by Cina, Joshua A. Perper, Stephen J. ; Cina, Joshua A. Perper, Stephen J.
In 1885, Daniel Carrion, a 26-year-old Peruvian medical student, proved that two Central American diseases believed to be distinct, were actually caused by the same bacterium. The diseases were Verruca Peruana, characterized by the development of warts, fever and joint pains and Oroya Fever, manifested by a high fever, chills, and abdominal pain that progressed to severe anemia and heart disease. In spite of strong disapproval by his professors and friends, Carrion had blood taken from Boldly Going Where No Man Has Gone Before
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a patient’s wart injected into his arm. He eventually developed and died of Oroya Fever, now named Carrion’s Disease in his honor.
In 1900, Dr. Jesse Lazear, an American surgeon who had extensively researched Yellow Fever, attempted unsuccessfully to infect himself with the disease through multiple stings by mosquitoes exposed to patients with Yellow Fever. Despite carefully controlled conditions, he could not contract the disease. Ironically, he died of Yellow Fever from the sting of a wild mosquito shortly thereafter.
Dr. August Bier, a German surgeon, was the pioneer of spinal anesthesia. He volunteered to be the guinea pig of an experiment in which his assistant, Dr. Hildebrandt, was supposed to inject him with cocaine into his spinal canal. Initially the assistant performed the procedure properly but he could not continue because the needle he was using was the wrong size. The roles were then inverted with Dr. Hildebrandt turning into the experimental subject. The procedure was very successful with Dr. Hildebrandt reportedly feeling nothing below the level of the injection. Dr. Bier wanted to be sure that the anesthesia was effective, so he stabbed Hidebrandt in the legs with pins, squeezed his skin with a hooked forceps, hammered his shin bone, burned his legs with a cigar, pulled his pubic hair and, for good measure, forcefully squeezed his testes. Apparently, the two had a close working relationship. After the cocaine effects wore off, in spite of lingering pain, the experimenters celebrated their achievement with plenty of booze and dinner – and perhaps some mood music.
In 1961, Dr. Victor Herbert almost died after he attempted to prove that megaloblastic anemia (an anemia associated with abnormally large red blood cells and neurological damage) was caused by a folic acid dietary deficiency. This B vitamin is found in fresh vegetables and is easily destroyed by boiling or cooking. He lived on a monotonous and tasteless diet of thrice-boiled vegetables for 5 weeks prior to developing irritability, forgetfulness, and, ultimately, megaloblastic anemia as intended. Unbeknownst to him, his diet was also deficient in potassium. He developed paralysis and cardiac abnormalities that probably would have killed him if he had not been treated by a meat-eating colleague.
Few self-experimenters have earned worldwide recognition and fame for their achievements. The stories of Dr. Werner Forssmann, the innovator of cardiac catheterization, and Dr. Barry Marshall, who discovered the infectious nature of stomach ulcers, are exceptions. For their individual efforts, they were each awarded Nobel Prize in Medicine.
In 1929 in a small town of Northeast Germany, just 30 miles away from Berlin, Dr. Werner Forssmann became intrigued by drawings he saw in a French physiology book that depicted a man standing beside a horse and inserting a catheter into its jugular vein to reach the heart. Forssman believed that a similar procedure could be performed on humans in order to inject life saving drugs during resuscitation efforts. He relayed his theory to his supervisor, Dr. Richard Schneider, and asked permission to test it on either terminal patients or on himself. Dr. Schneider categorically rejected Forssman’s requests, as it was believed at the time that any entry into the heart would be fatal. Forssman decided to test his theory anyway to either refute or confirm this medical myth. As he needed access to a suitable catheter to reach his heart, he convinced a nurse, Gerda Ditzen, to assist him in his efforts.
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The nurse consented on the condition that she would be his first experimental subject. Forssman agreed, but at the last moment distracted her, anesthetized his own elbow, and inserted a urinary catheter into a vein in his arm and pushed until he felt that that the catheter reached his heart. Though Gerda was initially furious she eventually relented and took Forssman to the hospital’s basement where an X-ray proved that it had entered the heart’s upper right chamber with no adverse effects.When Forssmann self-experimentation became known he was immediately fired for insubordination.
Despite the significance of his discovery he was forced to switch from cardiology to urology. The popular press highly praised his achievement and considered him a hero, but the medical establishment saw his work as unreliable trickery and for more than a decade refused to acknowledge its value. However in the mid 1940s two cardiologists, Drs. Andre Cournard and Dickinson Richards, re-discovered his work and applied it successfully first to volunteers and then to real cardiac patients.
In 1956, all three of them were jointly awarded the Nobel Prize. Hundreds of thousands of patients worldwide have reaped the benefits of Forssman’s self-experimentation.
In July 1984 Dr. Barry Marshall, a medical resident at Freemantle Hospital in Perth, Western Australia, attempted to decisively prove that many stomach ulcers are related to a bacterial infection. In contradistinction to the mainstream belief that bacteria could not survive in the stomach because of the high acidity of the gastric juices and that ulcers were only a result of stress and diet, he theorized that infection with Helicobacter pylori could wreak havoc with the gastric lining. He was unwilling to experiment on human volunteers as he stated later that he “was the only one informed enough to give consent.” Having obtained the appropriate consent from himself, he drank a cocktail containing millions of Helicobacter micro-organisms from a lab beaker. For 3 days, Marshall experienced “rumbling” of his stomach, bloating, and fullness after evening meals. This was later followed by vomiting and halitosis (putrid breath). To solidify his theory, 10 days later he developed gastritis (an inflammation of stomach’s lining) and a stomach ulcer. He subsequently treated himself successfully with Tinidazole, an antibiotic which kills Helicobacter. Marshall documented the results of his experiments very carefully by repeated gastroscopies, x-rays, bacteriological cultures, and evaluation of gastric biopsies (small samples of the stomach lining that are pinched off and examined microscopically) obtained both before and after his experiment.
Initially the medical community rejected Dr. Marshall’s findings until they were repeatedly verified. Ultimately, Dr. Barry Marshall and his colleague, pathologist Dr. Robert Warren, were awarded the Nobel Prize and congratulated by the Nobel Committee of Sweden’s Karolinska Institute for their “tenacity and a prepared mind to challenge prevailing dogmas.” Despite the fact that their research has led to the treatment of millions of people with gastritis, ulcers, and gastric lymphomas, ethical condemnation by some peers did not fade away. The critics chided that self-experimenters had a moral duty not to put their life and limb at almost suicidal risk in order to advance medicine. Sounds like a bit of sour grapes to us. It also reminds us of those whiners who don’t want to drill for oil somewhere because it may endanger the indigenous Rhodesian striped wombat.
What Were They Thinking?
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The latest self-experimentation worthy of note was that of Indian virologist Pradeep Seth, a leading researcher at the All India Institute of Medical Sciences (AIIMS), in New Delhi. Having already successfully tested a vaccine directed at the Human Immunodeficiency Virus (HIV) in mice and on monkeys, Dr. Seth was very eager to know the human body’s reaction to his formulation. Unfortunately, human trials were not due to start until 2005. When he injected himself with the vaccine in 2003, India’s medical community considered the experiment unethical because the vaccine had yet to be cleared for human trials. Despite the fact that Dr. Seth showed no ill-effects from the vaccine, it has not yet been used in India although millions are infected with the virus.
Some self-experiments have been based on incorrect hypotheses or mis
conceptions. For example, in 1882 a German physician by the name of Max von Pettenkofer stubbornly believed that cholera, a potentially fatal intestinal disease, was not caused by an infection with Vibrio cholera. He chose to ignore the experiments of the famous German bacteriologist Robert Koch who grew the organisms from polluted water in India two decades before. Dr. Pettenkoffer believed, as did many others at that time, that cholera was the result of a “miasma,” an airborne invisible emanation possibly coming from dirty soil or from decomposition of the feces of cholera patients. So certain was Pettenkofer of his theory that he publicly drank a test tube with a bouillon containing myriads of the bacteria. He promptly became sick with profuse diarrhea, the hallmark of cholera, but recovered rapidly (probably because he was immune to the disease having had prior exposure to a mild form of the illness). Despite this apparent cause-and-effect experience, he and his supporters did not abandon their mistaken belief in the “miasma” theory.
Similarly, Stubbing Firth (1784–1820), an American medical student from the University of Pennsylvania believed that Yellow Fever was caused by heat and stress rather than a virus since it was more common in summer than in winter.
To prove it, he smeared black vomit from patients with yellow fever on cuts in his arms and on his eyes, inhaled vapors from boiled vomit, and even swallowed black vomit, sweat, urine and other waste products of patients with Yellow Fever. As he did not acquire the disease, he concluded that his hypothesis was correct and even published papers and books on the topic. Despite his good luck (and probably bad breath) his grotesque self-experimentation was in vain as Yellow Fever was ultimately proven to be an infectious disease transmitted by mosquitoes. Firth’s fundamental error was that he had collected samples from patients who were already in the recovery process and were no longer contagious. Yet he did make a valuable contribution to medicine – he set the standard for what we can expect medical students to go through over the course of their training.
What Were They Thinking?
An aggregate of factors may be at play in motivating these self-experimenters. The doctors seem to share a sense of altruism, adventurism of spirit, an almost fanatical confidence in the truth of their theories, an abhorrence of bureaucratic “red tape,”
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an inability to accept the status quo, and a reluctance to put others at risk prior to experimenting on themselves. There also seems to be some sort of triggering event in at least some of these cases. Dr. Seth injected himself with the HIV vaccine when the government cogs stalled; Dr. Forssman gained inspiration from drawings of horses; Dr. Simpson witnessed too many painful labors and wanted to change things for the better; Dr. Hunter wanted to eradicate gonorrhea (his motivation remains unclear).
Dr. William J. Harrington, the physician who elucidated the nature of an autoimmune type of anemia called idiopathic thrombocytopenic purpura (ITP) was motivated by the tragic death of one of his patients. In 1945, a 17-year-old girl presented with severe vaginal bleeding to the Emergency Room of Cambridge City Hospital in Boston. Although she was initially thought to be aborting a pregnancy, eventually the doctors correctly diagnosed her with ITP, a disease characterized by diffuse bleeding into the skin and other organs. The only successful cure at that time was splenectomy.
Tragically, the patient died following a surgical mishap leading Dr. Harrington to swear to himself that he would find the cause of this mysterious disease. He keenly noted that infants born to mothers with ITP developed a temporary anemia and theorized that this might be due to a factor transmitted from the mother’s blood through the placenta and into the baby. With only that observation to go on, he injected himself intravenously with about 8 ounces of blood from a patient with ITP and succeeded in developing a temporary anemia. He survived and his experiment set the foundation for further research, which led to the recognition of ITP as an autoimmune blood disorder – a disease in which the body tries to destroy its own blood cells.
The story of Dr. Wolfgang Krause illustrates well the aggregate of factors that may prompt a physician to engage in risky self-experimentation. Krause was an orthopedic surgeon in Kassel, West Germany, a hard working practitioner with little interest in research. As an adolescent he was amongst the top 50 skiers in Germany and most likely would have chosen an athletic career but for an accidental back injury that thwarted his dreams. Having come from a family of physicians, he easily converted from skier to orthopedic surgeon (“the jocks of docs”). In 1968, Dr. Krause was greatly dismayed when a dozen of his hip repair surgery patients developed progressively increasing fevers and died within 10 days in spite of intense efforts to maintain a totally sterile environment during surgery. Paradoxically, the administration of strong antibiotics (which treat even most virulent bacteria) worsened the condition of his patients, so it was initially believed that they might have succumbed to a viral infection. Much to their surprise, autopsies demonstrated that all of the patients had died of a widespread fungal infection due to Monilia ( Candida albicans). Dr. Krause plunged into the literature of Moniliasis and surmised that the fungus was able to pass through the bowel wall and into the patient’s blood during or just after this highly invasive surgery. He decided to test his hypothesis but first he needed an experimental human subject.
The relatively fresh memory of the horrific Nazi atrocities performed in the name of Science was a clear barrier to any risky experimentation on human volunteers. Dr. Krause said, “In Germany doctors would have considered this experiment on another man a moral crime. Perhaps doctors of another nationality might have Physicians and Suicide
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had a different attitude but not in Germany.” Clearly, Dr. Krause was unwilling to test a potentially dangerous hypothesis on human volunteers and later stated, “I could have asked a patient but I did not believe anyone would be willing.
Man is not an (experimental) animal. The patient could have died.” In the end there was only a single suitable candidate left – Wolfgang Krause.
Dr. Krause believed that given his youth and excellent health the intended experiment was not likely to be dangerous. The German experts that he consulted prior to the trial were much more sanguine and feared that a massive, intentional fungal exposure could lead to a lethal, systemic infection. To cover his bases and to minimize the economic loss to his family if things were to go awry, Dr. Krause prudently purchased a large life insurance policy before initiating the experiment. In spite of last minute second thoughts, he decided to cross the experimental Rubicon and ingested two steins of a concoction containing millions of fungal organism followed by another stein of mineral water “to clean the palate.” Krause was able to rapidly quaff three steins of fluid with no difficulty, reportedly saying that such drinking could not possibly be a problem for a former German medical student.
Only 2 hours after swallowing the fungal concoction he became ill and in the next 7 hours his temperature climbed to 101°F. Although he felt horrible physically, his spirits remained high. Cultures of both his blood and urine confirmed that the fungus had breached his bowel wall and spread throughout his body in a matter of hours. Krause fully recovered in less than 2 days following two doses of Epsom salts to purge his intestines and intravenous and oral Nystatin, an antifungal medication. After publishing the results of his study, Dr. Krause ended his foray into experimental research and happily returned to his beloved orthopedic practice. We would imagine that he has since put his steins to better use.
Altman perhaps provided the best argument for self-experimentation in his book
“Who Goes First.” He boldly states, “Why call self-experimentation foolish when we climb mountains, become test pilots, build bridges and skyscrapers? In any experiment, the outcome is not known ahead of time. If the researcher claims there is no risk, why is the researcher unwilling to try it? Doctors’ lives are no more valuable than those of the other members of society whom they ask to volunteer for t
heir research.” Physicians may be motivated by compassion, fame, financial gain, professional prestige, or mental illness to experiment on themselves. Many researchers will spend decades trying to prove their theories and die with their pens clutched in their hands (or slumped over their laptops), never knowing if their convictions held true. Others will put their money where their mouths are and find out once and for all if they were right or terribly wrong.
Physicians and Suicide
Just like other animals, humankind has a strong ancestral instinct for self-preservation, in most cases choosing to avoid danger and delay, as much as possible, the inevita-bility of death. Physicians, by virtue of their profession, know better than anyone 110
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the manifold manifestations of death and are committed professionally to combat it, day in and day out. As they are so familiar with our common enemy, The Grim Reaper, one would think that it would inspire less dread in them than in their patients. In fact, quite the opposite is true is some cases. Many physicians who become sick are closet hypochondriacs to the extreme and seriously contemplate their impending doom whenever they fall ill. Their medical knowledge works against them: every headache becomes meningitis, backaches become pancreatic cancer, and indigestion must be a heart attack. In short, physicians share a fear of the great unknown with their patients. Doctors are, in fact, human and are born with a will to survive; most will run from death as fast as they can.
On the other hand, the Freudian school of psychology contends that the instinct for self-preservation is balanced by an innate drive towards death, destruction and non-existence. This theory claims that an ingrained “death drive” is responsible for widely prevalent subconscious or conscious aggression and violent behavior towards others, culminating in homicide, as well as for compulsive self destructive behavior leading to premature death. The manifestations of the latter such as drug and alcohol abuse, self-neglect, avoidance of proper medical care, and risk taking behavior keep medical examiners in business. Without the Freudian death drive, there would be a glut of unemployed forensic pathologists writing books.