Human Subject: An Investigational Memoir

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18. Physician, Investigate Thyself

“Car, il ne faut pas s'y tromper, la morale ne défend pas de faire des expériences sur son prochain ni sur soi-même; dans la pratique de la vie, les hommes ne font que faire des expériences les uns sur les autres.”

I made it through the Valtrex washout period without waking up the wily pathogen in my spine. Thanks to Cymbalta, I didn’t get so anxious about having an outbreak that I had an outbreak. Then it was on to the three-pills-a-day regimen.

And then, as if I didn’t have enough medication to keep track of, I decided to perform a clinical trial on myself.

After four weeks on Cymbalta, it was time for what would probably be my last visit with Dr. J. I told him that I felt generally pretty good, though not fantastic. At my final visit as an actual subject, the study coordinator had said that the purpose of this last appointment would be to monitor my two adverse events, but Dr. J said that, because my blood pressure had returned to normal as of the previous visit, there was only one AE that was unresolved: my lack of libido. I personally thought that lethargy was a more serious side effect, but I let him go on thinking it was all about sex. That seemed to make him happy.

I had heard of people using a drug called bupropion (Wellbutrin) in conjunction with other antidepressants to reduce the incidence of “sexual side effects.” Dr. J had never suggested this, so I asked him about it. He said that he had prescribed it for that purpose about ten times, and only one person had experienced any relief. But he was willing to let me give it a try, so he wrote me a prescription. He asked me to let him know if it did me any good.

Bupropion works differently from other antidepressants. In fact, it’s so different that, after studying it for decades, pharmacologists still don’t know quite how it works. About the only thing they’re sure of is that the drug has a slight inhibitory effect on the reuptake of three neurotransmitters: norepinephrine, serotonin, and dopamine. Dr. J told me that it’s prescribed for adult ADHD, so it might improve my concentration and make me feel more alert, in addition to restoring my interest in sex. It sure sounded like a miracle drug to me. I started taking 100 mg of it every morning and waited for the magic to happen.

On the first day I felt just as drawn to my bed in the afternoon as I had on every other day of my life with antidepressants. As I always try (and sometimes am able) to do, I resisted the urge to nap, and by evening I was alert again. The same thing happened the next two days, but by the fourth day I was slightly less sleepy in the afternoon (I napped through part of a documentary about an orphanage in Africa, but I don’t blame the drug for that). On the fifth day I had no urge to nap. I was also noticeably less groggy all day. Except for the persistently AWOL sex drive, there was a definite improvement. Bupropion was truly a miracle drug.

Or was it? I was more alert, and my powers of concentration were somewhat improved, but I was also starting to feel slightly depressed. I’m pretty sure I would have been eligible at that point for repetitive transcranial magnetic stimulation, but I wasn’t ready to set aside a minimum of two hours per day for up to four months. Instead I doubled the dose of bupropion, as Dr. J had suggested that I could do after a week at 100 mg. I didn’t want to take much more than 200 mg, because at higher doses it can cause seizures.

At first it seemed that the extra dose of bupropion was helping with my concentration and alertness. Then I noticed that my mind was wandering as much as ever, that I was getting even sleepier than before, and that I had definite symptoms of depression. I went back to 100 mg and found that I was less sleepy. Since I had many excellent reasons to feel depressed, I was just grateful that the bouts of self-pity and hopelessness were mild and short-lived.

You know the old joke that says you aren’t paranoid if people are really out to get you? OK, maybe there isn’t such a joke. (Feel free to make one up.) Anyway, I could see a parallel with my thoughts of worthlessness, incompetence, and unlovability. Just as some people who are labeled as paranoid really are victims of stalking or persecution, maybe some people diagnosed with depression really are worthless, incompetent, and unlovable. Yes, there are a lot of worthless jerks in the world, but the lucky ones are clueless or in denial about their repellent natures. The vast majority of jerks don’t exhibit signs of depression. For those who are perceptive enough to realize their true lack of worth, no amount of medication will help.

But enough about me. My pathetic little experiment with a two-drug cocktail was nothing compared to the heroism of investigators who test potential new cures and vaccines on themselves.

One of the first known self-experimenters was an Italian physician who lived during Shakespeare’s time. Santorio Santorio is best known for discovering “insensible perspiration,” i.e., the process by which the body loses large amounts of fluid without our being aware of it. He made the discovery by carefully weighing himself, and everything he ate and drank, and everything he excreted, every day for 30 years. Not too surprisingly, he seems to have lived alone.

I learned about Santorio in a book called Who Goes First? The Story of Self-Experimentation in Medicine by Lawrence K. Altman (Altman, 1987). The well-known self-experimenters described by Dr. Altman include the young Sigmund Freud, whose daring experiments with cocaine led to its use as a local anesthetic (he was criticized, however, for promoting other uses for cocaine and ignoring its potential for abuse). The book also recounts the exploits of less famous medical pioneers, like 19-year-old physician Anton Storck, who tested the poisonous plant hemlock on himself and then proceeded, along with other physicians in 18th century Vienna, to sicken or kill many patients, since hemlock has no known medicinal use. Greater success resulted from the experiments of 20-year-old Friedrich Serturner, who isolated the drug morphine from opium and then tested it on himself and three friends.

Not all the self-experimenters that Altman describes were fresh-faced youths. Albert Hofmann, the first person to synthesize lysergic acid diethylamide (LSD), was 37 when he tried a taste of his own medicine. And there was John S. Haldane, who at the age of 51 spent six weeks at the summit of Pike’s Peak, studying the effects of altitude on respiration.

Altman points out that, because animals can’t tell us what they see and feel, experimentation with hallucinogens requires human subjects. One would think that the same would be true for any medication that produces a subjective response, including painkillers. After all, dogs and frogs cannot rate the pain they’re feeling on a 10-point, or even a 5-point, scale. But it turns out that researchers have devised fairly accurate methods of rating the levels of pain in laboratory animals, using criteria such as how long a rat can stand on a hotplate without jumping. Other tests, like the forced swimming test mentioned in chapter 3, can measure changes in an animal’s brain chemistry.

At some point, however, the treatment must be tested on human beings, and sometimes the experimenter goes first. And sometimes he takes his friends and relations along with him. Several of the early experimenters, like Serturner, recruited their families, friends, and assistants to join them in trying out new treatments. Some associates or family members even insisted on participating, against the advice of the principal investigator. One of these noble souls was Mary Goldberger.

Joseph Goldberger was an intrepid medical investigator who began his career with the U.S. Public Health Service in 1899. In the course of his investigations, he contracted a number of serious illnesses (he discovered the source of one parasitic disease by keeping his own arm between two straw-filled mattresses for an hour). Then, in 1914, he was asked to take charge of the search for the cause of pellagra, a disease that affects the skin, brain, and digestive system.

Pellagra was assumed to be a contagious disease, but Goldberger soon noticed that it was not an equal opportunity affliction: Only people who were poor and malnourished got pellagra. To prove that the disease was caused by an unhealthy diet (lack of niacin, it turned out) rather than a microorganism, he conducted a series of experiments on himself and others. First he injected himself and a colleague with the blood of infected patients. Then he began swallowing capsules containing urine, feces, and skin from patients with severe cases of the disease. When he recruited several other male doctors to do the same, his wife volunteered, to represent women (she was definitely ahead of her time, since women weren’t regularly included in clinical trials until recently). Of course, the men refused to let the little lady swallow the noxious capsules, but they did inject her with some infected blood, which didn’t harm her.

Altman exposes one well-known self-experimenter as less courageous than some people may think: Walter Reed was the only researcher on his yellow-fever-hunting team who didn’t expose himself to the mosquitoes that carried the deadly virus. After one of his fellow researchers died, however, he did create the first informed-consent document, so maybe he deserved to have an Army medical center named after him. (Whatever his shortcomings, it hardly seems fair that today many people associate the name “Walter Reed” with substandard treatment at that facility.)

Altman found it surprising that self-experimentation is not addressed in the Common Rule and its supplemental parts. His book was published 20 years ago, so I decided to see what I could learn about current thinking on the subject.

Searching the IRB Forum for “self-experimentation,” I found only one question. It concerned a PI in 2003 who wanted to take part in his own experiment. This led to a discussion of “autoexperimentation” in general. Two people cited Directive 5 of the Nuremberg code, which seems to advocate serving as one’s own subject:

“No experiment should be conducted where there is an a priori reason to believe that death or disabling injury will occur; except, perhaps, in those experiments where the experimental physicians also serve as subjects.”

The original question was whether this situation presented a conflict of interest. Some of the IRB professionals didn’t see where the conflict lay, but others maintained that the integrity of the research could be compromised when an investigator is also a subject. One person pointed out that the doctor might assess the level of risk less objectively if he or she is willing to take it on, thinking, in essence, “If I’ll do it to myself, it can’t be very risky.” The last word on the subject came from a physician-researcher who suggested that any PI who isn’t willing to participate in his or her own research perhaps shouldn’t be conducting the research at all.

That same year an article advising researchers against self-experimentation appeared in the journal Accountability in Research. The author cited both quality control and ethics as reasons to refrain from participating in one’s own experiments. In the spirit of the Nuremberg directive, he acknowledged only one possible exception to this general prohibition: cases of unusually high risk. Historically these have been the cases where self-experimentation was most likely to occur, so he probably wasn’t giving researchers any more basis for decision-making than they already had. (Davis, 2003)

Sometimes the experiment is not only too risky, but also too bizarre, to inflict on subjects other than oneself. A recent example is the work done in 1993 by Robert A. Lopez, a Westport, N.Y., veterinarian who wanted to know whether infestation by ear mites (Otodectes cynotis) could be induced in human beings. He took about a gram of ear mites from the ear of a cat and placed them in his own left ear. After several weeks of unpleasant sensations, temporary hearing loss, and buildup of debris, he rinsed the remaining mites and debris out. He then repeated this experiment twice, finally concluding that human ears aren’t susceptible to ear-mite infestation. (Since the mites’ nightly feeding frenzy had made sleep impossible, he also concluded that the best time to apply ear mite remedies is at night.) (Lopez, 1994)

Dr. Lopez didn’t make any groundbreaking discoveries about ear mites, but the itching and the constant noise of the mites traveling up and down his ear canal did cause him to feel greater empathy for his patients. The experiment also earned Dr. Lopez an Ig Nobel prize in entomology. The Ig Nobels are awarded each year by the publishers of the Annals of Improbable Research for “achievements that first make people laugh, and then make them think.” (

Alas, Dr. Lopez may be the last of a valiant breed. I haven’t come across any other recent tales of self-sacrifice in the service of medical knowledge. But I hold out hope that the practice continues surreptitiously, perhaps in secret labs out of view of the regulatory enforcers.

My own self-experimentation continued for another month, as I altered the dose of each antidepressant for a week at a time. I had been on 60 mg of Cymbalta with 100 mg of Wellbutrin, but then I doubled the Wellbutrin again. This time it made me grind my teeth and gave me vivid dreams, though I slept a lot less (which was fine with me, as I needed to compensate for ten years of too much sleep while on Paxil). Then I tried reducing the Cymbalta to 30 mg, and I seemed to get groggier.

I was glad that there were so many treatment choices available to me. I could imagine a day when I would willingly lay down my pharmacological crutches and hobble on my own through the rugged terrain of life, but that day was still many refills away.

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