Stateville Penitentiary Malaria Study

Last updated December 03, 2023

The Stateville Penitentiary malaria study was a controlled but ethically questionable study of the effects of malaria on prisoners of Stateville Penitentiary near Joliet, Illinois, in the 1940s, conducted by the Department of Medicine at the University of Chicago in conjunction with the United States Army and the State Department. The Stateville experiment was viewed as coercive because it offered shortened sentences to participants.^[1] The Green report was written in 1945 about it by Andrew Conway Ivy, used in Nuremberg Medical Trial, which affected the Nuremberg Code, and used to discuss how medical experimentation on prisoners should be carried out.

Historical context

Demand for malaria research

The circumstances of World War II resulted in an urgent need for the development of new malaria treatments. First, U.S. soldiers were deployed to areas of the Pacific with extremely high rates of malaria infection.^[2] The U.S. Army estimated millions of man-hours lost due to malaria throughout the war; thus it was critically important to mitigate the effects of the disease in the interest of the military. Second, the conventional treatment for malaria, quinine, was largely unavailable throughout the war. Japanese control of the Philippines and Indonesia cut off the supply of quinine to the United States, adding to the need for alternate treatments.^[2] The new risks of malaria posed by World War II called for experimentation at an unprecedented scale, with a particular focus on human subjects.

Prison as a research center

The prison offered an environment conducive to controlled scientific experimentation on human subjects. The malaria experiments at Stateville Penitentiary are noteworthy for their utilization of this prison environment across all aspects of the experiments. A prison population allowed for researchers to limit extraneous variables across the subjects. Participants of the studies were exclusively white men, of similar age and health, which was the primary demographic of Stateville Penitentiary. The population of prisoners was also inherently homogenous in terms of behavior, due to the restrictions imposed by the maximum-security prison.^[3] Follow-up evaluations were possible for virtually all subjects of the study, since all had long-term sentences. Offers of parole reevaluation, as well as financial incentives, typically $25–$100 for an experimental trial (adjusted for inflation, $460–$1,860 in 2021), which yielded an exceptionally high availability of subjects willing to participate.^[4]

Malaria Research Project

In 1944, the U.S. Committee on Medical Research formed a contract with the University of Chicago to test novel malaria treatments at the Stateville Penitentiary. Alf Alving, a nephrologist from the University of Chicago, directed the research and oversaw the formation of a clinical research division of the prison hospital. Alving worked with Ray Dern and Ernest Beutler, two physicians also from the University of Chicago.^[4]^[5]

The Malaria Research Project was primarily conducted on a floor of the prison hospital in the Stateville Penitentiary. The study aimed to understand the effect of various antimalarial drugs on relapses of malaria, primarily from the 8-aminoquinoline group of compounds. The study marked the first human test of the antimalarial drug primaquine.^[6] For the experiment, doctors from the University of Chicago bred Anopheles quadrimaculatus mosquitoes. The mosquitoes were infected with a plasmodium vivax malaria strain that was isolated from a military patient. All five malaria strains are in the genus Plasmodium , protozoan parasites.

Experiments performed

The study considered the Chesson strain of P. vivax, sourced from a military patient infected in the Pacific.^[3]P. vivax, the predominant form of malaria in the Pacific, is associated with milder symptoms and unlike Plasmodium falciparum , it typically is not deadly. This strain was known for its resistance to the standard treatment of quinine, with frequent occurrences of relapse.^[4] Subjects at the prison maintained the strain via blood inoculations. For both control and test subjects, a constant number of mosquito bites from infected insects were administered; then, researchers dissected the mosquitoes to determine the intensity of the resultant infection.^[3]

The researchers tested patient responses to various potential treatments. The majority of these treatments had not yet been evaluated on humans, and their toxicity and potency was thus unknown. Most were 8-aminoquinoline compounds, analogs of pamaquine, an existing alternative to quinine that was unfavorable due to its higher toxicity. The researchers tested a wide range of doses, including some exceptionally high doses of treatments known to be toxic. The purpose of this was to establish a maximum margin of safety and to observe the manifestation of side effects. Thus, adverse side effects were intentionally caused to subjects, to demonstrate the possible worst-case reaction to extremely high-potency treatments. In one case, a subject died several days after he was injected with a high dosage of SN-8233, a potential treatment considered in the study.^[3]^[4]

Prisoner roles

The prison of the environment of the study created a unique and complex social dynamic, with prisoners involved in many aspects of the study, not only as subjects. A well-known participant of the study was Nathan Leopold, who (together with Richard Loeb, who was killed after being sentenced) kidnapped and murdered a teenager, while they were students at the University of Chicago. Serving his sentence at Stateville Penitentiary, Leopold took interest in the malaria studies, first enrolling as a subject. Throughout the experiment he assumed many other roles, recruiting subjects, observing experiments, serving as an X-ray technician, and dissecting mosquitoes. As a technician, he was assigned roles critical to the success of the research, and the flow of knowledge, communication, and resources critically depended on him at times. These accounts of his participation largely come from his autobiography Life Plus 99 Years, the factual accuracy of which is verified through reputable accounts of the study.^[4] While Leopold’s range of roles was exceptional, numerous other prisoners assumed similar responsibilities in the experiments.^[7]

Legacy of the study

The experiments were widely publicized, though in a controlled manner. In 1944, Life magazine documented the experiments with a photo series. Accounts of prisoner subjects were included, though these were allegedly scripted.^[4]

While a series of research publications came out of the Stateville Penitentiary experiments, the results had a minimal long-term impact on malaria treatment methods. The main legacy of the study is instead the ethical contention raised by prisoner experimentation, manifesting in the trials of Nazi Germany for its experiments on human subjects.

Nuremberg medical trial

In the 1946 Nuremberg trials in Germany, the International Military Tribunal prosecuted leaders of former Nazi Germany for war crimes and events of the Holocaust, in particular, experimentation on human subjects. The Stateville malaria experiments were used as a critical point of defense for the Nazis, who argued similarities between their prisoner experimentation and the United States’ at Stateville Penitentiary.^[8]

Andrew Ivy, a physician from Chicago, testified as an expert witness in the trials. He was asked to differentiate Nazi malaria experiments at the Dachau concentration camp and the Stateville Penitentiary malaria experiments.^[9] There were key distinctions, such as a higher rate of subject fatalities and lack of voluntary consent in the Nazi experiments. However, the procedures, motives and premise of the studies were arguably similar.

The U.S. supported Ivy’s claims of fundamental differences and publicized them as a justification for continuing the Stateville experiments. The international Nuremberg Code of human experimentation ethics, which resulted from the trials, contained clauses directly violated by the Stateville experiments. The U.S. never formally ratified the code, however, calling into question the ethics of prisoner experimentation and the Stateville Penitentiary malaria experiments in particular.^[4]

Effect on prisoner experimentation

Public opposition to medical experimentation on prisoners was scant during the war. The Green Report was published in the Journal of the American Medical Association and opened the door for legal, ethical experimentation on prisoners in the United States. Until later in the century, the medical community in the United States largely regarded the Nuremberg Code to be applicable to war criminals and not to the practices of U.S. researchers.

Related Research Articles

Malaria is a mosquito-borne infectious disease that affects humans and other vertebrates. Human malaria causes symptoms that typically include fever, fatigue, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. Symptoms usually begin 10 to 15 days after being bitten by an infected Anopheles mosquito. If not properly treated, people may have recurrences of the disease months later. In those who have recently survived an infection, reinfection usually causes milder symptoms. This partial resistance disappears over months to years if the person has no continuing exposure to malaria.

The Nuremberg Code is a set of ethical research principles for human experimentation created by the court in U.S. v Brandt, one of the Subsequent Nuremberg trials that were held after the Second World War.

Antimalarial medications or simply antimalarials are a type of antiparasitic chemical agent, often naturally derived, that can be used to treat or to prevent malaria, in the latter case, most often aiming at two susceptible target groups, young children and pregnant women. As of 2018, modern treatments, including for severe malaria, continued to depend on therapies deriving historically from quinine and artesunate, both parenteral (injectable) drugs, expanding from there into the many classes of available modern drugs. Incidence and distribution of the disease is expected to remain high, globally, for many years to come; moreover, known antimalarial drugs have repeatedly been observed to elicit resistance in the malaria parasite—including for combination therapies featuring artemisinin, a drug of last resort, where resistance has now been observed in Southeast Asia. As such, the needs for new antimalarial agents and new strategies of treatment remain important priorities in tropical medicine. As well, despite very positive outcomes from many modern treatments, serious side effects can impact some individuals taking standard doses.

Human subject research is systematic, scientific investigation that can be either interventional or observational and involves human beings as research subjects, commonly known as test subjects. Human subject research can be either medical (clinical) research or non-medical research. Systematic investigation incorporates both the collection and analysis of data in order to answer a specific question. Medical human subject research often involves analysis of biological specimens, epidemiological and behavioral studies and medical chart review studies. On the other hand, human subject research in the social sciences often involves surveys which consist of questions to a particular group of people. Survey methodology includes questionnaires, interviews, and focus groups.

Plasmodium vivax is a protozoal parasite and a human pathogen. This parasite is the most frequent and widely distributed cause of recurring malaria. Although it is less virulent than Plasmodium falciparum, the deadliest of the five human malaria parasites, P. vivax malaria infections can lead to severe disease and death, often due to splenomegaly. P. vivax is carried by the female Anopheles mosquito; the males do not bite.

Plasmodium knowlesi is a parasite that causes malaria in humans and other primates. It is found throughout Southeast Asia, and is the most common cause of human malaria in Malaysia. Like other Plasmodium species, P. knowlesi has a life cycle that requires infection of both a mosquito and a warm-blooded host. While the natural warm-blooded hosts of P. knowlesi are likely various Old World monkeys, humans can be infected by P. knowlesi if they are fed upon by infected mosquitoes. P. knowlesi is a eukaryote in the phylum Apicomplexa, genus Plasmodium, and subgenus Plasmodium. It is most closely related to the human parasite Plasmodium vivax as well as other Plasmodium species that infect non-human primates.

<span class="mw-page-title-main">Gerhard Rose</span> German expert on tropical medicine; defendant at the Nuremberg Doctors Trial (1896–1992)

Gerhard August Heinrich Rose was a Nazi German physician and war criminal who performed medical atrocities on concentration camp prisoners at Dachau and Buchenwald without the subjects' consent. He infected Jews, Romani people, and the mentally ill with malaria and typhus. Following the Doctors' Trial, Rose was convicted of war crimes and sentenced to life in prison, but he was released in 1955.

The Green report was written by Andrew Conway Ivy, a medical researcher and vice president of the University of Illinois at Chicago. Ivy was in charge of the medical school and its hospitals. The report justified testing malaria vaccines on Statesville Prison, Joliet, Illinois prisoners in the 1940s. Ivy mentioned the report in the 1946 Nuremberg Medical Trial for Nazi war criminals. He used it to refute any similarity between human experimentation in the United States and the Nazis.

<span class="mw-page-title-main">8-Aminoquinoline</span> Chemical compound

8-Aminoquinoline is the 8-amino derivative of quinoline. Often abbreviated AQ, it is a pale yellow solid. It is structurally analogous to 8-hydroxyquinoline.

<span class="mw-page-title-main">Pamaquine</span> A drug (of the 8-aminoquinoline class) formerly used to treat malaria

Pamaquine is an 8-aminoquinoline drug formerly used for the treatment of malaria. It is closely related to primaquine.

Andrew Conway Ivy was an American physician. He was appointed by the American Medical Association as its representative at the 1946 Nuremberg Medical Trial for Nazi doctors, but later fell into disrepute for advocating the fraudulent drug Krebiozen.

The history of malaria extends from its prehistoric origin as a zoonotic disease in the primates of Africa through to the 21st century. A widespread and potentially lethal human infectious disease, at its peak malaria infested every continent except Antarctica. Its prevention and treatment have been targeted in science and medicine for hundreds of years. Since the discovery of the Plasmodium parasites which cause it, research attention has focused on their biology as well as that of the mosquitoes which transmit the parasites.

Nazi human experimentation was a series of medical experiments on prisoners by Nazi Germany in its concentration camps mainly between 1942 and 1945. There were 15,754 documented victims, of various nationalities and age groups, although the true number is believed to be more extensive. Many survived, with only a quarter of documented victims killed. Survivors generally experienced severe permanent injuries.

Throughout history, prisoners have been frequent participants in scientific, medical and social human subject research. Some of the research involving prisoners has been exploitative and cruel. Many of the modern protections for human subjects evolved in response to the abuses in prisoner research. Research involving prisoners is still conducted today, but prisoners are now one of the most highly protected groups of human subjects

Claus Karl Schilling, also recorded as Klaus Schilling, was a German tropical medicine specialist who participated in the Nazi human experiments at the Dachau concentration camp during World War II.

Numerous experiments which are performed on human test subjects in the United States are considered unethical, because they are performed without the knowledge or informed consent of the test subjects. Such tests have been performed throughout American history, but some of them are ongoing. The experiments include the exposure of humans to many chemical and biological weapons, human radiation experiments, injections of toxic and radioactive chemicals, surgical experiments, interrogation and torture experiments, tests which involve mind-altering substances, and a wide variety of other experiments. Many of these tests are performed on children, the sick, and mentally disabled individuals, often under the guise of "medical treatment". In many of the studies, a large portion of the subjects were poor, racial minorities, or prisoners.

Various organizations have created guidelines for human subject research for various kinds of research involving human subjects and for various situations.

Unethical human experimentation is human experimentation that violates the principles of medical ethics. Such practices have included denying patients the right to informed consent, using pseudoscientific frameworks such as race science, and torturing people under the guise of research. Around World War II, Imperial Japan and Nazi Germany carried out brutal experiments on prisoners and civilians through groups like Unit 731 or individuals like Josef Mengele; the Nuremberg Code was developed after the war in response to the Nazi experiments. Countries have carried out brutal experiments on marginalized populations. Examples include American abuses during Project MKUltra and the Tuskegee syphilis experiments, and the mistreatment of indigenous populations in Canada and Australia. The Declaration of Helsinki, developed by the World Medical Association (WMA), is widely regarded as the cornerstone document on human research ethics.

Plasmodium cynomolgi is an apicomplexan parasite that infects mosquitoes and Asian Old World monkeys. In recent years, a number of natural infections of humans have also been documented. This species has been used as a model for human Plasmodium vivax because Plasmodium cynomolgi shares the same life cycle and some important biological features with P. vivax.

References

↑ McDermott, Barbara (2014). "Coercion in Research: Are prisoners the only vulnerable population" (PDF). Semantic Scholar. S2CID 19593967. Archived from the original (PDF) on 2019-03-01.
1 2 Miller, Franklin G. (2013-01-01). "The Stateville penitentiary malaria experiments: a case study in retrospective ethical assessment". Perspectives in Biology and Medicine. 56 (4): 548–567. doi:10.1353/pbm.2013.0035. ISSN 1529-8795. PMID 24769747.
1 2 3 4 Alving, A. S.; Craige, B.; Pullman, T. N.; Whorton, C. M.; Jones, R.; Eichelberger, L. (1948-05-01). "Procedures Used at Stateville Penitentiary for the Testing of Potential Antimalarial Agents 1". The Journal of Clinical Investigation. 27 (3 Pt 2): 2–5. doi:10.1172/JCI101956. ISSN 0021-9738. PMC 438882 . PMID 16695630.
1 2 3 4 5 6 7 Comfort, Nathaniel (2009-09-01). "The prisoner as model organism: malaria research at Stateville Penitentiary". Studies in History and Philosophy of Biological and Biomedical Sciences. 40 (3): 190–203. doi:10.1016/j.shpsc.2009.06.007. ISSN 1879-2499. PMC 2789481 . PMID 19720327.
↑ Lichtman, M. A. (2001-04-01). "Introduction of Ernest Beutler, MD". Leukemia. 15 (4): 656–657. doi:10.1038/sj.leu.2402054. ISSN 0887-6924. PMID 11368370.
↑ Clinical Treatment of Malaria, Alf S. Alving, M.D.
↑ Weindling, Paul (2004-01-01). Nazi medicine and the Nuremberg Trials : from medical war crimes to informed consent. Palgrave Macmillan. ISBN 9780230506053. OCLC 69410176.
↑ Shuster, E. (1997-11-13). "Fifty years later: the significance of the Nuremberg Code". The New England Journal of Medicine. 337 (20): 1436–1440. doi: 10.1056/NEJM199711133372006 . ISSN 0028-4793. PMID 9358142. S2CID 9950045.
↑ Morgan., Capron, Alexander; Swift., Glass, Eleanor (1973-01-01). Experimentation with human beings : the authority of the investigator, subject, professions, and state in the human experimentation process . Russell Sage foundation. ISBN 9780871544384. OCLC 468014255.{{cite book}}: CS1 maint: multiple names: authors list (link)

External links

They were cheap and available: Prisoners as research subjects in twentieth-century America, Allen Hornblum

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.

[1] McDermott, Barbara (2014). "Coercion in Research: Are prisoners the only vulnerable population" (PDF). Semantic Scholar. S2CID 19593967. Archived from the original (PDF) on 2019-03-01.

[:0-2] 1 2 Miller, Franklin G. (2013-01-01). "The Stateville penitentiary malaria experiments: a case study in retrospective ethical assessment". Perspectives in Biology and Medicine. 56 (4): 548–567. doi:10.1353/pbm.2013.0035. ISSN 1529-8795. PMID 24769747.

[:1-3] 1 2 3 4 Alving, A. S.; Craige, B.; Pullman, T. N.; Whorton, C. M.; Jones, R.; Eichelberger, L. (1948-05-01). "Procedures Used at Stateville Penitentiary for the Testing of Potential Antimalarial Agents 1". The Journal of Clinical Investigation. 27 (3 Pt 2): 2–5. doi:10.1172/JCI101956. ISSN 0021-9738. PMC 438882 . PMID 16695630.

[:2-4] 1 2 3 4 5 6 7 Comfort, Nathaniel (2009-09-01). "The prisoner as model organism: malaria research at Stateville Penitentiary". Studies in History and Philosophy of Biological and Biomedical Sciences. 40 (3): 190–203. doi:10.1016/j.shpsc.2009.06.007. ISSN 1879-2499. PMC 2789481 . PMID 19720327.

[5] Lichtman, M. A. (2001-04-01). "Introduction of Ernest Beutler, MD". Leukemia. 15 (4): 656–657. doi:10.1038/sj.leu.2402054. ISSN 0887-6924. PMID 11368370.

[6] Clinical Treatment of Malaria, Alf S. Alving, M.D.

[:3-7] Weindling, Paul (2004-01-01). Nazi medicine and the Nuremberg Trials : from medical war crimes to informed consent. Palgrave Macmillan. ISBN 9780230506053. OCLC 69410176.

[8] Shuster, E. (1997-11-13). "Fifty years later: the significance of the Nuremberg Code". The New England Journal of Medicine. 337 (20): 1436–1440. doi: 10.1056/NEJM199711133372006 . ISSN 0028-4793. PMID 9358142. S2CID 9950045.

[9] Morgan., Capron, Alexander; Swift., Glass, Eleanor (1973-01-01). Experimentation with human beings : the authority of the investigator, subject, professions, and state in the human experimentation process . Russell Sage foundation. ISBN 9780871544384. OCLC 468014255.{{cite book}}: CS1 maint: multiple names: authors list (link)

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]