The document provides an overview of the Tuskegee Syphilis Study and discusses its legacy and impact. Some key points: 1) The Tuskegee Syphilis Study began in 1932 and involved observing the natural progression of untreated syphilis in African American men in Alabama over 40 years without their informed consent. 2) Penicillin became the standard treatment for syphilis in the 1940s but the men were deliberately denied treatment even when it was widely available. 3) The study caused immense harm and distrust in the medical system among the African American community. It highlighted the need for ethical guidelines around informed consent and protecting vulnerable populations in research. 4) While it provided important lessons

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The Legacy of the
Tuskegee Syphilis Study
PRS 565D
Lisa M Carlson, MPH, MCHES
Tuskegee analysis adapted in part from Parker, Alvarez and Thomas
The Tuskegee Experiment
§ Heralded by Booker T Washington as an
economic development program for African-
Americans
§ The study was but one part of the program
Tuskegee
“All public health research is
conducted in the shadow of the actual
study and the cultural icon that it has
become.”
– Parker, Alvarez, and Thomas
“Just like Tuskegee”
§ A “cultural icon”
§ “Symbol of what it means to conduct
unethical research on human beings”
§ “Emotionally charged meanings”
§ “Can cloud careful and accurate analysis of
what is actually at stake”
Terminology
§ Official title: “The Tuskegee Study of Untreated
Syphilis in the Negro Male”
§ Are others more historically accurate?
– “US Public Health Service Study of Untreated Syphilis
in the Negro Male”
– “Cooperative project of the PHS, Tuskegee Institute,
Tuskegee Medical Society and Macon County Health
Dept of Alabama”
§ “Tuskegee Syphilis Study” – does this unfairly
taint the Tuskegee Institute name?
§ “Tuskegee Experiment” – inappropriate because
there was an intervention tested: “experiment in
withholding treatment”
§ Common reference: TSUS
More Terminology
§ “Participants”
– Current terminology for study enrollees (which in itself
would be a misleading term in this case since there was
no informed consent)
– Suggests collaborative interaction
§ “Subjects”
– Perpetuates status as people to whom things were done
– Accurate to what happened, but to maintain is to show a
lack of respect
§ The men in the study

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The Men in the Study*
§ 624 men in total in the study
– 427 men
– 185 controls
– 12 controls switched to the syphilitic arm
§ Over the course of the study, wives and
children were infected
§ Last man died in 2004, last wife died in
2009
* CDC seminar, 3.2.12
History of the Tuskegee Study
§ 1920s – medical and public health communities
hypothesized that blacks and whites had different
responses to disease
§ PHS felt it had an ideal opportunity to study the
course of disease in blacks and to compare the
course of disease to whites
– A study of the natural course of untreated syphilis in 2000
white patients had been completed in Oslo, Norway
(1891-1910) (google this)
– In Macon County, Alabama, 35-40% of those tested were
positive for syphilis
§ Study began in 1932
§ Planned to provide treatment, which included
arsenic, mercury and bismuth
The Major Players
§ Nurse Eunice Rivers (black woman,
graduate of Tuskegee Institute) was hired as
the study coordinator – primary contact
§ The Tuskegee Institute was promised
training and employment for its doctors and
nurses for participating
§ The men were told they were being tested
for “bad blood” and were not given
information that they had syphilis or about
its transmission or treatment
Extending the Study
§ Original study was to last 6-12 months
– Minimal course of treatment – not enough for cure, may
have made them noninfectious
§ It was extended to track the men until their death,
perform autopsies, and track the complete natural
course of untreated syphilis
§ Nurse Rivers encouraged dying men to enter
hospital and families to consent to autopsy
§ The Milbank Memorial Fund provided $50 burial
stipends to families in exchange for permission to
perform the autopsy
The Men
§ The men received placebos of iron and
aspirin, which did improve their general
health
§ They were thus enthusiastic participants
§ They were receiving more medical care than
they could afford on their own
Awareness of VD Rising
§ Those running the study thought it important
that it not be compromised by the men
receiving treatment
§ 1930s and early 1940s, PHS clinics treating
syphilis with a week-long course of arsenic
§ Nurse Rivers coordinated with PHS clinics
to ensure that the men were not given
treatment

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Penicillin
§ In 1942, PHS clinics began using penicillin
to treat syphilis
§ Alabama passed a law that all those 14-50
be tested for venereal disease and treated
§ The men in the study were not tested or
treated
§ PHS arranged that WWII draftees be
exempted from the military or treatment
§ In 1951, penicillin became standard
treatment for syphilis
No Objections Were Raised
§ PHS conducted a full-scale review of the study,
which continued
§ The Nazi experiments were revealed and the
Nuremburg Code set forth
– Emphasized informed consent and do no harm
§ Declaration of Helsinki by WHO
– Stringent informed consent
§ Conference presentations and published papers
§ 1960s – PHS guidelines for clinical trials
– Forerunners of IRB, not applied to the PHS studies
Raising Questions
§ 1964 –article covering the last 30 years of
the study appeared
§ Dr. Irwin Schatz (MI) raised questions about
the ethics of the study, but it continued
§ Late 1960s – Dr. Peter Buxton (PHS) voiced
concerns
§ PHS convened a blue-ribbon panel
PHS Blue Ribbon Panel
§ All white doctors
§ All but one knew of the study already
§ Only the previously uninvolved member
recommended treatment for the men
§ Others emphasized the risks of penicillin
§ One panelist asserted men would not accept
treatment
§ Determined that informed consent could not be
obtained from the men, so went to the Macon
County Medical Society (MCMS) for surrogate
consent
§ MCMS, mainly comprised of black doctors, agreed
the study should continue and agreed not to
provide treatment to the men
Ending the Study
§ Dr. Buxton told the story to AP reporter Jean
Heller in 1972
§ Article: “Human guinea pigs: Syphilis
patients died untreated” in the Washington
Star
§ The study ended 40 years after it began and
nearly 20 years after penicillin had become
standard treatment for syphilis
Some facts about the men
§ By 1972….
– 28 of the men had died directly of syphilis
– 100 were suffering from related complications
– 40 of their wives were infected
– 19 of their children had been born with
congenital syphilis
– http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.0030040

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Prospective IRB Review
§ 1974 National Research Act
– Mandated establishment of IRBs
§ To prevent participants’ rights from being
violated
§ Has limitations
– Often staffed by volunteers who are not
compensated
– Time-consuming and demanding work
– After review, complacency can set in
1991 HHS Common Rule –
Title 45 CFR Par 46
§ “Legally effective informed consent”
1. Statement that the study involves research, a
description of the research and its purposes
2. Description of reasonably foreseeable risks
3. Description of reasonably expected benefits
4. Disclosure of appropriate alternatives
5. Statement about maintenance of confidentiality
6. Explanation of possible compensation if injured
7. Information about how to get questions answered
8. Statement that participation is voluntary
Vulnerable Populations
§ “Groups of potential research subjects who
may be more than usually susceptible to
exploitation…may be more likely to be
pressured to participate or may be more
likely to fail to understand the full
implications of participation and may
therefore be misled…”
§ Children, prisoners, pregnant women,
mentally disabled persons, or economically
or educationally disadvantaged persons (45
CFR 46)
The Legacy
§ Regulatory changes – IRB, informed consent
§ Regulations around “vulnerable” populations
– Resulted in these populations being excluded
from research
– Protected from research-related risks, but also
less likely to share in any benefits – both during
the study and later when results are generalized
– Also, conditions disproportionately affecting
minority groups and women unstudied
– In 1993, NIH mandated proportional
representation, without a compelling reason to
exclude
Legacy of Mistrust
§ Reinforced mistrust by African-Americans of
the government and medical establishment
– A phone survey showed that 9% of 500 black
households believed HIV/AIDS were part of a
plot to kill blacks; only 1% of “general
population” responded similarly. (Richardson, 1997)
– A substantial number of African-Americans view
informed consent as legal protection for the
researchers and as their signing away their
rights (Corbie-Smith et al, 1999)
The Settlement
§ In 1973, a class-action suit by the men was
settled out of court for $10 million
– Living syphilitic men received $37,500
– Heirs of deceased syphilitic men received
$15,000
– Infected wives, ex-wives, and widows received
lifetime medical and health benefits. The last
widow receiving THBP benefits died in 2009. In
2011, there were 15 offspring receiving lifetime
medical and health benefits.
www.cdc.gov/tuskegee/faq.htm

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The Apology –
Towards Restoration of Trust
§ In 1997, President Clinton apologized for
the government’s involvement in the study
– Included establishment of a memorial and
scholarships for minority bioethics students
The Debate
§ Some argue that original design was “scientifically
appropriate and ethical”
§ Six potential justifications at the start (Benedeck and Erlen 1999)
– Syphilis was a major public health problem
– Syphilis was more prevalent in blacks, there was evidence that
blacks and whites were affected differently, and whites had been
studied
– No standard treatment had been proven
– All treatment courses were lengthy and painful and thus, were
completed by a very low percentage of persons
– A large proportion of persons were never treated; the men were not
denied treatment they would have received
– Oslo study showed the majority of cases were cured spontaneously,
so doctors believed lack of treatment was not adverse
More Debate
§ In 1935, it was standard medical practice
not to treat latent syphilis in men over 50
– 30% of the men in the study were over 50
§ In the 1930s and 1940s, it was standard
medical practice not to treat syphilis in a
patient who had it more than 15 years
– 52% of the men in the study met this criteria
§ There was a study of untreated syphilis at
Stanford with affluent white subjects (White, 2000)
Community Based Research?
§ Dr. Bill Jenkins said at APHA in 2010 that
the study can be seen as an early form of
community based research
§ Nurse Rivers – cultural competence
§ Evidence that what starts well can end badly
Where TSUS Went Wrong
§ Most view the point where the study became
unethical to be the introduction of penicillin and the
study’s continuation, including attempts to prevent
the men from being treated
– Some argue that penicillin was not without its dangers
§ The men never gave informed consent
– This concept was not formulated til 1957
– However, the deception, withholding truth, causing pain,
taking advantage of trust, and treating others as one
would not want to be treated do not justify the actions
taken in the study
“Just like Tuskegee”
Does Tuskegee provide a
useful framework for
considering ethical issues?

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What about Guatemala?
§ In October 2010, President Obama
apologized to Guatemala for medical
research conducted by the US between
1946-1948
§ “At least 5500 prisoners and mental
patients, soldiers and children were drafted
into the experiment, including at least 1300
who were exposed” to STDs (syphilis,
gonorrhea and chancroid)*
http://www.washingtonpost.com/national/health-science/us-scientists-knew-1940s-guatemalan-std-studies-were-unethical-panel-finds/2011/08/26/gIQA2CxLoJ_story.html
“Ethically Impossible”
§ In a 1947 note in the NYT, science editor
Waldemar Kaempffert described an
experiment involving “intentional exposure
syphilis prophylaxis” that showed promise to
reduce the spread of syphilis “if only similar
research could be conducted in humans”
§ Kaempffert offered it would be “ethically
impossible” to “shoot living syphilis germs
into human bodies”
http://bioethics.gov/cms/sites/default/files/Ethically-Impossible_PCSBI.pdf
Major Players
§ Dr John Charles Cutler
– US Public Health Service Physician
– Led studies in Guatemala through an NIH grant
– Was involved in the later stages of Tuskegee and in the
Terre Haute Prisoner Experiments (in your readings)
§ Dr Thomas Parran, JR
– US Surgeon General at the time
– Acknowledged the work couldn’t be done in US
– Hid details from Guatemalan officials
§ Pan-American Sanitary Bureau
– Some Guatemalan officials approved study
Differences from Tuskegee
§ Tuskegee followed the natural course of the
disease
§ In Guatemala, researchers paid infected
prostitutes with syphilis to have sex with
prisoners or directly inoculated subjects
§ Goal may have been to study penicillin as
treatment option
§ Researchers appear to have known actions
were unethical and performed experiments
anyway
“Ethically Impossible: STD
Research in Guatemala, 1946-8”
§ Report of the Presidential Commission for
the Study of Bioethical Issues
– PDF is in Required Reading (see schedule for
pages assigned)
– Includes information on the Terre Haute Prison
Experiments, 1943-1944, which presaged
Guatemala in salient ways, and which involved
Dr. Cutler and PHS
3 CLASSIC ETHICAL DILEMMAS
Exercises

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THE HEINZ DILEMMA
Case 1
The Heinz Dilemma
§ Mr. Heinz is ordinarily a law-abiding man. One day, his wife
becomes gravely ill. Heinz takes her to the doctor, who
prescribes a medication for her. She does quite well on this
medication and begins to recover. However, Heinz has no
insurance and runs out of money quickly paying for this
expensive medication. After a few months, he can no
longer purchase the medication and his wife begins to take
a turn for the worse. One day, he is in the pharmacy and
notices that no one is behind the counter. The medication
is in plain view. Should he steal the medication to help his
sick wife?
THE OLD WOMAN AT THE
AIRPORT
Case 2
The Old Woman at the Airport
§ You are in the airport, trying to catch a flight
that is about to leave. As you run down the
crowded corridor, an elderly woman
suddenly slips in front of you and falls to the
ground with a cry. Do you stop to help, if you
know you will miss your flight because of it?
THE TROLLEY
Case 3, in two scenarios
Trolley, Scenario 1
§ A trolley is running out of control down a
track. In its path are 5 people who have
been tied to the track by a mad philosopher.
Fortunately, you can flip a switch which will
lead the trolley down a different track.
Unfortunately, there is a single person tied
to that track. Should you flip the switch?
Why?

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Trolley, Scenario 2
§ As before, a trolley is hurtling down a track
towards five people. You are on a bridge
under which it will pass, and you can stop it
by dropping a heavy weight in front of it. As
it happens, there is a man next to you - your
only way to stop the trolley is to push him
over the bridge and onto the track, killing
him to save five. Should you proceed?
Why? How is this case different from the
first?
“Would You Kill the Fat Man?”
§ By David Edmonds
§ Required text for this course
– See schedule for assigned pages
§ Subtitle: “The Trolley Problem and What
Your Answer Tells Us about Right and
Wrong”
§ 10 versions of the Trolley problem and a lot
of context
AND WE’RE OFF…..
Thanks for a great opening weekend