Last year, Daniel Zagury, a French physician, injected himself with an experimental AIDS vaccine to see if his body would produce antibodies. It did, and the widely publicized experiment galvanized AIDS research.
To be sure, Zagury did not give himself AIDS. The vaccine was a genetically engineered mating of a protein found in the AIDS virus and the oldest known vaccine–harmless vaccinia (cowpox) virus–that protects us against smallpox. Nonetheless, Zagury was following a dangerous and unheralded tradition in medicine, one that Lawrence Altman has spent 30 years unraveling. ”I`ve always been fascinated by people who felt they had no right to do something to someone else if they hadn`t done it to themselves first,” says Altman, the senior medical correspondent for the New York Times.
”Medicine has swept the idea of self-experimentation under the rug. Medical students aren`t taught about it. Journalists weren`t present at the experiments, and history pays the price for not chronicling them in detail. No one knows how many self-experimenters there have been, or how many there are now. But I have no question that it still goes on everywhere today.”
Himself a physician (an internist and specialist in infectious diseases), Altman has investigated these researchers–considered either quiet heroes or reckless fools by other doctors–since 1958, when he was a medical student. Whenever he could, Altman would seek out guinea-pig doctors, make rounds with them, later travel from the Arctic to the tropics to interview them, and spend his spare time in medical libraries backtracking others through history.
Of necessity, his quest became his hobby. Altman in 1969 was able to combine two loves by becoming the first physician to go to work full-time as a newspaper reporter. As the Timesman responsible for coverage of such major stories as AIDS, organ transplants, artificial hearts and the medical treatment of popes and presidents, Altman is kept busy.
Nonetheless, after three decades, this meticulous journalist who thinks like a doctor finally has published his report–a provocative, critically acclaimed book, ”Who Goes First?” (Random House, $22.50).
”Everything in medicine that is now standard was once experimental,”
Altman reminds. ”Good health today stems from literally millions of earlier experiments. Whenever we take a pill, or undergo a medical test, receive an inoculation, eat a food or drink water free from typhoid and cholera, we never consider that those who lived before us took great risks from which we now benefit.
”Someone had to make the decision to go first. Very often, it was the physician or researcher who decided the first human subject should be himself.”
No one today remembers Anton Storck, a 19-year-old Viennese doctor who in 1760 repeatedly sipped tea laced with hemlock, said to be the suicide drug of Socrates and believed in Storck`s time to be beneficial against pain. The experiment so terrified Storck that he lost the ability to speak temporarily, but he suffered no lasting ill effects.
But Altman traces a direct line from Storck to the Americans Frederick Prescott and Scott Smith, who in the 1940s had themselves so paralyzed temporarily by curare that not even an eyelid could blink, thus demonstrating that the deadly poison could immobolize patients and revolutionize surgery.
Throughout medical history, Altman found, researchers have served deliberately as guinea pigs because animal experiments can work only up to a point.
As geneticist J.B.S. Haldane once noted, ”It is difficult to be sure how a rabbit feels at any time. Indeed, many rabbits make no serious attempt to cooperate with one.”
Altman painstakingly has collected more than 400 cases of guinea-pig doctors, of which he includes about 150 in his book, covering every human organ system, every important drug, diet, medical test and every medical specialty–”I tried to do a comprehensive investigation, and it was only possible because I`ve been fascinated by the topic since I was in medical school.”
Doctors drop like flies in Altman`s book. Then they pick themselves up and pass out again. They routinely endure agonizing pain, hallucinations and violent diarrhea.
Researchers let thousands of disease-carrying mosquitoes bite them. They sniff, inject, taste, swallow, vomit and are poisoned by the most
objectionable substances one can imagine. And they do so repeatedly, knowing what will happen, to test themselves over and over again. Some of them die, but, surprisingly, not many.
Of them all, one man impresses Altman the most.
”It`s just a personal reaction,” he says, smiling. ”The bravery of Werner Forssmann amazes me.”
Well into this century, ”Don`t touch the heart” was a medical dictum that reigned supreme. Surgeons had invaded most of the body–abdominal organs, limbs, face, chest, even the brain. The heart only lies three inches beneath the skin, yet encased in its bony cage of ribs, constantly pumping blood and bleeding profusely when cut, it remained inviolate. Doctors could only diagnose heart ailments with their hands and ears. Too often, only an autopsy would tell them what was wrong.
In the early 1920s, Forssmann, a young German physician, grew obsessed by a sketch in his physiology textbook. It showed French physiologists standing in front of a horse. They held a thin tube that had been placed into the jugular vein in the animal`s neck, then guided into its heart. An inflated rubber balloon recorded the changes in pressure inside one of the heart chambers. The horse, and its heart, seemed undisturbed by the procedure.
The diagnostic value of putting a tube into the human heart would be incalculable, Forssmann knew, although he believed that entry by the jugular would be rejected by patients for cosmetic reasons. The veins in the elbow crease would be better. By 1929, he was determined to try the experiment.
At the time, physicians were expected to be independently wealthy. Forssmann wasn`t. He was working at a small Red Cross hospital 50 miles outside Berlin as a $50-a-month apprentice to Dr. Richard Schneider, a general surgeon and family friend. Forssmann appealed to Schneider to let him try to place a tube into the human heart. Forssmann admitted that he didn`t know what would happen when the tip of the rubber tube reached the sensitive inside lining of the heart. So he offered to do it to himself first.
”I was convinced that when the problems in an experiment are not very clear, you should do it on yourself and not on another person,” Forssmann would tell Altman years later.
Schneider forbade Forssmann to try. If Forssmann died, who would support his widowed mother? Moreover, an accident would create a scandal.
But Forssmann decided to do the experiment anyway, in secret. He somehow had to gather the equipment–scalpels, sutures, a painkiller to anesthetize the elbow crease he would pierce. For his sterile tubing he selected a ureteral catheter, the thin tubing that urologists use to drain urine from the kidneys. The crucial equipment was locked in the operating room under the care of a nurse, Gerda Ditzen. Forssmann had to no choice but to enlist her aid.
”I started to prowl around Gerda like a sweet-toothed cat around the cream jug,” he recalled later. He showed her the picture of the horse. He took her to dinner. He convinced her of the importance of his idea and bemoaned his frustration at having been forbidden to proceed. Intrigued by her chance to be part of medical history, the nurse even volunteered to be the guinea pig. Forssmann agreed.
In the operating room, nurse Ditzen gave Forssmann the medical gear he needed. Then she climbed onto the operating table. Forssmann strapped down her arms and legs and stepped out of her view.
As she waited for him to begin, he daubed iodine on his own left elbow crease, injected novocaine to numb the area and made an incision. When he reached a large vein, he picked up a hollow needle, gently pushed it into the vein and left it in place. A small amount of blood spilled over his arm.
Then Forssmann took the rubber tubing, pushed it through the hollow needle and slowly, carefully, slithered it along. He felt warmth but no pain. When the tube reached the level of his shoulder, he stopped. He would need an X-ray of his chest to document the experiment. The X-ray machine was in the basement. Once again, he would need nurse Ditzen, who by this time was growing impatient on the table. When Forssmann loosed her bonds, she took one look and realized she had been duped. She was furious.
Forssmann calmed her and tied a handkerchief around his arm. Then they walked down to the X-ray department. Forssmann stepped behind the fluoroscopic X-ray screen and asked the nurse to hold up a mirror so he could follow the position of the catheter on the fluoroscope. As they watched, fascinated, the X-ray technician slipped from the room.
Forssmann inched the catheter toward his beating heart. Still no pain, only warmth. Once, he touched something sensitive and felt an urge to cough. He suppressed the urge.
Another doctor, alerted by the technician, burst into the room. Horrified, he tried to yank the catheter from Forssmann`s arm.
”I fought him off, yelling, `Nein, nein, I must push it forward!` I kicked his shins and pushed the catheter until the mirror showed that the tip had reached my heart.
” `Take a picture,` I ordered. I knew the main point was to get radiographic proof that the catheter was indeed in the heart and not in the vein.”
Satisfied, Forssmann carefully slid the tube out of his heart, worked it back through the veins in his chest and arm and out his elbow crease. When Schneider, his boss, saw the landmark X-ray pictures, he took everyone out for several bottles of wine.
Forssmann repeated the experiment on himself five more times in the next four weeks, painstakingly documenting the procedure and seeking clearer X-rays. He finally took to threading the cathether from a vein in his upper leg, to the thigh, to the abdomen and further into the main vein that drains blood from the lower half of the body and on into its connection with the heart.
Ultimately, he would give himself nine angiograms, as the procedure came to be called, courting death by squirting dye into his heart–he had no idea what would happen when he did so–and taking X-ray pictures, a tricky matter because the heart beats so rapidly and radiopaque chemicals, or dyes, were then primitive. The exposures had to be made quickly and at the precise moment. By viewing 30 of them in sequence, Forssmann proved that the action of the heart could be shown.
The revolution of cardiac catheterization and angiography spawned by Forssmann was not appreciated for years. He even was denied employment because officials worried that if he had done such experiments on his own heart, what would he do to the hearts of patients.
To support his family, Forssmann spent his career as a urologist in a small German farming community, plucked from obscurity only in 1956 when he shared the Nobel Prize in Medicine and Physiology.
A few months before his death in 1979 at age 74, he said what must have been on his mind for 50 years:
”It was very painful. I felt that I had planted an apple orchard, and other men who had gathered the harvest stood at the wall, laughing at me.”
Adds Altman: ”When I met with him, he told me nobody had ever interviewed him in depth before.”
The lack of valid documentation of many such experiments has led to historical mistakes, Altman says. One involves Dr. Walter Reed, head of a four-man American military team that went to Cuba in 1900 and proved through daring human experiments that mosquitoes transmitted yellow fever, and that something submicroscopic in the blood–now known as a virus–caused the disease.
”Walter Reed embodies the symbol of the valiant investigator who in hopes of improving human welfare willingly risks contracting a fatal disease. Every schoolchild knows that Reed let the mosquitoes bite him, and he still receives primary credit for the breakthrough.
”But Reed actually was the only member of the research team who did not allow himself to be bitten by infected mosquotos to test the hypothesis,”
Altman says. ”One of his colleagues who did, Jesse Lazear, died as a result. ”Reed had pledged to participate, but he left for Washington the next morning. No one knows why he left. He leaves us no clues. Reed died from appendicitis in 1902, not from yellow fever as is often thought. He was a first-rate scientist, who, for his own reasons, refused to go first. It is one of the greatest ironies of medical history that he alone remains the hero of this extraordinary scientific discovery.”
Some institutions, such as Barnes Hospital in St. Louis, have a proud tradition of practicing ”kamikaze medicine,” Altman says. Some drug companies, he suspects, still quietly honor the legacy of the Danish company, Medicinalco, now known as Dumex, whose employees during World War II jocularly referred to themselves as ”the Death Battalion” and tested new drugs on themselves.
Even cancer has not paralyzed researchers. In 1954, at Barnes, Thomas Brittingham repeatedly injected into himself white blood cells from a leukemia victim to test for the presence of antibodies against the alien white cells. He did not believe he would get cancer, but as he told a colleague, ”Wouldn`t it be great if I could also prove that leukemia was a transmissible disease?” In 1901, Chicago surgeon Nicholas Senn had implanted cancerous tissue in his body to demonstrate that cancer was neither contagious nor communicable, but Brittingham still was charting unknown territory.
He failed to contract leukemia, even after transfusing into himself a total of a quart of leukemic blood. Brittingham became violently ill, yet still insisted on performing his own blood counts.
”It was fantastic, a colleague reported, ”to watch him sit there at the microscope having shaking chills and almost getting black and blue around the eyes looking through the eyepiece of the microscope.”
Altman can understand what drives such men. As a young clinical researcher at the University of Washington, he studied a rare genetic disease, PXE (pseudoxanthoma elasticum), that blinds, causes bleeding, damages the skin and leads to early death from heart attacks and strokes. The study required that, for comparison, a skin biopsy be performed on a normal subject. Altman did not hesitate to be that subject.
”The experiment was simple and held no unusual risk,” he says, ”and I thought it was only fair. Then, I found that a bond developed between me and my patients. I was asking them to something they knew I had done.
”Many researchers don`t want to do this, so they deny that self-experimentation goes on today. Their careers and grants are dependent on others taking risks. And yet they wouldn`t subject themselves to what they`re asking others to do. The attitude bothers me, I must admit. I find it troublesome.”
