Medicine owes a huge debt of gratitude to pioneering clinicians and researchers who were courageous enough to use themselves as experimental subjects to advance scientific knowledge. There is a long tradition of self-experimentation in toxicology. In the early 1800s, British surgeon Edward Jukes demonstrated the effect of immediate gastric lavage by ingesting an overdose of laudanum (tincture of opium) and then having his stomach washed out through a half-inch diameter gum elastic tube. He survived and suffered only minimal clinical manifestations of opiate toxicity.
In 1852, the chemist Pierre-Fleurus Touéry stunned the French Academy of Medicine when, before a large audience, he ingested 10 times the lethal dose of strychnine mixed with 15 gm of charcoal. He showed no ill effects.
But for weird — and I mean way weird — examples of self-experimentation in toxicology, we have to look to the late 1800s when the medical world was beginning to realize that cocaine acted as a local anesthetic and potentially could be used to facilitate surgical procedures. In 1884, Karl Koller reported that the topical application of cocaine solution could take away the pain of eye surgery. In that same year, a young Sigmund Freud published his monograph On Coca, in which he also recommended cocaine's use as a local anesthetic. (Then again, he also suggested that cocaine could be used as a cure for morphine addiction.)
In the October 25, 1884, issue of the Medical Record, there was a remarkable paper with the bland title, “Hydrochlorate of Cocaine-Experiments and Application.” It was written by Dr. H. Knapp, a professor of ophthalmology at the University of the City of New York, and explains how after reading about the numbing effects of cocaine, he investigated its action on himself, his wife, their 15-year-old son, and some patients. He found that when he painted a 2% solution of silver nitrate on his own eye, applying cocaine relieved the irritation and discomfort. He did further experiments on the ear, mouth, and nose.
There are, of course, other mucus membranes whose sensation could be dulled by the application of cocaine, and Dr. Knapp did not hesitate to proceed fearlessly where no man had gone before. I quote from his paper:
“The urethra. My urethra is very sensitive to the introduction of instruments. I injected, by means of an Eustachian catheter and a balloon, a four percent solution of cocaine, and held it in for a few minutes. In ten minutes the glans had become pale and insensible to touch. I repeated the injection. Seven minutes later I introduced a catheter and other instruments into the urethra. I did not feel them at all as far as 3”; when pushed farther I felt them very unpleasantly painful. Evidently the cocaine had not penetrated more deeply.
“Before the injection of cocaine I felt the instruments very keenly from the beginning of the urethra. To test the loss of sensibility of the cocainized urethra in another direction, I injected a one percent solution of arg. nitr. [silver nitrate] into the anterior part by means of an Anel's syringe, introduced as far as 1–1/2″. I had no sensation at all. … This experiment shows, and I feel convinced, that cocaine will prove most beneficial in uro-genital surgery. It not only destroys the sensibility of the parts, and therefore admits the easy performance of many surgical procedures, but by being painless these procedures will not incite reflex phenomena, spasm, and the like.
“The rectum. – For the sake of completeness, I injected also cocaine into the rectum. The sensibility, which was not great anyhow, was reduced.”
Even more, um, impressive were the studies carried out several years later by Drs. August Bier and August Hildebrandt in Germany. The first diagnostic spinal tap had been reported in 1886, and it occurred to the German physicians that injecting cocaine into the spinal canal might produce regional anesthesia in the lower part of the body. To determine if this was in fact feasible, they decided to try the procedure on each other.
As described in Lawrence K. Altman's enlightening and entertaining book, Who Goes First? The Story of Self-Experimentation in Medicine, Hildebrandt first injected cocaine in Bier's spinal canal but failed to produce adequate anesthesia, most likely because of poor technique. Then the roles were reversed:
“When the more experienced Bier injected the solution into Hildebrandt's back, just a few drops escaped. Within seven minutes Hildebrandt could feel pinpricks only as pressure; tickling of the sole of the foot hardly bothered him. A minute later, Bier drew a large curved needle through the skin of Hildebrandt's thigh. Again his assistant sensed no pain. Two minutes later Bier thrust a needle into Hildebrandt's thigh bone; he felt nothing.
“Thirteen minutes after the spinal injection, Bier put the lighted end of his cigar on Hildebrandt's legs. The burn caused no pain. Hard hammer blows against his shins were painless. On and on, Bier battered Hildebrandt. Pulling out pubic hair felt like lifting a skin fold, although plucking hairs from the chest was painful. Strong pressure and tugging on Hildebrandt's testicles produced no sensation.
“It took forty-five minutes for the effect of the drug to wear off and normal sensitivity to return.”
In his forward to Dr. Altman's book, Lewis Thomas notes that any history of medical research will involve a certain amount of “human nuttiness and grabbiness.” In the history of drug and toxicology self-experimentation, there may be some grabbier but certainly few seemingly nuttier than Drs. Knapp, Hildebrandt, and Bier.