASA, report of 1 February 1963-31 January 1964, 7-8.

87 . Ibid., 5-6.

88 . Ibid., 6.

89 . Ibid., 12.

90 . Because the Advisory Committee did not receive all of the progress reports on this study, the total number of patients cannot be determined. Nor could the Advisory Committee determine what type of teletherapy unit the investigators used. Memorial Hospital was the site of the second Manhattan Project experiment under Dr. Craver. Dr. Nickson was the author of the report on the third Manhattan Project experiment at Chicago; he came to Sloan-Kettering after World War II.

91 . Sloan-Kettering Institute for Cancer Research to AFSWP, report of 1 March 1958 ("Quarterly Report-Study of the Post-Irradiation Syndrome in Humans") (ACHRE No. DOD-062194-A-9).

92 . Sloan-Kettering Institute for Cancer Research to AFSWP, report of 1 May 1956 ("Annual Report") (ACHRE No. DOD-060794-A-1), abstract page.

93 . Captain E. Richard King, "Use of Total-Body Radiation in the Treatment of Far Advanced Malignancies," Journal of the American Medical Association 177 (2 September, 1961): 86-89.

94 . Ibid., 613.

95 . Ralph R. Cavalieri, Milton Van Metre, F. W. Chambers, and R. Richard King, "Taurine Excretion in Humans Treated by Total-Body Radiation," Journal of Nuclear Medicine 1 (1960): 186, 187, 190. Taurine is an amino acid that is excreted in the urine. A 1962 request for funding document from the Navy Bureau of Medicine and Surgery proposed to continue the biological dosimeter project through 1967 by collecting "daily urine specimens from patients exposed to total body irradiation for therapeutic purposes." U.S. Navy, Bureau of Medicine and Surgery, 1 June 1962 ("Biological Dosimeter of Radiation Injury") (ACHRE No. DOD-090994-C-3), 1-4. The Navy informed the Advisory Committee that there is no evidence that this project was ever funded.

96 . Standard Form 522, revised August 1954 ("Authorization for Administration of Anesthesia and for Performance of Operations and other Procedures") (ACHRE No. DOD-020695-B-1). Standard Form 522 was modified for TBI procedures. A second form was sometimes used for "consent to drastic radiation/chemical therapy," which states that "[t]he possibility that drastic radiation therapy may be useful . . . , the results expected, and the consequences likely to ensue, have been explained to me and I hereby give my consent. . . ." NHBETH Form 27B, August 1959 ("Consent to Drastic [Radiation] Therapy") (ACHRE No. DOD-020695-B-2).

97 . Shields Warren, "Ionizing Radiation and Medicine," Scientific American, September 1959, 165.

98 . AG Central Files, January-May 1962 ("Conference, Meetings, Military, Naval and All Divisions") (ACHRE No. DOD-081994-A-1), 2.

99 . Over the course of the eleven-year DOD study, ten researchers participated in the project and contributed to the DASA reports: Eugene L. Saenger, M.D.; Edward B. Silberstein, 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.

100 . Dr. Saenger had developed an interest in studying the "effect of whole body radiation on the patient suffering from cancer" while serving in the military as chief of the radioisotope laboratory at Brooke General Hospital, Fort Sam Houston, Texas. Raymond Suskind et al. to Dean of the College of Medicine, University of Cincinnati, January 1972 ("The Whole Body Radiation Study at the University of Cincinnati") (ACHRE No. DOD-042994-A-2) (hereafter "Suskind Report"), 40. He also "had treated occasional private patients with leukemia and lymphoma in my office using whole body radiation and had been impressed with its potentiality." Saenger’s response to "Questions from the [Suskind] Committee" (undated) (ACHRE No. DOD-042994-A-24), 2.

101 . Philip A. Pizzo et al., "Solid Tumors of Childhood," in Cancer: Principles and Practice of Oncology, 4th ed., eds. Vincent T. Devita, Samuel Hellman, and Steven A. Rosenberg (Philadelphia: J. B. Lippincott, Co., 1993), 1782-1783.

102 . Robert W. McConnell, President of the American College of Radiology, to U.S. Senator Mike Gravel, 3 January 1972 ("This letter represents our response . . .") (ACHRE No. DOD-042994-A-7). The ACR is the principal organization serving radiologists, with programs that focus on the practice of radiology and the delivery of comprehensive radiological health services. The stated purposes of the ACR are to advance the science of radiology, improve radiologic service to the patient, study the economic aspects of the practice of radiology, and encourage improved and continuing education for radiologists and allied professional fields. The ACR committee consisted of Drs. Henry Kaplan (Stanford), Frank Hendrickson (Chicago Presbyterian-St. Lukes), and Samuel Taylor (also Presbyterian-St. Lukes).

103 . Suskind report (released in February 1972). The Suskind Committee was appointed by the dean of the medical school at the University of Cincinnati. It was constituted of eleven physicians from the University of Cincinnati; one of the members, Dr. Bernard S. Aron, had worked on the TBI program.

104 . Junior Faculty Association, 25 January 1972 ("A Report to the Campus Community") (ACHRE No. DOD-042994-A-8). The JFA was a group of untenured arts and sciences faculty who organized at the University of Cincinnati in the late 1960s to protect each other’s rights to speak out on social issues and to work for fair tenure procedures. In the fall of 1971, a committee of this association, chaired by Martha Stephens, currently professor of English at the university, obtained the reports submitted to the DOD by the Cincinnati doctors and studied the TBI project’s history of consent, as

105 . James M. Cox, past Chairman of the ACR Commission on Radiation Oncology, statement at Hearing on Radiation Experiments Conducted by the University of Cincinnati Medical School with Department of Defense Funds before the Subcommittee on Administrative Law and Governmental Relations of the House Judiciary Committee, 103d Cong., 2d Sess., 11 April 1994 (ACHRE No. IND-091594-A-1).

106 . Dr. Eugene Saenger, University of Cincinnati, to Department of the Army, Office of Surgeon General, 25 September 1958 ("Application for Research Project: Metabolic Changes in Humans Following Total Body Irradiation") (ACHRE No. UCIN-103194-A-1).

107 . Dr. Saenger is also a long-standing member of the American College of Radiology and has served on the National Council on Radiation Protection and Measurements (NCRP) and the BEIR (Biological Effects of Ionizing Radiation) Committee in 1972. In 1963, he wrote the AEC's handbook on Medical Aspects of Radiation Accidents and regularly consulted for the AEC on radiation accidents and workers' claims of radiation exposure. Saenger has written almost 200 articles in the medical literature on radiology and other topics. Eugene L. Saenger, statement at Hearing on Radiation Experiments Conducted by the University of Cincinnati Medical School with Department of Defense Funds before the Subcommittee on Administrative Law and Governmental Relations of the House Judiciary Committee, 103d Cong., 2d Sess., 11 April 1994 (ACHRE No. IND-091594-A-1).

108 . Saenger to the Department of the Army, 25 September 1958, 3. Dr. Saenger's proposal to the DOD was restricted to a description of the post-TBI metabolic studies for which he was requesting funding, and it made no mention of a primary clinical purpose for the TBI such as a medical therapy or therapeutic research.

109 . University of Cincinnati College of Medicine to the Defense Atomic Support Agency, report of February 1960-October 1961 ("Metabolic Changes in Humans Following Total Body Irradiation") (ACHRE No. DOD-042994-A-1), 1.

110 . University of Cincinnati College of Medicine to the Defense Atomic Support Agency, report of 1 November 1961-30 April 1963 ("Metabolic Changes in Humans Following Total Body Irradiation") (ACHRE No. DOD-042994-A-1), 3.

111 . See, for example, ibid., 3 ("Patients with solid neoplasms which are not radiosensitive are sought."). Three children with Ewing’s sarcoma were also treated and included in the study. In addition, the original grant proposal stated that they would compare one group of patients "with relatively radio-resistant lesions (e.g., stomach, bowel, brain)" with a second group "with highly radio-sensitive tumors (lymphomas)." Saenger to the Department of the Army, 25 September 1958, 4-5. The records indicate that the latter group was never used.

112 . Eugene Saenger and Ben Friedman, 14 November 1962 ("An appraisal of Human Studies in Radiobiological Aspects of Weapons Effects") (ACHRE No. DOD-091894-A-1).

113 . University of Cincinnati College of Medicine to the Defense Atomic Support Agency, report of February 1960-30 April 1966 ("Metabolic Changes in Humans Following Total-Body Irradiation") (ACHRE No. DOD-042994-A-1), 2.

114 . University of Cincinnati College of Medicine to DASA, report of 1 November 1960-30 April 1963, 19.

115 . Eugene L. Saenger et al., "Whole Body and Partial Body Radiotherapy of Advanced Cancer," American Journal of Roentgenology 117 (1973): 670-685. The article makes no mention of the Defense Department-related funding or studies that were performed as part of this program.

116 . Eugene Saenger, M.D., interview by Ron Neumann, M.D., Gary Stern, and Gilbert Whittemore (ACHRE staff), transcript of audio recording, 15 September 1994 (ACHRE Research Project Series, Interview Program File, Targeted Interview Project), 50-51.

117 . Suskind report, 12; ACR report, 10.

118 . Calculated from 3,804 patient days at approximately $114 per day. Eugene L. Saenger, statement at Hearing on Radiation Experiments Conducted by the University of Cincinnati Medical School with Department of Defense Funds before the Subcommittee on Administrative Law and Governmental Relations of the House Judiciary Committee, 103d Cong., 2d Sess., 11 April 1994 (ACHRE No. IND-091594-A-1), 7.

119 . Interview with Saenger, 15 September 1994, 50; Saenger testimony, 11 April 1994, 7.

120 . Interview with Saenger, 15 September 1994, 54.

121 . Interview with Saenger, 20 October 1994, 22-23.

122 . Interview with Saenger, 15 September 1994, 64.

123 . Ibid., 94.

124 . Eugene L. Saenger to Dr. Steven Kessler, DASA Project Officer, 19 February 1969 ("Enclosed are eight copies . . ."), item 9 ("Dosimetry").

125 . Lieutenant Colonel James B. Hartgering, Director of the Army Division of Nuclear Medicine and Chemistry, to Lieutenant Colonel Arthur D. Sullivan, Assistant Chief of the Army Medical Research and Development Command, 7 November 1958 ("Application for Research Contract") (ACHRE No. DOD-042994-A-18) (reviewing application submitted by Dr. Eugene Saenger).

126 . Lieutenant Colonel Arthur D. Sullivan, Assistant Chief of the Army Biophysics and Astronautics Research Branch, to Colonel Hullinghorst, 12 November 1958 ("Application for Research Contract") (ACHRE No. DOD-042994-A-19).

127 . Captain David Lambert, Deputy Chief of DASA Weapons Effects and Tests, to DASA Director of Logistics, 29 October 1959 ("Negotiation of Contract") (ACHRE No. DOD-042994-A-20).

128 . Colonel John A. Isherwood to Assistant Chief of the Army Biophysics and Astronautics Research Branch, 22 October 1958. Isherwood also described Dr. Saenger as "well qualified to conduct such research."

129 . University of Cincinnati College of Medicine to DASA, report of February 1960-October 1961, 1.

130 . Dr. Saenger informed the Advisory Committee that he did not believe that he was required to submit the marrow proposal to the FCR, but elected to do so on his own. Interview with Saenger, 20 October 1994, 6.

131 . Dr. Edward A. Gall, FCR Chairman, to Dr. Clifford G. Grulee, Dean of the University of Cincinnati College of Medicine, 6 May 1966 ("This relates to a request . . .") (ACHRE No. DOD-042994-A-11).

132 . Dr. George Shields to Dr. Edward A. Gall, FCR Chairman, 13 March 1967 ("Protection of Humans with Stored Autologous Marrow") (ACHRE No. DOD-042994-A-11). Shields also indicated that he was withdrawing from the FCR subcommittee "for reasons of close professional and personal contact with the investigators and with some of the laboratory phases of this project." Ibid.

133 . Thomas E. Gaffney to Dr. Edward A. Gall, FCR Chairman, 17 April 1967 ("I cannot recommend approval . . .") (ACHRE No. DOD-042994-A-11). In a subsequent letter, dated 18 May 1967, Gaffney indicated to Gall his approval subject to a proviso (ACHRE No. DOD-042994-A-11).

134 . Dr. Clifford G. Grulee, Dean of the College of Medicine, to Dr. Ben I. Friedman, 23 May 1967 ("The Research Committee has reported . . .") (ACHRE No. DOD-042994-A-11).

135 . Dr. Evelyn V. Hess, FCR Chairman, to Drs. Edward B. Silberstein and Eugene L. Saenger, 22 July 1971 ("The Therapeutic Effect of Total Body Irradiation Followed by Infusion of Autologous Marrow in Humans") (ACHRE No. DOD-042994-A-11), 2.

136 . Dr. Edward B. Silberstein to Dr. Evelyn Hess, 4 April 1972 ("Enclosed is the protocol . . .") (ACHRE No. DOD-042994-A-11[5]).

137 . Dr. Evelyn Hess, FCR Chairman, to Clifford G. Grulee, Jr., Dean, College of Medicine, 28 August 1972 ("Evaluation of the Therapeutic Effectiveness of Wide-Field Radiotherapy . . .") (ACHRE No. 042994-A-11[25]).

138 . Evelyn Hess, 20 December 1971 ("Historical Review of the Total Body Irradiation and the Faculty Research Committee Reviews") (ACHRE No. CORP-080195-A-1).

139 . FCR Chairman to the Members of the Faculty Committee on Research, 18 April 1969 ("NIH Review . . .") (ACHRE No. DOD-042994-A-21), 1 (describing meeting with Dr. Mark Connor, NIH representative from the Institutional Relations Division).

140 . D. T. Chalkley, Ph.D., Chief of the NIH Office for Protection of Research Risks, to U.S. Senator Sam Nunn, 9 December 1974 ("Thank you for your notes . . .") (ACHRE No. DOD-042994-A-12[5]),1-2. In his letter to Senator Nunn, Chalkley states that "[w]hole-body radiation at levels of a few hundred rads is lethal only when it destroys the blood building cells of the bone marrow. In the treatment of these patients who had widespread metastatic cancer, a large part of the marrow was first removed, the patient was then treated and the marrow returned. None of the patients involved died from radiation sickness." However, the marrow transplants that Chalkley refers to were not successfully performed until 1969 and were done on only eight of the eighty-eight patients. See Saenger et al., "Radiotherapy of Advanced Cancer," 682.

141 . University of Cincinnati College of Medicine to the Defense Atomic Support Agency, report of 1 May 1966-30 April 1967 ("Metabolic Changes in Humans Following Total-Body Irradiation") (ACHRE No. DOD-042994-A-1).

142 . University of Cincinnati College of Medicine to DASA, report of February 1960-30 April 1966, 31.

143 . Ibid., 17.

144 . Saenger, et al., "Radiotherapy of Advanced Cancer," 682.

145 . University of Cincinnati College of Medicine to DASA, report of February 1960-October 1961, 20 (emphasis added). Note that the Sloan-Kettering study sought patients in similar condition.

146 . University of Cincinnati College of Medicine to the Defense Atomic Support Agency, report of 1 May 1968-30 April 1969 ("Radiation Effects on Man: Manifestations and Therapeutic Effects") (ACHRE No. DOD-042994-A-1), 1 (emphasis added).

147 . University of Cincinnati College of Medicine to the Defense Atomic Support Agency, report of 1 May 1969-30 April 1970 ("Radiation Effects on Man: Manifestations and Therapeutic Effects") (ACHRE No. DOD-042994-A-1), 1 (emphasis added).

148 . Ibid., 34. Over the course of the study, twenty-eight patients lived more than one year after being irradiated; seventeen survived for more than two years, at least three people lived more than five years.

149 . Suskind report, 65.

150 . Ibid., 63.

151 . McConnell to Gravel, 3 January 1972, 8. Autopsies were performed on only eight patients, so bone marrow biopsies were used for this evaluation.

152 . Eugene L. Saenger et al., "Radiotherapy of Advanced Cancer," 677.

153 . Eugene L. Saenger, 20 October 1994 ("How Can the Quality and Length of Life of a Cancer Patient Be Determined?") (ACHRE No. IND-021095-B-2).

154 . The article 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. Saenger et al., "Radiotherapy of Advanced Cancer," 672-676.

155 . Suskind report, 59.

156 . Ibid.

157 . University of Cincinnati College of Medicine to the Defense Atomic Support Agency, report of February 1960-October 1961 ("Metabolic Changes in Humans Following Total Body Irradiation") (ACHRE No. DOD-042994-A-1), 3-4. When asked by ACHRE staff 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 "we would not have [had that period of silence]." Interview with Saenger, 15 September 1994, 74. In the second interview he said that he probably would still have withheld the information. Interview with Saenger, 20 October 1994, 12. A number of contemporary articles discuss the use of compazine in the treatment of radiation sickness. See, for example, Joseph H. Marks, "Use of Chlorpromazine in Radiation Sickness and Nausea from Other Causes," New England Journal of Medicine (June 1954): 999-1001; M. J. Solan, "Prochlorperazine and Irradiation Sickness," British Medical Journal (21 November 1959): 1068-1069; G. H. Berry, W. Duncan, and Carol M. Bowman, "The Prevention of Radiation Sickness: Report of a Double Blind Random Clinical Trial Using Prochlorperazine and Metopimazine," Clinical Radiology 22 (1971): 534-537.

158 . Melville L. Jacobs and Fred J. Marasso, "A Four-Year Experience with Total-Body Irradiation," Radiology 84 (1965): 452-456 (twelve of fifty-two patients still experienced some degree of nausea and vomiting). This was the only known U.S. TBI-effects study that performed TBI on patients with radioresistant cancers that does not appear to have been funded by the DOD. Sixteen of the fifty-two patients had radioresistant carcinomas and were chosen because they had life expectancies of less than one month. Ibid.

159 . Three main consent forms were used: the first beginning in 1965; the second beginning in 1967; and the third beginning in 1971 (ACHRE No. DOD-042994-A-22).

160 . Dr. Saenger stated that he was prompted to begin the use of written consent when he received a letter in 1964 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. Interview with Saenger, 15 September 1994, 77.

161 . A second form went into effect at the same time for bone marrow aspiration and storage and is basically the same as the above.

162 . Gore Hearing, 35-36.

163 . University of Cincinnati Medical Center, Faculty Committee on Research, 1967, "Voluntary Consent Statement."

164 . University of Cincinnati, "Consent Form," 1971.

165 . Interview with Saenger, 20 October 1994, 7-8. This procedure is also described by Dr. Silberstein in "Extension of Two-part Consent Form," New England Journal of Medicine 291 (1974): 155-156.

166 . Advisory Committee on Human Radiation Experiments, transcript of Cincinnati Small Panel Meeting, 21 October 1994, 136.

167 . Suskind report, 50.

168 . ACR report, 7.

169 . Suskind report, 28-29. It also notes approximately 2 percent of all patients (both in- and outpatient) at the hospital were private patients. Ibid., 29.

170 . In 1969, several of the University of Cincinnati researchers reported on the effects of TBI and PBI on cognitive and emotional processes based on a study involving sixteen of the patients. The published article notes that the "relevant intellectual characteristics of the patient sample were as follows: a low-educational level (ranging from 0 to eight years of education with a mean of 4.2 years), a low-functioning intelligence quotient (ranging from 63 to 112 on the full-scale Wechsler-Bellevue with a mean of 84.5), and a strong evidence of cerebral organic deficit in the baseline (preradiation) measure of most of the patients." Louis A. Gottschalk, Eugene L. Saenger et al., "Total and Half Body Irradiation: Effect on Cognitive and Emotional Processes," Archives of General Psychiatry 21 (November 1969): 574, 575. Although these findings suggest that there may have been serious issues about competence among the Cincinnati subjects, questions have been raised about this interpretation. For example, Martha Stephens, former chair of the JFA, has argued as follows: "These citizens were not necessarily dumb or defective, and nothing whatever, in my view, can be judged from the batteries of tests of the psychologists; in the very face of them, they are unconvincing and contradictory. . . . These individuals were in a bad place in life--cancer was more frightening then than it is now, and so were public hospitals. To find people coming to tumor wards (or in the hospital for evaluation of their cancers) to be depressed and upset and somewhat disoriented, and not particularly interested in answering irrelevant questions . . . would be quite normal, I would guess. . . . It seems to be best not to lead the public to believe that what happened in Cincinnati could only have happened to people who weren't smart enough to protect themselves, were virtually retarded." Martha Stephens to Gary Stern, Advisory Committee staff, 3 June 1995 ("I want to thank you for the documents . . .") (ACHRE No. IND-060595-A), 10-11.

171 . ORINS was renamed the Oak Ridge Associated Universities (ORAU) in 1966. In 1991, ORAU became the contractor of the Oak Ridge Institute for Science and Education (ORISE).

172 . Following standard retention schedules, NASA destroyed funding and procurement records on the Oak Ridge project in 1980. Additional administrative, technical monitoring, and contractor reports still exist. Medical records associated with this project were never in the possession of NASA and always resided with ORINS/ORAU.

173 . ORINS had training courses in the handling and use of radioisotopes; it also helped develop the supervoltage cobalt 60 teletherapy machine.

174 . Gore Hearing, 110.

175 . Howard L. Rosenberg, "Informed Consent: How the Space Program Experimented with Dwayne Sexton's Life," Mother Jones, September/October 1981, 31-44. On 13 March 1994, 60 Minutes aired a story based on the Mother Jones article.

176 . Gore Hearing, 110.

177 . Gore Hearing, 144.

178 . Gore Hearing, 161 (statement of Andrew J. Stofan, Acting Associate Administrator for NASA Office of Space Sciences).

179 . Ibid., 200. See also page 151 (testimony of William R. Bibb, Director of the Research Division, Oak Ridge Operations Office) and 159-63 (testimony of Stofan).

180 . Ibid., 290.

181 . G. A. Andrews et al., paper of December 1970 for Oak Ridge Associated Universities ("Hematologic and Therapeutic Effects of Total-Body Irradiation (50 R-100 R) in Patients with Malignant Lymphoma, Chronic Lymphocytic and Granulocytic Leukemias, and Polycythemia Vera"), 2, reprinted in Gore Hearing, 49.

182 . Gore Hearing, 264.

183 . Ibid., 291.

184 . Ibid., 293.

185 . Ibid., 294-295. Following the Gore Hearing, Dr. Helen Vodopick, one of the ORAU physicians who testified, wrote a memo to the file stating that "the therapy given was different from other therapy given that had been tried at that time. However, the other therapies that were being investigated were also radically different. . . . All of these various approaches were tried since nothing had worked before and certainly

186 . Reprinted in Gore Hearing, 32-33.

187 . U.S. Atomic Energy Commission, report of 16 April 1974 ("ORAU Review"), reprinted in Gore Hearing, 186. William Bibb testified that this report was written for the purpose of shutting down the hospital, which had outlived its purposes and could no longer be justified as a necessary AEC program. Accordingly, he stated, some of the statements in the report were "overstatements in order to accomplish what we felt should be accomplished, knowing full well that closing down any Government hospital is hard, closing down that hospital was extraordinarily hard." Gore Hearing, 182.

188 . H. R. Resolution 1010, 97th Cong., 2d Sess. 186 (1983). The Committee noted that a later hearing was held on the state of radiation epidemiology within DOE on 19 May 1982. Ibid.

189 . It had recommended that ORAU compare the effect of TBI with 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." U.S. Atomic Energy Commission, report of 16 April 1974, reprinted in Gore Hearing, 247.

190 . Ibid., reprinted in Gore Hearing, 252.