Abstract
Debates on human experiments in developing countries focus on ethical principles such as informed consent, accountability, involvement of the concerned communities, and the improvement of local health services. Public health specialists who conducted human experiments in Rio de Janeiro (1902–1905) and in Guatemala (1947–1948) believed, however, that they were acting in the best interests of local populations, were aware of the importance of informed consent, were closely collaborating with local health professionals, and were contributing to the development of local health structures. Nevertheless, their investigations went dramatically wrong. An initial desire to conduct ethically and scientifically sound studies was undermined by pressure to obtain results and to save the researchers’ initial investment, the possibility of freely using hospitalized patients as experimental participants, uncritical help from local professional elites, and structural pitfalls of experimenting with severely deprived people. These elements can still be found in trials of preventive methods in the Global South.
“Distinguished Dr. Cutler, It’s a privilege for us to manifest to you, by means of these lines, our everlasting gratitude which will remain for ever in our hearts because of your noble and gentlemanly way with which you alleviated the suffering of the guards and prisoners in this penitentiary. You have really been a philanthropist, your disinterestedness, your constancy are evident samples of your nobleness.”
—Roberto Robles Chinchilla, chief of the medical service of Guatemala’s Central Prison, December 8, 19481
“I’m asking the Minister of Colonies permission to honor the members of the Mission for the Study of Yellow Fever, MM Simond et Marchoux, for their outstanding contribution to the Mission’s work and the impressive intelligence they brought to this extremely difficult and dangerous endeavor.”
—Letter sent to the French minister of colonies, November 23, 19052
ROBERTO ROBLES CHINCHILLA’S tribute to John Cutler’s “noble and gentlemanly ways,” and praise of his “philanthropy” and “disinterestedness,” refer to studies of the prevention of venereal disease conducted in Guatemala in 1947 and 1948 and funded by the US Public Health Service (PHS) through a grant to the Pan American Sanitary Bureau (PASB). It is reasonable to assume that Cutler (1915–2003) was proud of this letter; he placed it on the first page of his 1955 report on his studies of syphilis in Guatemala. Cutler probably did not view these studies, in which hundreds of people—prisoners, soldiers, and psychiatric patients—were infected with venereal diseases without their consent, as problematic. In 1990, he transmitted his documents on the Guatemala studies to the University of Pittsburgh archives. As a consequence, the historian of medicine Susan Reverby found them while researching Cutler’s role in the Tuskegee syphilis study, and started a chain of events that led to an apology to the Guatemalans issued by US Secretary of State Hillary Clinton and Secretary of Health and Human Services Kathleen Sebelius and a call from US President Barack Obama to Guatemala’s president, Alvaro Colom.3
Cutler and his colleagues in Guatemala had studied the prevention of sexually transmitted diseases. Human experiments were often motivated by scientists’ enthusiastic and sometimes obsessive search for new scientific knowledge.4 From the 1970s on, human experiments in developing countries often have been conducted by pharmaceutical firms that are testing new drugs, a practice that has led to fears of the exploitation of vulnerable populations.5 Studies like the one conducted by PHS researchers in Guatemala belong to a third category of human experiments: public health investigations.6 Such studies are often conducted by investigators who sincerely strive to alleviate the burden of disease and reduce human suffering.7
I examine two preventive experiments using human participants: studies of yellow fever conducted by Pasteur Institute scientists in Rio de Janeiro and Petropolis, Brazil, in 1902 through 1905 and studies of venereal diseases performed by PHS researchers in Guatemala in 1947 and 1948. These experiments were conducted in radically different political contexts. Early 20th-century Brazil was a truly (not only formally) independent country, and public health interventions were seen as a part of an effort to consolidate its national identity.8 French researchers were welcome in Rio de Janeiro because of their country’s cultural cachet, not because of France’s political influence in Brazil. By contrast, in the 1940s and 1950s Guatemala was dominated by the United States. Guatemala’s subordinate status may explain the extraordinary freedom of the US PHS researchers there.9 Moreover, the two experiments were not identical: studies of yellow fever involved fewer participants and were more dangerous.10 Nevertheless, the Brazilian and the Guatemalan projects shared important traits. In both, the starting point of the study was the infection of healthy people with a transmissible disease, the main stumbling block was the discovery that such an infection was more difficult to treat than initially believed, and researchers increasingly deviated from their original project to produce artificial contamination. The result was an increasingly chaotic experimental design, poorly executed studies, and ethically questionable interventions.
Scholars who have attempted to explain why investigators sincerely committed to public health ideals conducted unethical human experiments have evoked the belief that they were warriors fighting against an insidious and cruel enemy, but were also ignorant of ethical principles and affected by hubris and racism.11 These are surely plausible explanations. On the other hand, an exclusive focus on personal failings of individual researchers may mask structural causes that favor the conduct of unethical human experiments in developing countries: pressure to obtain results and save the researchers’ initial investment, gray zones of experimentation on hospitalized or institutionalized patients, local professional elites’ wish to achieve new developments in science and medicine, and the difficulty of conducting ethical experiments on severely deprived participants.12 All these elements can also be found in present-day human experiments. Good intentions are not enough to prevent messy outcomes.
The Pasteur Institute Mission to Rio de Janeiro was funded by the French Ministry of Colonies, eager to limit the economic harm produced by yellow fever in French colonies in Africa and the Caribbean islands.13 The members of the mission were Paul Luis Simond (1858–1947), a researcher who had already made a name for himself through studies of the role of fleas in the transmission of plague, Emile Marchoux (1862–1943), and Alexandre Taurelli Salimbeni (1867–1942). They arrived in Rio de Janeiro in November 1901.14 At that time, Walter Reed and his colleagues from the US Army Mission to Cuba had already established, through human experiments conducted in Havana in 1900, that yellow fever was transmitted by Stegomyia fasciata mosquitoes (today, Aedes aegypti).15
Members of the Pasteur Institute Mission established a bacteriology laboratory in the São Sebastião hospital, the main yellow fever hospital in Rio de Janeiro.16 However, in 1902 possibilities for studying yellow fever in the laboratory were very limited. There were no diagnostic tests, no animal models, no ways to cultivate the disease’s agent, and no cure.17 In September 1902, Simond complained that in spite of their intensive efforts the results they had obtained so far were very modest.18 In March 1902, Emile Roux, who was supervising the work of the Pasteur Institute Mission, proposed that they focus on investigating sera from patients and convalescents.19 He speculated on the possibility of protecting people from yellow fever through the administration of inactivated serum, and added, “[I]t’s really a pity you cannot conduct experiments on men of good will, as was done in Cuba.”20
A year later, the French researchers found a way to conduct such experiments. Volunteers—all new immigrants to Brazil—were gathered in a camp in Petropolis, a town near Rio de Janeiro, too high in the mountains to allow the survival of the S fasciata mosquito.21 Human experiments started in mid-April 1903. According to the published report of these experiments, they were conducted on 27 consenting participants: “The men who participated in our experiments were warned before witnesses about the risks involved in these experiments, and all freely agreed to it.”22 In their publication, the Pasteur Institute scientists arranged their experiments in a logical order. Simond’s notebook from that period gives a very different picture—of studies conducted in a chaotic and opportunistic way.23 Most of the experimental participants were injected with inactivated serum from yellow fever patients and then exposed to contaminated mosquitoes to check their resistance to infection.24 The quantity of injected serum and its origin, the treatment and the intervals between injections, all varied greatly and with no apparent logic. Moreover, entirely negative outcomes—in which the experimental participant did not develop yellow fever—were difficult to interpret.25 Not every bite of an infected mosquito transmitted yellow fever, and Simond was not sure that all the experimental participants were susceptible to the disease.26
In the meantime, the Pasteur Institute scientists were required to justify the investment in their studies. Simond and Marchoux had had a major falling out, and news about their disagreements had reached Paris. In May 1903, Roux urged Simond to transmit as rapidly as possible their results up to then to the Ministry of Colonies, to neutralize the bad impression they had created. He also told Simond about growing difficulties in obtaining the money that had been allocated to the mission.27 Roux’s message might have put additional pressure on the French researchers. In late May, 13 experimental participants who had not developed yellow fever were exposed to bites of freshly infected mosquitoes. Only two of them subsequently developed the disease. In June, the remaining 11 men were injected with infected blood.
On June 3, 1903, Simond recorded the murder of an experimental participant named Sollers. The same day, he noted that another experimental participant, Rolf, had “escaped”—an event that was perhaps related to Sollers’s murder.28 On June 10 and 11, four experimental participants were injected with the blood of yellow fever patients. On June 17, one of them, Geronimo, came down with a fever. On June 15, the remaining seven men were injected with the blood of Bardach, an experimental participant who had developed a severe case of yellow fever.29 Bardach died in the early morning of June 18. The same morning, Geronimo escaped from the Petropolis camp. As Simond recorded it in his notebook,
He takes the 7h30 train to Rio de Janeiro, arrives at Rio da Serra, gets off the carriage with his luggage and starts to walk along the rails. He stops after several hundred meters. He is brought to the station by the station’s workers, and dies there after two or three hours.30
On June 18, two experimental participants from the Petropolis camp had just died from yellow fever, and three of those injected with infected blood had high fever. On June 19, the five men inoculated with Bardach’s blood who remained healthy received 10 cubic cemtimeters each of a convalescent’s blood, probably in a hurried attempt to protect them from a deadly disease. The last entries in Simond’s notebook are from the morning of June 20.
In their publication of the Petropolis experiments, members of the Pasteur Mission affirmed that “experiments on man are legitimate only if they produce new and important results.”31 However, nearly all the results reported in their heavily edited retelling of their experiments either confirmed observations made by other researchers, were inconclusive, or could not be repeated.32 In hindsight, in the absence of an animal model of yellow fever, Pasteur Institute scientists’ efforts to find a way to protect people from this disease were highly unlikely to succeed.33 The human experiments conducted in 1903 by Marchoux, Salimbeni, and Simond in Rio may be described as illegitimate, even according to their own criteria.
Human experiments in Guatemala were sponsored by the Venereal Diseases Section of the PHS and conducted officially under the supervision of the PASB and by a grant from the National Institutes of Health. They were viewed as a continuation of studies made in the Terre Haute federal penitentiary in 1943 and 1944. In these experiments, prisoners who volunteered to be infected with gonorrhea received accurate information on the nature of the experiment. The PHS investigators, however, had difficulty in artificially infecting people with gonorrhea. The head of the Guatemalan Venereal Disease Control Department, Juan Funes, who in 1945 worked as a one-year fellow at the PHS’s Venereal Diseases Research Laboratory in Staten Island, New York, proposed to study venereal disease prevention in Guatemala. In that country, prisoners were allowed to pay for the services of a prostitute, making it possible to produce a “natural” infection through sexual intercourse with a contaminated sex worker. The availability of penicillin, the PHS researchers believed, made such an infection practically risk free.34 PHS put in charge of this study a junior researcher, John Cutler.
The original project, however, rapidly ran into a major difficulty: the “natural” transmission of venereal disease was also found to be inefficient. In addition, the plan to use volunteers from the federal penitentiary in Guatemala in the syphilis studies did not work as expected. Prisoners were difficult to control. Cutler therefore welcomed an offer by the director of the Insane Asylum, Carlos Salvado, to conduct experiments on the asylum’s inmates.35 Most of the syphilis experiments, and some of the chancroid experiments, were conducted on psychiatric patients.36 PHS researchers used two additional groups of people: children from an orphanage, a source of normal sera for the calibration of serological tests, and soldiers, used in studies of gonorrhea and chancroid.37 A study that originally should have relied on well-informed volunteers ended by almost exclusively using people who did not know they were participating in a medical experiment, and were often deceived about the true aims of the researchers’ activities.38 Moreover, the persistent difficulty of infecting healthy people with venereal diseases led to a gradual drift of the experimental design toward an increasingly “unnatural,” aggressive, painful, and potentially harmful experimentation, especially on psychiatric patients.39
Cutler’s papers indicate that PHS-sponsored studies in Guatemala were not only ethically questionable, but also poorly executed and difficult to interpret.40 One of the reasons for the chaotic conduct of the experiments might have been Cutler’s belief that he should provide results rapidly; otherwise, he might lose financial support and therefore “a scientific opportunity which comes only rarely.”41 In the fall of 1947, Cutler’s hierarchical superior John Mahoney was worried about negative reactions to the slow progress of the Guatemala investigations:
In the event of the prophylaxis angle proving to be impossible of resolution, we will have left only the serology study and the work in penicillin therapy. We would surely have difficulty in selling an expensive project of this kind to the Service.42
The PHS investigators’ willingness to bend rules to produce results may have been related to their wish to justify the considerable investment in the Guatemala project.43 At the same time, they seem to have been aware how questionable their approach was. In 1948, when Thomas Parran was scheduled to leave his job as surgeon general, Mahoney wrote to Cutler that with this change:
We know that we have lost a very good friend and that it appears to be advisable to get ducks in line. In this regard we feel that the Guatemala project should be brought to the innocuous stage as rapidly as possible.44
Pasteur Institute investigators had explained that risky human experiments could be justified only when the results were truly new and important, but they had conducted badly planned and poorly executed studies. PHS researchers observed sound scientific principles and ethical rules in the Terre Haute penitentiary, but abandoned these rules in Guatemala. The isolation of a small group of researchers in a foreign country may partly explain their failure to respect the principles they themselves proclaimed.45 In addition, however, such behavior may have been prompted by external pressure from hierarchic superiors who wanted to justify costly experiments abroad, and by internal pressure felt by scientists who had found out that their project was not working as expected. They might have been led to hurried attempts to infect participants by their belief that otherwise everything would be lost: their goals, ambition, and reputation, along with the time, money, and effort invested in their study up to then, but also their sincere hopes to alleviate the plight of people who suffered from transmissible diseases.
Before they started experiments on healthy people, the Pasteur Institute researchers attempted to treat patients at the São Sebastião hospital with convalescent sera. Seven of the treated patients stayed alive and four died.46 Human experiments at the hospital continued in 1905 and 1906. In 1906, Simond and Marchoux believed they held conclusive proof that the yellow fever agent could pass from an infected female mosquito to her female offspring.47 This conviction was grounded in a single human experiment. A young immigrant was bitten by mosquitoes hatched in the laboratory from the eggs of an infected female and developed mild but typical yellow fever. To confirm that the disease was indeed yellow fever, mosquitoes that had fed on a deadly case of yellow fever were allowed to bite the same participant. He remained healthy.48 In 1912, Simond recognized that the experiment was not conclusive: other investigators had failed to repeat it.49 Simond’s notebook for 1904 and 1905 indicates that Simond (and perhaps Marchoux) conducted other “unofficial” human experiments. Simond’s notes from that period are very fragmentary and mainly cover February and March 1905. We learn nevertheless about attempted experimental infection of seven additional participants; their subsequent fate remains unkown.50
In his 1955 report, Cutler explained that he had abandoned his original plan to use volunteers recruited in the national penitentiary because the prisoners had refused repeated blood drawings. Members of the Presidential Commission on Bioethical Issues noted, however, that the experiments in the Insane Asylum started only a few days later than those in the prison.51 It seems possible that Cutler and his colleagues could not resist the temptation to conduct experiments on humans without going to the trouble of negotiating an agreement. Psychiatric patients were never informed that they were being artificially infected with syphilis, and even some of the asylum’s staff believed at first that the “inoculation” was part of a treatment.52 The sum of $1500, originally intended to pay volunteers in the prison, was given to the psychiatric hospital’s administration to acquire equipment that would benefit the community. The US researchers also supplied the asylum with an antiepileptic drug, Dilantin.53 Cutler believed that this was a fair arrangement:
Although we gave medicines and supplies to the institution the patients were not aware of it and it would have meant nothing even though the patients had been mentally fit and cognizant of the fact.54
Bioethical debates on experimentation on human beings usually focus on activities clearly labeled “experiments,” and tend to neglect regular medical practice. This is problematic because not infrequently physicians—driven by the wish to “do something” for people they are treating, and by poor judgment, hubris, and a desire to advance their career, or a mixture of these motivations—conduct scientifically unsound and ethically doubtful experiments on their patients. Such experiments tend to remain invisible.55
Schematic views of human experiments in developing countries sometimes oppose “Western scientists” to “local communities,” and overlook the complicated role of the mediating entity “local scientific communities.” The Pasteur Institute scientists in Rio de Janeiro benefited from the protection of Oswaldo Cruz, the head of Rio de Janeiro’s Department of Public Health, and were greatly helped by the director of the São Sebastião hospital, Carlos Siedl.56 Cruz had studied bacteriology at the Pasteur Institute, and in the early stages of his career presented himself as a student and follower of Emile Roux and a promoter of “pasteurian science.”57 Siedl was flattered that his establishment was elected to host illustrious French researchers.58 Siedl’s and Cruz’s strong support may explain why the French researchers did not face the hostile press and “malignant gossip” that complicated the task of the United States Army Mission to Cuba.59
Siedl went out of his way to provide the best possible working conditions for the French researchers. He gave them laboratory space, scientific collaborators, and technical help, and even hired a French cook to prepare their meals.60 More importantly, he gave them access to the hospital’s patients, an indispensable source of the yellow fever virus and potential experimental participants.61 In return, the French scientists shared their knowledge of laboratory methods. They brought with them a complete set of equipment from a bacteriology laboratory, organized a formal bacteriology course for the São Sebastião physicians, and provided tutoring in bacteriological techniques.62 At the end of their mission, Simond and Marchoux left all their laboratory equipment, with the exception of the microscopes, at the São Sebastião hospital.63 The members of the Pasteur Mission in Rio de Janeiro, Siedl explained later, taught their Brazilian colleagues how to study human diseases in the laboratory and how to conduct a scientific investigation.64
John Cutler and his colleagues were invited to Guatemala by Juan Funes.65 The PHS’s sponsored research was strongly supported by numerous other Guatemalan officials, such as Constantino Alvarez, division chief at the Guatemalan Ministry of Health, Luis Galich, director of public health of Guatemala, and Carlos Tejeda, chief of the Medical Services of the Military Hospital.66 Helping the PHS scientists provided Guatemalan doctors with opportunities to advance their careers. Salvado, the director of the Insane Asylum, received a scholarship to work in the United States. In 1948, Salvado and Funes were hired by the PHS to continue the observations started by Cutler and his collaborators, and in the early 1950s Funes became vice-chairman of the World Health Organization’s syphilis study commission.67 Abel Luna, a physician from the Guatemala Public Health Service who helped the PHS researchers, received a fellowship to study in the Venereal Disease Research Laboratory in Staten Island, New York. Salvado and Funes continued to send biological material (sera and spinal fluid) to the United States, and Carlos Tajeda, chief of Guatemala’s army medical department, made arrangements to open in Guatemala a training center in tropical diseases for American physicians from the PHS, the US Army, and the US Navy.68 Moreover, when the PHS project in Guatemala came to an end in summer 1948, the PASB laboratory was transformed into a permanent center for training of Latin American scientists and the standardization of syphilis tests.69
Scientists in “peripheral” countries hope to gain access to knowledge and practices elaborated in recognized scientific centers.70 In exchange for such access, their Western colleagues may get an opportunity to use interesting “research material,” including human participants. Their help in organizing human experiments may thus provide important professional benefits for local scientists.71 At the same time, they can easily persuade themselves that such experiments are advancing medical research in their country and contributing to the improvement of its inhabitants’ health.72 Scientists who work today in developing or intermediary countries are probably no less eager than their predecessors to collaborate with colleagues from prestigious scientific centers and reap the intellectual and practical advantages of such collaborations. A sincere wish to use human experiments to promote biomedical research and the development of local health structures may become hopelessly entangled with ambitious professionals’ desire to advance their own interests.
The majority of the volunteers recruited for experiments on the transmission and prevention of yellow fever in Cuba and Brazil were in all probability attracted by the promise of considerable financial compensation.73 ”
Healthy participants in risky medical experiments may be motivated by an altruistic wish to help a scientific inquiry, but more often they are lured by the possibility of material advantages. The majority of the volunteers recruited for experiments on the transmission and prevention of yellow fever in Cuba and Brazil were in all probability attracted by the promise of considerable financial compensation.73 Simond’s record of the Petropolis experiments starts with a list of people paid by the French scientists.74 In his description of Reed’s experiments in Cuba, Paul de Kruif dissociates “true” volunteers—US soldiers ready to risk their life in the interest of science—from the mercenary participants
ignorant immigrants, hardly more intelligent than animals…. there were five of these mercenary fellows—whom I shall simply call Man 1, 2, 3, 4—just as microbe hunters often mark animals: Rabbit 1, 2, 3.75
The Insane Asylum in Guatemala, Cutler explained in his 1955 report, lacked basic equipment, did not have essential drugs, and was severely understaffed.76 Cutler and his colleagues seem to have accepted this situation as normal. The decision to buy for the asylum a supply of the antiepileptic drug Dilantin was legitimated by the observation that it would facilitate the conducting of syphilis studies.77 PHS researchers exploited the inmates’ extreme material and emotional deprivation to advance their goals:
The institute’s staff was so small that the group of experimental workers appreciably increased the amount of a physician’s time given to each inmate. As reported earlier, cigarettes were a most valuable, even indispensable, adjunct to the whole program… . The patients would often attempt to make numerous trips past the physicians, for blood letting, cisternal puncture or examination, just to augment their supply of tobacco.78
“Without the availability of cigarettes,” Cutler explained, “the type of patients management [sic] that we were able to achieve, we feel, would have been impossible.”79
The experiments conducted by PHS experts in Guatemala are an extreme case of abuse of participants in research, but debates on clinical trials in the Global South continue today. In the second half of the 20th century, such debates focused on three issues: clinical testing and mass diffusion of contraceptives, transfer of clinical trials of new drugs to developing and intermediary countries, and clinical trials of preventive strategies, especially the reduction of HIV infection. Each issue is different. Population experts presented mass diffusion of contraceptives as a way to help people in poor countries to better their condition. It is seen today by many scholars as an effort to disarm the “population bomb,” perceived at that time as a major threat to the Western way of life.80 The testing of new drugs on people who often cannot afford access to them stems mainly from the pharmaceutical companies’ desire to reduce the costs of research and development.81 Questionable practices, such as the testing of the antibiotic Trovan in Nigeria, undermined confidence in Western medicine and led to efforts to better regulate this activity.82 Finally, clinical trials of HIV vaccines or methods to prevent HIV transmission from mother to fetus were designed (mainly) to limit AIDS epidemics in Africa and Asia, but some were criticized for their ethical failings.83
The AIDS crisis has intensified debates on human experiments in developing countries, increasingly conducted with the active participation of experts from the Global South.84 These debates usually focus on informed consent, the ethics of trials against placebo, the importance of securing benefits for participating communities, and the need to protect local populations and researchers against exploitation.85 They rarely problematize the polysemic term “community,” evoke the possibility that the interests of local professional elites may conflict with those of other social groups, or examine the consequences of conducting experiments on severely deprived populations.86
One notable exception to the paucity of attention on the role of deprivation was the debate over field trials of anti-HIV microbicides (substances applied locally and meant to protect women from HIV infection). Activists who promoted such trials had found that
it is very difficult to balance the need to make a reliable trial with a right understanding of what organizers of this trial can do—and what they cannot—in order to avoid bothersome meddling with local health structures, raising non realistic expectations, and doing more harm than good.87
Organizers of clinical trials of anti-HIV microbicides were unable to find a satisfactory way to ensure that women who became infected with HIV during a prevention trial could access care and treatment after the study was over. They were obliged to recognize that research often could not help rectify long-standing inequities in access to global health resources, and that even the most carefully crafted protocols could not address the root causes of disintegrating health systems, such as poverty and gender inequalities.88
When people who volunteer to participate in a clinical experiment are driven by an inability to fulfill an elementary need—be it of care or of subsistence—the notion of informed consent becomes very questionable. Many doctors and bioethicists believe that experimenting on humans is not a problem if they are willing participants. They forget that the individual or collective decision to participate in an experiment may be founded on misinformation, misplaced trust in the profession, or, not infrequently, on pecuniary circumstances.89 The insistence on informed consent without paying sufficient attention to the circumstances of receiving such consent may lead to a perilous dissociation of the process of consent from its clinical and social setting.90 A guard at Pennsylvania’s Holmesburg Prison, where dermatologists from the University of Pennsylvania conducted painful and sometimes risky experiments on prisoners, explained to a social researcher surprised by such “volunteering,” “Look, you and I wouldn’t do it, sell ourselves for chump change to some strange college doctors, but… this is their only way to make money in jail.”91 Informed consent is about the possibility to choose, but it is not a choice when options are severely limited.
Present-day reflections on human experiments, and evaluations of past experiments, are shaped by contemporary bioethical debates.92 Such debates have been stimulated by revelations of severe ethical failings in the conduct of such experiments. Names such as Tuskegee, Willowbrook—and, today, Guatemala—have become synonyms of scientific misconduct.93 Other past experiments on humans are presented as ethical, sometimes on the strength of partial evidence. In an oft-quoted text on “Ethics and Human Experimentation,” David Rothman presents two historical examples of principled behavior of scientists. One is Louis Pasteur’s first test of the rabies vaccine. Pasteur, Rothman explains, agonized about the decision to treat the first victim of a rabid dog, consulted with two colleagues, and decided in favor of treatment only when he was assured that otherwise the victim’s death appeared inevitable.94 The source of this often-told story is a hagiographic biography of Pasteur, written by his son-in-law.95 Other sources present a very different image of Pasteur’s human experiments, including “unofficial” experimentation and falsification of evidence.96 Rothman’s second case is studies carried out by PHS researchers in the Terre Haute penitentiary in 1943 and 1944. Scientists who conducted these studies were aware of their problematic legal and ethical aspects and established special protocols of informed consent, elements that did not exist in the Guatemala experiments supervised by the same people.97
Walter Reed’s yellow fever studies are another frequently cited example of ethical human experiments.98 Reed’s biographer explains that all the volunteers in the Cuban experiments signed a contract that enumerated their risks and benefits and specified that
the undersigned binds himself not to leave the bounds of this camp during the period of the experiment, and will forfeit all the rights to the benefits named in this contract if he breaks this agreement.99
The notion of a freely respected contract is, however, at odds with General William Gorgas’s description of Reed’s experiments:
They established an experimental station in the country and half-a-mile or more from any habitation, placed non-immunes in the camp under military control so that they could not leave it, kept them there a sufficient length of time to be certain that they had not contracted yellow fever, and then experimented upon them.100
In Gorgas’s version, a key element of the success of Reed’s experiments was not a signed contract but the presence of armed guards.
If no new documents come to light, we may never know how participants in the Cuban yellow fever experiments reacted to their confinement. Without the chance arrival of Simond’s laboratory notebooks in the Pasteur Institute Archives in the 1990s, the only source of information about the Petropolis experiments would have been the heavily edited official report of the Pasteur Institute Mission.101 The relative abundance of documents on the PHS studies in Guatemala is probably an exception. It is difficult to count on the possibility that researchers will keep potentially compromising records.102
Obstacles to finding out what really happened during a given human experiment are not limited to historical studies. Discussions on present-day experiments tend to be centered on rules and regulations, institutional reviews and protocols, declared goals and proposed results. The final report of The Presidential Commission on Bioethical Issues, Moral Science: Protecting Participants in Human Subjects Research, released in December 2011, focuses on elements that should promote such protection: informed consent, increased accountability, expansion of education in bioethics, compensation for research related injury, and the promotion of “community engagement.”103 Moral Science does not dwell, however, on the need to supervise ongoing human experiments and gather reliable information on what is actually going on in these experiments, especially in those conducted in developing and intermediary countries. To avoid the risk of investigating the “bioethics of the imaginary,” it may be important to considerably increase the number of observational studies of human experiments, including those with public health goals.104 Such studies should help to answer the “how” question—What should be done to reduce the risk of unethical behavior?—but also the “whether” question: What are the political, socioeconomic, and institutional conditions under which experiments on humans should not take place, even when the researchers who plan to conduct them have the best possible intentions?
Acknowledgments
This study was partly funded by Agence Nationale de Recherche sur le Sida (grants 2009-436 and 2010-375), in the framework of a larger study on the history and present uses of the prevention of sexually transmitted infections.
I thank Denise Ogilvie and Daniel Demellier of the Pasteur Institute Archives for their invaluable assistance with Paul Louis Simond’s papers, and the Journal’s anonymous reviewers, who greatly helped me to improve this article.
