Clinics in Dermatology (2008) 26, 570–573 DERMATOLOGIC DISQUISITIONS AND OTHER ESSAYS Edited by Philip R. Cohen, MD Self-experimenters in medicine: heroes or fools? Part I. Pathogens Paul T. Martinelli, MDa,⁎, Adam Czelusta, MDb, S. Ray Peterson, MDc aCharles D. Kennard, MD PA, Arlington, TX 76017, USA bKaty Dermatology, PA, Katy, TX 77450, USA cMohs Surgery Unit, Central Utah Clinic, Provo, UT 84604, USA Introduction influencing diverse fields such as dermatology, infectious disease, immunology, anesthesiology, cardiology, surgery, Human experimentation in medicine enjoys a long, and and oncology. often dubious, history that dates back to antiquity. The The first of this two part series will focus on those question as to which humans would serve as the most scientists and physicians whose self-experimentation helped appropriate subjects has also long been debated. It is to elucidate various pathogenic organisms. The second essay recorded that two 16th century French physicians, while will cover other self-experimenters, whose contributions standing over the body of an impoverished savant, said in added to the knowledge of anesthesia, medications, surgical Latin, “Do your experiment on some cheap body.”1 techniques, vaccinations, and vitamin supplementation. Although poverty-stricken, the savant apparently understood Latin well enough to quickly remove himself from the care of his doctors. Although many physicians did not subscribe to Pathogens such sentiments, further atrocities involving human subjects would ultimately lead to the drafting and acceptance of the Nuremberg Code after World War II, which set ethical and One of the principal objectives among some of the most legal standards on the practice of human experimentation. famous self-experimenters was to prove, or disprove in some Throughout history, however, there were numerous cases, the etiology of various maladies. Several of the scientists and physicians who did not believe in using individuals in this category are fairly well known and include “ “some cheap body,” or another body for that matter, to Dr John Hunter (sometimes dubbed the father of modern ” ό conduct their studies. Instead, they decided to use themselves. surgery ) and Dr Daniel Carri n (for the disease that bears his The motivating factors to self-experiment were varied and name). Many, however, remain in relative obscurity. Therefore, ranged from stubborn arrogance, a desire for recognition, the contributions made by Jesse Lazear, Max von Pettenkofer, nationalistic pride, and, often, an altruistic and genuine desire David Robinson, and Barry Marshall toward the understanding to better the lives of others. Likewise, their objectives were of various disease processes will also be discussed. also myriad. Overall, despite the motivation or objectives of these curious individuals, their results would leave a lasting John Hunter: syphilis and gonorrhea and indelible impression on the face of modern medicine, John Hunter's self-experiment is one of the most ⁎ Corresponding author. Tel.: +1 817 460 4444; fax: +1 817 460 8844. celebrated in history. Born 10th of 10 children to a family E-mail address: [email protected] (P.T. Martinelli). with limited resources in Scotland in 1728, Hunter would 0738-081X/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.clindermatol.2007.07.005 Self-experimenters. Part I. Pathogens 571 become a famous surgeon as well as a prolific and influential Carriόn undertook his experiment in 1885 as a 26-year-old anatomist. After encouragement from his older bother medical student at the Facultad de Medicina in Lima, Peru. William, who was a teacher of anatomy in London, Hunter To obtain his medical degree, Carriόn was required to began his work as a dissector in William's laboratory in complete an original thesis. For this purpose, he chose to 1748. As he quickly began to master the subject, his career study the epidemiology and clinical manifestations of advanced at a remarkable pace, and in the ensuing decades verruga peruana, particularly the earliest phases. Hunter became a lecturer in anatomy, formally studied Endemic for centuries in the steep valleys of the Peruvian surgery, was elected a Fellow of the Royal Society, and cordillera, verruga (Spanish for “wart”) peruana is character- eventually served as surgeon to King George III. ized by multiple, nodular, vascular eruptions of the skin and Syphilis and gonorrhea, both known at the time as the mucous membranes, accompanied by fever and severe “pox,” were common ailments in 18th century England, and rheumatic pains. According to one account by Carriόn, the the diseases captured Hunter's interest. He noted that the pox pains would “worsen at night (and) invade the joints one by presented in two manners. In one form, it began as a pimple one”4 Myalgias may cause muscle rigidity and possible on the penis, which would evolve into a chancre. The contractures, and “in severe cases, many cannot endure (the chancre would then disappear, and, in several weeks, a skin extreme pain) without shouts and moans.”4 The bright red to rash, sore throat, and arthralgias would develop. Hunter purple verrugas typically appeared anytime from 3 weeks to noted that if high fevers did not kill the patient at this point, 8 months after these initial symptoms. the disease may be cured, and topical mercury may speed the At the time, some physicians felt that there may have been cure. In its second form, the soft tissue of the urethra was a link between these verrugas and another mysterious and involved and caused severe dysuria, or in the case of females, often fatal disease that struck workers on the Oroya railway infertility due to fallopian scarring. It was hypothesized by line in the Peruvian Andes. Called Oroya fever, this disease some that the pox was two different diseases, now known to was marked by a severe anemia, fever, and high mortality. As be syphilis and gonorrhea. Hunter, however, believed that some patients afflicted with Oroya fever later developed the two presentations represented two different forms of the verruga peruana, a link between the diseases was postulated. same disease. He reasoned that the presentation of the Fueled by his curiosity and by a nationalistic desire to find disease depended only on which tissue type was affected. clues about verruga peruana before rival Chilean doctors did, This laid the groundwork for his famous experiment. Carriόn made plans for an experiment. On August 27, 1885, In 1767, one of Hunter's patients sought treatment for a with the assistance of a fellow student, Carriόn inoculated yellowish penile discharge. “To ascertain several facts himself with blood taken from a verruga on the right relative to the venereal disease,”2 Hunter obtained a drop eyebrow of a 14-year-old boy hospitalized in Lima. Three of the patient's discharge on his lancet and proceeded to weeks later, on September 21, Carriόn made the first entry in make “two punctures … on (his own) penis…one puncture his diary since the experiment, reporting vague discomfort was on the glans, the other on the prepuce.”2 According to and pain in his left ankle. Within days, he developed a high Hunter's notes, he began to experience pain, redness, and fever, chills, abdominal cramps, pains in his bones and joints, itching at the injection sites within 2 days, and within a week and a severe anemia. Although he only attempted to study developed the dysuria and pyuria characteristic of gonorrhea. the prodromal phase of verruga peruana, Carriόn had, in his Furthermore, within several weeks a syphilitic chancre also words, provided “evident proof that Oroya fever and the developed, enabling Hunter to proclaim triumphantly that the verruga have the same origin.”5 pox was truly one disease. The patient from whom the fluid Daniel Carriόn died on October 5, 39 days after his self- was taken, however, probably had a dual infection with both inoculation. Carriόn's disease is now known to be caused by gonorrhea and syphilis. a bacterium, Bartonella bacilliformis, which is transmitted John Hunter died in 1793 at the age of 65 after an by sandflies. To this day, a statue of Carriόn stands in Lima, argument at a meeting at St George's Hospital in London. memorializing the man whose daring experiment helped Ironically, an aortic aneurysm, presumably caused by tertiary solve a mystery about a deadly South American disease. syphilis, was found at his autopsy. Although some historians dispute that Hunter actually used himself as a subject,3 the Jesse Lazear: yellow fever majority believe that he in fact did, an opinion supported by his very detailed notes. It would not be until the next century, To the north, at approximately the same time in history, with the flourishing of microbiology and the notion of yellow fever was shaping the face and culture of the North infectious organisms, that Hunter's theory would finally be American continent. Dr Jesse Lazear was sent to Cuba as a proven incorrect. member of a four-man medical military team, under the direction of Walter Reed, to investigate the etiology and Daniel Carrion: bartonellosis transmission of the deadly illness. Before the team's investigations in 1900, the cause of yellow fever and its Nearly one century later and on another continent, Daniel mode of transmission were unknown. At the time, it was Carriόn was preparing his own historic self-inoculation. believed that the disease could be passed via contact either 572 P.T. Martinelli et al. with an infected individual or with contaminated inanimate who already died of the disease. Although he did develop objects called fomites. Earlier studies, however, involving diarrhea and produced cholera bacilli in his stools, the consumption or injection of black vomitus (due to Pettenkofer escaped serious illness. It is possible that he gastrointestinal hemorrhage) from infected individuals did developed some level of immunity to the disease given his not produce disease in the experimenter, casting doubt on exposures during previous epidemics or he may have simply this form of transmission.