Jayant Radhakrishnan
Chicago, Illinois, United States

Scientists have conducted experiments on themselves on many occasions for a variety of reasons.^1,2 Karl Landsteiner was awarded the Nobel Prize for Physiology or Medicine in 1930 for discovering human blood groups. He found it convenient and economical to carry out the experiments on himself and his associates. By demonstrating that serum from each person agglutinated the red blood cells of some but not all the others, he classified people into A, B, and C blood groups (“C” was later renamed “O”).³ His students, Alfred von Decastello and Adriano Stürli, described group AB a year later. His seminal discovery, which led to safe blood transfusions and various forensic uses, was initially a footnote on a pathologic anatomy paper with the following statement: “I hope this will be of some use to mankind.”⁴

Jonas Edward Salk and Albert Bruce Sabin had a different reason for first vaccinating themselves, their families, and their associates. They wished to demonstrate their complete confidence in the safety and effectiveness of the vaccines they had developed for polio.^5,6

Some self-experiments were drastic acts meant to open the eyes of a recalcitrant scientific community. Werner Theodor Otto Forssman ran a catheter into the right side of his heart through the antecubital vein, even though his advisor and family friend had expressly prohibited him from doing so. He was fired from his job, rehired, and fired again for “not meeting the scientific expectations” of his chief. Following that, he had difficulty finding a job, and he even worked as a lumberjack before setting up a urology practice. Eventually, his contribution was recognized after André Frédéric Cournand and Dickinson Woodruff Richards introduced cardiac catheterization for patient care, and all three were awarded the Nobel Prize in 1956.⁷

Barry James Marshall is another such individual. John Robin Warren and he published their letters to the editor of Lancet in 1983, pointing out the association of Helicobacter pylori infection with gastritis and peptic ulcers in contrast to prevailing views. Marshall failed to convince other physicians and could not grow the bacterium in piglets, so he decided to ingest the H. pylori himself. He did not inform his boss lest he be forbidden from doing so; however, when he had a baseline gastroscopy, his boss was suspicious but did not interfere with his plans. Marshall became ill upon ingesting the bacteria, and follow-up gastroscopy demonstrated the infection. It still took years before the role of H. pylori in peptic ulcer disease was acknowledged and surgery was abandoned.^8-10 Marshall and Warren received the Nobel Prize in 2005.

While these two headstrong individuals advanced patient care, two medical luminaries hindered progress by attempting to prove their incorrect beliefs by self-experimentation. John Hunter, the foremost authority on venereal diseases in the mid-eighteenth century, believed that the same disease presented as a syphilitic chancre when the skin was inoculated, but with a gonorrheal discharge if the inoculum initially contacted the urothelium. Therefore, he conducted the following experiment: “Two punctures were made on the penis with a lancet dipped in venereal matter from a gonorrhea; one puncture was on the glans, the other on the prepuce.” When the subject developed a gonorrheal discharge as well as a chancre, Hunter concluded that “matter from a gonorrhea will produce chancres.”¹¹ The possibility that the donor suffered from both diseases was not part of his calculation. Because of Hunter’s precise and detailed observations over a three-year period, it is generally believed that he experimented on himself, that he later suffered from cerebral syphilis, and that a syphilitic aortic aneurysm was found on his autopsy.¹² Qvist disagreed, believing Hunter’s physical and cerebral problems were the result of severe atherosclerosis and the lesion in the aorta was a post-stenotic dilatation. Qvist stated, “The subject of the experiment could well have been one of the many destitute outcasts of subnormal mentality who roamed the streets of London at that time, and Hunter could have kept him unobtrusively in his large household establishment so that he could make the necessary daily observations.”¹³ If true, it indicates a callous attitude towards the poor and disenfranchised. Hunter’s incorrect views held sway for over sixty years until Philippe Ricord clarified that they were two distinct diseases.¹⁴

European hygiene in the first half of the nineteenth century was terrible, leading a prominent hygienist, Max Joseph von Pettenkofer, to state “from time to time we send our underwear to be washed—instead of taking a bath ourselves.”¹⁵ He passionately advocated for proper sewage disposal, clean water, fresh air, good nutrition, healthy dwellings, and personal cleanliness. But he refused to believe that organisms, unassisted by additional factors in the soil, could cause a disease. To disprove Robert Koch’s discovery that Vibrio cholerae caused cholera, he obtained a bouillon of the organism from Koch and consumed it along with sodium bicarbonate to prevent stomach acid from killing the bacteria. He recovered from a resultant bout of diarrhea and claimed that he had proven Koch wrong because he did not die. The possibility that the sample may have been dilute or that a prior episode of cholera had rendered him immune was not entertained. His statements carried a lot of weight, and people doubted Koch.¹⁶

Self-experimentation is a convenient, expeditious, and economical way to carry out a preliminary test, but scientists do not always know the risks. When radiation was first discovered, its early effects on the skin were soon apparent, but the deadly long-term effects were not known. Marie Curie’s lethal aplastic anemia is believed to have been the result of bone marrow failure following long-term exposure to radiation. It could have been from her use of radiography on French soldiers during World War I without self-protection,¹⁷ or from carrying radium in her coat pocket and keeping it on a shelf in her work room because “the glowing tubes looked like faint, fairy lights,”¹⁸ or her attempts to isolate polonium and radium from pitchblende in a “poorly outfitted and ventilated” shed.¹⁹ It may have resulted from all three exposures combined.

Others also experimented without worrying about untoward effects in those days. Charles-Édouard Brown-Séquard’s followers were injecting and implanting substances from young animals and humans into their bodies in an effort to be rejuvenated. While the majority survived, Alexander Bogdanov, who believed that repeated blood transfusions from the young would stimulate his body to rejuvenate itself, developed a severe reaction after the twelfth transfusion and died.²⁰

Some scientists intentionally put themselves at risk.In 1885, Daniel Alcides Carrión García, a twenty-six-year-old Peruvian medical student, set out to determine the cause of verruga peruana (Peruvian warts)“to make an important contribution to aching humanity.” Against the advice of his professor and others, Carrión tried to inoculate himself with blood from a wartbut had difficulty, so Dr. Evaristo Chavez took the lancet and completed the inoculation. Three weeks later, Carrión developed a high fever, oliguria, and red urine. Later he became jaundiced and developed flea bite-like spots on the skin, a systolic murmur, and abdominal distress as his general condition deteriorated. He recognized that he had developed Oroya fever and that it had the same etiology as verruga. He died thirty-nine days following the inoculation. Dr. Chavez was temporarily arrested for murder, but he was released. Both diseases have been renamed bartonellosis or Carrión’s disease. Carrión Garcia ran the experiment because of his nationalistic fervor. Chile had just defeated Peru in a war, and he was bothered that a Chilean researcher had made observations on this Peruvian disease.²¹

The Reed Commission is an example of risk, intrigue, and the desire for preeminence. The commission was convened to determine the route of transmission of yellow fever, which had caused thirteen deaths for every combat mortality during the US invasion of Cuba in the 1898 Spanish-American War. Major Walter Reed was in charge of three contract surgeons, Jesse William Lazear, James Carroll, and Aristides Agramonte y Simoni. The Cuban physician, Carlos Juan Finlay, had postulated that the Culex cubensis (renamed Aedis egypti) mosquito transmitted the disease. Agramonte was immune, having previously contacted yellow fever. The others were susceptible, so they decided to let mosquitos that had previously fed on the blood of patients bite them. The experiment started with Lazear being bitten on August 16, 1900. Reed had left Cuba two weeks earlier, having written to his wife. “I didn’t want to give you worry, especially as I wasn’t myself taking any risks whatever.” Lazear recovered from a mild case, but about a month later, he visited a hospital outside the controlled experimental zone. Believing that he was immune, he permitted a mosquito that landed on him to satisfy its appetite. Unfortunately, he developed yellow fever and died. Carroll barely recovered from a severe case of yellow fever, having been bitten about ten days into the study, but he had also left the restricted zone. Reed chastised Carroll for not following the protocol but immediately wrote a report with himself as the primary author.^22,23

In the late nineteenth century, the management of abdominal gunshot wounds evolved from watchful waiting to early operation and repair of intestinal wounds. Nicholas Senn theorized that gas escaping from the perforated gastrointestinal (GI) tract into the peritoneal cavity and out of the abdominal wound would be a fail-safe diagnostic tool, and he set about finding ways to distend the GI tract. He learned that slow retrograde rectal instillation of hydrogen gas distracted the leaves of the ileo-cecal valve, permitting the gas to insufflate the upper GI tract and exit through the mouth by eructation. He proved that it was hydrogen by lighting it and seeing it burn with a “characteristic blue flame.” To assure practitioners that insufflation caused only mild discomfort, he made himself the subject of experiment Number 52. Next, he shot anesthetized dogs through the abdomen and demonstrated that hydrogen gas was escaping out of the abdominal wound by lighting it. The notion that lighting up hydrogen gas could blow up the patient, the operating suite, and even the hospital was not considered.²⁴ The technique was used clinically at least twice that year, with the escaping gas being ignited in one patient.²⁵ Fortunately, the maneuver was soon forgotten. In Senn’s time, many believed that cancers were contagious. To prove them wrong, he took tissue from a patient with carcinoma of the lower lip and had Dr. Lyman implant it into his forearm. He proved his point since the nodule disappeared in two weeks.²⁶

Scientists also chose to self-experiment to obtain information untainted by an intermediary observer’s biases, especially when dealing with sensory, potentially lethal, or psychogenic stimuli. Henry Head was a leading neurologist in the United Kingdom who studied nerve injuries and their recovery in the early twentieth century. He and his associate WHR Rivers believed that information derived from patients missed important information, and the only way to rectify that was for Rivers to divide sensory branches of Head’s left radial nerve at the elbow and to record the sensations reported by him. Interestingly, instead of using the contralateral forearm, they chose to use sensations of the glans penis as the control for the experiment. Consequently, for the next four years, Rivers would draw back Head’s foreskin, dip the glans in water at varying temperatures, and note what Head sensed.²⁷ Another quirky experiment was by Evan O’Neill Kane, a surgeon in Pennsylvania. In the 1920s, general anesthesia was risky, particularly for the elderly with coexisting medical problems. When Kane developed appendicitis, he decided that undergoing the operation under local anesthesia would give him insight into what a patient would feel and how to use the local anesthetic appropriately. For no apparent reason, he chose to operate on himself. The procedure was successful, but an associate had to bail him out the next time he tried to operate on himself.²⁸

Scientists have also chosen to obtain information themselves when dealing with potentially lethal situations. Nicolae S. Minovici, a Romanian forensic scientist, hanged himself on twelve occasions to document physiologic and psychologic effects. His assistants would release the noose before it was too late. However, the repeated hangings permanently damaged his vocal cords and eventually resulted in his death.²⁹ In 1943, Lieutenant Colonel William Randolph Lovelace II made a parachute jump from a height of 40,200 feet from a Boeing B-17E Flying Fortress to test high altitude oxygen equipment. The shock of the parachute opening knocked him out, but he regained consciousness at around 30,000 feet and landed safely with the only damage being frostbite on the hand that had lost its glove during the jump.³⁰ Another death-defying experiment was carried out by US Air Force flight surgeon John Paul Stapp. At the end of World War II, the maximum G-force limit a pilot ejecting from a plane could withstand was unknown. Stapp decided to investigate with rapid deceleration tests while strapped onto a high-speed sled. At Holloman Air Force Base in New Mexico, the speed of the sled was progressively increased until it reached 632 miles per hour (MPH) in five seconds and at the end of the run it stopped in 1.4 seconds. This subjected Stapp to 46.2 Gs, similar to hitting a brick wall at 120 MPH. The world’s fastest man, as Time magazine labeled him, was temporarily blinded because of burst blood vessels in his eyes, had cracked ribs, fractures of both wrists, and his breathing and circulation were affected. Undaunted, he was planning a more extreme test while still recovering from this adventure, but the Air Force decided this was enough. Stapp’s studies not only helped the Air Force with ejection dynamics, but they also improved the safety of seats and harnesses used in planes and cars.³¹

For many years, scientists interested in drugs that change the level of consciousness or induce hallucinations and illusions have depended on their own experiences. Sir Humphrey Davy had a very pleasant experience with inhaled nitrous oxide, which he renamed “laughing gas” and prophesied its future use as an anesthetic. Conversely, upon inhaling carbon monoxide, he “seemed sinking into annihilation.”³² Clearly, Davy and others who have self-experimented have been fortunate,^1,2,33-35 unlike Edwin Katskee of Nebraska. He was a proctologist who used cocaine as a local anesthetic. While attempting to determine its effects on patients, he accidentally overdosed and was unable to take the prepared antidote. As the cocaine took effect, he scribbled notes about his sensations and reactions on the wall until he died. The correct sequence of the notes was deciphered by his progressively worsening handwriting. His death was ruled a suicide by the local authorities even though he had written “cocaine poisoning—not suicide,” and also, “My little way of contributing to the medical and surgical archives of clinical research.”³⁶

The brilliant Oscar Levant said, “There’s a thin line between genius and insanity. I have erased that line.”³⁷ The same could be said of some of these scientists.

References

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