APRIL 2008


"I shall die in the service of science"

Self experimentation puts doctors' lives in peril, but MDs persist

Rocket-powered Air Force physician John Stapp performed tests in the 40s and 50s on humans' ability to withstand an impact, landing himself on the cover of Time... and in hospital
Photo credit: United States Air Force

Dr James Kennedy held up a glass of 5-aminolevulinic acid, the skin cancer drug he'd been testing on mice in his lab at Queen's University. He was frustrated. The mice weren't responding to the treatment. "It should have worked. But it didn't."

He decided to take a sip.

"It tasted like lemon juice," he recalls. Then he checked to see what would happen if he poured some on his skin. No scarring. He injected some under his skin. No pain. Next test: his face. "I have a beard and I tried it on the left side of my face. I got some skin reactions, but I pulled on my beard every few days and nothing fell out."

This was far from the first time Dr Kennedy dabbled in self experimentation. Before that, he used to test each batch of Bacille Calmette-Guérin, the tuberculosis vaccine, on himself before he used it in an experiment, to make sure it was active. "Sometimes it propagates through the body and triggers cancer, but that's rare. Occasionally I got the injection a little too deep and it went systemic on me," he says, but nothing worse than some flu symptoms ever came of it, he insists.

His colleagues seemed worried but tolerated the acid experiments. "They figured I was crazy anyways," he explains.

Dr Kennedy decided it would be better not to tell his wife or kids about his little experiments. "They might have worried about it," he says, in something of an understatement.

Sipping 5-aminolevulinic acid sounds like the beginning of a new Dr Jekyll and Mr Hyde adaptation or the basis of a Spiderman villain, but this is actually how Dr Kennedy went about studying the drug, called ALA for short. "It's handy to have your experimental animal with you at all times," he says. "Anytime you want to do an experiment, it's available."

In a matter of days, Dr Kennedy's understanding of the substance's effects on humans — specifically, himself — had advanced by leaps and bounds.

ALA was completely safe, he concluded, and he managed to wrangle an essentially unlimited ethics approval from Queen's to start clinical trials. In 1999, ALA was approved in the United States, becoming the first light-activated drug ever available to treat precancerous actinic keratoses. Since then, over 300,000 people have been treated with ALA and Dr Kennedy has won two major scientific awards.

With that, Dr Kennedy joined the illustrious, centuries-old and often off-kilter ranks of self experimenting physicians. (See "Self experimentation's checkered past," below for more.)

Doctors have been performing experiments on themselves - n of 1 trials - for a long, long time. Some have died; others have been wildly successful and earned Nobel Prizes.

In the early 50s, Dr John Sutherland and a senior colleague at Tufts University in Boston had a patient who they suspected of having hemolytic anemia. To see if they were right, Dr Sutherland injected a pint of the patient's type O blood into his own type A. "Then every few days, I would take a sample of my blood and mix it with anti-A serum," he says. "That would coagulate all my red blood cells and those still loose would be the patient's, and I could graph the course of the patient's blood in my system." The doctors determined that the blood was fine and they diagnosed the patient with an overactive spleen. Dr Sutherland contracted a low-grade fever that cleared up within a week or so.

"Yes, it is dangerous," he admits. "There is no way we would do an experiment like that now, giving blood from somebody with an unknown disorder. And the other disadvantage it is a series of one case." But he firmly believed, and still does, that self experimentation is a heroic act.

Dr Sutherland later co-wrote a book, If I Die In The Service of Science, named after a famous self experiment on hygiene in 19th century Germany by a physician named Max von Pettenkofer.

Just before he gulped down a flask full of cholera, Dr von Pettenkofer had told his students, "Even if I be mistaken and this experiment that I am making imperils my life, I shall look death quietly in the face, for what I am doing is no frivolous or cowardly act of suicide, but I shall die in the service of science as a soldier perishes on the field of honour." He survived the experiment.

Self experimentation's checkered past

Sigmund Freud & Karl Koller
Sigmund Freud tested dream interpretation — and cocaine — on himself. Unfortunately for Dr Freud, however, he was on vacation in 1884 when his coke-snorting pal, the ophthalmology intern Karl "Coca" Koller, made the discovery (testing it on a patient this time) that cocaine could be used as a local anesthetic in eye surgery.

Jesse Lazear
Dr Lazear, a US physician during the Spanish-American War, became convinced that yellow fever, which was decimating American forces, was spread by mosquitoes, not poor sanitation. In late August 1900, Dr Lazear got some infected mosquitoes, rolled up his sleeze and let them have a go at him. His theory was right: he died a few weeks later.

Frederick Banting
Canada can lay claim to its own Nobel-winning, self experimenting physician: Frederick Banting. The man who discovered insulin (which he tested on himself) also decided to find out what mustard gas burns felt like, and was saved from near death inside a decompression chamber of his own design when his laboratory staff refused to follow his instructions to keep reducing the pressure.

Werner Forssman
In 1929, German surgeon Werner Forssman became the first person to perform a cardiac catheterization. The department chief told him not to do it; Dr Forssman ignored him. A nurse tried to stop him; he tied her to the operating table to keep her out of the way. Then he opened a vein in his arm, stuck in a urethral catheter and stood in front of a fluoroscopy screen to guide it into the right atrium of his heart. Then he sauntered upstairs to the X-ray department and took the image that revolutionized cardiology. Despite later joining the Nazi party, Dr Forssman was awarded the 1956 Nobel Prize for Physiology or Medicine.

John Stapp
Few people realize that Murphy's Law originated during an extraordinary series of self experiments conducted in the 1940s and 50s in the California desert. While studying Air Force records, Dr John Stapp (pictured above) realized that simple, everyday car accidents — not plane crashes — were responsible for a huge proportion of pilots' deaths. Dr Stapp decided to test the limits of humans' ability to withstand an impact to demonstrate the need for proper restraints in airplanes and in cars. One of the tests, in 1954, in which Dr Stapp, "the fastest man on earth," rode a rocket-powered sled from zero to 1,019 km/h in five seconds and then came to complete stop in 1.4 seconds, temporarily blinded him due to retinal hemorrhages, broke both of his wrists and caused other injuries. In an earlier test, an engineer named Edward Murphy managed to install both of the two sensors incorrectly, rendering the data useless. "If there are two or more ways to do something and one of those results in a catastrophe, then someone will do it that way," Captain Murphy declared after seeing Dr Stapp emerge from the sled bloodied and hurt, spawning his famous law.

Barry Marshall & Robin Warren
The two Australian physician-researchers shared the 2005 Nobel Prize in Physiology or Medicine for their research that proved the bacteria Helicobacter pylori caused stomach ulcers. In 1984, after failing to see results in animal tests, Dr Marshall decided to try it out on himself. He didn't tell the hospital ethics committee, nor his wife. "She was already convinced about the risk of these bacteria and I knew I would never get her approval," he wrote. "This was one of those occasions when it would be easier to get forgiveness than permission." The experiment was a success, so to speak: Dr Marshall fell ill and changed the world's understanding of the causes of gastric ulcers. And his wife forgave him.



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