Stateville Penitentiary Malaria Study
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The Stateville Penitentiary malaria study was a controlled but ethically questionable study of the effects of
malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...
on prisoners of Stateville Penitentiary near
Joliet, Illinois Joliet ( ) is a city in Will County, Illinois, Will and Kendall County, Illinois, Kendall counties in the U.S. state of Illinois, located southwest of Chicago. It is the county seat of Will County, Illinois, Will County. It had a population of ...
, in the 1940s, conducted by the Department of Medicine at the
University of Chicago The University of Chicago (UChicago, Chicago, or UChi) is a Private university, private research university in Chicago, Illinois, United States. Its main campus is in the Hyde Park, Chicago, Hyde Park neighborhood on Chicago's South Side, Chic ...
in conjunction with the
United States Army The United States Army (USA) is the primary Land warfare, land service branch of the United States Department of Defense. It is designated as the Army of the United States in the United States Constitution.Article II, section 2, clause 1 of th ...
and the State Department. The Stateville experiment was viewed as coercive because it offered shortened sentences to participants. The Green report was written in 1945 about it by
Andrew Conway Ivy Andrew Conway Ivy (February 25, 1893 – February 7, 1978) was an American physician. He was appointed by the American Medical Association as its representative at the Doctors' Trial, and later fell into disrepute for advocating the fraudulent drug ...
, used in Nuremberg Medical Trial, which affected the
Nuremberg Code The Nuremberg Code () is a set of research ethics, ethical research principles for human experimentation created by the court in ''Doctors' trial, U.S. v Brandt'', one of the Subsequent Nuremberg trials that were held after the World War II, Seco ...
, and used to discuss how
medical experimentation on prisoners 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 evo ...
should be carried out.


Historical context


Demand for malaria research

The circumstances of
World War II World War II or the Second World War (1 September 1939 – 2 September 1945) was a World war, global conflict between two coalitions: the Allies of World War II, Allies and the Axis powers. World War II by country, Nearly all of the wo ...
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. The U.S. Army estimated millions of
man-hours A man-hour or human-hour is the amount of work performed by the average worker in one hour. It is used for estimation of the total amount of uninterrupted labor required to perform a task. For example, researching and writing a college paper mi ...
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 Quinine is a medication used to treat malaria and babesiosis. This includes the treatment of malaria due to ''Plasmodium falciparum'' that is resistant to chloroquine when artesunate is not available. While sometimes used for nocturnal leg ...
, 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. 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 conductive 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. 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.


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 Nephrology is a specialty for both adult internal medicine and pediatric medicine that concerns the study of the kidneys, specifically normal kidney function (renal physiology) and kidney disease (renal pathophysiology), the preservation of kid ...
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 Ernest Beutler (September 30, 1928 – October 5, 2008) was a German-born American hematologist and biomedical scientist. He made important discoveries about the causes of a number of diseases, including anemias, Gaucher disease, disorders of ...
, two physicians also from the University of Chicago. 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 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. Drug derivatives The derivatives primaquine, tafenoquine and pamaquine have been te ...
group of compounds. The study marked the first human test of the
antimalarial drug 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 c ...
primaquine Primaquine is a medication used to treat and prevent malaria and to treat ''Pneumocystis'' pneumonia. Specifically it is used for malaria due to ''Plasmodium vivax'' and '' Plasmodium ovale'' along with other medications and for prevention if ot ...
. For the experiment, doctors from the University of Chicago bred ''
Anopheles quadrimaculatus ''Anopheles'' () is a genus of mosquito first described by the German entomologist J. W. Meigen in 1818, and are known as nail mosquitoes and marsh mosquitoes. Many such mosquitoes are vectors of the parasite ''Plasmodium'', a genus of protoz ...
''
mosquito Mosquitoes, the Culicidae, are a Family (biology), family of small Diptera, flies consisting of 3,600 species. The word ''mosquito'' (formed by ''Musca (fly), mosca'' and diminutive ''-ito'') is Spanish and Portuguese for ''little fly''. Mos ...
es. The mosquitoes were infected with a ''
Plasmodium vivax ''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 huma ...
'' malaria strain that was isolated from a military patient. All five malaria strains are in the genus ''
Plasmodium ''Plasmodium'' is a genus of unicellular eukaryotes that are obligate parasites of vertebrates and insects. The life cycles of ''Plasmodium'' species involve development in a Hematophagy, blood-feeding insect host (biology), host which then inj ...
'',
protozoa Protozoa (: protozoan or protozoon; alternative plural: protozoans) are a polyphyletic group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic debris. Historically ...
n
parasite Parasitism is a Symbiosis, close relationship between species, where one organism, the parasite, lives (at least some of the time) on or inside another organism, the Host (biology), host, causing it some harm, and is Adaptation, adapted str ...
s.


Experiments performed

The study considered the Chesson strain of ''P. vivax'', sourced from a military patient infected in the Pacific. ''P. vivax'', the predominant form of malaria in the Pacific, is associated with milder symptoms and unlike ''
Plasmodium falciparum ''Plasmodium falciparum'' is a Unicellular organism, unicellular protozoan parasite of humans and is the deadliest species of ''Plasmodium'' that causes malaria in humans. The parasite is transmitted through the bite of a female ''Anopheles'' mos ...
'', it typically is not deadly. This strain was known for its resistance to the standard treatment of quinine, with frequent occurrences of relapse. 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. 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.


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 Nathan Freudenthal Leopold Jr. (November 19, 1904 – August 29, 1971) and Richard Albert Loeb (; June 11, 1905 – January 28, 1936), usually referred to collectively as Leopold and Loeb, were two American students at the University of Chicago ...
, who (together with
Richard Loeb Nathan Freudenthal Leopold Jr. (November 19, 1904 – August 29, 1971) and Richard Albert Loeb (; June 11, 1905 – January 28, 1936), usually referred to collectively as Leopold and Loeb, were two American students at the University of Chicago ...
, 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. While Leopold's range of roles was exceptional, numerous other prisoners assumed similar responsibilities in the experiments.


Legacy of the study

The experiments were widely publicized, though in a controlled manner. In 1944, ''
Life Life, also known as biota, refers to matter that has biological processes, such as Cell signaling, signaling and self-sustaining processes. It is defined descriptively by the capacity for homeostasis, Structure#Biological, organisation, met ...
'' magazine documented the experiments with a photo series. Accounts of prisoner subjects were included, though these were allegedly scripted. 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 International is an adjective (also used as a noun) meaning "between nations". International may also refer to: Music Albums * ''International'' (Kevin Michael album), 2011 * ''International'' (New Order album), 2002 * ''International'' (The T ...
prosecuted leaders of former
Nazi Germany Nazi Germany, officially known as the German Reich and later the Greater German Reich, was the German Reich, German state between 1933 and 1945, when Adolf Hitler and the Nazi Party controlled the country, transforming it into a Totalit ...
for war crimes and events of the
Holocaust The Holocaust (), known in Hebrew language, Hebrew as the (), was the genocide of History of the Jews in Europe, European Jews during World War II. From 1941 to 1945, Nazi Germany and Collaboration with Nazi Germany and Fascist Italy ...
, 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. 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 Dachau (, ; , ; ) was one of the first concentration camps built by Nazi Germany and the longest-running one, opening on 22 March 1933. The camp was initially intended to intern Hitler's political opponents, which consisted of communists, s ...
and the Stateville Penitentiary malaria experiments.{{Cite book, title=Experimentation with human beings : the authority of the investigator, subject, professions, and state in the human experimentation process, last1=Morgan., first1=Capron, Alexander, last2=Swift., first2=Glass, Eleanor, date=1973-01-01, publisher=Russell Sage foundation, isbn=9780871544384, oclc=468014255, url-access=registration, url=https://archive.org/details/experimentationw0000katz 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 The Nuremberg Code () is a set of research ethics, ethical research principles for human experimentation created by the court in ''Doctors' trial, U.S. v Brandt'', one of the Subsequent Nuremberg trials that were held after the World War II, Seco ...
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.


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 ''JAMA'' (''The Journal of the American Medical Association'') is a peer-reviewed medical journal published 48 times a year by the American Medical Association. It publishes original research, reviews, and editorials covering all aspects of ...
'' 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.


See also

*
Human experimentation in the United States Numerous human subject research, experiments which were performed on human test subjects in the United States in the past are now considered to have been Unethical human experimentation, unethical, because they were performed without the knowled ...
*
List of medical ethics cases Some cases have been remarkable for starting broad discussion and for setting precedent in medical ethics Medical ethics is an applied branch of ethics which analyzes the practice of clinical medicine and related scientific research. Medical eth ...
*
Research involving prisoners 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 evo ...
*
Tuskegee syphilis experiments The Tuskegee Study of Untreated Syphilis in the Negro Male (informally referred to as the Tuskegee Experiment or Tuskegee Syphilis Study) was a study conducted between 1932 and 1972 by the United States Public Health Service (PHS) and the Cent ...


References


External links


They were cheap and available: Prisoners as research subjects in twentieth-century America
Allen Hornblum Allen M. Hornblum is an author, journalist and a former criminal justice official and political organizer based in Philadelphia, US. He has written eight non-fiction books running the gamut from organized crime and Soviet espionage to medical et ...
Malaria Human subject research in the United States Clinical trials 1940s in Illinois American medical research Medical experimentation on prisoners Aftermath of World War II in the United States Health in Illinois