Self-experimentation in medicine

There is no formal definition of what constitutes self-experimentation. A strict definition might limit it to cases where there is a single-subject experiment and the experimenter performs the procedure on himself. A looser definition might include cases where the experimenters put themselves amongst the volunteers for the experiment. According to S. C. Gandevia of the University of New South Wales, who was looking at the question from the perspective of ethics, it is only self-experiment if the would-be self-experimenter would be named as an author on any subsequent published paper. That is, the person who would receive the academic credit for the experiment must also be the subject of it. ==Motivations==

being sentenced at Nuremberg There are many reasons experimenters decide to self-test, but amongst the most fundamental is the ethical principle that the experimenter should not subject the participants in the experiment to any procedure they would not be willing to undertake themselves. This idea was first codified in the Nuremberg Code in 1947, which was a result of the trials of Nazi doctors at the Nuremberg trials accused of murdering and torturing victims in valueless experiments. Several of these doctors were hanged. Point five of the Nuremberg Code requires that no experiment should be conducted that is dangerous to the subjects unless the experimenters themselves also take part. The Nuremberg Code has influenced medical experiment codes of practice around the world, as has the exposure of experiments that have since failed to follow it such as the notorious Tuskegee syphilis experiment. Critics of self-experimenters point to other less savoury motivations such as simple self-aggrandisement. Some scientists have resorted to self-experiment to avoid the "red tape" of seeking permission from the relevant ethics committee of their institution. Werner Forssmann was so determined to proceed with his self-experiment that he continued with it even after permission had been denied. He was twice dismissed for this activity, but the importance of his work was eventually recognised in a Nobel Prize. Some researchers believe that self-experimentation is not permitted. However, this is not true, at least in the United States where the same rules apply regardless of who the subject of the experiment is. Self-experimentation is also criticised for the risk of over-enthusiastic researchers, eager to prove a point, not accurately noting the results. Against this it is argued by those supporting self-experiment that medically trained persons are in a better position to understand and record symptoms, and self-experiment is usually at the very early stage of a program before volunteers have been recruited. A wish to commit suicide is sometimes offered as a reason for self-experimentation. However, Lawrence K. Altman, author of Who Goes First?: The Story of Self-experimentation in Medicine, while acknowledging that this may sometimes occur, after extensive research could find only one verified case of attempted suicide by self-experimentation. This was Nobel Prize winner Élie Metchnikoff, who, in 1881, suffering from depression, injected himself with relapsing fever. This was his second suicide attempt, but according to his wife, Olga, he chose this method of death so that it would be of benefit to medicine. However, Metchnikoff survived and in 1892 also self-experimented with cholera, but this is not thought to have been a suicide attempt. Perhaps the noblest motivation is the simple altruistic desire to do something of benefit to humanity regardless of the risks. There most certainly are risks, as Jesse Lazear found to his cost when he died of yellow fever after deliberately infecting himself. Max von Pettenkofer, after ingesting cholera bacteria said: According to Ian Kerridge, professor of bioethics at the University of Sydney, the most common reason for undertaking self-experimentation is not so much anything noble, but rather "an insatiable scientific curiosity and a need to participate closely in their own research". ==Ethics==

As already mentioned, it is an ethical principle that the researcher should not inflict on volunteers anything that the researcher would not be willing to do to themself, but the researcher is not always a suitable, or even possible, subject for the experiment. For instance, the researcher may be the wrong sex if the research is into hormone treatment for women, or may be too old, or too young. The ethical question for the researchers is would they agree to the experiment if they were in the same position as the volunteers? That remained the case until the yellow fever program was referenced in the drafting of the Nuremberg Code. This was further developed in the Declaration of Helsinki in 1964 by the World Medical Association which has since become the foundation for ethics committees' guidelines. at the Bronx VA Hospital in 1977 Some researchers believe that experimental research is too complex for the general public ever to be able to give proper informed consent. One such researcher is Eugene G. Laforet, who believes that the researchers taking part in the experiment themselves is more valuable to the volunteers than a legal consent form. Another is 1977 Nobel Prize winner Rosalyn S. Yalow who said "In our laboratory we always used ourselves because we are the only ones who can give truly informed consent." On the other side of the coin, there is the possibility that members of a research team may be coerced into participating by peer pressure. The question of who should be first to try the procedure in a new experiment is an ethical one. However, according to Altman it is not a question that can successfully be legislated. A law requiring self-test would force researchers to take risks that may sometimes be inappropriate. A code forbidding it might inhibit valuable discoveries. Self-experimentation has a role in medical education. Although no longer encouraged, in former times it was perfectly standard to expect medical students to try for themselves the drugs they were going to be prescribing. Charles-Édouard Brown-Séquard, whose own self-experiments led him to the concept of what are now called hormones, was a nineteenth century proponent of the practice: ==Value==

Self-experimentation has value in rapidly obtaining the first results. In some cases, such as with Forssmann's experiments done in defiance of official permission, results may be obtained that would never otherwise have come to light. However, self-experiment lacks the statistical validity of a larger experiment. It is not possible to generalise from an experiment on a single person. For instance, a single successful blood transfusion does not indicate, as we now know from the work of Karl Landsteiner, that all such transfusions between any two random people will also be successful. Likewise, a single failure does not absolutely prove that a procedure is worthless. Psychological issues such as confirmation bias and the placebo effect are unavoidable in a single-person self-experiment where it is not possible to put scientific controls in place. Such concerns do not apply so much if the self-experimenter is just one of many volunteers (as long as the self-experimenter is not also responsible for recording the results) but his or her presence still has value. As noted above, this can reassure the other participants. It also acts as a check on the experimenter when considering whether the experiment is ethical or dangerous. ==Notable examples==

Anaesthesia Dentist Horace Wells made multiple experiments with nitrous oxide, diethyl ether, and chloroform while trying to determine their uses as anaesthetics. The first, conducted in 1844, consisted of having his assistant John Riggs dose him with nitrous oxide and then extract one of his teeth. His later self-experimentation of ether and chloroform took place in 1848, and he eventually became addicted to chloroform due to excessive use. He inhaled chloroform as an anaesthetic shortly before committing suicide on January 24, 1848. Lidocaine, the first amino amide–type local anaesthetic, was first synthesized under the name xylocaine by Swedish chemist Nils Löfgren in 1943. His colleague Bengt Lundqvist performed the first injection anaesthesia experiments on himself. Cancer In 1901, Nicholas Senn investigated whether cancer was contagious. He surgically inserted under his skin a piece of cancerous lymph node from a patient with cancer of the lip. After two weeks, the transplant started to fade and Senn concluded that cancer is not contagious. Much earlier, in 1808, Jean-Louis-Marc Alibert injected himself with a discharge from breast cancer. The site of injection became inflamed, but did not develop cancer. Infectious diseases and vaccines COVID-19 in 2020 In February 2020, Huang Jinhai, an immunologist at Tianjin University, claimed that he had taken four doses of a COVID-19 vaccine developed in his lab even before it had been tested in animals. In March 2020, the Rapid Deployment Vaccine Collaborative (also known as RaDVaC) developed, produced, and published technical specifications for a modular, intranasal COVID-19 vaccine. Numerous scientists working directly and indirectly on the group's vaccine development also began self-experimentation using the project's multiple vaccine candidates. In March 2020, Hans-Georg Rammensee, professor of immunology at University of Tübingen and co-founder of CureVac began testing a COVID-19 vaccine on himself. In May 2020, Alexander Gintsburg, director of the Gamaleya Research Institute of Epidemiology and Microbiology announced that several vaccine specialists had begun self-experimentation with the Sputnik V COVID-19 vaccine. AIDS vaccine Daniel Zagury, in 1986, was the first to test his proposed AIDS vaccine. Bartonellosis Daniel Alcides Carrión, in 1885, infected himself from the pus in the purple wart (verruga peruana) of a female patient. Carrión developed an acute form of bartonellosis now known as Carrion's disease or Oroya fever. This is a rare disease found only in Peru and certain other parts of South America. He kept detailed notes of his condition and succeeded in showing through this self-experiment that the chronic and acute forms were the same disease. He died from the disease after several weeks. A student who had assisted Carrion in carrying out this work was arrested and charged with murder, but later released. Cholera Max von Pettenkofer, in October 1892, drank bouillon deliberately infected with a large dose of cholera bacteria. Pettenkofer was attempting to disprove the theory of Robert Koch that the disease was caused by the bacteria Vibrio cholerae alone. Pettenkofer also took bicarbonate of soda to counter a claim by Koch that stomach acid killed the bacteria. Pettenkofer escaped with mild symptoms and claimed success, but the modern view is that he did indeed have cholera, luckily just a mild case, and possibly had some immunity from a previous episode. Marshall's experiment debunked the long-held belief of the medical profession that stress was the cause of gastritis. This cleared the way for the development of antibiotic treatments for gastritis and peptic ulcers and a new line of research into the likely role of H. pylori in stomach cancer. Campylobacter jejuni Marshall's investigation was preceded by David A. Robinson who, in 1980, ingested Campylobacter jejuni, a bacterium found in cow's milk, to investigate whether gastritis could be caused by drinking milk infected with C. jejuni. Robinson became sick as a result. Robinson needed to do a human experiment because the alternative, testing on cows, was not viable as infected cows frequently do not become ill. Staphylococcus Gail Monroe Dack (1901–1976), a former president of the American Society for Microbiology, gave himself food poisoning by eating cake tainted with Staphylococcus. Attempts to send infected snails, the intermediate host, by mail had been unsuccessful. He refused treatment, despite being desperately ill by December, so as not to lose the eggs for further study. He finally passed 4,630 eggs in his semen and 200 eggs in his urine. The U.S. government decided not to use the eggs, so his self-sacrifice was to no avail. It was November 1945 before he finally cleared all the parasites, after treatment with tartar emetic. Non-infectious diseases Anaemia William Bosworth Castle, in 1926, ate minced raw beef every morning, regurgitated it an hour later, and then fed it to his patients suffering from pernicious anaemia. Victor Herbert made himself folate deficient to prove the deficiency causes pernicious anemia; the special diet also resulted in potassium and iron deficiencies. Hyperthyroidism Elliott Cutler (1888–1947) took sufficient thyroid extract to give himself hyperthyroidism and enable him to study the effect of the condition on kidney function. Drugs Cocaine In 1936, Edwin Katskee took a very large dose of cocaine. He attempted to write notes on his office wall, but these became increasingly illegible as the experiment proceeded. Katskee was found dead the next morning. Furan Chauncey D. Leake, in 1930, took furan as a possible substitute for aspirin but it just gave him a splitting headache and painful urination that lasted three days. Ibuprofen As part of the team who developed ibuprofen in the 1960s, Stewart Adams initially tested it on a hangover. Psychoactive drugs Friedrich Sertürner isolated morphine from opium in 1804. Morphine was the first-ever alkaloid isolated from any plant. Sertürner wanted to prove his findings to his colleague with a public experiment on himself and three other friends. Jacques-Joseph Moreau published his study "Du Hachisch et de l'aliénation mentale" in 1845. He self-experimented with hashish and observed its varying effects on other people. Moreau insisted that researchers should self-experiment to gain understanding of the altered states of consciousness produced by psychoactive substances. Psychopharmacologist Arthur Heffter isolated mescaline from the peyote cactus in 1897 and conducted experiments on its effects by comparing the effects of peyote and mescaline on himself. Albert Hofmann discovered the psychedelic properties of LSD in 1943 by accidentally absorbing it and later intentionally ingesting it to verify that the effects were caused by LSD. He was also the first to isolate psilocybin from psilocybin mushrooms and self-experimented with it to prove it to be the active principle of psilocybin mushroom's psychoactive effects. Timothy Leary took LSD and was a well-known proponent of the social use of the drug in the 1960s. He developed a system known as the Shulgin Rating Scale for his research group to use during the self-experimentation of psychedelics. Gases Hydrogen Around 1886, Nicholas Senn pumped nearly six litres of hydrogen through his anus. Senn was a pioneer of using this technique to determine if the bullet in gunshot wounds had penetrated the intestinal tract. In experiments on gunshot wounds to dogs, Senn verified that the gas escaping from the wound was hydrogen by setting light to it. Reports that Senn used helium in this experiment but not isolated until 1895, and extractable reserves not found until 1903. Synthetic gases Humphry Davy self-experimented with breathing of several different gases, most notably nitrous oxide. Genes Self-experimentation with gene therapies have been reported. Every gene therapy has a unique risk of harm, including the risk associated with the gene delivery method (i.e., the particular viral vector or form of transfection) that is used and the risk associated with a specific genetic modification. Examples of potential risks for some gene therapies include tissue damage and an immune response to foreign DNA, Pain Thomas Lewis and Jonas Kellgren studied pain in the 1930s. To do this, they injected hypertonic saline into various parts of their own bodies. His 1990 revised paper covered 78 such species. Physical experiments Hanging In the early 1900s Nicolae Minovici, a professor of forensic science in Bucharest, undertook a series of experiments into hanging. At first he put the noose around his neck while lying down and had an assistant put tension on the rope. He then moved on to full suspension by the neck. Finally, he attempted suspension with a slipping hangman's knot, but the pain was too great for him to continue. He could not swallow for a month. Minovici was determined to surpass a record set by Dr. Fleichmann of Erlangen, who in 1832, self-asphyxiated for two minutes. However, Minovici could not get close to this and disbelieved Fleichmann. Minovici and Fleichmann are not the only ones to self-experiment with strangulation. Graeme Hammond, a doctor in New York, tried it in 1882. Francis Bacon described an even earlier occasion in 1623 when the self-experimenter stepped off a stool with a rope around his neck, but was unable to regain his footing on the stool without assistance. that brought it to a rapid stop in around 1.4 seconds. In the most severe test, Stapp underwent an acceleration of 20 g as the rocket engine accelerated the vehicle up to speed and 46 g of deceleration (also a record) as the vehicle was brought to a stop. Stapp suffered numerous injuries in these tests (previous animal tests had shown that limbs could be broken merely by being pulled into the air stream), and several concussions. In the last test his eyes were bloodied as blood vessels burst in his eyes. These tests were carried out for the US Air Force to determine the forces that pilots could be subjected to and to enable better restraining straps to be designed. The result was the 1614 publication De Statica Medicina ("On Medical Measurements"). Poisons Black widow spider venom Allan Blair of the University of Alabama, in 1933, deliberately caused a black widow spider to bite him. At the time there was some doubt that the reported symptoms of some victims were the result of a spider bite or some other cause. Blair's experiment was intended to settle the matter. Blair became seriously ill and was hospitalised for several days in great pain, but survived. Hydrogen cyanide Joseph Barcroft, in 1917, tested hydrogen cyanide on himself as part of research into poison gas in World War I. He was shut in a chamber with a dog and exposed to the gas. Barcroft continued with the experiment even after the dog went into tetanic convulsions and appeared to die. The experiment was continued for less than two minutes. The next morning the dog was found to be alive and apparently fully recovered. It is not known why dogs are more susceptible to the gas than humans. • For other self-experiments by Barcroft, see Snake venom Tim Friede created his own vaccine against snakebite using pure venom injections from all four species of mambas, and four cobra species to achieve high immunity. He also survived anaphylactic shock six times during the development of his vaccine. Others have also injected venom to create immunity to snake venom: Bill Haast, Harold Mierkey, Ray Hunter, Joel La Rocque, Herschel Flowers, Martin Crimmins, and Charles Tanner. Tetrachloroethylene and carbon tetrachloride In 1921, Maurice Crowther Hall ingested carbon tetrachloride to test its safety with a view to its possible use as a treatment for hookworm. Hall reported mild side effects. Carbon tetrachloride has since been found to cause acute liver failure. In 1925, Hall ingested tetrachloroethylene (the most common dry cleaning fluid) for the same purpose. Surgical and psychological procedures Cardiac catheterization Clinical application of cardiac catheterization began with Werner Forssmann in the 1930s, who inserted a catheter into the brachial vein of his own forearm, guided it fluoroscopically into his right atrium, and took an X-ray picture of it. Forssmann did this procedure without permission. He obtained the assistance of a nurse by deceiving her that she was to be the subject of the experiment. He tied down her arms while inserting the catheter into his own arm, only releasing her at the point it was too late to change, and he needed her assistance. Forssmann was twice fired for carrying out these self-experiments, but shared the Nobel Prize in Physiology or Medicine in 1956 for this achievement. Cardiac catheterization is now a routine procedure in heart surgery. However, the first surgeon to carry out this self-operation, Evan O'Neill Kane in 1921, did so with an element of experiment. Although Kane's operation was necessary, it was not necessary to do it himself, so that in itself was experimental. More than that, Kane wished to experience the operation under local anaesthetic before trying the procedure on his patients. Kane advocated a reduction in the use of general anaesthetic by surgeons. In 2023, Michael Raduga, a Russian lucid dreaming researcher, performed self-neurosurgery that included trepanation, electrode implantation, and electrical stimulation of the motor cortex. Sensory deprivation John C. Lilly developed the first sensory deprivation tanks and self-experimented them with the intention to study the origin of consciousness and its relation to the brain by creating an environment which isolates an individual from external stimulation. Temperature and pressure Joseph Barcroft, in 1920, spent six days in a sealed glass chamber to investigate respiration at altitude. The partial pressure of oxygen was initially 163 mmHg falling to 84 mmHg (equivalent to an altitude of 18,000 ft) as the experiment progressed. Barcroft was attempting to disprove a theory of John Scott Haldane that the lungs actively secrete oxygen into the blood (rather than just through the process of passive diffusion) under conditions of low oxygen partial pressure. Barcroft suffered from severe hypoxia. At the end of experiment, part of Barcroft's left radial artery was removed for investigation. Neural adaption to immobilization Nico Dosenbach wore a pink cast over his (unbroken) right arm for two weeks in order to examine how brain circuits controlling movement are impacted by immobilizing illnesses or injuries. He did a 30-minute resting state fMRI study daily and identified an undiscovered pattern of pulses of rs-fMRI signal in motor regions controlling the disused anatomy. In a second experiment, he took psilocybin while in an fMRI scanner in a study he led as principal investigator. ==See also==