Intro

It is the 9th of December 1946 and 23 men are led into courtroom 600 at the palace of justice, Nuremberg Germany. Traumatised This marks the beginning of the fascinating yet chilling Nuremberg doctors trial. Part of one of the indictments laid at the defendants feet was: War crimes: performing medical experiments, without the subjects' consent, on prisoners of war and civilians of occupied countries, in the course of which experiments the defendants committed murders, brutalities, cruelties, tortures, atrocities, and other inhuman acts. The trials aimed to prove and hold responsible those who conducted truly horrific experiments on prisoners at a number of concentration camps. The evidence was plentiful and damming ranging over several gruesome experiments on both live and dead subjects including the study of malaria. A difficult case to rebut But the defence council thought they had an ace up their sleeve. The US had been studying malaria as well in a widely publicised experiment, and on the face of it, similarly on imprisoned individuals, albeit the stateside experiments involved criminals and not victims of genocide. But the defences attempt at “but what about them” has meant that the prosecution now needs to show the difference, and this will bring a questionable expert witness. Although a U.S.A. v. Karl Brandt et al is a fascinating court case that would lead to the vital Nuremberg code, today we are focusing on the study that offered a glimpse of hope for the evil men on the stand in 1946 to 1947. My name is John and We are delving into the 1944 stateville malaria study welcome to the dark side of science. ///// Background to the study.

Background

Our story starts with the USA’s entry into WW2, with Japan launching multiple attacks on US and British holdings in Asia and the west pacific. Pretty soon the full power of the American military was brought to bear and this resulted in thousands of soldiers being deployed to the pacific and Africa. A long known hazard to soldiers working in tropical and subtropical zones has been that of malaria. This mosquito born infectious disease has throughout history stopped armies in their tracks. The disease's symptoms include fever, tiredness, vomiting, and headaches this is caused by mosquito bites transmitting single-celled microorganisms of the Plasmodium group. The most deadly of which, Plasmodium falciparum has a history closely linked with our own, when around 10,000 years ago it’s population exploded around the same time humans became an agrarian species. As populations grew in towns and cities so did Plasmodium falciparum. The bite passes the parasites into a victims body and into the bloodstream, from there they pass to the liver and reproduce and symptoms begin between 10-14 days. Infection can lead to death for reference. The year 2020 had 241 million world wide known cases of which 627k were fatal. But even if you don’t die from malaria you won’t have a great time if untreated, relapses can happen years after exposure. The best way to defeat malaria is to prevent infection in the first place, as such mosquito nets are an essential part of life in parts of the world where malaria is common. The evolution of Treatment followed the many wars and colonial disputes in the first half of the 20th century. Pre 1920s quinine was the main form of treatment, it is derived from the tree Cinchona calisaya. It was discovered by the indigenous peoples of Peru who used it as a muscle relaxant, and with most great things from South America it was taken and exploited by Europeans from the 16th century. It was later discovered By Jesuit Agostino Salumbrino, an apothecary by training who lived in Lima observed the Quechua using the bark of the cinchona tree to treat shivering a common symptom of malaria. Anyway to cut a long story short it was found to be an effective treatment for malaria, and throughout the 1800s became a Crucial component in the colonisation of Africa by Europeans. Which could be a dark side of science video in its own rights. During the 1st world war blockades of Germany resulted in restricted access to Cinchona calisaya which by now was grown in South America and in Dutch plantations in Java and Sumatra. This led to its first successful synthesis by German scientist Peter Mühlens, resulting in the drug pamaquine, or plasmochin. The drug, although very effective at killing malaria, was also effective at killing people if treatment wasn’t closely supervised. This was discovered when the drug was tested on United fruits’ West Indian African descended workforce. Ah lovely the story just keeps on getting darker and darker, of course these impoverished laborers were not given informed consent of treatment with a new drug. Newer drugs were formulated each with lower toxicity but greater potenentcy. Strangely this branch of drugs had a horrible Side effect in people of black African ethnicity, that is of anemia, needless to say the plasmochin wasn’t a golden bullet. And as such good old quinine was still required. As Japan swept through Asia in the late 1930s and early parts of the 1940s the allies were cut off from the vital Dutch plantations, which by the 1930s produced over 90% of the world's supply. With dwindling stocks of the drug the age old foe of an army came back with avengance. And this was the issue the US armed forces were facing in the2nd world war. In 1942 the US Army Medical Corps were estimating 251 cases per 1,000 troops. Needless to say this can be a massive drain on military resources, and not surprisingly searches for more effective treatments were a top priority for militaries around the world. this is where the University of Chicago comes into our story. Starting in July 1941 the newly created US committee of medical research, sought out to find the most effective treatment of malaria sufferers. their plan was twofold, firstly to attempt to source quinine from the South American market, which by now was pretty derelict after Dutch dominance from their plantations. And secondly to develop new malaria drugs. The committee found human testing desirable as it would speed up drug development and the study of disease. Malaria would however not be the first for human experimentation, as the US military had several experiments running looking at illnesses linked to maintaining an army, such as stds. Although eager to use human subjects a number of ground rules were set including “When any risks are involved, volunteers only should be utilized as subjects, and these only after the risks have been fully explained’. Consent forms would be signed for later access. But who to use, the military was not eager to use soldiers as well they were needed for soldering, but there were two sections of society that in the eyes of military officials had a debt to pay. The first was conscious objectors and the second prisoners. The latter would be preferable as they offered a unique opportunity in that their environment was completely controlled thus offering the perfect human ginepigs. A contract was drafted with the university of Chicago to launch an investigation into the disease. The Stateville penitentiary malaria study.

The Study

Just 30 miles south of the university of Chicago would be the setting for the study. Stateville penitentiary was at the time of the experiment's conception just under 20 years old. It featured a round house based on Jeremy Bentham panopticon concept, a layout that would help the experimenters. You see the panopticon architectural design is a stroke of genius, prisons have always had one big issue, and that is of constant surveillance. The panopticon concept fixes this by placing every cell entrance on a walkway around the circumference of a roundhouse, a tower is built in the center, this allows guards in the tower to be able to observe any prisoner at any time. But the prisoners' view of the tower is obscured, which means they can’t see if the guards are watching them. This in theory results in the concept of constant supervision as you can’t tell whether or not you're being watched. As such the prisoners self regulate their behaviour and act as if they are always being watched. This would help the experimenters throughout the study. The team was headed up by Alf Sven Alving, a nephrologist at the University of Chicago. Much of the team were doctors just past residency, doing their military service. Interestingly the prisoners would be employed not just as subjects but also as technicians. They would study two types of malaria P. vivax and P. falciparum, the former is mild but causes repeat relapses of sickness and the latter is short lived but deadly. However most tests were performed with vivax as it was more common in Asia. Before the study began mosquitoes were bred at the university of Chicago and infected with the chesson strain of vivax. The source of malaria came from a us soldier who had been infected in the pacific campaign. During the setup of the experiment the prison warden allocated the top floor of the prison hospital for the study, this was away from the round house and thus gave a kind of relief to the prisoners of constant observation. Initially the participants were immune to any punishment but quickly this was revoked. When the request was put out for participation over the prison radio, over 2 times the required 200 men applied for the first round of experiments. The opportunity for earlier parole and a payment of between 25-100$ also didn’t hurt. Each infected mosquito was kept inside a circular plastic cage with a gauze bottom, this allowed the cage to be placed on the subject's skin and the mosquito to bite without escaping. The subjects selected were sentenced for longer than 18 months this allowed an almost 100% follow up rate, and were white men, of similar age and health. A medical history was taken and physical examinations were made on candidates. In addition, a complete blood count, urinalysis, blood typing, chest x-ray, and electrocardiogram were undertaken on the subjects. Deliberately infecting a person with malaria wasn’t a new thing however, it was actually a form of treatment of syphilis in the early 1900s pre discovery of penicillin. The fever it produced was enough to kill the temperature sensitive Syphilis bacteria. The patient would then be treated for malaria with quinine. But I digress. The inmates were usually infected in groups of 3, 2 of whom would be used to test out potential antimalarial drugs with the final person acting as a control by not receiving anything. HOwever sometimes the infection group would be just done in pairs. As part of the infection process 1 mosquito would be used to infect all 3 men, and each man would be bitten by 10 mosquitos in total. After infection the mosquitos would be dissected. But infection is just the start of the experiment, testing of potential drugs came next. For the PROPHYLACTIC TESTS The drugs were administered to the inmate the day before infection the day of infection and for 6 days after, they were encapsulated in gelatine, and were strictly controlled to ensure the right doses were issued. This test was to see if any drugs could prevent the onset of malaria or at the least reduce its symptoms. Blood tests were taken after the 8th day post infection, at the same time temperature and pulse measurements were taken. Subjects Were admitted to the hospital when fever and symptoms became too much to handle in their cell. During any hospitalization period rectal temperatures, puls, and respirations were monitored every 4 hours, if the fever ran above 103f then this would be increased to every 30 minutes. Every day blood pressure, urine samples, fluid intake, and special tests to establish drug toxicity were taken. The next set of tests were aimed at curative treatments, that is to stop sickness after the onset of disease. The curative tests could make use of previous participants as long as the prophylaxis test had failed in the individual or they had been used as a control. They would be administered drugs once their temperature had exceeded 103f.— This is where various different versions of synthetic quinine would be tested at 4 hour intervals. In a typical scenario this could be for around 14 days. Throughout the study over 30 new compounds were tested on the volunteers at stateville. One of which was Primaquine and the study marked the first case of human testing of the compound. They also tested analogs of pamaquine, an existing alternative to quinine but had high toxicity levels. These analogues were tested in the human subjects even though their toxicity was not fully known, thus risking the health of the participants. Some doses were increased past what was known to be safe In Order to observe side effects of the substances. The testing of SN-8233, resulted in one prisoners death after it caused a heart attack, many subjects would complain of heart conditions after the studies. The experiment allowed the military to find out how much of each analogue could be administered before adverse side effects would be felt. There is No doubt however that the experiment proved useful especially in saving the lives of allied soldiers but we need to talk about the ethical considerations.

Informed Consent

Informed consent or informed coercion Although the study for its time was considered an ethical milestone by getting written consent from its participants, the administrators still left a lot of the risks, shall we say, unexplained. The form only stated that the prisoner was agreeing to take part in ‘investigations of the life-cycle of the malarial parasite’ and to ‘accept all risks connected with the experiment’. Pretty vague by modern standards, but the idea of informed consent is hard to define, especially when the participants are in an inherently coercive environment. The motives of the subjects can be pretty much split into 3 groups, mercenary for the money in offer, corporeal in the sense that the punishing life in prison may be lessened or philosophical in that participation offered a feeling of working towards a greater good or the war effort. A notorious participant was Nathan Leopald, who would later insist it was pure altruism that led him to volunteer. Leopald along with an accomplice were serving a life sentence for the kidnap and murder of Bobby franks. He would be paroled in 1958 partially influenced by his time during the malaria study. The last of the 3 being obviously the most praiseable. Even amongst large swaves of the prison population the war was seen as a good thing, the pitching of good vs evil and all that. So really the question is how unethical was the actions of the research team. They most certainly made the most of the use of prisoners in that I can’t think of any other population that could be tested on with potentially lethal drugs and society not be too concerned. Even with volunteers from the civilian or military world the testing of unknown drugs couldn’t be done, as in the eyes of the public a death from either would be considered a tragedy, something that is unlikely for a prisoner. It is open to debate the ethics of the study, something that is still questioned today, and this brings us back to 1946 and1947 during the doctor's Nuremberg trial. The malaria study at the time was widely publicised leading it to be the most well known top secret project it even featured in life magazine. As such and in preparing an argument for their clients in the USA vs Karl Brandt trial the defence council sought to compare the German malaria study undertaken in concentration camps to the stateville study. Even though the US study by today’s standards stands on ethically shaky ground, the crimes committed in the name of science at dachau are on another level. Talking specifically about the malaria study the victims at the concentration camps were not given any form of information about what they would have to endure, let alone be asked about participating. It is estimated that around 1200 were used to test malaria at dachau, approximately half would die, any who had received any debilitating side effects but survived were murdered Needless to say in the doctors trial this poor defence of ‘what about’ didn’t work and out of 23 defendants 7 would be acquitted 7 given the death penalty and the remains serving various terms in prison. In the wake of the trial a new code for human experimentation was set out that would take the name of the city Nuremberg. Ironically the experiment used to defend the perpetrators if compared to the new code would actually have failed to meet its standards. The malaria study would continue past the 2nd world war a soviet some really bizarre experiments with prisoner to prisoner blood transfusions, but that will be a story for another time maybe. Now where would you rate this subject on my ethical scale 1 being all ok 10 being pure evil?

Rating

I’m going to say around a 3. All videos on the channel are creative commons Attribution-ShareAlike. Plainly difficult videos are produced by me John, in a wet and windy suburban Southeast corner of London, uk. Help the channel grow by liking commenting and subscribing! Check out my twitter for all sorts of photos and odd and sods, as well as hints on future videos! I've got patreon and youtube membership as well so if you fancy check them out! All that's left to say is thank you for watching! 2461 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC438882/pdf/jcinvest00390-0002.pdf https://www.ifcc.org/media/477732/15vollmann-j-1996.pdf https://archive.org/details/experimentationw0000katz https://www.archives.gov/files/research/captured-german-records/microfilm/m887.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2789481/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC438887/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC438887/pdf/jcinvest00390-0034.pdf