Conclusion

Chapter 6: Footnotes

2 . The press release announcing the program noted that, in addition to technical qualifications of researchers, "An additional qualification will require all groups using the isotopes for fundamental research or applied science to publish or otherwise make available their findings, thereby promoting further applications and scientific advances." Headquarters, Manhattan District (Oak Ridge, Tennessee), 14 June 1946 ("For Release in Newspapers Dated June 14, 1946") (ACHRE No. NARA-082294-A-31), 1.

3 . "Availability of Radioactive Isotopes: Announcement from Headquarters, Manhattan Project, Washington, D.C.," Science 103 (14 June 1946): 697-705.

4 . Harry H. Davis, New York Times Magazine (typescript), 22 September 1946 ("The Atom Goes to Work for Medicine") (ACHRE No. DOE-051094-A-408),2.

5 . Ibid., 6.

6 . Cohn, 3 January 1946, 10.

7 . Ibid., 14.

8 . R. E. Cunningham, 20 February 1971 ("Historical Summary of the Subcommittee on Human Applications") (ACHRE No. NRC-012695-A), 6.

9 . AEC Subcommittee on Human Applications of the Committee on Isotope Distribution, 13 March 1949 ("Revised Tentative Minutes of March 13, 1949, Meeting of Subcommittee on Human Application of the Committee on Isotope Distribution of U.S. Atomic Energy Commission: AEC Building, Washington, D.C.") (ACHRE No. NARA-082294-A-62), 7.

10 . Advisory Subcommittee on Human Applications of the Interim Advisory Committee on Isotope Distribution Policy, 11 July 1946 ("Minutes of Initial Meeting--Held June 28, 1946; Oak Ridge, Tennessee") (ACHRE No. NARA-082294-A-84), 1.

11 . Ibid., 2-8.

12 . Ibid., 5.

13 . Ibid., 6.

14 . Ibid., 10.

15 . For example, proposals to study possible therapeutic uses of UX1/ UX2, a "naturally radioactive pair [that] behaves chemically as UX1, a thorium isotope (Th 234). . . . Aside from the danger of bone damage, the material would have to be used with much caution because of likely kidney damage. No advantage could be seen in the use of radiothorium over the use of certain other beta ray emitting radioisotopes which deposit in bone." Ibid., 9.

16 . Ibid.

17 . "In general, there is more of a need for speed in handling requests for human applications than for others because: (1) therapeutic action may be needed urgently, (2) the case may be an exceptionally good one for some purpose and may only be available for study immediately (for example, the chance to obtain tracer samples resulting from a special operation)." Ibid., 10.

18 . Isotopes Branch, Research Division, Manhattan District, Oak Ridge, Tennessee, 3 October 1946 ("Details of Isotope Procurement") (ACHRE No. NARA- 082294- A-31).

19 . Isotopes Branch, Research Division, Manhattan District, Oak Ridge, Tennessee, 3 October 1946 ("Agreement and Conditions for Order and Receipt of Radioactive Materials") (ACHRE No. NARA- 082294- A-31), 2.

20 . The statement read:

This is to certify that the undersigned has adequate facilities for the investigation to be conducted by him as proposed in the 'Interim Period Request for Radioelement, Form 313,' Serial Number _____, and that such drug will be used solely by him or under his direction for the investigation, unless and until an application becomes effective with respect to such drug under section 505 of the Federal Food, Drug and Cosmetic Act, Isotopes Branch, Research Division, Manhattan District, Oak Ridge, Tenn.

Isotopes Branch, Research Division, Manhattan District, Oak Ridge, Tennessee, 3 October 1946 ("Certificate . . . EIDM Form 465") (ACHRE No. NARA-082294-A-31), 1.

21 . Isotopes Branch, Research Division, Manhattan District ("Report of Requests Received to July 31, 1946," "2nd Report of Request Received August 1 to 31, 1946," "3rd Report of Request Received September 1 to 30, 1946," "4th Report of Requests Received October 1 to 31, 1946") (ACHRE No. NARA-082294-A-31).

22 . Franklin asked:

What is the relationship of the Atomic Energy Commission Medical Division to the Isotopes Branch and the medical and biological aspects of the isotope distribution program?

(1) Will allocations for human administration be subject to medical review and what control will be exercised?

(2) What responsibilities does the Atomic Energy Commission bear for the human administration of isotopes (a) by private physicians and medical institutions outside of the Project, and (b) by physicians within the Project? This latter category includes contractor personnel employing Atomic Energy Commission funds (indirectly) to perform tracer research, some of which is of no immediate therapeutic value to the patient. What are the criteria for future human tracer research?

(3) What responsibilities does the Atomic Energy Commission bear for the safe handling by the recipient of the more hazardous radioisotopes?

(4) What responsibilities does the Atomic Energy Commission bear

for radioactive waste disposal outside the Project?

J. C. Franklin, Manager, Oak Ridge Operations, to Carroll Wilson, AEC General Manager, 26 September 1947 ("Medical Policy") (ACHRE No. DOE-113094-B-3), 2.

23 . Research Division, Manhattan District, 3 October 1946 ("Isotope Request, For Manhattan Project Use Only . . . EIDM Form 558") (ACHRE No. NARA-082294-A-31), 1.

24 . In a 5 October 1949 memorandum to Carroll Tyler, Manager of Los Alamos, Paul Aebersold, Chief of the Isotopes Division, noted that "Dr. [Shields] Warren instructed that such allocations would be made by the Isotopes Division only after review and approval by the Subcommittee on Human Applications of the Commission's Committee on Isotope Distribution. It should be emphasized that the instruction applies even though the radiomaterial is produced in the laboratory where it is to be used.

25 . Presumably codifying existing practice, 10 C.F.R. 30.10 (1951 supplement to 1949 edition) states:

The regulations in this part do not apply to persons to the extent that such persons operate Commission-owned facilities in carrying out programs on behalf of the Commission. In such cases, the acquisition, transfer, use, and disposal of radioisotopes are governed by the contracts between such persons and the Commission, and internal bulletins, instructions and directives issued by the Commission.

26 . Carroll L. Wilson, AEC General Manager, to Principal Staff, Washington, and Managers of Operations, 7 June 1950 ("Bulletin GM-161, Procedure for Securing Isotopic Materials and Irradiation Services") (ACHRE No. NARA-122994-B), 1.

27 . Subcommittee on Human Applications, 13 March 1949, 1.

28 . Ibid., 3.

29 . Ibid. These minutes include a review of the minutes of the 22-23 March 1948, meeting.

30 . Ibid., 10-11.

31 . Ibid., 10.

32 . Ibid., 12-13.

33 . Ibid., 4.

34 . Ibid.

35 . Paul Aebersold, Chief, Isotopes Division, Oak Ridge Operations, to Hymer Friedell, G. Failla, Joseph G. Hamilton, and A. H. Holland, Jr., 9 March 1948 ("Meeting of Subcommittee on Human Applications in Washington, March 22 and 23") (ACHRE No. NARA-082294-A-17), 2.

36 . Subcommittee on Human Applications, 13 March 1949, 5-6.

37 . Ibid.

38 . Clemens Benda, Director of Research and Clinical Psychiatry, to AEC Subcommittee on Human Applications, 29 September 1953 ("This letter is written in order to elicit your permission to administer a dose of 50 uc Ca45 to a moribund gargoyle patient now hospitalized in our institution . . ."), 1. Reproduced at appendix B-27, Task Force on Human Subject Research, to Philip Campbell, Commissioner, Commonwealth of Massachusetts Executive Office of Health and Human Services, Department of Mental Retardation, April 1994 ("A Report on the Use of Radioactive Materials in Human Subject Research that Involved Residents of State-Operated Facilities within the Commonwealth of Massachusetts from 1943 to 1973") (ACHRE No. MASS-072194-A).

39 . Clemens Benda, Clinical Director, to "Parent," 28 May 1953 ("In previous years we have done some examinations in connection with the nutritional department of the Massachusetts Institute of Technology . . ."), 1. Reproduced at appendix B-23, Task Force on Human Subject Research, to Philip Campbell, April 1994.

40 . Task Force on Human Subject Research, to Philip Campbell, April 1994, 16.

41 . Subcommittee on Human Applications, 13 March 1949, 8.

42 . AEC Isotopes Division, "General Authorizations for Procurement of Radioisotopes," Isotopics: Announcements of the Isotopes Division 1 (April 1951): 1-3.

43 . AEC Isotopes Division, "General Authorizations for Clinical Use of Radioisotopes," Isotopics: Announcements of the Isotopes Division 2 (April 1952): 1-2.

44 . Subcommittee on Human Applications, 13 March 1949, 11.

45 . Paul C. Aebersold, Chief, AEC Isotopes Division, to William E. Barbour, Jr., President, Tracerlab, Inc., 11 April 1949 ("Violation of 'Acceptance of Terms and Conditions for Order and Receipt of Byproduct Materials [Radioisotopes]'") (ACHRE No. NARA-082294-A-4), 1.

46 . William Barbour, President, Tracerlab, Inc., to Employees, April 1949 ("Violation of AEC Regulations") (ACHRE No. NARA-082294-A-4), 1. Barbour stated that a recurrence would

mean cessation of all radiochemical operations of the Company. In turn this would jeopardize the investments of several thousand new stockholders who have placed great faith in the integrity and ability of the management. A violation of a specific agreement with the AEC would be a breach of that faith and could only result in the automatic dismissal of anyone contributing to such a violation.

47 . AEC Isotopes Division, 23 March 1950 ("Meeting of the Advisory Committee on Isotope Distribution, March 23 and 24, 1950, Washington, D.C., Minutes") (ACHRE No. NARA-122994-B-1), 4.

48 . AEC Isotopes Division, September 1949 ("Supplement No. 1 to Catalogue and Price List No. 3") (ACHRE No. DOD-122794-A-1), 1.

49 . Paul C. Aebersold, Director, Isotopes Division, to T. H. Johnson, Director, Division of Research, 2 November 1954 ("Providing Radioisotopes at Reduced Prices

50 . 10 C.F.R. 37 (1961).

51 . A conscious decision was made not to include detailed standards in the regulations. The discussion is summarized in Advisory Committee on Isotope Distribution, 23 March 1950, 7-8. The regulations were first promulgated in 10 C.F.R. 30.50 (1951 supplement to 1949 edition).

52 . AEC Isotopes Division, 6 December 1948 ("Isotopes Division Circular D-4: Radioisotopes for Use in Medicine") (ACHRE No. DOE-101194-A-5); Isotopes Division, "Supplement No. 1," September 1949; Isotopes Extension, Division of Civilian Application, U.S. Atomic Energy Commission, "The Medical Use of Radioisotopes: Recommendations and Requirements by the Atomic Energy Commission," RC-12 (February 1956).

53 . Isotopes Extension, February 1956, 14.

54 . Ibid., 15.

55 . R. E. Cunningham, "Historical Summary," 5.

56 . AEC Division of Materials Licensing, "Non-Routine Medical Uses of Byproduct Material," A Guide for the Preparation of Applications for the Medical Use of Radioisotopes (November 1965), 47-48.

57 . See, for example, Bryant L. Jones, Division of Oncology and Radiopharmaceuticals, Bureau of Medicine, Food and Drug Administration, 18 May 1967 ("FDA Responsibility in Radiopharmaceutical Research") (ACHRE No. DOE-051094-A-236).

58 . Advisory Subcommittee on Human Applications, 11 July 1946, 6.

59 . This requirement is stated in Aebersold's memo of 5 October 1949, quoted earlier in endnote 24, which notified AEC labs that their applications for human use would now be reviewed by the Subcommittee on Human Applications of the AEC's Committee on Isotope Distribution. Concerning local isotope committees, the memo states: "It should be emphasized that each application should be accompanied by a formal, written endorsement, signed by the Chairman of the local "Isotopes Committee," the recommended membership of which is outlined on pages 30 and 31 of the catalog." Paul Aebersold, Chief, Isotopes Division, to Carroll Tyler, Manager, Los Alamos, 5 October 1949 ("Use of Radioisotopes in Human Subjects") (ACHRE No. DOE-021095-B-4); Paul Aebersold, Chief, Isotopes Division, to W. E. Kelley, Manager, New York, 5 October 1949 ("Use of Radioisotopes in Human Subjects") (ACHRE No. DOE-012795-B).

60 . AEC Isotopes Division, Isotopics 1, 1.

61 . Isotopes Extension, February 1956, 7. The full description of the functions of the Medical Isotope Committee is:

1. Formation of a Medical Isotopes Committee. The Medical Isotope Committee shall include at least three members. Membership should include physicians expert in internal medicine (or hematology), pathology, or therapeutic radiology and a person experienced in assay of radioisotopes and protection against ionizing radiations. It is often appropriate that a qualified physicist be available to the Committee, at least in

consulting capacity. It is recognized that the composition of local isotope committees may vary from institution to institution depending upon the individual interests of a particular medical facility.

2. Duties of the Medical Isotopes Committee

Generally, the Committee should have the following responsibilities:

a. Review and grant permission for, or disapprove, the use of radioisotopes within the institution from the standpoint of radiological health safety and other factors which the Committee may wish to establish for medical use of these materials.

b. Prescribe special conditions which may be necessary, such as physical examinations, additional training, designation of limited area or location of use, disposal methods, etc.

c. Review records and receive reports from its radiological safety officer or other individual responsible for health-safety practices.

d. Recommend remedial action when a person fails to observe safety recommendations and rules.

e. Keep a record of actions taken by the Committee.

62 . The Advisory Committee also reviewed materials from the AEC's Oak Ridge, Los Alamos, Argonne, and Brookhaven laboratories, the Air Force School of Aviation Medicine, and the University of California. The development of research at the University of California at Berkeley and San Francisco is the subject of a case study appearing in a companion volume to this report.

63 . N. W. Faxon, Director, Massachusetts General Hospital, to Drs. Aub, Moore, Shulz, and Rawson, 3 May 1946 ("At the meeting of the General Executive Committee held on May 1, 1946, consideration of the use of radioactive isotopes was discussed . . .") (ACHRE No. HAR-100394-A-1), 1.

64 . "It should be emphasized that the University Radiation Policy Committee was established to deal with all types of radiation problems at the University and was not limited to the scope of 'radioisotope committees' suggested by the AEC for radioisotope procurement. In fact this Committee predated the earliest suggestions of the AEC by almost a year." W. W. Meinke, Chairman, University of Michigan Radiation Policy Committee, to I. Lampe, 27 February 1956 ("On October 13, 1950, the President of the University of Michigan established the Radiation Policy Committee . . .") (ACHRE No. MIC-010495-A-2), 1.

65 . Consisting of Hugh Morgan (Vanderbilt University), Stafford Warren (University of California at Los Angeles), Hymer Friedell (Case Western Reserve University ), Shields Warren (AEC Division of Biology and Medicine), and Perrin Long (Johns Hopkins University).

66 . There was some debate at the beginning as to the name of the units. With "radioactive" still a charged word for much of the population, an early memo suggested that "it could to advantage be called a Metabolism Ward." Veterans Administration, 15 September 1948 ("Minutes of the Meeting, Central Advisory Committee on Radioisotopes, U.S. Veterans Administration") (ACHRE No. UCLA-100794-A), 23.

67 . The chairman listed the already-achieved benefits to thyroid gland research and blood volume diagnosis, and claimed, "It is not an overstatement to say that progress can be expected to be rapid and on a wide front as greater use is made in medical and biological research when this new tool is applied in attempts to solve such problems." Ibid., 3.

68 . Framingham, Massachusetts; Bronx, New York; Cleveland, Ohio; Hines, Illinois; Minneapolis, Minnesota; Van Nuys, California; Los Angeles, California; and Dallas, Texas.

69 . Joseph C. Aub et. al., to the Executive Committee, Massachusetts General Hospital, 17 June 1946 ("The Radioactive Isotope Committee had its first meeting on June 15th . . .") (ACHRE No. HAR-100394-A-2), 1-2.

70 . William Sweet, interviewed by Gilbert Whittemore (ACHRE), transcript of audio recording, 8 April 1995 (ACHRE Research Project Series, Interview Program File, Targeted Interview Project), 20.

71 . VA Central Advisory Committee on Radioisotopes, 15 September 1948, 26.

72 . Ibid.

73 . University of Michigan Subcommittee on Human Use of Isotopes, 10 December 1956 ("Minutes, Meeting of the Subcommittee on Human Use of Isotopes") (ACHRE No. MIC-010495-A-3), 1.

74 . William H. Beierwaltes to Edward A. Carr, Chairman, University of Michigan Subcommittee on Human Use of Radioisotopes, 20 May 1968 ("Enclosed are our calculations to date on our first two patients studied in the Clinical Research Unit . . .") (ACHRE No. MIC-010495-A-6), 3. The form includes space for a signature by a witness as well as the patient.

75 . In an effort to develop an overall assessment of the possible harm from radioisotope experiments conducted in the past, the Advisory Committee extracted dose data from our Experiment Database, whenever available, in order to perform risk analyses using contemporary standards. Unfortunately, most of the data recovered by the Committee was fragmentary and did not provide a sufficient basis for an analysis of possible harm in most cases.

76 . Massachusetts General Hospital Radioactive Isotope Committee, 15 March 1955 ("Meeting of the Massachusetts General Hospital Radioactive Isotope Committee") (ACHRE No. HAR-100394-A-4), 1.

77 . Ibid.

78 . One proposal, for example, involved saturating gelfoam with silver 111 or yttrium 90, and then implanting the gelfoam into the tumor. Preliminary work had been done on animals in the previous year on normal brain tissue. After extensive animal testing, the procedure was to be attempted on those humans who already suffered brain cancer and had undergone surgery. Theodore Rasmussen, 29 May 1952 ("Local Application of Beta Ray Isotopes to Brain Tumors") (ACHRE No. DOE-122194-A).

79 . For example, in 1953 the Chicago committee approved a proposal to use tritium and C-14-labeled acetate to trace the development of adrenal cholesterol in advanced cancer patients as well as a control group. The committee noted that the doses "are smaller than have been used in human studies at other institutions and in no case involve amounts which will produce internal radiation in excess of maximum permissible dose." George V. LeRoy, Chairman, Radioisotope Committee, 24 February 1953 ("Minutes of the Radioisotope Committee Meeting") (ACHRE No. DOE-122194-A), 1.

80 . This included recommendations for using the minimum amounts of isotopes possible, a limitation of 1 rep [roentgen equivalent physical] for tracers, mandatory blood tests before administration and forty-eight hours after, and a listing of dose recommendations. The policy on patients and children was specific: "Adult humans who are ill and who are expected to receive benefit from the procedure, shall not receive tracer doses of radioactive material giving off radiation in excess of a total of 4 rep. Children (all patients below 15 years of age) shall not receive more than a total of 0.8 rep." J. C. Aub, A. K. Solomon, and Shields Warren, Harvard Medical School, 7 May 1949 ("Tracer Doses of Radioactive Isotopes in Man") (ACHRE No. HAR-100394-A-3), 1.

81 . The committee stated that all volunteers receiving Na-22 and K-42 should be subjected to doses no more than 100 millirads for the whole body, nor more than one-third the maximum permissible values to a specific organ. University of Michigan Subcommittee on Human Use of Isotopes, 10 December 1956, 1.

82 . W. F. to University of Chicago Radioisotope Committee, 28 September 1953 ("Permission is requested to administer intravenously 500 microcuries, or less, of radio-mercury to a patient . . .") (ACHRE No. DOE-122194-A-2), 1.

83 . Harvard Medical School Committee on Medical Research in Biophysics, August 1957 ("Tracer Doses of Radioactive Isotopes in Man") (ACHRE No. HAR-100394-A-5), 2.

84 . University of Michigan Subcommittee on Human Use of Isotopes, 27 September 1955 ("Minutes of Human Use Committee Meeting") (ACHRE No. MIC-010495-A), 2.

85 . A 1963 memorandum indicates the committee's unwillingness to allow a procedure involving selenium 75-labeled methionine for parathyroid scanning limited to use in patients over forty years old, while in a 1966 letter Carr stated that he was "strongly inclined to refuse to permit the use of radioisotopes in all volunteers below the age of 21, unless there are special mitigating circumstances approved by the whole subcommittee." Ronald C. Bishop, Acting Chairman, Subcommittee on Human Use, 13 August 1963 ("Dr. E. A. Carr has asked me to act as chairman of the Subcommittee on Human Use in his absence . . .") (ACHRE No. MIC-010495-A-4), 1; Edward A. Carr to Dr. Bishop, 3 September 1966 ("To Members of the Subcommittee on Human Use of Radioisotopes") (ACHRE No. MIC-010495-A-5), 1.

86 . In 1968 the committee approved a proposal for an experiment that involved doses of NM-125 labeled with I-131 or I-125 for patients with melanomas or a reasonable clinical suspicion of melanoma for thirty patients, and then wished to see results before approving of further administration. Likewise, the committee gave approval to a closely related experiment involving use of the same substances in patients with lung cancer. For that regime, the committee demanded feedback after fifteen patients. For a further related matter involving the same substances in patients with pulmonary carcinoma, the committee limited the work to five patients. In each case the dose was to exceed 2 millicuries per patient. Edward A. Carr, Chairman, Subcommittee on Human Use, to William H. Beierwaltes, Director, Nuclear Medicine, 27 September 1968 ("This is to inform you that the Sub-committee on Human Use of Radioisotopes, at its meeting of September 26, 1968, approved the use of a single dose of NM-113 . . .") (ACHRE No. MIC-010495-A-6), 1.

87 . A researcher had applied to use sodium 22 in a tracer procedure with several patients. The committee was concerned that "a small but significant fraction of one of the radioisotopes might remain localized in the body for a long period of time . . ." Edward A. Carr, 3 June 1968 ("Sub-committee on Human Use of Radioisotopes, Minutes of the Meeting of June 3, 1968") (ACHRE No. MIC-010495-A-7), 1.

88 . George V. LeRoy, 3 November 1953 ("Minutes of the Radioisotope Committee Meeting") (ACHRE No. DOE-122194-A-3), 1.

89 . Paul C. Aebersold, Chief, Isotopes Division, to John Z. Bowers, Assistant to Director, Division of Biology and Medicine, 18 March 1948 ("Investigation of Patients Who Have Received Radioactive Isotopes") (ACHRE No. DOE-061395-E-1), 1.

90 . A comprehensive history of the application of radioisotopes is well beyond the scope of this chapter and would needlessly duplicate substantial histories already written. See, for example, J. Newell Stannard, Radioactivity and Health: A History (Springfield, Va.: Office of Scientific and Technical Information, 1988).

91 . An example is Konstantin N. Pavlou, William P. Steffee, Robert H. Lerman, and Belton A. Burrows, "Effects of Dieting and Exercise on Lean Body Mass, Oxygen Uptake, and Strength," Medicine and Science in Sports and Exercise 17 (1985): 466-471. The study was conducted at the Boston University Medical School and the Boston VA Medical Center.

92 . There is a vast literature on radioiodine and the thyroid. Government studies specifically noted by the Veterans Administration as significant are the following: H. C. Allen, R. A. Libby, and B. Cassen, "The Scintillation Counter in Clinical Studies of Human Thyroid Physiology Using I-131," Journal of Clinical Endocrinology and Metabolism 11 (1951): 492-511; B. A. Burrows and J. A. Ross, "The Thyroid Uptake of Stable Iodine Compared with the Serum Concentration of Protein-Bound Iodine in Normal Patients and in Patients with Thyroid Disease," Journal of Clinical Endocrinology and Metabolism 13 (1953): 1358-1368; S. A. Berson and R. S. Yalow, "Quantitative Aspects of Iodine Metabolism: The Exchangeable Organic Iodine Pool, and the Rates of Thyroidal Secretion, Peripheral Degradation and Fecal Excretion of Endogenously Synthesized Organically Bound Iodine," Journal of Clinical Investigation 33 (1954): 1533-1552; M. A. Greer and L. J. DeGroot, "The Effect of Stable Iodide on Thyroidal Secretion in Man," Metabolism 5 (1956): 682-696; K. Sterling, J. C. Lashof, and E. B. Man, "Disappearance from Serum of I-131 Labeled I-Thyroxine and l-Triiodothyronine in Euthyroid Subjects," Journal of Clinical Investigation 33 (1954): 1031; K. Sterling and R. B. Chodos, "Radiothyroxine Turnover Studies in Myxosema, Thyrotoxicosis, and Hypermetabolism Without Endocrine Disease," Journal of Clinical Investigation 35 (1956): 806-813.

93 . See, for example, J. F. Ross, "Cooperative Study of Radioiodine Therapy for Hyperthyroidism," Bulletin of the Committee on Veterans Medical Problems (National Academy of Sciences) (1952): 576-578.

94 . Gould A. Andrews, M.D., Samuel W. Root, M.D., and Herbert D. Kerman, M.D., "Clinical Studies with Gallium-72," 570-588 in Marshall Brucer, M.D. (ed.), Gould Andrews, M.D., and H.D. Bruner, M.D., "Clinical Studies with Gallium-72," Radiology 66 (1953): 534-613.

95 . OncoScint, developed by Cytogen, was approved by the FDA for diagnosis of colorectal and ovarian cancers on 29 December 1992, Product License Application no. 89-0601, with Amendment no. 90-0278. The use of monoclonal antibodies to treat cancer is discussed in Oliver W. Press, M.D., Ph.D., et al., "Radiolabeled-Antibody Therapy of B-Cell Lymphoma with Autologous Bone Marrow Support," New England Journal of Medicine 329 (21 October 1993): 1219-1224. Progress in the field is reviewed in an accompanying editorial, Robert C. Bast, Jr., M.D., "Progress in Radioimmunotherapy," New England Journal of Medicine 329 (21 October 1993): 1266-1268.

96 . Strontium 89, commercially available as Metastron from Amersham-Mediphysics, was approved on 18 June 1993, New Drug Application no. 20134. One of its therapeutic uses is described in an article by Arthur T. Porter. M.D., and Lawrence P. Davis, M.D., "Systemic Radionuclide Therapy of Bone Metastases with Strontium-89," Oncology 8 (February 1994): 93-96.

97 . R. S. Yalow and S. A. Berson, "Assay of Plasma Insulin in Human Subjects by Immunological Methods," Nature 184 (1959): 1648.