“Something of an Adventure”: Postwar NIH Research Ethos and the Guatemala STD Experiments

Lynch H. F. , “Ethical Evasion or Happenstance and Hubris? The U.S. Public Health Service STD Inoculation Study,” The Hastings Center Report 42, no. 2 (2012): 30 (“There is a new entry in the long catalog of historic research abuses.”). Soldiers and prisoners had sexual intercourse with infected sex workers, and soldiers and psychiatric patients were injected with infected material in many parts of their bodies including genitals, eyes, and spinal columns. See generally, Reverby S. , ‘Normal Exposure’ and Inoculation Syphilis: A PHS ‘Tuskegee’ Doctor in Guatemala, 1946–48,” Journal of Policy History 23, no. 1 (2011): 6–28; see also, Presidential Commission for the Study of Bioethical Issues (Bioethics Commission 118), “‘Ethically Impossible:’ STD Research in Guatemala from 1946–1948,” (2011). Both Dr. Reverby and the Bioethics Commission describe this research in detail. In this article, the authors have chosen to cite directly to primary documents, rather than repeating citations to secondary sources, so that readers can easily verify the sources cited in this article and to encourage future scholarship on original sources. Many of the PCSBI Human Subjects Protection (HSP) I Archives sources are available online at <http://bioethics.gov/node/654> (last visited July 26, 2013). All of the PCSBI I Archives sources are available at the National Archives in Morrow, GA under Research Group 22, PCSBI, Record of the Guatemala Study. All of the documents archived by John C. Cutler are available at the National Archives online collection at <http://www.archives.gov/research/health/cdc-cutler-records/> (last visited August 13, 2013).

Faulty scientific design plagued the studies. Investigators altered or omitted data and information in final reports. See Bioethics Commission, supra note 1, at 95.

Secretary of State H. R. Clinton and Secretary of Health and Human Services Sebelius K. , “Joint Statement by Secretaries Clinton and Sebelius on a 1946–1948 Study” (2010), available at <http://www.state.gov/secretary/rm/2010/10/148464.htm> (last visited July 26, 2013); President Obama B. , “Memorandum re: Review of Human Subjects Protection (2010),” available at <http://bioethics.gov/cms/sites/default/files/news/Human-Subjects-Protection-Letter-from-President-Obama-11.24.10.pdf> (last visited July 26, 2013).

See Obama , supra note 3.

See Bioethics Commission, supra note 1, at 6.

See Minogue K. , “U.S. Officials Apologize for ‘Appalling’ 1940s Syphilis Study,” ScienceInsider, October 1, 2010, available at <http://news.sciencemag.org/scienceinsider/2010/10/usofficials-apologize-forappalling.html> (last visited July 26, 2013). While media accounts have generally focused on the role of Dr. Cutler, accounts in the scholarly literature, e.g. Reverby and the Bioethics Commission, supra note 1, as well as other more recent publications cited in this paper, have provided a broader analysis of the Guatemala episode.

There has been a movement in the rhetoric of human research away from humans being “subjects of” research towards “participants in” research. See Boynton P. M. , “Letters: People should participate in, not be subjects of, research,” British Medical Journal 317 (Nov. 28, 1998): 1521. The vulnerable populations involved in the Guatemala research, however, were clearly subjects of unethical research. In addition, 45 C.F.R. 46 currently uses the term “subject.” Therefore, for the purposes of this paper, we used the term “subject” for the Guatemalans involved in the STD research and when referencing current federal regulation, but “participant” when discussing the current research environment. Also, the increasing importance of statistical argument in designing clinical trials, and the infrastructure that grew to support them is described in detail in Marks H. M. , The Progress of Experiment: Science and Therapeutic Reform in the United States, 1900–1990 (New York: Cambridge University Press, 1997). Marks also discusses the early work on penicillin by scientists like Joseph Earle Moore on the National Research Council, and the transition of funding from the National Research Council to the NIH in detail, see id., at 98–128. Victoria Harden also provides a history of the legislative and administrative initiatives that led to establishment of the NIH in Harden V. , Inventing the NIH: Federal Biomedical Research Policy, 1887–1937 (Baltimore: Johns Hopkins University Press, 1986).

See, e.g., the recent Advanced Notice of Proposed Rulemaking on “Human Subjects Research Protections” which still grapples with ensuring that government regulated participant protections are “commensurate with the level of risk of the research study” in order to protect participants in high risk studies, while allowing lower risk studies to proceed more efficiently. Human Subjects Research Protections, Department of Health and Human Services, “Enhancing Protections for Research Subjects and Reducing Burden, Delay, and Ambiguity for Investigators,” 76 Fed. Reg. 44512, 44514–44521. See also, Basken P. , “NIH Considered Anonymity for Grant Applications,” The Chronicle of Higher Education, December 10, 2012, available at <http://chronicle.com/article/NIHConsiders-Anonymity-for/136227/> (last visited July 29, 2013); and Wessely S. , “Peer Review of Grant Applications: What Do We Know?” The Lancet 352, no. 9124 (1998): 301–302. For a look at the continued challenges of conflict of interest disclosure generally see Loewenstein G. , “The Unintended Consequences of Conflict of Interest Disclosure,” JAMA 307, no. 7 (2012): 669–670.

Van Slyke C.J. , “Health Sciences,” Oral History Research Office, Columbia University (1976): At 29.

Stewart I. , Organizing Scientific Research for War: The Administrative History of the Office of the Scientific Research and Development (Boston: Little, Brown and Company, 1948): At 4.

Id., at 5, 7.

Roosevelt F. D. , Executive Order 7065, The National Resources Committee is Created, available at <http://www.presidency.ucsb.edu/ws/index.php?pid=15075> (last visited July 29, 2013).

National Resources Committee, Research – A National Resource (Washington, D.C.: United States Government Printing Office, 1938): 16.

An Advisory Council was also established “to advise and assist the Director with respect to the co-ordination of research activities carried on by private and governmental research groups. …” See Stewart (1948), supra note 10, at 36–37. These contracts were originally that of the National Defense Research Committee, which was charged with coordinating, supervising, and conducting scientific research on problems underlying the development, production, and use of mechanisms and devices of warfare. The National Defense Research Committee later became advisory to the Office of Scientific Research and Development. Id., at 7–8, 37–38.

Id., at 39.

Id., at 103.

See Stewart (1948), supra note 10, at 5. In June of 1940, the National Research Council decided to create a Subcommittee on Venereal Disease to make “general recommendations to The Surgeons General of the Army and Navy concerning the prevention and treatment of the venereal diseases and with acting in a consultative capacity on questions in its special field that might originate from the armed services.” Padget P. , “Diagnosis and Treatment of the Venereal Diseases: Historical Note,” International Medicine in World War II, Vol. II: Infectious Diseases (Washington D.C.: Office of the Surgeon General, Department of the Army, 1963): At 409.

Letter from Moore J. E. , Chairman, Subcommittee on Venereal Diseases to Richards A. N. , Chairman, Committee on Medical Research (Oct. 9, 1945) in PCSBI HSP I Archives, NARA-II_0000117.

Stewart I. , First Draft of Proposed C.M.R. Chapter for Irvin Stewart's Administrative History of OSRD (1945): 20–21 in PCSBI HSPI Archives, NARA-II_0000373–74.

Mandel R. , A Half Century of Peer Review 1946–1996 (Bethesda, MD: Division of Research Grants, National Institutes of Health, 1996): At 8.

Id., at 11.

Id., at 12.

Miles R. E. Jr. , The Department of Health, Education, and Welfare (New York: University Press of America, 1974): At 169.

Mandel , supra note 20, at 11–12.

Id., at 20.

Mahoney J. F. , “An Experimental Resurvey of the Basic Factors Concerned in Prophylaxis in Syphilis,” The Military Surgeon (1936): 351–363, at 351.

Letter from Moore J. E. , Chairman, Subcommittee on Venereal Diseases, National Research Council to Richards A. N. , Chairman, Committee on Medical Research, National Research Council (Feb. 1, 1943) in PCSBI HSPI Archives, NARA-II_0000176.

See Mandel , supra note 20, at 15–16, 23. Three physicians including Mahoney John Drs. Arnold R.C. (both later involved in the Guatemala STD experiments) discovered in 1943 that penicillin cured syphilis. Mahoney J. F. Arnold R. C. Harris A. , “Penicillin Treatment of Early Syphilis: A Preliminary Report,” American Journal of Public Health and the Nation's Health 33, no. 12 (1943): 1387–91.

See Miles , supra note 23, at 169; see, e.g., “Medicine: New Magic Bullet,” Time Magazine, October 25, 1943.

“The practical experience and specific progress from 1942 through 1945 brought about a new philosophical attitude toward government's role in science and health and new optimism about the power of science, particularly organized science.” Strickland S. P. , The Story of the NIH Grants Program (New York: University Press of America, 1989): At 17.

“By carefully nurturing the peer review process and by cultivating rapport with Congress, Surgeon General Parran and NIH Director Dyer won the allegiance of a substantial majority of academic scientists and laid the institutional foundations for the nationwide extramural structure that would emerge in the following decade.” Mandel , supra note 20, at 15–16.

Endicott K. M. Allen E. M. , “The Growth of Medical Research 1941–1953 and the Role of Public Health Service Research Grants,” Science 118, no. 3065 (1953): 337–43, at 337.

See Mandel , supra note 20, at 22.

See Miles , supra note 23, at 169.

See Mandel , supra note 20, at 19.

See Stewart (1948), supra note 10, at 103.

See Van Slyke C. J. , “New Horizons in Medical Research,” Science 104, no. 2711 (1946): 559–67, at 559.

See Mandel , supra note 20, at 20, 22; Van Slyke C. J. , “Standard Form 61: Appointment Affidavits” (n.d.) in PCSBI HSPI Archives, NPRC_0002846.

See Strickland , supra note 30, at 31.

See Van Slyke , supra note 37, at 559.

Id.

See Mandel , supra note 20, at 30. This article was a major policy statement about the direction that government funding grants would take and the role of scientific independence in that program.

See Van Slyke , supra note 37, at 563.

Id.

Van Slyke C. J. , ‘Research Grants Awarded by National Institute of Health,’ (Sept. 23, 1947) 1, in PCSBI HSPI Archives, MISC_0000037.

See Strickland , supra note 30, at 32.

See Mandel , supra note 20, at 22. As Assistant Chief of the DRG during the Guatemala experiments, Dr. Allen was also the one to convey to the researchers that they could use the remaining grant money to continue their work in Guatemala for up to 6 months after the grant's expiration. Letter from Allen E. M. to Murdock J. R. (June 28, 1948) in PCSBI HSPI Archives, CTLR_0001182.

See Endicott Allen , supra note 32, at 341.

Id.

See Van Slyke , supra note 9, at 29.

Id.

Id., at 42–43.

Shannon Dr. was the chair of the Malaria Study Section in 1947 and became the Associate Director of Research under Van Slyke Dr. at the National Heart Institute in 1948. See Van Slyke (1976), supra note 9, at 50. Allen E. M. , “Historical View: Early Years of NIH Research Grants,” NIH Alumni Association Newsletter (II)(1980): 6–8, also in PCSBI HSPI Archives, MISC_0000064.

This Committee was investigating NIH expenditures. Shannon J.A. , “The Administration of Grants by the National Institutes of Health,” Hearings Before the Subcommittee on Intergovernmental Relations of the Committee on Government Operations of the House of Representatives 87th Cong. (March 28–30, 1962): At 14. Lawmakers had challenged the NIH budget, and other questions had been raised in light of the seeming avalanche of new funding that NIH had disbursed. Stark L. , Behind Closed Doors: IRBs and the Making of Ethical Research (Chicago: University of Chicago Press, 2012): At147–48.

See Shannon , supra note 54, at 14.

See Mandel , supra note 20, at 1; Miles , supra note 23, at 177.

Van Slyke , supra note 9, at 28–29. Van Slyke Dr. later elaborated that setting up the Division this way was ‘the easiest way to run it … It just puts your responsibilities on somebody else's shoulders. But those shoulders are a devil lot more competent to carry it than any single federal bureaucrat I know of.’ Id., at 64.

See Van Slyke , supra note 37, at 561.

See Mandel , supra note 20, at 46.

See Van Slyke , supra note 37, at 562.

See Miles , supra note 23, at 180.

See Van Slyke , supra note 37, at 562.

See Mandel , supra note 20, at 23; see also Memorandum from Allen E.M. to Dyer R.E. , (Mar. 8, 1946) in PCSBI HSPI Archives, NARA-II_0000129.

Letter from Moore J.E. , Chairman, Subcommittee on Venereal Diseases to Richards A.N. , Chairman, Committee on Medical Research (Oct. 9, 1945) in PCSBI HSPI Archives, NARAII_0000117.

See Padget , supra note 17, at 409; Van Slyke , supra note 37, at 567. Prior to the Subcommittee on Venereal Disease's recommendations, the diagnosis and treatment of syphilis in the Army followed the protocol outlined by Dr. Stokes in Modern Clinical Syphilology. Stokes J. H. , Modern Clinical Syphilology (Philadelphia: W.B. Saunders Co., 19236).

Other members included: Price David E. (NIH), Reed Lowell J. (Johns Hopkins School of Hygiene and Public Health), Solomon Harry C. (Boston Psychopathic Hospital), Maj. Altshuler L. N. (Army), Cdr. George W. Mast (Navy), and Bascom Johnson (Veterans Administration). Van Slyke , supra note 37, at 567.

[Draft] letter from Moore J. E. , Chairman, Syphilis Study Section to Van Slyke C.J. (May 1947), found in letter from Moore J.E. , Chairman, Syphilis Study Section to Members of the Syphilis Study Section, National Institute of Health (May 26, 1947), in PCSBI HSPI Archives, NARA-II_0000033.

National Advisory Health Council Meeting, U.S. Public Health Service (Mar. 8–9, 1946): At 13, in PCSBI HSPI Archives, NARA-II_0000547. Even though a later memo by Dr. Allen states that ‘[c]opies of the minutes of the meeting and of papers presented are on file in the Research Grants office …’ the protocol for the Guatemala STD research or minutes of this meeting have not been located. Memorandum from E.M. Allen to R.E. Dyer (Mar. 8, 1946), in PCSBI HSPI Archives, NARA-II_0000129.

See National Advisory Health Council, supra note 68 at 10, 13.

Id.

Cutler J. C. , Final Syphilis Report (Feb. 24, 1955): At 9, in PCSBI HSPI Archives, CTLR_0000641.

Supplemental Information Submitted in Connection with 1948 Amendment to Budget: Status of Grants, State of Illinois; Grants Paid, Fiscal Yr 1946 & 1947: At 5, in PCSBI HSPI Archives, NARA-II_0000076. When the grant was renewed in 1947, Soper Fred Dr. , the Director of the Pan American Sanitary Bureau, was listed as the Principal Investigator. National Advisory Health Council, U.S. Public Health Service, Minutes of Meeting (Mar. 14–15, 1947), in PCSBI HSPI Archives, NARA-II_0000047. While it appears from correspondence that Dr. Soper did visit the Guatemala experiments, it is not clear how much he knew about what they entailed. See, e.g., Letter from Mahoney J. F. to Cutler J. C. (June 30, 1947), in PCSBI HSPI Archives, CTLR_0001077.

“Organizational expert Harold Seidman has characterized scientific research as ‘the only pork barrel for which the pigs determine who gets the pork.’” See Miles , supra note 23, at 179.

Supplemental Information Submitted in Connection with 1948 Amendment to Budget, supra note 72, at 5.

The minutes of this meeting have not been located, see supra note 68. However, the listing of “Guatemala” as the grantee and the “Pan American Union” as the investigator may have allowed Dr. Mahoney to recommend the grant. See National Advisory Health Council (1946), supra note 68 at 13.

See Mahoney , supra note 28.

Mahoney J. F. Ferguson C. Buchholtz M. Van Slyke C. J. , “The Use of Penicillin Sodium in the Treatment of Sulfonamide-Resistant Gonorrhea in Man,” The American Journal of Syphilis, Gonorrhea, and Venereal Disease 27, no. 5 (1943): 525–528.

See Cutler , supra note 71, at 7, in PCSBI HSPI Archives, CTLR_0000639. Orvusmapharsen was a 10-percent argyrol (i.e., silver) intra-urethral instillation.

Id.

Id.

Id., at 22, PCSBI HSPI Archives, CTLR_0000654. Cutler J. C. , Experimental Studies in Gonorrhea (Oct. 29, 1952): At 1, in PCSBI HSPI Archives, CTLR_0001278.

See Cutler , supra note 71, in PCSBI HSPI Archives, CTLR_0000629.

See Van Slyke , supra note 37.

See Mandel , supra note 20, at 25. By December, however, it appears Van Slyke Dr. was replaced with Price Dr. . See Van Slyke , supra note 37, at 567.

See Allen , supra note 53, at 1, in PCSBI HSPI Archives MISC_0000063; Van Slyke , supra note 9, at 23.

Letter from J. C. Cutler to Mahoney J. F. (Mar. 12, 1947), in PCSBI HSPI Archives, CTLR_0001054.

Cutler J. C. to Arnold R. C. (Aug. 21, 1946) in PCSBI HSPI Archives CTLR_0001216. Almost 600 photographs in Guatemala were taken of the subjects, prophylactic procedures, and symptomatic results of the STD exposures. Bioethics Commission, supra note 1, at 110.

Letter from Mahoney J. F. to Cutler J. C. (June 30, 1947) in PCSBI HSPI Archives CTLR_0001077. Those reports otherwise went to Drs. Mahoney and Arnold – not Syphilis Study Section members.

Letter from Mahoney J. F. to Cutler J. C. , (Oct. 15, 1946) in PCSBI HSPI Archives, CTLR_0001200. It is unclear if Dr. Moore actually visited the Guatemala study site.

Mahoney J. F. Van Slyke C. J. Cutler J. C. Blum H. L. , “Experimental Gonococcic Urethritis in Human Volunteers,” American Journal of Syphilis, Gonorrhea, and Venereal Disease 30, no. 1 (1946): 1–39.

Kaempffert W. , “Notes on Science: Syphilis Prevention,” New York Times, April 27, 1947, at E9.

Letter from Mahoney J. F. to Cutler J. C. (May 5, 1947) in PCSBI HSPI Archives, CTLR_0001243.

See Mahoney , supra note 89.

Letter from Coatney G. R. to Cutler J. C. (Feb. 17, 1947) in PCSBI HSPI Archives CTLR_0001051. See Lynch , supra note 1, for further debate regarding the Parran comment. In addition, as this article was under review, the American Sexually Transmitted Diseases Association decided to remove the name of Dr. Thomas Parran from its lifetime achievement award, in large part because of his role in the Guatemala research described in this article. See Altman L. K. , “Of Medical Giants, Accolades and Feet of Clay,” New York Times, April 1, 2013, at D3. For a series of essays discussing Parran's Dr. legacy, see also Sexually Transmitted Diseases 40, no. 4 (2013): 275–284.

Letter from Mahoney J. F. to Cutler J.C. (Feb. 19, 1948) in PCSBI HSPI Archives, CTLR_0001223.

See Stewart , supra note 10, at 103.

See Van Slyke , supra note 37, at 563.

Letter from Cutler J. C. to Mahoney J. F. (Oct. 31, 1946) in PCSBI HSPI Archives CTLR_0001199.

Letter from Cutler J. C. to Mahoney J. F. (June 22, 1947) in PCSBI HSPI Archives CTLR_0001241. See, e.g., Letter from Murdock J. R. to Cutler J. C. , forwarded by McAnally W. J. , Jr. (Dec. 26, 1947) in PCSBI HSPI Archives, CTLR_0001102.

Soper F. L. , Report of the Director of the Pan-American Sanitary Bureau to the Member Governments of the Pan American Sanitary Organization: January 1947-April 1950 (n.d.): At 30, in PCSBI HSPI Archives, PAHO_0000486. The Pan American Sanitary Bureau later became part of the Pan American Sanitary Organization, which then was renamed the Pan American Health Organization. Cueto M. , The Value of Health: A History of the Pan American Health Organization (Rochester: University of Rochester Press, 2007): 63–108.

See Bioethics Commission, supra note 1, at 116.

Letter from Cutler J. C. to Mahoney J. F. (June 22, 1947) in PCSBI HSPI Archives CTLR_0001241.

Letter from Mahoney J. F. to Cutler J.C. (June 30, 1947) in PCSBI HSPI Archives CTLR_0001077.

National Advisory Health Council, supra note 68, at 10, 13, PCSBI HSPI Archives, NARA-II_0000544, NARA-II_0000547.

Cutler J. C. , Gonorrheal experiment #1 (1947) in PCSBI HSPI Archives, CTLR_0001736–79.

National Advisory Health Council, U.S. Public Health Service, “Minutes of Meeting March 14–15” (1947): At 58, in PCSBI HSPI Archives, NARA-II_0000473, NARA-II_0000530.

See Cutler , supra note 71, PCSBI HSPI Archives, CTLR_0000694.

The funding was authorized through June 1948. Letter from Cutler J. C. to Mahoney J. F. , forwarded by McAnally W. J. Jr. , (Aug. 26, 1948) in PCSBI HSPI Archives, CTLR_0001163.

Letter from Mahoney J. F. to Cutler J. C. , forwarded by Soper F. L. , Director, Pan-American Sanitary Bureau (Sept. 3, 1948) in PCSBI HSPI Archives, CTLR_0001161.

Letter from Allen E. M. to Murdock J. R. (June 28, 1948) in PCSBI HSPI Archives, CTLR_0001182.

This annual report has not been located, but would have described the “scientific progress” up to that point.

See National Resources Committee, supra note 13, at 16.

See Van Slyke , supra note 9, at 35.

See Cutler , supra note 81, at 2, PCSBI HSPI Archives, CTLR_0001279; Cutler, supra note 71, at 8, PCSBI HSPI Archives, CTLR_0000640.

If the researchers could not establish what percentage of subjects became infected after exposure to an STD naturally, they could not establish the preventative effect of the prophylactic wash.

See Cutler , supra note 71, at 8, PCSBI HSPI Archives, CTLR_0000766.

Letter from Mahoney J. F. to Cutler J. C. (May 5, 1947) in PCSBI HSPI Archives, CTLR_0001243.

Letter from Mahoney J. F. to Cutler J. C. (Sept. 8, 1947) in PCSBI HSPI Archives, CTLR_0001234.

Letter from Mahoney J. F. to Cutler J. C. (Sept. 8, 1947) in PCSBI HSPI Archives, CTLR_0001233.

See Cutler , supra note 81, at 12, PCSBI HSPI Archives, CTLR_0001290; Cutler, supra note 71, PCSBI HSPI Archives, CTLR_0000701.

See Cutler , supra note 71, at 5, PCSBI HSPI Archives, CTLR_0000763.

Id., PCSBI HSPI Archives, CTLR_0000728.

Id., at 13, PCSBI HSPI Archives, CTLR_0000836.

See Insane Asylum ( de Alienados Asilo ) and Prison Patient Records (Various dates), in PCSBI HSPI Archives, CTLR_0004157.

Cutler J. C. , Chancroid Experiment (n.d.) in PCSBI HSPI Archives, CTLR_0000951, CTLR_0000969.

See Bioethics Commission, supra note 1, at 117.

See Van Slyke , supra note 9, at 22–23.

See Bioethics Commission, supra note 1, at 97–101.

Beecher H. K. , “Ethics and Clinical Research,” New England Journal of Medicine 274, no. 24 (1966): 1354–60, at 1354–55.

Id., at 1360.

See Allen , supra note 53, at 6–8, in PCSBI HSPI Archives MISC_0000064.

See Mandel , supra note 20, at vii.

Examples include the Tuskegee syphilis experiments, the Jewish Chronic Disease Hospital cancer experiments, and the Willowbrook State School Hepatitis A experiments. See Arras J. D. , “The Jewish Chronic Disease Hospital Case,” Jones J. H. , “The Tuskegee Syphilis Experiment,” and Robinson W.M. Unruh B.T. , “The Hepatitis Experiments at Willowbrook State School,” in Emanuel E. J. , eds., The Oxford Textbook of Clinical Research Ethics (New York: Oxford University Press, 2008): At 73–96. 13442 C.F.R. 52h.2, 52h.5 (2004).

42 C.F.R. 52h.5 (2004).

“Scientific Peer Review of Research Grant Applications and Research and Development Contract Projects,” 69 Fed. Reg. 272, 275 (Jan. 5, 2004).

42 C.F.R. Part 52h.5(d) (2004).

Basken P. , “NIH Considered Anonymity for Grant Applications,” The Chronicle of Higher Education, December 10, 2012, available online at <http://chronicle.com/article/NIHConsiders-Anonymity-for/136227/> (last visited August 13, 2013).

45 C.F.R. §46.111 (2009).