DOE Openness: Human Radiation Experiments: Roadmap to the Project
Chapter 7: Footnotes1 . As noted in the report of the Massachusetts Task Force, "many of the people who became residents of the Walter E. Fernald School . . . were not admitted with a diagnosis of mental retardation. Societal and cultural norms of the day permitted persons to be admitted to state-operated institutions for a number of reasons. All were labeled mentally retarded just by virtue of having lived within the facility." 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), 1.
2 . Task Force on Human Subject Research, 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"); and the Working Group on Human Subject Research to Philip Campbell, June 1994 ("The Thyroid Studies: A Follow-up 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 through 1973") (ACHRE No. MASS-072194-B).
3 . Unfortunately, the published reports of the twenty-one research projects we review in this chapter often provide little or no information that could be used to identify the individual children. Many published reports provide information only about the child's age, weight, and diagnosis. Other reports provide only the child's initials and diagnosis. In either case, it would be difficult or impossible to identify specific individuals from this limited information. An existing chart may or may not confirm a child's involvement in a research project. If the investigators maintained records, those could serve as a key to identify the individuals. Even if the hospital records do exist, however, records for a period of several years prior to publication of the research would have to be reviewed in order to match a set of initials with a diagnosis. However, it is unlikely that research records have been maintained for many of these projects for the past three to five decades. Finally, the identification of an individual would be only the first step in tracking him to his current location.
Many of the children at the Wrentham and Fernald Schools have been located through extensive local efforts. The existence of the research records, as well as the records of these long-term residential institutions, have made these identifications possible.
4 . There are a few exceptions to the usual involvement of parents in decisions concerning their minor children. Children who are considered either "emancipated minors" or "mature minors" are generally able to receive routine medical care without any need for parental involvement. Emancipated minors are minor children who have taken on adult responsibilities, such as maintaining financial independence and/or living away from the parents' home. A mature minor, on the other hand, is considered to be decisionally capable under special circumstances because he or she has demonstrated the maturity and ability to decide treatment decisions for himself or herself. Adolescents can be considered emancipated or mature minors and are thereby exempted from parental consent. In addition, if a minor is close to the age of majority (at least fifteen), the treatment clearly benefits the minor and is medically necessary, there is good justification for not obtaining parental consent, and if the procedure is not extraordinary or one involving substantial risk to the child, then practitioners are usually able to deliver medical care without parental permission. A number of states permit minors to give consent to the diagnosis or treatment of venereal disease, drug addiction, alcoholism, pregnancy, or for purposes of giving blood. For more information on this subject, please see: A. R. Holder, Legal Issues in Pediatrics and Adolescent Medicine (New Haven, Yale University Press, 1985), 123; and Robert H. Mnookin and D. Kelly Weisberg, Child, Family, and State: Problems and Materials on Children and the Law (Little Brown and Company, New York, 1995).
5 . Mnookin and Weisburg, Child, Family, and State, 536. In addition, parents are considered to be "legally responsible for the care and support of their children," and "the parental consent requirement protects parents from having to pay for unwanted or unnecessary medical care and from the possible financial consequences of supporting the child if unwanted treatment is unsuccessful."
6 . In addition to the exceptions given in endnote 4, there are other standard common law and statutory limitations and exceptions to the general parental consent requirement. "These relate to mandatory immunizations and screening procedures (applicable to all children), the neglect limitation (where a court may override a parental decision for an individual child), the emergency treatment of children (where no parental consent is required if the parent is unavailable)." Ibid.
7 . "Some medical procedures are required of all children and in this sense represent generally applicable limitations on parental prerogatives. The Supreme Court has held, for example, that a state could impose a compulsory smallpox vaccination law as a 'reasonable and proper exercise of police power.' Jacobsen v. Massachusetts, 197 U.S. 11, 35 (1905) quoting Viemeister v. White, 72 N.E. 97 (1904). A vaccination requirement may act to protect society from various public health hazards created by communicable diseases where a parental decision may endanger not only a particular child but society at large." Mnookin and Weisburg, Child, Family, and State, 551.
8 . The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Research Involving Children: Report and Recommendations (Washington, D.C.: GPO, 1977), and Protection of Human Subjects, 45 C.F.R. [[section]] 46, subpart D.
9 . Protection of Human Subjects, 45 C.F.R. [[section]] 46.408.
10 . Ibid., [[section]] 46.404.
11 . Ibid., [[section]] 46.406.
12 . Ibid., [[section]] 46.407.
13 . Susan E. Lederer and Michael A. Grodin, "Historical Overview: Pediatric Experimentation," in Children as Research Subjects: Science, Ethics, and Law, eds. Michael A. Grodin and Leonard H. Glantz (New York: Oxford University Press, 1994), 4.
14 . Ibid., 5.
15 . Ibid., 6.
16 . "Orphans and Dietetics," American Medicine 27 (1921): 394-396.
17 . Lederer and Grodin, Children as Research Subjects, 11-12.
18 . Ibid., 14.
19 . Ibid., 12.
20 . Ibid., 15.
21 . This ruling is summarized in Jay Katz, Experimentation with Human Beings, the Authority of the Investigator, Subject, Professions, and State in the Human Experimentation Process (New York: Russell Sage Foundation, 1972), 972-974.
22 . Ibid.
23 . Ibid.
24 . Ibid.
25 . This case is also discussed in "Use of Fifteen Year Old Boy as Skin Donor Without Consent of Parents as Constituting Assault and Battery: Bureau of Legal Medicine and Legislation Society Proceedings," Journal of the American Medical Association 120 (17 October 1942): 562-563.
26 . For more information on the Nuremberg Code, please see United States v. Karl Brandt, et al., "The Medical Case," Trials of War Criminals before the Nuremberg Military Tribunals under Control Council Law No. 10 (Washington, D.C.: GPO, 1949), 2; Jay Katz, "Human Experimentation and Human Rights," St. Louis University Law Journal 38 (1993); and George J. Annas and Michael A. Grodin, eds., The Nazi Doctors and the Nuremberg Code: Human Rights in Human Experimentation (New York: Oxford University Press, 1992).
27 . Irving Ladimer, "Legal and Ethical Implications of Medical Research on Human Beings," (S.J.D. diss., George Washington University, 1958), appendix II, 202-208.
28 . Ibid., 207.
29 . Ibid., 206.
30 . Ibid., 208.
31 . Henry Seidel, interview by Gail Javitt (ACHRE), transcript of audio recording, 20 March 1995 (Research Project Series, Oral History Project), 67-68.
32 . Ibid.
33 . William Silverman, interview by Gail Javitt (ACHRE), transcript of audio recording, 14 February 1995 (Research Project Series, Oral History Project), 26.
34 . Ibid.
35 . Boston University, Law-Medicine Research Institute, 1 May 1961 ("Conference on Social Responsibility in Pediatric Research")(ACHRE No. BU-062394-A). This was part of a larger LMRI project (which was funded by NIH) to investigate actual practices in clinical research. The project began in early 1960 and continued until 1963, resulting in a lengthy final report, which was never published.
36 . Ibid., 5. In this document, speakers are identified by initials. A list of participants found in these same records generally makes identifying particular speakers in the transcripts quite straightforward. In this case, however, a complexity arises because the speaker is identified as "WF." The list of participants reveals no one with these initials, and "WF" appears only once in the transcripts. It is almost certain that "WF" is a typographical error, and given the flow of the transcripts, it is also almost certain that "WF" should have been "WS"--William Silverman.
37 . Ibid., 7.
38 . Ibid., 3.
39 . Ibid.
40 . Ibid., 2.
41 . Ibid., 6.
42 . Ibid., 17.
43 . Ibid., 15.
44 . Ibid.
45 . The Declaration of Helsinki can be found in many sources, but its earliest published appearance was perhaps "Human Experimentation: Code of Ethics of the World Medical Association," British Medical Journal 2 (1964): 177.
46 . Ibid.
47 . Ibid.
48 . Ibid.
49 . Ibid.
50 . Much has been written on the Willowbrook studies; for a short summary of this episode see Ruth R. Faden and Tom L. Beauchamp, A History and Theory of Informed Consent (New York: Oxford University Press, 1986), 5, 163-164.
51 . Henry Beecher, Research and the Individual: Human Studies (Boston: Little, Brown, and Company, 1970), 122-127.
52 . There were many exchanges in the medical literature over the hepatitis studies conducted by Saul Krugman at the Willowbrook State School. Stephen Goldby wrote an editorial to The Lancet, expressing his outrage over The Lancet's position on Krugman's research, saying that the research was "quite unjustifiable, whatever the aims, and however academically or therapeutically important are the results. . . . Is it right to perform an experiment on a normal or mentally retarded child when no benefit can result to that individual?" The editors of The Lancet responded to Goldby's letter, expressing agreement with his position, stating, "The Willowbrook experiments have always carried a hope that hepatitis might one day be prevented there and in other situations where infection seems almost inevitable; but that could not justify the giving of infected material to children who would not directly benefit." Krugman responded to these editorials by arguing,
Our proposal to expose a small number of newly admitted children to the Willowbrook strains of hepatitis virus was justified in our opinion for the following reasons: 1) they were bound to be exposed to the same strains under the natural conditions existing in the institution, 2) they would be admitted to a special, well-staffed unit where they would be isolated from exposure to other infectious diseases which were prevalent in the institution. . . . Thus, their exposure in the hepatitis unit would be associated with less risk than the type of institutional exposure where multiple infections could occur; 3) they were likely to have a subclinical infection followed by immunity to the particular hepatitis virus; and 4) only children with parents who gave informed consent would be included.
The debate over these experiments continued, as evidenced by editorials by Geoffrey Edsall, Edward Willey, and Benjamin Pasamanick in The Lancet and through an editorial in JAMA as well. Jay Katz, Experimentation with Human Beings, 1007-1010; Geoffrey Edsall, "Experiments at Willowbrook," The Lancet (10 July 1971): 95; Edward N. Willey and Benjamin Pasamanick, "Experiments at Willowbrook," The Lancet (22 May 1971): 1078-1079; and "A Shedding of Light," Journal of the American Medical Association 212 (11 May 1970): 1057-1058.
53 . S. Allan Lough, Chief of the Radioisotopes Branch, AEC Isotopes Division, to Drs. Hymer L. Friedell, G. Failla, Joesph G. Hamilton, A. H. Holland, Members of AEC Subcommittee on Human Applications, 19 July 1949 ("Revised Tentative Minutes of March 13, 1949 Meeting of Subcommittee on Human Applications of Committee on Isotope Distribution of U.S. Atomic Energy Commission, AEC Building, Washington, D.C.") (ACHRE No. NARA-082294-A-24). For price list and isotope catalogue, see AEC Isotopes Division, Supplement No. 1 to Catalogue and Price List No. 3, September 1949 (ACHRE No. DOD-122794-A), 3-4.
54 . S. Allan Lough, 19 July 1949 ("Revised Tentative Minutes of March 13, 1949 Meeting . . ."), 10.
55 . AEC General Manager Carroll Wilson's two 1947 letters that address the consent issue (see chapter 1) did not specifically mention children. The second letter, dated November 1947, required that "the patient give his complete and informed consent in writing, and (c) that the responsible nearest of kin give in writing a similarly complete and informed consent. . . ." It is not clear, however, that Wilson's phrase, "responsible nearest of kin," was written out of concern for children and other patients not capable of giving "complete and informed consent," as opposed, for example, to adult patients who were too sick to give such consent. Moreover, it is not even clear whether the letter was intended to apply to experiments with healthy subjects, as opposed to sick patients, or to experiments using tracer amounts of radioactive substances. The second letter is specifically focused on "substances known to be, or suspected of being, poisonous or harmful." It is plausible, for example, that tracer amounts of radionuclides were considered "harmless," especially since the Wilson letter expressly prohibited the administration of "harmful" substances unless there was a reasonable hope that "such a substance will improve the condition of the patient." Carroll L. Wilson, General Manager of the AEC, to Stafford Warren, the University of California, Los Angeles, 30 April 1947 ("This is to inform you that the Commission is going ahead with its plans . . .") (ACHRE No. DOE-051094-A-439), 1. Also C. Wilson, General Manager, AEC, to Robert Stone, University of California, 5 November 1947 ("Your letter of September 18 regarding the declassification of biological and medical papers was read at the October 11 meeting of the Advisory Committee on Biology and Medicine.") (ACHRE No. DOE-052295-A).
56 . J. H. Lawrence, "Early Experiences in Nuclear Medicine," The Journal of Nuclear Medicine 20 (1979): 561. (Publication of speech given in 1955). Dr. Lawrence concludes, however, that "as a matter of fact, in the 20 years since we first used artificially produced radioisotopes in humans, we have not run into delayed effects or complications as some of the skeptics predicted we would." Ibid., 562.
57 . This correspondence can be found in Task Force on Human Subject Research, A Report on the Use of Radioactive Materials, appendix B, documents 16-18.
58 . Citations for the studies for which the Committee performed detailed risk analysis can be found in the supplemental volumes.
59 . S. H. Silverman and L. Wilkins, "Radioiodine Uptake in the Study of Different Types of Hypothyroidism in Childhood," Pediatrics 12 (1953): 288-299.
60 . V. C. Kelley et al., "Labeled Methionine as an Indicator of Protein Formation in Children with Lipoid Nephrosis," Proceedings of the Society for Experimental Biology and Medicine 76 (1950): 153-155.
61 . M. A. Van Dilla and M. J. Fulwyler, "Thyroid Metabolism in Children and Adults Using Very Small (Nanocurie) Doses of Iodine-125 and Iodine-131," Health Physics 9 (1963): 1325-1331.
62 . For more information, please see the "Introduction: The Atomic Century," sections entitled "How Do We Measure the Biological Effects of Internal Emitters?" and "How Do Scientists Determine the Long-Term Risks From Radiation?"
63 . International Commission on Radiological Protection, Publication 53: Data for Protection Against Ionizing Radiation from External Sources (New York: Pergamon Press, 1973); see also National Council on Radiation Protection and Measurements, Report 80: Induction of Thyroid Cancer by Ionizing Radiation--Recommendations of the National Council on Radiation Protection and Measurements (New York: The Council, 1985).
64 . R. E. Shore et al., "Thyroid Tumors Following Thymus Irradiation," Journal of the National Cancer Institute 74 (1985): 1177-1184.
65 . E. Ron and B. Modan, "Thyroid and Other Neoplasms Following Childhood Scalp Irradiation," in J. D. Boice, Jr., and J. F. Fraumeni, Jr., eds., Radiation Carcinogenesis: Epidemiology and Biological Significance (New York: Raven, 1984), 139-151.
66 . R. L. Prentice et al., "Radiation Exposure and Thyroid Cancer Incidence among Hiroshima and Nagasaki Residents," National Cancer Institute Monographs 62 (1982): 207-212.
67 . National Council on Radiation Protection and Measurements, Report 80: Induction of Thyroid Cancer by Ionizing Radiation. The BIER V report recommends a figure of 0.66 but with a broad confidence interval of (0.14-3.15). National Research Council, Board on Radiation Effects Research, Committee on the Biological Effects of Ionizing Radiation, Health Effects of Exposure to Low Levels of Ionizing Radiation: BIER V (Washington, D.C.: National Academy Press, 1990), 5, 298.
68 . Task Force on Human Subject Research, "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."
69 . Protection of Human Subjects, 45 C.F.R. [[section]] 46.102.
70 . Ibid., [[section]] 46.406.
71 . F. P. Castronovo, "An Attempt to Standardize the Radiodiagnostic Risk Statement in an Institutional Review Board Consent Form," Investigative Radiology 28 (1993): 533-538.
72 . W. L. Freeman, "Research with Radiation and Healthy Children: Greater than Minimal Risk," IRB: A Review of Human Subjects Research 5, no. 16 (1994): 1-5.
73 . B. J. Duffy and P. J. Fitzgerald, "Thyroid Cancer in Childhood and Adolescence: A Report of Twenty-eight Cases," Cancer 3 (November 1950): 1018-1032.
74 . R. Murray, P. Heckel, and L. H. Hempelmann, "Leukemia in Children Exposed to Ionizing Radiation," New England Journal of Medicine 261 (1959): 585-597.
75 . Eugene L. Saenger et al., " Neoplasia Following Therapeutic Irradiation for Benign Conditions in Childhood," Radiology 74 (1960): 889-904. For more information on the work of Eugene Saenger, please see chapter 8, "Total-Body Irradiation: Problems When Research and Treatment Are Intertwined."
76 . Ibid., 889.
77 . Ibid., 901.
78 . S. A. Beach and G. W. Dolphin, "A Study of the Relationship Between X-Ray Dose Delivered to the Thyroids of Children and the Subsequent Development of Malignant Tumors," Physics in Medicine and Biology 6 (1962): 583-598.
79 . Ibid., 583.
80 . One rep (roentgen equivalent physical), a unit that is no longer used, is approximately equivalent to one rem (roentgen equivalent man).
81 . 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-100395-A). It appears that at least one physician-researcher of the time determined to avoid an unknown risk by not administering radioisotopes in studies with pregnant women and children. In his recent autobiography, Dr. Francis Moore, an eminent Boston-based surgeon, recalled that "in pregnancy, even very small doses of radiation are dangerous to the unborn child, so we did not use radioactive isotopes in studying the body composition in pregnant women or in young children." Presumably Dr. Moore is referring to the 1940s when he began his pioneering research employing radioisotopes to determine the composition of the body, although this is not clear. Whether Dr. Moore's view was informed by dialogue with the relevant pediatric perspectives reviewed here also is unclear. Francis D. Moore, M.D., A Miracle and a Privilege: Recounting a Half Century of Surgical Advance (Washington, D.C.: Joseph Henry Press, 1995), 109, 111.
82 . L. Van Middlesworth, "Radioactive Iodide Uptake of Normal Newborn Infants," American Journal of Diseases of Children 88 (1954): 441.
83 . Malcom J. Farrell, Superintendent, Walter E. Fernald State School, to Parent, 2 November 1949 ("The Massachusetts Institute of Technology and this institution are very much interested . . ."), as cited in the Task Force for Human Subject Research, "A Report on the Use of Radioactive Materials," appendix B, document 19.
84 . This form states,
To the Superintendent of the Walter E. Fernald State School: This is to state that I give my permission for the participation of ___________ in the project mentioned in your letter of________ Witnessed by: ________________ _______________ Signature Date:________________ _________________ Relationship
Permission form from Parent to the Superintendent of the Walter E. Fernald State School, 2 November 1949 ("This is to state that I give my permission . . ."), as cited by the Task Force on Human Subject Research, in "A Report on the Use of Radioactive Materials," appendix B, document 19.
85 . Clemens E. Benda, Director of Research, the Walter E. Fernald State School, to Parent, 28 May 1953, as cited by the Task Force on Human Subject Research, in "A Report on the Use of Radioactive Materials," appendix B, document 23.
86 . As stated in the Massachusetts Task Force report, the purpose of the nutritional research studies was to "understand how the body obtained the minerals iron and calcium from dietary sources and to find out whether compounds in cereals affected their absorption . . . the immediate goal of the research was to understand if either of these cereals was preferable from a nutritional point of view." Ibid., 16.
87 . Ibid., 43.
88 . Fred Boyce, transcript of audio testimony before the Advisory Committee on Human Radiation Experiments, 16 December 1994, 38.
89 . Task Force on Human Subject Research, in "A Report on the Use of Radioactive Materials," 33.
90 . Susan E. Lederer and Michael A. Grodin, "Historical Overview: Pediatric Experimentation," 12-13.
91 . Boston University, Law-Medicine Research Institute, 1 January 1960 to 31 March, 1963, A Study of the Legal, Ethical, and Administrative Aspects of Clinical Research Involving Human Subjects: Final Report of Administrative Practices in Clinical Research, Research Grant No. 7039 (ACHRE No. BU-053194-A), 34.
92 . Fred Boyce, 16 December 1994, 38.
93 . Robert S. Harris, Professor of Biochemistry and Nutrition, Massachusetts Institute of Technology, to Clemens E. Benda, 1 May 1953, as cited by the Task Force on Human Subject Research, in "A Report on the Use of Radioactive Materials," appendix B, document 21, 1.
94 . Ibid.
95 . Children who are considered "wards of the State or any other agency, institution, or entity" can become subjects of research if the research is related to their status as wards and conducted in a setting in which the majority of children involved in the research are not wards. If the research meets these conditions, the IRB must then appoint a special advocate not associated in any way with the research, who will act in the best interests of the child. Protection of Human Subjects, 45 C.F.R. [[section]] 46.409.
96 . There are also no special regulations protecting institutionalized adults. The Committee believes that the federal government should inplement public policies to fill this regulatory gap.
97 . This conclusion does not hold for people who believe that it is never acceptable to use children as subjects in nontherapeutic research, even if the research is risk-free.
98 . G. S. Kurland et al., "Radioisotope Study of Thyroid Function in 21 Mongoloid Subjects, including Observations in 7 Parents," Journal of Clinical Endocrinology and Metabolism 17 (1957): 552-60; A. Friedman, "Radioactive Uptake in Children with Mongolism," Pediatrics 16 (1955): 55; S. H. Silverman and L. Wilkins, "Radioiodine Uptake in the Study of Different Types of Hypothyroidism in Childhood," 288-299; and E. H. Quimby and D. J. McCune, "Uptake of Radioactive Iodine by the Normal and Disordered Thyroid Gland in Children," Radiology 49 (1947): 201-205.
99 . Boston University Law-Medicine Research Institute, Final Report of Administrative Practices in Clinical Research, 34.