Clinics in Dermatology (2008) 26, 657–661 DERMATOLOGIC DISQUISITIONS AND OTHER ESSAYS Edited by Philip R. Cohen, MD Self-experimenters in medicine: heroes or fools? Part II. Anesthesia, surgery, therapeutics, vaccinations, and vitamin C 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 Director, Central Utah Clinic, Provo, UT 84604, USA Introduction a patient awaiting a procedure. Dilute narcotics, brandy, and even blows to the head with a hammer are all recorded.2 Self-experimentation has helped to transform various medical fields. The first part of this 2-part series examined Horace Wells: nitrous oxide how various physicians and scientists, in their willingness to experiment on themselves, contributed to the knowledge of It was no small feat that Dr Horace Wells, a dentist from various pathogenic microorganisms and hence to the expan- Hartford, Conn, helped develop surgical anesthesia. His sion of the field of infectious disease.1 This second and introduction to anesthesia first came at the age of 26, when, concluding essay will focus on how other self-experimenters on December 10, 1844, a traveling entrepreneur named would forever change and advance the realms of anesthesia, Gardner Colton performed a demonstration in which young surgery, therapeutics, vaccinations, and vitamin C. men volunteered to inhale a gas called nitrous oxide. After a drugstore clerk inhaled the gas, he became combative and, while running across the stage, he fell and severely cut his Anesthesia leg. To Wells's amazement, the man apparently did not feel the pain from his injury until the effects of the gas had Procedure-oriented medical specialties such as anesthe- worn away. siology, surgery, and cardiology have also benefited from Inspired, Wells wondered if the gas could be given to those researchers who chose to use themselves as their first patients during dental extractions, which had been almost human subjects. For centuries, physicians have striven for the prohibitively painful up to that point. He decided to test his development of painless surgery. Although largely taken for theory on himself by having one of his own teeth extracted granted today, the development of proper and effective while under the influence of the experimental gas. The next anesthetics was very elusive. There are anecdotes, some day, Wells convinced one of his colleagues, Dr John M. humorous and others frightening, of doctors using a variety of Riggs to perform the procedure. According to Wells, the techniques to sedate, subdue, or somehow render unconscious experiment was a resounding success, and after he woke up to the discovery of his extracted tooth said he “didn't feel as much the prick of a pin.”2 In the weeks that followed, Wells ⁎ Corresponding author. Tel.: +1 817 460 4444; fax: +1 817 460 8844. worked rapidly, trying to learn about the properties of his E-mail addresses: [email protected] (P.T. Martinelli). newly tested anesthetic agent. During this time, he used 0738-081X/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.clindermatol.2007.07.006 658 P.T. Martinelli et al. nitrous oxide in his own practice, reportedly extracting teeth Dr Werner Forssmann shared the 1956 Nobel Prize in painlessly from about 15 patients.2,3 Physiology or Medicine with Drs Cournand and Richards, Wells confided in his former partner, Dr William T.G. who performed a heart catheterization on a patient in 1940. Morton, who was then a medical student at Harvard. To his surprise and dismay, the medical community in Boston “ ”3 regarded his experiment as humbug. Morton, however, Therapeutics eventually continued research into anesthesia using ether and eventually found acceptance during a demonstration at Harvard in 1846. Gerhard Domagk: sulfonamides Wells supposedly became depressed in the years that followed and became estranged from his wife and family du- The pioneering work of self-experimenters extends beyond ring that time. Sadly, in 1848, while under the influence of a the discovery of an etiologic basis of disease. With the advent new substance he was testing, chloroform, Horace Wells took and development of microbiology in the second half of the his own life by slashing his femoral artery. Ironically, it would 19th century, a logical next step would be the development of not be until after his death that the Parisian Medical Society therapeutic techniques to combat the newly recognized officially awarded Wells with the discovery of anesthesia.3 pathogens. By and large, before the early 20th century, the concept of a chemical acting internally against a specific microorganism without causing significant toxicity was not widely accepted, and some researchers focused their efforts on Surgery developing appropriate chemotherapeutic agents. Early chemicals used consisted largely of azo dyes, Not all self-experimenters inoculated themselves with a arsenicals, and other heavy metal compounds. Although the potentially pathogenic substance or inhaled unstudied gases. first generation of antimalarials would ultimately arise from Some performed surgical procedures on themselves to these chemical classes, the drugs proved ineffective in advance knowledge in their field. treating bacterial infections. In 1932, German pathologist Gerhard Domagk was experimenting with a chemical called Werner Forssmann: cardiac catheterization Prontosil, a synthetic azo dye, which contained an attached sulfonamido group. He noted that Prontosil, although inactive Dr Werner Forssmann was one such individual. in vitro, had a pronounced in vivo effect in mice infected with Forssmann grew up and worked in Nazi Germany during human Streptococcus hemolyticus. Although the drug was in the 1920s. After studying sketches of the catheterization of a clinical trials for only approximately 2 years, the most famous horse's heart in his physiology text, Forssmann became experiment with Prontosil was soon to come. Domagk interested in performing the same experiment on a human. He injected his own daughter with the new drug, which “ rejected the proposal of his mentor, Dr Richard Schneider, to reportedly saved her from the threatening consequences of ”5 attempt the procedure on animals first, stating that the French septicemia. Although there are no reports of Domagk ever physiologists had already determined its safety in animal using the agent on himself, its use in a loved one may be models. Therefore, he decided to attempt it on himself first. considered just as, if not more, daring. Ultimately, sulfani- After prepping his left antecubital area with iodine and lamide was determined to be the active metabolite of injecting novocaine locally, he made his incision. Finding a Prontosil, and within the decade a new class of antimicrobial large vein, he passed a hollow needle into the vessel to hold it agents, the sulfonamides, was introduced into the therapeutic open and then gently pushed a sterile 65-cm rubber ureteral arsenal for previously untreatable bacterial pathogens. catheter through the vein and toward his heart. Standing behind a fluoroscopic screen, he documented the rubber Beppino Giovanella: thymidine catheter tip entering the right atrium. Forssmann acknowl- edged that the “method opens up numerous prospects… in the Self-experimentation with potential therapeutic agents investigation of…cardiac function,”2 and, as history would has continued to nearly the present day. In the late 1970s, prove, the procedure had tremendous implications on the Dr Beppino Giovanella was the senior scientist on the diagnosis and management of cardiac disease. thymidine project at the Stehlin Research Foundation in Forssmann would go on to catheterize his own heart a Houston, Tex. Encouraged by initial results that thymidine total of 9 times without complications.4 With the aid of shrank certain cancers in mice with minimal toxicity, hindsight, it may be said that Forssmann was very fortunate Dr Giovanella attempted to persuade the Food and Drug not to have suffered from any cardiac dysrythmias as the Administration to allow thymidine, a well-studied substance rubber tube contacted the endocardium. Expressing the with no known side effects, to proceed straight to human sentiment of many self-experimenters, however, he said that clinical trials without the lengthy toxicity and safety testing that “when the problems in an experiment are not very clear, is normally required. When the FDA refused, Dr Giovanella you should do it on yourself and not on another person.”2 reportedly consumed thymidine himself, at first orally and then Self-experimenters-Part II-Essay and Commentary 659 intravenously, in an attempt to prove its low risk of adverse the next 5 years, with mostly favorable results. It was also effects.3 With the exception of some abdominal cramping and offered to British troops engaged in the South African Boer diarrhea, Giovanella reported no other adverse reactions, even War, although it is estimated that only about 4% consented to as his serum concentration reached a point when needlelike take it.2 Wright's work and his self-experiment not only helped crystals composed of a thymidine metabolite supposedly provide protection against typhoid, it also established the appeared in his urine samples. When presented with this feasibility of using a killed vaccine preparation. information, the FDA reversed its decision and allowed thymidine to proceed