STATE OF THE ART

Fiftieth Anniversary of Uncovering the Tuskegee Syphilis Study

The Story and Timeless Lessons
Martin J. Tobin1,2
1
Division of Pulmonary and Critical Care Medicine, Hines Veterans Affairs Hospital, Hines, Illinois; and 2Stritch School of Medicine,
Loyola University of Chicago, Maywood, Illinois

Abstract recognize them as exemplars of people they encounter in daily

life—these flesh-and-blood characters convey the principles of
This year marks the 50th anniversary of the uncovering of the research ethics more vividly than a dry account in a textbook of
Tuskegee syphilis study, when the public learned that the Public bioethics. The study spurred reforms leading to fundamental
Health Service (precursor of the CDC) for 40 years intentionally changes in the infrastructure of research ethics. The reason
withheld effective therapy against a life-threatening illness in 400 people fail to take steps to halt behavior that in retrospect
African American men. In 2010, we learned that the same everyone judges reprehensible is complex. Lack of imagination,
research group had deliberately infected hundreds of rationalization, and institutional constraints are formidable
Guatemalans with syphilis and gonorrhea in the 1940s, with the obstacles. The central lessons from the study are the need to
goal of developing better methods for preventing these infections. pause and think, reflect, and examine one’s conscience; the
Despite 15 journal articles detailing the results, no physician courage to speak; and above all the willpower to act. History,
published a letter criticizing the Tuskegee study. Informed although about the past, is our best defense against future errors
consent was never sought; instead, Public Health Service and transgressions.
researchers deceived the men into believing they were receiving
expert medical care. The study is an especially powerful parable Keywords: research ethics; racism; vulnerable patient groups;
because readers can identify the key players in the narrative and researcher responsibilities; medical history

Contents The Story Breaks Lessons

The PHS Syphilis Study Why Was the PHS Syphilis Study
Peter Buxtun Undertaken?
The Guatemalan Epilogue

The history of medicine is presented as a medical experiments are more ignominious the experiment was uncovered in 1972, it was
cavalcade of triumphal breakthroughs than that conducted by physicians who for difficult to imagine that the PHS could
leading to marked increases in life 40 years (1932–1972) intentionally withheld contain a worse chapter in its history (2). Yet
expectancy. Advances arise from the effective therapy from hundreds of African in 2010, we learned that the same group of
ingenuity and industry of innumerable American men known to have a life- researchers had deliberately infected
investigators but also depend on millions of threatening illness (1). hundreds of Guatemalans with syphilis and
patients who selflessly make their bodies One of the most disturbing features of gonorrhea in the 1940s in the hope of
available for experimentation. The this experiment is the realization that it was developing a better means of preventing
interaction between investigators and conducted by the major health arm of the these infections.
patients is a source of pride but on occasion federal government: the Public Health The PHS study has its origin with
has also been a reason for shame. Few Service (PHS; precursor of the CDC). When researchers who wanted to study the natural

(Received in original form January 19, 2022; accepted in final form March 8, 2022)
This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0.
For commercial usage and reprints, please e-mail Diane Gern ([email protected]).
Supported by National Institute of Nursing Research grant R01-NR016055 and Veterans Administration Research Merit Review Award 1 I01
RX002803-01A1.
Correspondence and requests for reprints should be addressed to Martin J. Tobin, M.D., Division of Pulmonary and Critical Care Medicine,
Hines Veterans Affairs Hospital, Hines, IL 60141. E-mail: [email protected].
This article has an online supplement, which is accessible from this issue’s table of contents at www.atsjournals.org.
Am J Respir Crit Care Med Vol 205, IIss 10, pp 1145–1158, May 15, 2022
Copyright © 2022 by the American Thoracic Society
Originally Published in Press as DOI: 10.1164/rccm.202201-0136SO on May 2, 2022
Internet address: www:atsjournals:org

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history of untreated syphilis. The site chosen, opportunity for the study of the effects of path-breaking discoveries that revolutionized
Macon County, Alabama, had a population untreated syphilis” (1). In time, this thought the ability of physicians to manage the
of 27,000 in 1932, of whom 82% were became the Tuskegee Study of Untreated disease (15). Therapy was transformed in
African American (1). The PHS sought the Syphilis in the Negro Male. 1908 when Sahachir o Hata (1873–1938) and
cooperation of the nearby Tuskegee Institute, The men remained untreated only Nobelist Paul Ehrlich (1854–1915)
the Black university founded by Booker because the government doctors deliberately discovered an arsenical compound,
T. Washington (1856–1915), and made use withheld therapy over a 40-year period and arsphenamine, which was highly toxic to
of the facilities of Andrew Memorial misled the men into believing that the spirochetes and much less so to humans (15).
Hospital, located on the campus (3). The medications they received (vitamin tonics Arsphenamine was marketed as Salvarsan in
study population consisted of 600 Black men: and aspirin as placebo) were effective against 1910; Boeck became quickly convinced of its
399 with syphilis and 201 free of the disease their disease (6) (Figures 2 and 3). When efficacy and immediately terminated the
who served as control subjects (4). By 1969, seeking assistance from the principal of the Oslo study (16).
at least 28 and perhaps 100 men had died as Tuskegee Institute, the surgeon general, Once PHS investigators had enrolled
a direct result of syphilis; despite this Dr. Hugh Cumming (1869–1948), wrote to the Alabama men and obtained baseline
knowledge, the government scientists him in 1932 saying that the study “offers an measurements, they next decided to check
continued the experiment (1, 5). unparalleled opportunity for carrying on this for evidence of neurosyphilis. Dr. Raymond
“In 1932, Macon County was still very piece of scientific research which probably Vonderlehr realized that the men might
much tied to its plantation past,” Britt Rusert cannot be duplicated anywhere else in the refuse lumbar puncture if they realized it was
avows (Figure 1). “Most of the men selected world.” Presumably, Dr. Cumming did not solely for diagnostic purposes. “My idea,” he
for the syphilis experiments were poor intend any irony (12). wrote to his collaborators, is that “details of
sharecroppers with little or no formal The background knowledge that led to the puncture techniques should be kept from
education who worked under white farmers the PHS study came from the Oslo Study of them as far as possible” (1). To entice the
in a system of debt peonage” (6). The men Untreated Syphilis (9). Convinced that men to cooperate, he told them he would
agreed to participate because the available therapy, primarily mercury give them a special therapy: free “spinal
investigators offered them free medical care compounds that had been used since the shots,” deceiving them into believing that
and burial insurance (1). Informed consent 16th century, was harmful, Dr. Caesar Boeck lumbar punctures were therapeutic
was never sought. On the contrary, PHS withheld treatment from almost 2,000 (Figure 4) (9).
researchers deceived the men into believing syphilitic patients between 1890 and 1910 The final step in data collection was to
they were being treated for “bad blood,” a (13). Like tuberculosis, syphilis had been one obtain pathological specimens at autopsy.
colloquialism for several ailments (1). The of the most feared scourges of mankind, “As I see it,” another PHS investigator, Dr.
term is included in the title of a book by estimated to affect 1 in every 10 Americans Oliver Wenger, wrote to Dr. Vonderlehr,
James Jones, Bad Blood: The Tuskegee in the early 20th century (14). Around this “we have no further interest in these patients
Syphilis Experiment (1981), regarded as the time, German investigators made a series of until they die” (underlining in original) (17).
definitive history of the experiment (7) and
“the single most important book ever written
in bioethics” (8).
As an active physician who has spent
more than 45 years conducting research on
patients and a former journal editor-in-chief
who investigated various problems of
research ethics and imposed sanctions on
researchers for malfeasance, I reflect on how
physician-scientists who dedicate their lives
to a noble cause can persuade themselves
that it is morally acceptable to perform
disturbing experiments on unwitting
individuals to attain their goals. A more
detailed version of this article is available in
the online supplement.

The PHS Syphilis Study

The idea for the experiment originated with
Dr. Taliaferro Clark, director of the Venereal
Disease Division of the PHS (9–11).
Dr. Clark was analyzing data from an earlier
study when “the thought came to me that the Figure 1. Unidentified study participant in a cotton field. Reproduced from file of photographs
Alabama community offered an unparalleled of participants in the Tuskegee syphilis study, National Archives (in public domain).

1146 American Journal of Respiratory and Critical Care Medicine Volume 205 Number 10 | May 15 2022
STATE OF THE ART

may be made of the disease processes.” PHS

investigators feared the enrollees would quit
if they knew they would be autopsied.
Dr. Wenger wrote to Dr. Vonderlehr, “If the
colored population become aware that
accepting free hospital care means a
postmortem every darkey will leave Macon
County” (17).
To coax enrollees into the hospital when
they became severely ill, the PHS promised
to cover their burial expenses. Given the
importance of funeral rites in the cultural life
of rural Black persons, this was a particularly
strong inducement (9). “The grotesque
violation of these men’s bodies,” chides Britt
Rusert, “extended even into their death:
family members were required to turn over
the corpse for an autopsy to secure funeral
benefits” (6).
Shortly after commencing his tenure as
surgeon general (1936–1948), Dr. Thomas
Parran (1892–1968) launched a vigorous
campaign to eradicate venereal disease using
Figure 2. PHS staff members Dr. David Allbritton, nurse Eunice Rivers, and Dr. Walter mass screening and mobile treatment clinics
Edmondson, conducting an annual roundup in Macon County, 1953. On the side of the
(18). Dr. Parran, who had visited Tuskegee in
vehicle, “U.S. Department of Health, Education, and Welfare, Public Health Service” is
prominently displayed. Reproduced from National Archives (in public domain). PHS = Public
the early 1930s, is credited for the great
Health Service. strides made by this nationwide campaign
(Figure 5). When the mobile unit reached
The surgeon general, Dr. Cumming, stressed our desire to continue observation on the Macon County, PHS staff members alerted
this step in a letter to the director of Andrew cases selected for the recent study and if local doctors about enrollees and instructed
Hospital: “Since clinical observations are not possible to bring a percentage of these cases physicians: “He’s under study and not to be
considered final in the medical world, it is to autopsy so that pathological confirmation treated” (1).
In 1943, Dr. John Heller succeeded
Dr. Vonderlehr as director of the Division
of Venereal Diseases (1). One year later,
penicillin became the therapy of choice for
syphilis (19), and in 1947 PHS established
rapid treatment centers across the country.
There was no discussion of treating the
men enrolled in the study. Given the
effectiveness of penicillin, PHS scientists
insisted that it was all the more urgent for
the experiment to continue—it had
become a never-again-to-be-repeated
opportunity.
Although physician-scientists
intentionally withheld penicillin, the
experiment was fundamentally flawed
because “the vast majority of the patients”
had received “effective and undocumented”
penicillin “in the happenstance manner
while under treatment for other
conditions” (20). As such, the study was
not one of untreated syphilis, but rather of
undertreated syphilis (21).
When Dr. Heller left the Division of
Figure 3. Dr. Walter Edmondson of the PHS drawing a blood sample from a study participant Venereal Diseases in 1948, he became
during an annual roundup in Milstead, Macon County, 1953. Reproduced from National director of the National Cancer Institute and,
Archives (in public domain). PHS = Public Health Service. in 1960, president of the Memorial

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terminate it. Dr. Brown noted that 83 men

had shown evidence of syphilis at death,
but he personally believed the disease was
the primary cause of death in only 7 of
them (1).
Dr. Lawton Smith emerged as the
leading advocate for continuing the study.
He stressed, “You will never have another
study like this; take advantage of it,” and
boasted that “20 years from now, when these
patients are gone, we can show their
pictures” (28). (Today one can access the
Lawton Smith Lecture Series on a website
hosted by the North American Neuro-
Ophthalmology Society [29].) Of 17
panelists, only Dr. Gene Stollerman saw the
men as patients and believed they had a right
to be treated: “You should treat each
individual case as such, not treat as a group”
(5). The blue-ribbon panel dismissed this
objection and continued to refer to the
survivors as a group of subjects rather than as
Figure 4. Lumbar puncture, 1933. From left: Dr. Jesse J. Peters, nurse Eunice Rivers, and individual patients. It was almost as if the
unidentified study participant. Reproduced from National Archives (in public domain).
words, “399-Alabama-Black-rural-
sharecropping-illiterate-men” constituted a
Sloan-Kettering Cancer Center in New journals spread over 37 years, no physician single word (21).
York. His years as leader of the PHS study or scientist from anywhere around the world Dr. Brown wrote to Peter Buxtun
coincided with the introduction of published a letter or commentary criticizing informing him that a blue-ribbon panel had
penicillin for syphilis and promulgation of the ethics of the experiment (21). reviewed the experiment and decided against
the Nuremberg Code. There is no evidence treating the men. Buxtun made no attempt to
that the PHS study was ever discussed in challenge the panel’s medical authority but
the light of the Nuremberg Code (1). When Peter Buxtun asked, “What is the ethical thing to do?” (1).
the experiment was brought to public The CDC did not answer him. Buxtun
attention in 1972, Dr. Heller shocked the In December 1965, Peter Buxtun was hired discussed the matter with several law
public by telling journalists, “There was no by the PHS to interview patients with professors, who were sympathetic but offered
racial side to this. It just happened to be in venereal disease. Within a year, the 29-year- little encouragement—an illustration of Ian
a black community. I feel this was a old Czech-born psychiatric social worker Kershaw’s adage that the road to Auschwitz
perfectly straightforward study, perfectly sent a letter to Dr. William Brown, director was paved with indifference (30). Buxtun
ethical, with controls” (9). When Dr. Heller of the Division of Venereal Diseases of the contacted a journalist, and the story finally
died in 1989, the New York Times CDC, expressing grave moral concerns about broke in the Washington Star on July 25,
published a glowing obituary, listing his the PHS study (1) (Figure 6). The CDC 1972, and as front-page news in the New
many accomplishments without remained silent for months and then invited York Times the following day (31).
mentioning the PHS study (22). Buxtun to a meeting in Atlanta. As soon as
Some believe the PHS experiment was a Buxtun entered the conference room,
secret study (6). On the contrary, the first Dr. John Cutler, a PHS investigator (26, 27), The Story Breaks
report was published in JAMA in 1936 (23), began to harangue him. “He had obviously
and PHS researchers issued subsequent read my material,” Buxtun recalled, “thought The American public found it hard to wrap
papers every 4–6 years until 1973 (24). For of me as some form of lunatic who needed its mind around the idea that government
those who did not read the entire articles, the immediate chastisement and he proceeded to doctors had been intentionally duping men
titles were sufficient to have aroused administer it” (1). with a disease as serious as syphilis for
suspicion. “The Tuskegee Study of Untreated In November 1968, Buxtun again wrote 40 years (24). The Afro-American of
Syphilis; the 30th Year of Observation” was to Dr. Brown, who showed the letter to Baltimore exclaimed, “How condescending
the title of a 1964 article in Archives of Dr. David Sencer, director of the CDC and void of credibility are the claims that
Internal Medicine (25). A 1955 article on (1966–1977). Realizing they had a problem racial considerations had nothing to do with
autopsy findings communicated that more on their hands, Sencer and Brown convened the fact that 600 [all] of the subjects were
than 30% of the men had died directly from a blue-ribbon panel in February 1969 to black” (1). A number of physicians defended
advanced syphilitic lesions (26). Despite discuss the study (1). CDC scientists the study, the most spirited defense coming
repeated accounts of the ravages of untreated presented an overview of the study and said from Vanderbilt’s Rudolph Kampmeier
syphilis, appearing in 15 articles in reputable they needed advice on deciding whether to (1898–1990), former president of the

1148 American Journal of Respiratory and Critical Care Medicine Volume 205 Number 10 | May 15 2022
STATE OF THE ART

scientific understanding of syphilis (treated

and untreated), and prevailing cultural and
social forces at the time.
In the early decades of the 20th century,
eugenics was a worldwide force and judged
to represent cutting-edge biology research
(37, 38). PHS study leaders were vocal
advocates of eugenic measures (39).
Dr. Taliaferro Clark earned his PHS stripes
by undertaking eugenics-motivated projects
on rural schoolchildren (40). Dr. Clark’s data
would later be used by the state of Indiana to
select individuals for sterilization. Because of
its influence on the future of the “the race,”
venereal disease was considered “directly
antagonistic to the eugenic ideal” (14).
Recognizing its threat to the family, several
states enacted eugenic marriage laws, making
venereal disease a bar to matrimony.
Racist views were not confined to the
postbellum South nor directed solely at the
lower echelons of Black society. When 5,000
Black physicians petitioned for membership
in the American Medical Association (AMA)
in 1939, their application was rejected (41).
Figure 5. Thomas Parran, Jr., M.D., sixth U.S. surgeon general (1936–1948), in 1946, the year Not only did the AMA refuse to admit Black
the Guatemala research commenced (reproduced from Reference 109) (in public domain). physicians as members, but it also did not
allow them to attend its annual conferences.
This discrimination lasted well into the civil
American College of Physicians (1967–1968) that the experiment be terminated and that rights era. Between 1944 and 1965, more
and editor of the Southern Medical Journal the men receive immediate medical care. In than a dozen attempts to include Black
(32). Dr. Kampmeier blasted journalists for February and March 1973, Senator Edward physicians were rebuffed by the AMA
raising “a great hue and cry,” chastised them Kennedy conducted congressional hearings (42, 43). Black physicians consequently
for their “complete disregard for their into the study, which led to the passage of the founded their own organization, the
abysmal ignorance,” and trumpeted that his National Research Act and, in turn, the National Medical Association, which
analysis would “put this ‘tempest in a teapot’ establishment of institutional review boards, continues to publish its own journal to this
into proper historical perspective” (33). principles of informed consent, and day (44, 45). The AMA did not officially
Dr. Kampmeier considered the protection of vulnerable populations (5). desegregate until 1968 (46).
insinuation “that treatment was purposefully Legal proceedings against any Fast forward to February 23, 2021:
withheld” from the enrollees as unjust. On physician-scientist were never initiated (34). JAMA broadcasted a 16-minute podcast with
the contrary, “the subjects were not deterred In 1997, President Clinton finally the Twitter headline “No physician is racist,
from obtaining treatment if they desired it tendered the government’s apology: “What so how can there be structural racism in
or bothered to get what was available” (33). the United States government did was health care?” The host, Ed Livingston, M.D.,
In his mind, it was the fault of the men that shameful. . . . To our African American a “fulltime editor of JAMA,” dismissed
they did not request penicillin as treatment citizens, I am sorry that your federal structural racism as “an unfortunate term,”
for their syphilitic aortitis: “Since these men government orchestrated a study so clearly insisting that people are “turned off by the
did not elect to obtain the treatment racist” (35). whole structural racism phenomenon,”
available to them, the development of aortic concluding that “personally, I think taking
disease lay at the subject’s door and not in racism out of the conversation will help”
the Study’s protocol.” Regarding higher Why Was the PHS Syphilis (47). Critics claimed the podcast exposed a
mortality in subjects with syphilis than in Study Undertaken? culture of systemic racism in medicine. The
control subjects, Dr. Kampmeier coolly furor arising from the podcast led to the
observed, “This is not surprising. No one has The HEW panel report, issued in April 1973 resignation of Dr. Livingston, and the editor-
ever implied that syphilis was a benign (36), failed to address two central questions: in-chief, Howard Bauchner, M.D., was
infection” (33). “Why was the experiment undertaken?” and placed on administrative leave on March 25
The Department of Health, Education, “Why did it continue for 40 years?” The and resigned on June 30 (48).
and Welfare (HEW) announced that it answers are complex. Insights are gained Assumptions that racial differences are
would undertake a review (1). In October from examining the beliefs of the PHS genetic in origin have become embedded
1972, the Ad Hoc Advisory Panel advised investigators who initiated the study, within medical practice, with half of White

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Another common criticism, failure to

obtain informed consent, also obscures the
historical facts of the experiment. That
informed consent, as we know it today, was
not a component of a research protocol in
the 1930s does not diminish PHS
researchers’ obligations. In 1907 William
Osler wrote on “the limits of justifiable
experimentation upon our fellow creatures,”
emphasizing, “For man absolute safety and
full consent are the conditions which make
such tests allowable” (61). A more
fundamental point is that the Tuskegee men
never saw themselves as volunteers in a
scientific experiment. They were told and
they believed that they were getting free
treatment from expert government doctors
for a serious disease.

The Guatemalan Epilogue

While accumulating material for her book
Examining Tuskegee (2009) (5), historian
Susan Reverby traveled to the University of
Figure 6. Mr. Peter Buxtun, a 29-year-old social worker, communicated with the CDC about
Pittsburgh in 2003 to investigate the stored
the ethics of the PHS study and subsequently revealed details of the study to a newspaper
reporter (reproduced from Reference 110) (in public domain). PHS = Public Health Service.
records of Dr. Thomas Parran. Library staff
members informed her that Dr. John Cutler
(1915–2003) had donated his research
medical students and residents holding false whitewash (60). Members traveled to records to the university in 1990 (62, 63). On
beliefs about biological differences between Tuskegee and conducted taped interviews opening the files, Reverby found almost
Black and White individuals (49), which with study staff members and participants nothing about the Alabama study but
result in undertreatment of pain (among (5). On their return, the tape was burned at copious records of PHS studies conducted
other consequences) (50, 51). For years, Dr. Butler’s insistence (5, 60). A cover letter between 1946 and 1948 wherein American
researchers have treated race as an innate to HEW on the front page of the final report physicians deliberately infected hundreds of
genetic attribute, whereas the perspective of of April 28, 1973, contains the statement, Guatemalans with syphilis and gonorrhea
race as a social construct is now widely “The Chairman specifically abstains from without their knowledge or consent.
embraced (52). The term “structural racism” concurrence in this final report” (36). In a In 2010, Reverby submitted a
is used to convey that racism has a systemic private letter, Dr. Butler wrote that the manuscript to the Journal of Policy History
basis, embedded in social policy and norms panel had become “advocates,” and had (64), sending a preprint to a former director
and not simply private prejudices of “lost their objectivity” (5). Dr. Butler died of the CDC. The information made its way
individuals (53, 54). Structural racism is without leaving papers to shed light on his through layers of government to reach the
the common denominator to the PHS actions (5). White House. President Obama appointed a
experiments, inferior medical care Many commentators focus on the commission to investigate the matter, and
(49–51, 55–57) and increased coronavirus failure of PHS researchers to administer the results were published in two reports in
disease (COVID-19) mortality among penicillin once it became standard therapy. late 2011 (65, 66).
African Americans (58), and police violence That argument betrays a basic The ideas that led to the Guatemalan
against Black individuals (59). misunderstanding of the purposes of the research originated during the second World
The Ad Hoc Advisory Panel that experiment, as it assumes that satisfactory War. The effect of sexually transmitted
investigated the PHS study in 1972 was therapy for syphilis did not exist before 1945 disease on military manpower is always a
constrained by the narrowness of the charges (16). By the 1920s, leading experts had concern in wartime (67), and the United
HEW gave them (36). The nine-member become convinced that Salvarsan-based States was experiencing more than half a
panel included five Black and four White therapy was effective in decreasing morbidity million new cases of syphilis each year (68).
members, with Broadus Butler, Ph.D. and mortality (15). The administration of To develop better prophylaxis regimens, PHS
(1920–1996), president of historically Black any effective medication, not just penicillin, investigators drew up plans for an
Dillard University and a former World War to the men would have violated the rationale experimental model wherein infection would
II Tuskegee Airman, as chairman (5). Several of the experiment, which was to study the be induced in healthy subjects. The principal
panel members subsequently claimed that natural course of untreated syphilis until investigator, Dr. Mahoney, began
Dr. Butler engaged in a government death and autopsy. experiments in September 1943.

1150 American Journal of Respiratory and Critical Care Medicine Volume 205 Number 10 | May 15 2022
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encountered unexpected difficulties, they

began to conduct studies on Guatemalan
soldiers, inmates in the country’s only mental
hospital, and children in the national
orphanage (64) (Figures 9 and 10). Because
the rate of infection resulting from
intercourse with prostitutes was lower than
expected (,10%) (10), the NIH-sponsored
researchers attempted to artificially inoculate
subjects with syphilis, gonorrhea, and
chancroid.
The investigators’ notebooks contain
graphic accounts of steps in these
experiments. A physician held the penis of a
participant, pulled back the foreskin, and
“with some force, rolled the large inoculating
swab over the mucosa so as to try to
contaminate the entire fossa navicularis”
(65). If enrolled prostitutes were uninfected,
investigators inoculated women by
moistening a cotton-tipped swab with
gonorrheal pus, inserting it into the woman’s
cervix, and “swabb[ing] it around . . . with
considerable vigor” (65).
Only five infections resulted when 93
soldiers engaged in 138 episodes of sexual
intercourse with 12 prostitutes (65). A higher
rate of transmission, 17.9%, was achieved by
inserting an infected pledget under the
Figure 7. John F. Mahoney, M.D. (1889–1957), director of the Venereal Diseases Research
Laboratory (progenitor of the CDC) of the U.S. Marine Hospital on Staten Island, New York.
foreskin (65). To achieve a still higher rate of
Reproduced from the National Library of Medicine (in public domain). infection, the PHS physicians used a
hypodermic needle to abrade the dorsal
surface of a subject’s glans “short of drawing
John Mahoney (1889–1957) graduated was legal in Guatemala and that it was also blood” and then covered the abraded area
from medical school in 1914 and after legal for prostitutes to visit men in penal with a pledget soaked in Treponema
clinical training joined the PHS and was institutions (64). To PHS investigators, pallidum, achieving a 91.6% rate of
appointed director of the Venereal Diseases Guatemala presented an opportunity to transmission (65). Many participants actively
Research Laboratory (progenitor of the transmute the Terre Haute disappointment objected. One psychiatric patient “fled the
CDC) of the U.S. Marine Hospital on Staten into a success (65). room” after being subjected to penile
Island, New York, in 1929 (67) (Figure 7). Funding was sought from the NIH, and scarification and was not found for several
The 54-year-old physician-scientist in March 1946, the first ever study section hours (65).
supervised the experiments on federal approved the proposal for “the Guatemalan The American physicians also studied
prisoners, while 28-year-old John Cutler, study dealing with the experimental other modes of transmission, including oral
M.D., assisted by other PHS researchers, transmission of syphilis to human volunteers ingestion of syphilitic material and
conducted on-site work in Terre Haute, and improved methods of prophylaxis” (72), inoculating the rectum, urethra, and eyes of
Indiana. Dr. Cutler was born in Cleveland in providing $146,000 in funding (equivalent to participants (65). One psychiatric patient,
1915 and graduated from Western Reserve $2.1 million today) (73). Study section Berta, had syphilis injected into her arm in
University Medical School in 1941, joining members included physician-scientists from February 1948. She developed bumps and
the PHS 1 year later (65, 69) (Figure 8). A Harvard, Johns Hopkins, the University of skin wasting, and 6 months later Dr. Cutler
total of 241 prisoners participated in the Pennsylvania, and other institutions. In wrote that Berta appeared as if she was going
experiments, all of whom were inoculated August 1946, Dr. Cutler arrived in to die. The same day, August 23, he put
with Neisseria gonorrhoeae deposited into the Guatemala to conduct the experiments, gonorrheal pus from a male participant into
end of the penis. Investigators failed to assisted by other PHS physicians and staff Berta’s eyes, urethra, and rectum. Her eyes
consistently produce infection, and the members (65). filled up with pus, and four days later Berta
experiments ended in July 1944 (70). The original plan was to induce syphilis died (65).
In 1945, Guatemalan physician Dr. Juan in prisoners in Penitenciarıa Central through By December 1948, the NIH-sponsored
Funes spent a 1-year fellowship in the sexual intercourse with infected prostitutes investigators had intentionally exposed at
Venereal Diseases Research Laboratory (71). and then test the efficacy of prophylactic least 1,308 individuals to syphilis, gonorrhea,
He informed his supervisors that prostitution regimens. When the American physicians and chancroid (65, 74). Of those infected,

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many awardees receive both, as did

Landsteiner and Cori. Accordingly, it is not
an exaggeration to say that Dr. Mahoney was
the preeminent American physician-scientist
in 1946. As Dr. Mahoney received the award,
the presenter proclaimed, “Your name will
be joined in history with that of Paul Ehrlich”
(79).
In pursuit of a praiseworthy goal
(eradication of sexually transmitted disease),
the PHS investigators rationalized to
themselves that it was morally acceptable to
infect people with the same fearsome disease.
In all of the studies—Guatemala, Indiana,
and Alabama—vulnerable people were used
as a means to further the scientific ends and
careers of physicians they trusted.
Figure 8. John C. Cutler, M.D., in 1942, the year the 27-year-old physician joined the PHS. In their analysis of PHS research in
Reproduced from the National Library of Medicine (in public domain). PHS = Public Health Central America, the Presidential
Service. Commission for the Study of Bioethical
Issues devoted considerable space to how
stringent rules can prevent scientific
61–87% showed evidence of disease, and the investigator, wrote to Dr. Cutler about a misconduct. Yet, according to the
majority were not provided adequate conversation he had with the surgeon commission, PHS investigators recognized
treatment (75). Eighty-three deaths were general: “As you well know, he is very much the existence of such rules—clear evidence
reported (76). The rate of induced infection interested in the project and a merry twinkle that rules provide no substitute for individual
was unexpectedly low except for experiments came into his [Dr. Parran’s] eye when he conscience. None of the PHS investigators
involving scarification of participants’ said, ‘You know, we couldn’t do such an volunteered to serve as subjects in their own
membranes, which Dr. Mahoney considered experiment in this country’” (65). experiments. The commission considered
“beyond the range of natural transmission In June 1943, while submitting plans for self-experimentation “as quaint and
and [would] not serve as a basis for the study the Terre Haute experiments, Dr. Mahoney irrelevant” (65). As a physician-scientist who
of a locally applied prophylactic agent” (65). began experiments into the efficacy of has conducted numerous physiological
Among other considerations, this was a penicillin on syphilis (67). The antibiotic experiments on himself, I believe self-
major reason for stopping the experiments. caused rapid and complete disappearance of experimentation may prove a stronger
The Guatemala studies were halted spirochetal activity in infected men (77). deterrent than sets of rules.
abruptly in December 1948, and none of the Dr. Mahoney presented the unexpected The commission assumed—
experimental findings were published. One findings at a meeting of the American Public incorrectly—that Dr. Cutler wished to hide
motivation for terminating the research was Health Association in October 1943. The the results of the Guatemalan research.
Dr. Parran’s imminent departure from the presentation had an electrifying effect on the Researchers commonly fail to write up the
surgeon general’s office on April 6, 1948. As audience, with one attendee claiming, “This results of experiments that do not produce
that date drew near, Dr. Mahoney wrote to is probably the most significant paper ever clear answers. PHS researchers published
Dr. Cutler, “We have lost a very good friend presented in the medical field” (67). several papers on the basis of serological
and that it appears to be advisable to get our Penicillin revolutionized the management of studies conducted in Guatemala (80–83) and
ducks in line. In this regard we feel that the sexually transmitted disease. In 1940, the published other studies on the basis of
Guatemala project should be brought to the death rate for syphilis was 10.7 per 100,000; induction of infection through inoculation
innocuous stage as rapidly as possible” (63). in 1950 it fell to 5 per 100,000, and in 1970 it (65, 84). If Dr. Cutler had wished to be
Many journalists portray Dr. Cutler as a reached 0.2 per 100,000 (14). secretive, he would have destroyed the
Dr. Mengele–type scientist acting As the Guatemalan research was records rather than donate them to
autonomously. This characterization is commencing in 1946, Dr. Mahoney was University of Pittsburgh 40 years after
wrong. Although Dr. Cutler was the main awarded the Lasker Award for his completing the work. In donating his files, he
on-site investigator, the primary supervisor “distinguished service as a pioneer in the may have hoped that future scientists would
of the Guatemalan experiments, treatment of syphilis with penicillin.” Other build on his observations.
Dr. Mahoney, was kept fully apprised. A few awardees that year included Karl Landsteiner A striking feature of the Guatemalan
months after the research commenced, (1868–1943), discoverer of blood groups and research is that it did not arise through any
Dr. Mahoney wrote encouragingly to Rhesus factor (78), and Ferdinand Cori fault in the chain of command (65). The
Dr. Cutler, “Your show is already attracting (1896–1984), discoverer of the mechanism principal investigator was the most eminent
rather wide and favorable attention up here. whereby glycogen is metabolized and physician-scientist in the United States. The
We are frequently asked as to the progress of resynthesized (78). The Lasker Award is research plan was approved by an NIH study
your work” (65). Dr. Coatney, a PHS known as the American Nobel Prize because section, which included physician-investigators

1152 American Journal of Respiratory and Critical Care Medicine Volume 205 Number 10 | May 15 2022
STATE OF THE ART

Figure 9. Left: A 25-year-old female patient in Asilo de Alienados (Psychiatric Hospital) in Guatemala was exposed to syphilis once with no
record of treatment. Right: A 16-year-old female patient in Asilo de Alienados was exposed to syphilis twice and was treated with penicillin.
Records indicate that the patient was “uncooperative.” Reproduced from the National Archives and Records Administration (in public domain).

from the country’s leading medical schools. publications in reputable journals read all Caplan avers that the PHS study is “the
The surgeon general was enthusiastic about over the world. The experiment is a story single most important event in the rise of
the studies and was kept informed of their that needs to stay forever on the moral bioethics” (8). Reforms arising from the
progress. horizons of medical scientists, yet many Kennedy congressional hearings led to
young investigators know little of its details fundamental changes in the infrastructure of
or lessons (85). research ethics. Yet it is doubtful that these
Lessons For the final 25 years of the Alabama provisions benefited significantly the
experiment, the message of the Nuremberg segments of society affected by the study:
Lessons from the PHS experiments are Code had been widely disseminated. impoverished Black persons.
manifold. The Alabama investigation was Investigators looked on it as “a good code for Some argue that revolutionary changes
conducted in an open society, it extended barbarians” (86), and it had little impact in in research ethics obviate claims by HEW
over 40 years, and it resulted in numerous the United States (87, 88). Bioethicist Arthur advisory panel members of a government
whitewash (5, 60, 89). History is the story of
roads taken, and counterfactual history
contemplates what might have happened had
a different road been ventured. The
dominant factor that undergirded the PHS
study was racism (90), which was played
down to near invisibility in the HEW final
report (5). Had society confronted the
flagrant evidence of structural racism in 1972
and instituted fundamental reform of social
contributors to health, the stark racial
disparities of health outcomes exposed by the
klieg light of COVID-19 could have been
prevented (58, 91); likewise, root reform of
law enforcement in 1972 could have
prevented the many deaths of Black persons
consequent to unlawful police actions (59).
Figure 10. The injection site of a female psychiatric patient who was exposed to syphilis three As with many instances of scientific
times and received some treatment. Reproduced from the National Archives and Records misconduct, senior scientists were fully
Administration (in public domain). aware of the nature and magnitude of the

State of the Art 1153

 STATE OF THE ART

PHS irregularities and took no action. Yet the Tuskegee study is mentioned, the captured the distinction in a letter to his
when the information was communicated in university and townspeople are touched by a nephew: “An honest heart being the first
the lay press, the problem was immediately legacy of shame. Rather than besmirching blessing, a knowing head is the second”
obvious to the general public. How can it be the victims and their descendants, it would (100). Intelligence and education are not
that problems reported on the front page of be more accurate to label the experiment enough in human affairs: character and
the New York Times become clear in after the perpetrators: the Public Health conscience come first. It is tempting to
retrospect, yet, in the preceding years, Service Study of Partially Treated Syphilis compartmentalize the lessons of the PHS
extremely accomplished physician-scientists (93). study into those that apply to our actions as
saw no problem? Lack of imagination, None of the study scientists wrote researchers and those that apply to our
rationalization, and institutional constraints articles reflecting on its moral lessons. “No behavior as lay citizens. That would be a
are formidable obstacles in such situations. apologies were tendered. No one admitted mistake because the two blend into each
In Humanity: a Moral History of the any wrongdoing,” inveighs James Jones (1). other.
Twentieth Century, philosopher Jonathan In 1993, Dr. Cutler appeared on the PBS When we look back at the Alabama and
Glover (92) analyzes several genocides, Nova documentary “Deadly Deception” (94). Guatemala stories, we fall into the trap of
bringing together ethics and history, and When asked about the Tuskegee men, he placing ourselves on the side of the angels, of
concludes that only moral imagination (the declaimed, “It was important that they were grouping ourselves with the Buxtuns of this
ability to imagine ourselves in the shoes of supposedly untreated, and it would be world. Hindsight is comforting, but it is also
endangered individuals) can enable us to alter undesirable to go ahead and use large misleading (101). Coping with challenges as
our outlook and take steps to remedy a amounts of penicillin to treat the disease, they unfold in real time is very different.
threatening situation. Many factors deaden because you’d interfere with the study.” He Only one Peter Buxtun stood up over
moral imagination—groupthink, tribalism, remonstrated, “I was bitterly opposed to 40 years. It is more likely that most
obedience—and prevent us from taking action. killing off the Study for obvious reasons” researchers would have followed in the
Cultivation of moral imagination, Glover (95). Regarding the enrollees, he attested, footprints of Drs. Vonderlehr, Wenger, and
contends, holds the best hope of battling “They served their race very well.” Heller and the many other investigators
against comforting conventional attitudes and Dr. Parran served as surgeon general involved.
official policy, making vivid the destiny of (1936–1948) during the time that penicillin There is a natural tendency to believe
dehumanized individuals, and becoming was advocated to treat every American with that group effort and cooperation are more
determined to take action. A succession of syphilis—except men in Macon County. He effective than the actions of an individual.
physicians worked on the Tuskegee project. If did more than any other person to control Correction of the great ills of society has
the consciences of new recruits were troubled sexually transmitted infections (68, 96, 97). always started in the heart of one individual
on being first exposed to the study design, they He was founding dean of the University of and thereafter spread to a small group who
acted as if they did not notice the peril of the Pittsburgh Graduate School of Public Health recognized the same injustice. An especially
enrollees, looking away and keeping silent. The (1948–1958), and the school’s main building astute commentator on social affairs, Adam
consciences of these physicians were protected was named Parran Hall in 1969. In 1972, the Smith, wrote in 1763, “Slavery has hardly any
by moral inertia—finding it easier to fall in American Sexually Transmitted Diseases possibility of it being abolished. . . . [It] has
with the momentum of established routine Association named its highest award in his been universall [sic] in the beginnings of
and policy (92). honor (98). The Pittsburgh school society, and the love of dominion and
When officials are confronted with introduced the John C. Cutler Memorial authority over others will probably make it
major sociopolitical problems, they spin Lecture in Global Health in 2003 to honor perpetual” (102). A few years later, a 25-year-
themselves. They convince themselves that another former faculty member. A new dean old deacon, Thomas Clarkson (1760–1846),
raising the concern will be futile and may canceled the lecture series in 2008 because of started a movement that forced British
even backfire with worse consequences. The community sensitivities regarding Dr. Parliament to pass an act in 1807 abolishing
CDC used this argument when trying to Cutler’s role in the Tuskegee research (69). In the slave trade (102).
persuade Peter Buxtun that the PHS study 2013, American Sexually Transmitted Individuals such as Buxtun and
should not be stopped. The blue-ribbon Diseases Association members voted to Clarkson who set out to make a difference
panel argued that penicillin would be remove Dr. Parran’s name from its annual are usually branded as irrational, soft, or
dangerous (28). When the men were award (76); in 2018, his name was stripped naive. In official and administrative circles,
eventually treated with penicillin, not a single from the Pittsburgh Graduate School of where discussion is performed in the cold
complication was observed (1). Public Health building (99). language of interests, people who urge
When morals collide with actions, a There is a common perception that intervention on the basis of moral arguments
common response is to blame the victim— moral judgment is linked to education. Yet are considered “emotional.”
Dr. Kampmeier blamed study participants the person who stopped the PHS study, Peter The reason people fail to take steps to
for failing to request penicillin for aortitis Buxtun, had no training in research; he was a halt behavior that in retrospect everyone
(33). The prefix attached to the study by PHS social worker and had far less conventional judges reprehensible is complex. Scholars
investigators is a variant of the blame-the- education than the future director of the have long pondered the question. One of the
victim tactic. Tuskegee University, founded National Cancer Institute who led the study first to wonder what light the second World
by former slave Booker T. Washington in for years and many surgeons general who War shed on this question was Hannah
1881, should be celebrated as a milestone in had intimate knowledge of it. With Arendt (1906–1975). She deconstructed the
African American history. Instead, each time characteristic concision, Thomas Jefferson psychological and moral implications of evil

1154 American Journal of Respiratory and Critical Care Medicine Volume 205 Number 10 | May 15 2022
STATE OF THE ART

(103). In 1961, she attended the trial of war and, at bottom, worthy people have, in our information and decide not to intervene as
criminal Adolf Eichmann. Arendt published time, the most extraordinary fear about events unfold in real time.
a controversial book, Eichmann in Jerusalem: making judgments. This confusion about We must be careful not to use the
A Report on the Banality of Evil (1963). The judgment can go hand in hand with fine and Alabama and Guatemala research as an
expression “banality of evil” gave rise to strong intelligence, just as good judgment opportunity for letting off moralistic steam.
much criticism and misunderstanding. Some can be found in those not remarkable for Denouncing an injustice, observes Tzvetan
saw Arendt as exonerating Eichmann and their intelligence” (103). For Buxtun, Todorov, “constitutes a moral act only at
blaming the victims. When writing early exercising judgment was a matter of moral those times when such denunciation is not
drafts, Arendt was inclined to describe the courage. simply a matter of course and thus involves
evil quality of totalitarianism as something When faced with serious injustice in some personal risk. There is nothing moral
utterly “radical” (104). One of her mentors, their midst, the real reason people fail to in speaking out against slavery today” (105).
physician-philosopher Karl Jaspers intervene is a lack of willpower. Consider the One can legitimately make moral
(1883–1969), argued that such a Rwandan genocide—the most efficient demands only on oneself. To imagine
characterization made Nazism seem killing spree of the 20th century (107). oneself floating above the fields of Macon
somehow unique and thus, in an awful way, Across 100 days (April 6 to July 18, 1994), County and Guatemala City and wagging
“great” (103). As Arendt reflected on the 800,000 Tutsi and politically moderate Hutu an indignant finger at the shades of Dr.
matter, she arrived at the conclusion that evil were murdered—the equivalent of more than Vonderlehr and Dr. Cutler constitutes
arises from a simple failure to think. two World Trade Center attacks every day “moralism.” People who hold themselves
What struck Arendt when listening to for 100 days. In contrast to the broad support up as examples to others are in fact acting
Eichmann was his banality: “his penchant for for the United States after September 11, immorally, irrespective of how
‘officialese,’ for stock phrases, for shallow every country turned away when the Tutsi commendable their conduct may otherwise
elations, his ‘empty talk,’ his being ‘genuinely cried out. During the 3 months of the be (105). Hannah Arendt again: “Goodness
incapable of uttering a single sentence that genocide, the U.S. president never once can exist only when it is not perceived, not
was not a cliche’” (104). She continued, “The assembled his top policy advisers to discuss even by its author; whoever sees himself
longer one listened to him, the more obvious the killings (108). After being personally performing a good work is no longer good,
it became that his inability to speak was lobbied by Human Rights Watch, Anthony but at best a useful member of society” (104).
closely connected with an inability to think, Lake (born 1939), the president’s national Reflection on the PHS experiments
namely to think from the standpoint of security adviser, issued a statement calling on highlights that out of the crooked timber of
somebody else” (104). As Arendt inferred, Rwandan military leaders to “do everything humanity, nothing entirely straight can be
“The trouble with Eichmann was precisely in their power to end the violence fashioned. Everything we know about the
that so many were like him, and that the immediately.” PHS researchers informs us that they were
many were neither perverted nor sadistic, When Lake was informed 6 years after perceived as being decent people who did
that they were, and still are, terribly and the genocide that this statement constituted
much good in other parts of their
terrifyingly normal . . . this normality was the sum total of official public attempts to
professional lives. Given the actions of Drs.
much more terrifying than all the atrocities shame the Rwandan government, he was
Parran, Mahoney, and Cutler and other
put together” (104). In this sense, the evil of stunned: “You’re kidding,” he replied.
esteemed researchers, we need to approach
the PHS experiments is banal and not “That’s truly pathetic” (108). Here is a leader
today’s ethical challenges with “fear and
radical. Banality does not trivialize evil: it is who had acquired a reputation as a person of
trembling” (Kierkegaard’s phrase)—and
precisely what makes the behavior so conscience, who was in a position of
remember to pause and think, reflect and
dangerous (105). enormous power, and yet he failed to act;
examine our conscience, and have the
Allied to a lack of thinking is a lack of indeed, he appeared to be unaware that he
courage to speak and, above all, the
reflection, an examination of conscience— had not acted. So it is not only medical
willpower to act. 䊏
the courage to form a judgment. Peter researchers who fail to act on concerns that
Buxtun was not afraid to judge and be seem repellant in retrospect. In all walks of
counted. Today, we are constantly cautioned life, people who have reputations for good Author disclosures are available with the
text of this article at www.atsjournals.org.
against being judgmental—not to form a conscience, who are trained at the highest
moral opinion about the actions of others level, who possess all the facts and know the
Acknowledgment: The author thanks Sidney
(106). Ahead of her time, Arendt saw the harmful consequences, and who have the Wolfe, M.D., and Charles Natanson, M.D.,
dangers of ethical relativism. Writing to power to act, still fail to act. Instead, they find for comments on an earlier version of the
Jaspers in 1963, she reflected that “even good sound logical reasons to dismiss all the manuscript.

References apology and their influence on minority participation in biomedical

research. Am J Public Health 2008;98:1137–1142.
1. Jones JH. Bad blood: the Tuskegee syphilis experiment, new expanded 3. Dibble EH Jr, Rabb LA, Ballard RB. John A. Andrew Memorial Hospital.
ed. New York: Free Press; 1981, 1993. J Natl Med Assoc 1961;53:103–118.
2. Katz RV, Kegeles SS, Kressin NR, Green BL, James SA, Wang MQ, et al. 4. Reverby SM. The “Tuskegee” syphilis study as a “site of memory.”
Awareness of the Tuskegee syphilis study and the US presidential In: Katz RV, Warren RC, editors. The search for the legacy of

State of the Art 1155

 STATE OF THE ART

the USPHS syphilis study. Lanham: Lexington Books; 2013. Neuro-Ophthalmology Society; 2022 [accessed 2021 May 22].
pp. 29–40. Available from: https://library.med.utah.edu/NOVEL/Smith/.
5. Reverby SM. Examining Tuskegee: the infamous syphilis study and its 30. Kershaw I. Hitler, the Germans, and the final solution. New Haven, CT:
legacy. Chapel Hill, NC: University of North Carolina Press; 2009. Yale University Press; 2008.
6. Rusert B. “A study in nature”: the Tuskegee experiments and the New 31. Heller J. Syphilis victims in the US went untreated for 40 years. In:
South plantation. J Med Humanit 2009;30:155–171. Reverby SM, editor. Tuskegee’s truths: rethinking the Tuskegee syphilis
7. Reverby SM. Enemy of the people/enemy of the state: two great(ly study. Chapel Hill, NC: University of North Carolina Press; 2000. pp.
infamous) doctors, passions, and the judgment of history. Bull Hist Med 116–117.
2014;88:403–430. 32. Billings FT Jr. Memorial: Rudolph H. Kampmeier. Trans Am Clin Climatol
8. Caplan A. Bad blood: the Tuskegee syphilis experiment. Biosocieties Assoc 1991;102:lxii–lxv.
2007;2:275–276. 33. Kampmeier RH. The Tuskegee study of untreated syphilis. South Med J
9. Brandt AM. Racism and research: the case of the Tuskegee syphilis study. 1972;65:1247–1251.
Hastings Cent Rep 1978;8:21–29. 34. Reverby SM, editor. Tuskegee’s truths: rethinking the Tuskegee syphilis
10. Zenilman J. The Guatemala sexually transmitted disease studies: what study. Chapel Hill, NC: University of North Carolina Press; 2000.
happened. Sex Transm Dis 2013;40:277–279. 35. President William J. Clinton’s remarks. In: Reverby SM, editor.
11. Frieden TR, Collins FS. Intentional infection of vulnerable populations in Tuskegee’s truths: rethinking the Tuskegee syphilis study. Chapel Hill,
1946–1948: another tragic history lesson. JAMA 2010;304:2063–2064. NC: University of North Carolina Press; 2000. pp. 574–577.
12. Cumming HS. Cumming, surgeon general, to Dr. RR Moton, September 36. U.S. Department of Health, Education, and Welfare, Public Health
20, 1932. In: Reverby SM, editor. Tuskegee’s truths: rethinking the Service. Final report of the Tuskegee Syphilis Study Ad Hoc Advisory
Tuskegee syphilis study. Chapel Hill, NC: University of North Carolina Panel. Washington, DC: U.S. Department of Health, Education, and
Press; 2000. p. 77. Welfare, Public Health Service, 1973.
13. Hem E. Boeck’s sarcoidosis—a centennial. Int J Dermatol 2000;39: 37. Watson P. The modern mind: an intellectual history of the 20th century.
545–549. New York, NY: Perennial; 2001.
14. Brandt AM. No magic bullet: a social history of venereal disease in the 38. Lombardo PA. A child’s right to be well born: venereal disease and
United States since 1880, expanded ed. New York, NY: Oxford the eugenic marriage laws, 1913–1935. Perspect Biol Med 2017;
University Press; 1987. 60:211–232.
15. Porter R. The greatest benefit to mankind: a medical history of humanity. 39. Friedlander H. The origins of Nazi genocide: from euthanasia to the final
New York, NY: W.W. Norton; 1998. solution. Chapel Hill, NC: University of North Carolina Press; 1995.
16. Benedek TG. The “Tuskegee study” of syphilis: analysis of moral versus 40. Lombardo PA, Dorr GM. Eugenics, medical education, and the Public
methodologic aspects. J Chronic Dis 1978;31:35–50. Health Service: another perspective on the Tuskegee syphilis
17. Wenger OC. Dr Wenger to RA Vonderlehr, July 21, 1933. In: Reverby experiment. Bull Hist Med 2006;80:291–316.
SM, editor. Tuskegee’s truths: rethinking the Tuskegee syphilis study. 41. Proctor RN. Racial hygiene: medicine under the Nazis. Cambridge, MA:
Chapel Hill, NC: University of North Carolina Press; 2000. pp. 84–85. Harvard University Press; 1998.
18. Parran T. Shadow on the land: syphilis, the white man’s burden. In: 42. Davis RM. Achieving racial harmony for the benefit of patients and
Reverby SM, editor. Tuskegee’s truths: rethinking the Tuskegee syphilis communities: contrition, reconciliation, and collaboration. JAMA 2008;
study. Chapel Hill, NC: University of North Carolina Press; 2000. pp. 300:323–325.
59–69. 43. Baker RB, Washington HA, Olakanmi O, Savitt TL, Jacobs EA, Hoover E,
19. Mahoney JF, Arnold RC, Sterner BL, Harris A, Zwally MR. Penicillin et al. African American physicians and organized medicine, 1846–1968:
treatment of early syphilis: II. JAMA 1944;126:63–67. origins of a racial divide. JAMA 2008;300:306–313.
20. Lucas JB. Assistant chief, Venereal Disease Branch, Public Health 44. Baker RB, Washington HA, Olakanmi O, Savitt TL, Jacobs EA, Hoover E,
Service, to William J Brown, MD, chief, Venereal Disease Branch, et al.; Writing Group on the History of African Americans and the
September 10, 1970. In: Reverby SM, editor. Tuskegee’s truths: Medical Profession. Creating a segregated medical profession: African
rethinking the Tuskegee syphilis study. Chapel Hill, NC: University of American physicians and organized medicine, 1846–1910. J Natl Med
North Carolina Press; 2000. pp. 107–109. Assoc 2009;101:501–512.
21. Reverby SM. More than fact and fiction: cultural memory and the 45. Washington HA, Baker RB, Olakanmi O, Savitt TL, Jacobs EA, Hoover E,
Tuskegee syphilis study. Hastings Cent Rep 2001;31:22–28. et al.; Writing Group on the History of African Americans and the
22. Fowler G. Dr. John R. Heller Jr. dies at 84; headed National Cancer Medical Profession. Segregation, civil rights, and health disparities: the
Institute. New York Times 1989 May 6 [accessed 2021 May 22]. legacy of African American physicians and organized medicine,
Available from: https://www.nytimes.com/1989/05/06/obituaries/dr-john- 1910–1968. J Natl Med Assoc 2009;101:513–527.
r-heller-jr-dies-at-84-headed-national-cancer-institute.html. 46. Baker RB. The American Medical Association and race. Virtual Mentor
23. Vonderlehr RA, Clark T, Wenger OC, Heller JR Jr. Untreated syphilis in 2014;16:479–488.
the male Negro: a comparative study of treated and untreated cases. 47. American Association for the History of Medicine. AAHM news: AAHM
JAMA 1936;107:856–860. calls for properly archiving JAMA’s podcast on “Structural Racism for
24. Caplan AL. Twenty years after: the legacy of the Tuskegee syphilis study. Doctors.” Richmond, VA: American Association for the History of
When evil intrudes. Hastings Cent Rep 1992;22:29–32. Medicine; 2021 [accessed 2021 Jun 20]. Available from: https://www.
25. Rockwell DH, Yobs AR, Moore MB Jr. The Tuskegee study of histmed.org/announcements/news/aahm-news-aahm-calls-for-properly-
untreated syphilis; the 30th year of observation. Arch Intern Med archiving-jamas-podcast-on-structural-racism-for-doctors-3226.
1964;114:792–798. 48. Tanne JH. JAMA editor in chief steps down over controversial structural
26. Peters JJ, Peers JH, Olansky S, Cutler JC, Gleeson GA. Untreated racism podcast. BMJ 2021;373:n1433.
syphilis in the male Negro; pathologic findings in syphilitic and 49. Hoffman KM, Trawalter S, Axt JR, Oliver MN. Racial bias in pain
nonsyphilitic patients. J Chronic Dis 1955;1:127–148. assessment and treatment recommendations, and false beliefs about
27. Olansky S, Harris A, Cutler JC, Price EV. Untreated syphilis in the male biological differences between blacks and whites. Proc Natl Acad Sci U
Negro; twenty-two years of serologic observation in a selected syphilis S A 2016;113:4296–4301.
study group. AMA Arch Derm 1956;73:516–522. 50. Todd KH, Deaton C, D’Adamo AP, Goe L. Ethnicity and analgesic
28. Summary of Ad Hoc Committee to Consider the Tuskegee Study, Public practice. Ann Emerg Med 2000;35:11–16.
Health Service, Centers for Disease Control, US Department of Health, 51. Goyal MK, Kuppermann N, Cleary SD, Teach SJ, Chamberlain JM.
Education and Welfare, February 6, 1969: memorandum. In: Reverby Racial disparities in pain management of children with appendicitis in
SM, editor. Tuskegee’s truths: rethinking the Tuskegee syphilis study. emergency departments. JAMA Pediatr 2015;169:996–1002.
Chapel Hill, NC: University of North Carolina Press; 2000. pp. 463–472. 52. Braun L, Wolfgang M, Dickersin K. Defining race/ethnicity and explaining
29. North American Neuro-Ophthalmology Society. The J. Lawton Smith difference in research studies on lung function. Eur Respir J 2013;41:
neuro-ophthalmology collection. Salt Lake City, UT: North American 1362–1370.

1156 American Journal of Respiratory and Critical Care Medicine Volume 205 Number 10 | May 15 2022
STATE OF THE ART

53. Bailey ZD, Feldman JM, Bassett MT. How structural racism works—racist 72. Spector-Bagdady K, Lombardo PA. “Something of an adventure”:
policies as a root cause of US racial health inequities. N Engl J Med postwar NIH research ethos and the Guatemala STD experiments. J
2021;384:768–773. Law Med Ethics 2013;41:697–710.
54. Hardeman RR, Medina EM, Kozhimannil KB. Structural racism and 73. Zenilman JM. Ethics gone awry: the US Public Health Service studies in
supporting black lives—the role of health professionals. N Engl J Med Guatemala; 1946–1948. Sex Transm Infect 2013;89:295–300.
2016;375:2113–2115. 74. Reverby SM. Ethical failures and history lessons: the US Public Health
55. Eberly LA, Richterman A, Beckett AG, Wispelwey B, Marsh RH, Service research studies in Tuskegee and Guatemala. Public Health
Cleveland Manchanda EC, et al. Identification of racial inequities in Rev 2012;34:1–18.
access to specialized inpatient heart failure care at an academic 75. Reverby SM. Compensation and reparations for victims and bystanders
medical center. Circ Heart Fail 2019;12:e006214. of the U.S. Public Health Service research studies in Tuskegee and
56. Eneanya ND, Yang W, Reese PP. Reconsidering the consequences Guatemala: who do we owe what? Bioethics 2020;34:893–898.
of using race to estimate kidney function. JAMA 2019;322: 76. Spector-Bagdady K, Lombardo PA. US Public Health Service STD
113–114. experiments in Guatemala (1946–1948) and their aftermath. Ethics
57. Vyas DA, Eisenstein LG, Jones DS. Hidden in plain sight—reconsidering Hum Res 2019;41:29–34.
the use of race correction in clinical algorithms. N Engl J Med 2020; 77. Mahoney JF, Arnold RC, Harris A. Penicillin treatment of early
383:874–882. syphilis—a preliminary report. Am J Public Health Nations Health
58. Acosta AM, Garg S, Pham H, Whitaker M, Anglin O, O’Halloran A, et al. 1943;33:1387–1391.
Racial and ethnic disparities in rates of COVID-19-associated 78. Millar D, Millar I, Millar J, Millar M. The Cambridge dictionary of scientists.
hospitalization, intensive care unit admission, and in-hospital death in Cambridge, United Kingdom: Cambridge University Press; 1996.
the United States from March 2020 to February 2021. JAMA Netw 79. Lasker Foundation. Penicillin as a cure for syphilis: 1946 Albert Lasker
Open 2021;4:e2130479. Clinical Medical Research Award. New York, NY: Lasker Foundation;
59. Edwards F, Lee H, Esposito M. Risk of being killed by police use of force 2020 [accessed 2021 May 27]. Available from: https://laskerfoundation.
in the United States by age, race-ethnicity, and sex. Proc Natl Acad Sci org/winners/penicillin-as-a-cure-for-syphilis/.
U S A 2019;116:16793–16798. 80. Levitan S, Aragon HA, Cutler JC, Funes JM, Portnoy J, Paredes-Luna A.
60. Washington HA. Medical apartheid: the dark history of medical Clinical and serologic studies with reference to syphilis in Guatemala
experimentation on Black Americans from colonial times to the present. Central America. I. Studies of comparative performance of the Kahn,
New York, NY: Anchor Books; 2006. Kolmer, Mazzini, and VDRL slide tests as carried out in the national
61. Osler W. The evolution of the idea of experiment in medicine. In: orphanage. Am J Syph Gonorrhea Vener Dis 1952;36:379–387.
Transactions of the Congress of American Physicians and Surgeons, 81. Cutler JC, Levitan S, Arnold RC, Portnoy J. Studies on the comparative
Seventh Triennial Session. New Haven, CT: Congress of American behavior of various serologic tests for syphilis. II. A report on an
Physicians and Surgeons, 1907. pp. 1–8. observed pattern of entrance into seroreactivity among patients with
62. Reverby SM. “So what?” Historical contingency, activism, and reflections untreated primary syphilis. Am J Syph Gonorrhea Vener Dis 1952;36:
on the studies in Tuskegee and Guatemala. In: Baylis F, Dreger A, 533–544.
editors. Bioethics in action. Cambridge, United Kingdom: Cambridge 82. Portnoy J, Galvez R, Cutler JC. Clinical and serologic studies with
University Press; 2018; pp. 32–54. reference to syphilis in Guatemala, Central America. III. Studies of
63. National Archives. Records of Dr. John C. Cutler. Washington, DC: comparative performance of the Kahn, Kolmer, Mazzini, and VDRL
National Archives; 2017 [updated 2017 May 27; accessed 2021 May slide tests among leprosy patients. Am J Syph Gonorrhea Vener Dis
27]. Available from: https://www.archives.gov/research/health/cdc- 1952;36:566–570.
cutler-records/. 83. Funes JM, Cutler JC, Levitan S, Portnoy J, Funes R. Serologic and
64. Reverby SM. “Normal exposure” and inoculation syphilis: a PHS clinical studies of syphilis in Guatemala, Central America. II. Study of a
“Tuskegee” doctor in Guatemala, 1946–1948. J Policy Hist 2011;23: group of school children in the port of San Jose  [in Spanish]. Bol
6–28. Oficina Sanit Panam 1953;34:14–18.
65. Presidential Commission for the Study of Bioethical Issues. “Ethically 84. Magnuson HJ, Thomas EW, Olansky S, Kaplan BI, De Mello L, Cutler
impossible”: STD research in Guatemala 1946 to 1948. Washington, JC. Inoculation syphilis in human volunteers. Medicine (Baltimore)
DC: Presidential Commission for the Study of Bioethical Issues; 2011 1956;35:33–82.
[accessed 2021 May 27]. Available from: https://bioethicsarchive. 85. Jones JH. Foreword. In: Reverby SM, editor. Tuskegee’s truths:
georgetown.edu/pcsbi/sites/default/files/Ethically%20Impossible% rethinking the Tuskegee syphilis study. Chapel Hill, NC: University of
20(with%20linked%20historical%20documents)%202.7.13.pdf. North Carolina Press; 2000. pp. xi–xiii.
66. Presidential Commission for the Study of Bioethical Issues. Moral 86. Katz J. The consent principle of the Nuremberg Code: its significance
science: protecting participants in human subjects research. then and now. In: Annas GJ, Grodin MA, editors. The Nazi doctors and
Washington, DC: Presidential Commission for the Study of Bioethical the Nuremberg code: human rights in human experimentation. New
Issues: 2011 [accessed 2021 May 27]. Available from: https:// York, NY: Oxford University Press; 1992; pp. 227–239.
bioethicsarchive.georgetown.edu/pcsbi/sites/default/files/ 87. Caplan AL. Too hard to face. J Am Acad Psychiatry Law 2005;33:
Moral%20Science%20June%202012.pdf. 394–400.
67. Parascandola J. John Mahoney and the introduction of penicillin to treat 88. Caplan AL. Are existing safeguards adequate? J Calif Alliance Ment Ill
syphilis. Pharm Hist 2001;43:3–13. 1994;5:36–38.
68. Hook EW III. Remembering Thomas Parran, his contributions and 89. Reverby SM. Inclusion and exclusion: the politics of history, difference,
missteps going forward: history informs us. Sex Transm Dis 2013;40: and medical research. J Hist Med Allied Sci 2008;63:103–113.
281–282. 90. Katz RV, Warren RC, editors. The search for the legacy of the USPHS
69. Ove T. Before Tuskegee, the Guatemala experiment: a Pitt legend’s syphilis study. Lanham, MD: Lexington Books; 2013.
research is under scrutiny. Pittsburgh Post-Gazette 2011 June 12 91. Shiels MS, Haque AT, Haozous EA, Albert PS, Almeida JS, Garcıa-
[accessed 2021 June 22]. Available from: https://www.post-gazette. Closas M, et al. Racial and ethnic disparities in excess deaths during
com/opinion/Op-Ed/2011/06/12/The-Next-Page-Before-Tuskegee-the- the COVID-19 pandemic, March to December 2020. Ann Intern Med
Guatemala-Experiment-a-Pitt-legend-s-research-is-under-scrutiny/ 2021;174:1693–1699.
stories/201106120141. 92. Glover J. Humanity: a moral history of the twentieth century. London,
70. Mahoney JF, Van Slyke CJ, Cutler JC, Blum HL. Experimental United Kingdom: Jonathan Cape; 1999.
gonococcic urethritis in human volunteers. Am J Syph Gonorrhea 93. Fletcher JC. A case study in historical relativism: the Tuskegee (Public
Vener Dis 1946;30:1–39. Health Service) syphilis study. In: Reverby SM, editor. Tuskegee’s
71. Walter M. Human experiments: first, do harm. Nature 2012;482: truths: rethinking the Tuskegee syphilis study. Chapel Hill, NC:
148–152. University of North Carolina Press; 2000. pp. 276–298.

State of the Art 1157

 STATE OF THE ART

94. DiAnni D, director. The deadly deception. Nova. Boston, MA: 101. Henriksen K, Kaplan H. Hindsight bias, outcome knowledge
WGBH; 1993. and adaptive learning. Qual Saf Health Care 2003;12:ii46–ii50.
95. Junod T. Deadly medicine. In: Reverby SM, editor. Tuskegee’s truths: 102. Hochschild A. Bury the chains: prophets and rebels in the fight to free an
rethinking the Tuskegee syphilis study. Chapel Hill, NC: University of empire’s slaves. Boston, MA: Mariner Books; 2005.
North Carolina Press; 2000. pp. 509–524. 103. Judt T. Reappraisals: reflections on the forgotten twentieth century.
96. Stoner BP, Marrazzo JM. American Sexually Transmitted Diseases London, United Kingdom: Penguin Books; 2008.
Association and the Thomas Parran Award: past, present, and future. 104. Baehr P, editor. The portable Hannah Arendt. New York, NY: Penguin;
Sex Transm Dis 2013;40:275–276. 2000.
97. Altman LK. Of medical giants, accolades and feet of clay. New York 105. Todorov T. Facing the extreme: moral life in the concentration camps.
Times 2013 April 1 [accessed 2021 Jun 22]. Available from: https:// New York, NY: Owl Books; 1996.
www.nytimes.com/2013/04/02/health/link-to-ethical-scandals-tarnishes- 106. Warnock M. An intelligent person’s guide to ethics. Croydon, United
prestigious-parran-award.html. Kingdom: Duckbacks; 1998.
98. Zenilman JM. The legacy of sexually transmitted disease research: 107. Dallaire R. Shake hands with the devil: the failure of humanity in
lessons from Guatemala and Dr. Thomas Parran: the American STD Rwanda. Cambridge, MA: Da Capo Press; 2004.
Association Distinguished Career Award Lecture. Sex Transm Dis 108. Power S. A problem from hell: America and the age of genocide. New
2013;40:901–908. York, NY: Harper Perennial; 2002.
99. University of Pittsburgh. Parran Hall name disappears after Board of 109. ICP. John Albert [accessed 2022 Apr 3]. Available from: https://www.icp.
Trustees agrees with chancellor’s recommendation. University Times org/browse/archive/objects/thomas-parran-jr-sixth-surgeon-general-of-
2018 July 5 [accessed 2021 Jun 22]. Available from: https://www. the-united-states-new-york.
utimes.pitt.edu/news/parran-hall-name. 110. Becker B. Plagues & people. Irvine: University of California, Irvine
100. Pellegrino ED, Thomasma DC. The virtues in medical practice. New [accessed Apr 3]. Available from: http://faculty.humanities.uci.edu/
York, NY: Oxford University Press; 1993. bjbecker/plaguesandpeople/lecture10.html.

1158 American Journal of Respiratory and Critical Care Medicine Volume 205 Number 10 | May 15 2022