History of Research Ethics
Case studies
Tuskegee and Guatemala
Jeffrey D. Klausner, MD, MPH
Professor of Medicine and Public Health
Attending Physician Ronald Reagan Medical Center
Division of Infectious Diseases: Global Health
David Geffen School of Medicine
Department of Epidemiology
Karin and Jonathan Fielding School of Public Health
August 2015
Disclosures
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Dr. Klausner is a faculty member of the University of California Los Angeles
Dr. Klausner is a guest researcher with the US CDC Mycotics Diseases Branch
Dr. Klausner is a member of the WHO STI advisory group
Dr. Klausner is a board member of YTH.org
In the past 12 months, Dr. Klausner has received:
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Research grant funding, supplies or unrestricted gifts from the NIH, CDC, Hologic
Inc., Orasure Inc., Cepheid, Healthvana Inc.
JDKlausner@mednet.ucla.edu
Outline
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Quick review of ethical principles
Tuskegee syphilis experiment
Guatemala syphilis experiment
Small group discussion and report back
Research Ethical Principles
• Respect for Persons
• Beneficience
• Justice
http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.html [1979]
Application of Research Ethical Principles
Principle
Practice
Respect for Persons
Informed consent
Beneficience
Risks and benefits
Justice
Selection of subjects
Tuskegee Study
1932-1972
• Macon County, Alabama,
pop. 11,846
• To study the natural progression of
untreated syphilis in rural AfricanAmerican men
• US Public Health Services began
the study in 1932
• Investigators enrolled in the study
a total of 600 men:
• 399 who had previously
contracted syphilis
• 201 without syphilis
Tuskegee Study
1932-1972
• Research team included Tuskegee
Institute, US Public Health Service
doctors, Dr. Eugene Dibble and
Nurse Eunice Rivers
• Men were given free medical care,
meals and free burial insurance
• Study members were told they
were being treated for "bad blood",
a local term for various illnesses
that included syphilis, anemia and
fatigue
Tuskegee Study
1932-1972
• In 1947, penicillin proven to be
effective treatment for syphilis
• Study participants never
specifically told they had syphilis,
nor were they ever treated for it
• Researchers prevented men from
being treated elsewhere
• Post-World War II research
requirements changed but not the
Tuskegee Study
Tuskegee Study
1932-1972
• In 1966, Peter Buxton, a venerealdisease investigator in San Francisco,
raised concerns about the study
• The CDC reconfirmed the study’s value
along with:
• National Medical Association
• American Medical Association
• In 1972, Washington Star broke the
story, followed by NY Times
• Investigation ensued and study
terminated
Tuskegee Study
1932-1972
• USG paid $9M to survivors and families
• National Research Act 1974
• Belmont Report (1979) included guidelines for ethics in medical
research
President Clinton Apology
May 16th, 1997
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“…today America does remember the
hundreds of men used in research without
their knowledge and consent. Men who
were poor and African American, without
resources and with few alternatives, they
believed they had found hope when they
were offered free medical care by the
United States Public Health Service. They
were betrayed.”
The United States government did
something that was wrong—deeply,
profoundly, morally wrong. It was an
outrage to our commitment to integrity and
equality for all our citizens... clearly racist.
Real Time with Bill Maher
March 6, 2007
Video
American J Public Health, 1991
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The Tuskegee study of untreated syphilis in the Negro male is the longest non-therapeutic
experiment on human beings in medical history.
The strategies used to recruit and retain participants were quite similar to those being
advocated for HIV/AIDS prevention programs today. Almost 60 years after the study began,
there remains a trail of distrust and suspicion that hampers HIV education efforts in Black
communities. The AIDS epidemic has exposed the Tuskegee study as a historical marker for
the legitimate discontent of Blacks with the public health system.
The belief that AIDS is a form of genocide is rooted in a social context in which Black
Americans, faced with persistent inequality, believe in conspiracy theories about Whites
against Blacks. These theories range from the belief that the government promotes drug
abuse in Black communities to the belief that HIV is a manmade weapon of racial warfare. An
open and honest discussion of the Tuskegee Syphilis Study can facilitate the process of
rebuilding trust between the Black community and public health authorities. This dialogue can
contribute to the development of HIV education programs that are scientifically sound,
culturally sensitive, and ethnically acceptable.
Thomas SB, Quinn SC. The Tuskegee Syphilis Study, 1932 to 1972: implications for HIV education and AIDS risk education programs in the black community.
Am J Public Health. 1991 Nov;81(11):1498-505.
Community Impact of
Tuskegee Study
• What is the community impact?
• Distrust, conspiracy, fear
• ? Lack of participation in research
and preventive health care
Brandon DT J Natl Med Assoc. Jul 2005; 97(7): 951–956.
RV Katz et al. American Journal of Public Health June 2008; 98 (6): 1137–1142
Guatemala
1946-1948
• US Public Health Service
conducted syphilis experiments in
Guatemala from 1946 to 1948.
• Doctors infected soldiers,
prisoners, and mental patients with
syphilis without the informed
consent of the subjects, and then
treated them with antibiotics.
• In October 2010, the U.S. formally
apologized to Guatemala for
conducting these experiments
Special thanks to Prof. Jonathan Zenilman, Johns Hopkins University
What Was Known?
What were the Questions?
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By the end of World War II, the efficacy of Penicillin for Syphilis and
Gonorrhea was being determined
There was tremendous interest in preventive treatment of contacts
STDs had tremendous impact on military deployability
Standard medical texts of the day (eg Stokes, 1944) did not address
preventive treatment
Slide courtesy of J. Zenilman
Syphilis rates per 1000, US, 1940
Slide courtesy of J. Zenilman
Slide courtesy of J. Zenilman
The Guatemala Study Questions
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Can a preventive treatment regimen be evaluated in a model where
humans are infected under controlled conditions?
Comparison groups—Orvus-Mapharsen (arsenical); Penicillin (at
various doses), Controls
Studies done in syphilis, gonorrhea, chancroid
Sources of infected material—ground up solutions of syphilis
organisms from rabbits; or transfer of human material (TP, GC, HD)
Grant approved by the Syphilis Study Section, USPHS,
February 1946
Slide courtesy of J. Zenilman
Initial Approach--Develop the Model
“Natural” infection
Commercial Sex Workers Recruited
Experimentally infected with T. pallidum
Intercourse with Prison inmates or soldiers
Evaluated immediately post coital and serially
FINDING- Infection rate low—not useful for prevention
experiments
Slide courtesy of J. Zenilman
Direct Infection Model--Syphilis
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Subject Population-Asylum, Prisoners
Infection experiments:
 Evaluate pedigree T pallidum strains
 Swab transfer
 Pledgets
 Direct Inoculation
 Differences in dose, organism pedigree, swab
placement time, “adjuvants”
 Followed by clinical exam, multiple RPR tests, subset
lumbar punctures
Slide courtesy of J. Zenilman
Slide courtesy of J. Zenilman
7 months earlier…
NY Times
April 27, 1947
Slide courtesy of J. Zenilman
Guatemala Discovery Timeline
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2003—Dr Susan Reverby discovers
Cutler records at University of Pittsburgh
May 2010—Reverby notifies the former
director of the CDC—Dr David Sencer
Summer 2010—US recovers Cutler
documents and starts formal review
October 2010—Formal apology to
Guatemala
November 2010—President Obama
directs the Presidential Commission on
Bioethical Issues to investigate
August 2011—Public Hearing
December 2011—Full report
Slide courtesy of J. Zenilman
Susan M. Reverby, a Wellesley College Professor
Guatemala Apology
October 2010
Secretary of State Hillary Rodham Clinton and
Health and Human Services Secretary
Kathleen Sebelius apologized to the government of
Guatemala and the survivors and descendants of
those infected.
They called the experiments “clearly unethical.”
“Although these events occurred more than 64
years ago, we are outraged that such reprehensible
research could have occurred under the guise of
public health,” the secretaries said in a statement.
“We deeply regret that it happened, and we
apologize to all the individuals who were affected
by such abhorrent research practices.”
Slide courtesy of J. Zenilman
www.bioethics.gov
Discussion
• Were those syphilis studies unethical? Why?
• In what situation could such studies be ethical, if ever?
• What ethical principles were violated? What procedures
exist to uphold those principles?
• Tuskegee—Respect for Persons
• Guatemala—Beneficience
• How did the US respond to the study findings?
• How do those experiences and common history relate to
HIV/AIDS?
Discussion
• Agree or disagree and why?
“The Tuskegee study of untreated syphilis in the Negro male is the longest nontherapeutic experiment on human beings in medical history. The strategies used to
recruit and retain participants were quite similar to those being advocated for
HIV/AIDS prevention programs today. Almost 60 years after the study began, there
remains a trail of distrust and suspicion that hampers HIV education efforts in Black
communities. The AIDS epidemic has exposed the Tuskegee study as a historical
marker for the legitimate discontent of Blacks with the public health system. The
belief that AIDS is a form of genocide is rooted in a social context in which Black
Americans, faced with persistent inequality, believe in conspiracy theories about
Whites against Blacks. These theories range from the belief that the government
promotes drug abuse in Black communities to the belief that HIV is a manmade
weapon of racial warfare. An open and honest discussion of the Tuskegee Syphilis
Study can facilitate the process of rebuilding trust between the Black community and
public health authorities. This dialogue can contribute to the development of HIV
education programs that are scientifically sound, culturally sensitive, and ethnically
acceptable.”
S B Thomas and S C Quinn. The Tuskegee Syphilis Study, 1932 to 1972: implications for HIV
education and AIDS risk education programs in the black community. American Journal of Public
Health November 1991: Vol. 81, No. 11, pp. 1498-1505.