PHYSICIAN, HEAL THYSELF

By LEON JAROFF

Detachment, viewed as a virtue among scientists, often feels unnatural to medical practitioners, who see human involvement as central to the healing art. For those who have themselves been afflicted with disease or observed it in a loved one, the experience can become a driving force in their search for a cure. Here are five whose close encounters with illness have produced important contributions to medical science:

PAUL O'BYRNE Fighting asthma by inducing episodes in himself

Paul O'Byrne was a sickly child. He often had trouble breathing and woke frequently at night, coughing and wheezing. No medication or other treatment seemed to help, and when O'Byrne was six a Dublin doctor explained to his parents that, for some unknown reason, cold, damp climates worsened the child's asthma. He advised them to leave Ireland for a dryer, warmer place.

The change worked. Paul's family moved to Rhodesia, where he regained his health. Later he attended medical school in Ireland, and, motivated by his childhood illness, became a pulmonologist and a leading asthma expert. "I wish I could speak to that Dublin physician now. He had great insight," says O'Byrne, who has learned that his early asthma attacks were allergic reactions to dust mites, which thrive in damp conditions.

Today, as head of the Division of Respirology at McMaster University in Hamilton, Ont., O'Byrne, 46, works in a most unusual way to develop treatments for allergy-related asthma. In most of his studies, he himself is a test subject, periodically doing "challenges"--inhaling allergens to give himself short episodes of asthma. He has even examined his own bone marrow and tissue biopsied from his airways and lungs. "I'm a good subject," he says, "because I'm on time, and I do the test properly."

O'Byrne was shocked when he first viewed his airway tissue. It was "very abnormal, with a lot of scarring," and convinced him that "having a severe childhood disease and not treating it can change the airway forever." He believes that early treatment, particularly with inhaled steroids, outweighs the risk of side effects for children with recurrent asthma.

Discovering how those steroids work and finding which allergens inflame the airways of asthmatics are the goals of O'Byrne and his team of 15 researchers at McMaster. In their studies, O'Byrne will continue to be a test subject. "I wouldn't have learned the things I have about the disease," he says, "if I weren't looking at my own airways, my own cells, my own lungs."

--Reported by Nicole Nolan/Toronto

MAHLON JOHNSON Searching for an HIV "loophole" by dosing himself with highly toxic AIDS drugs

It was just another routine case," says Dr. Mahlon Johnson. In 1992, as the Vanderbilt University neuropathologist was removing the brain of a man who had died of AIDS, his hand suddenly slipped. The bloody scalpel sliced through his glove and deep into his left thumb. Because of that "freaky little slip of the scalpel," as Johnson ruefully characterizes it, he endured seven "nerve-racking" months. He took several HIV tests--all were negative. Then the result that he had been dreading came in: he was HIV positive.

At the time, most doctors with HIV-positive patients held off using powerful but highly toxic AIDS drugs during the early, "latency" period of the disease, when the virus was thought to be somewhat dormant. But Johnson was aware of new studies suggesting that the virus was in fact extremely active during this period, engaged in a winner-take-all struggle with the immune system.

Looking for what he calls "the loophole in the death sentence," Johnson became one of the first to confront the virus early with the most potent arsenal medicine had to offer. He regularly dosed himself with combinations of AZT, DDI and interleukin-2 (two antiretrovirals and an immune enhancer), enduring nausea and developing a rash as a result. For the past few years, doctors have been unable to detect any virus in his blood, although antibodies remain.

Has he been cured? "It seems unlikely," Johnson says. He points to the case of a patient who underwent similar successful therapy but in whom the virus became detectable again when he stopped his drug treatment. Johnson remains realistic but optimistic. In the battle against AIDS, he says, "we've switched from certain death to uncertain life. We used to ask, 'How soon will I die?' Now we ask, 'How long can I live?'"

Whatever the outcome, Johnson strongly advocates early, massive drug intervention--a point he emphasizes in his recent book, Working on a Miracle. Indeed, he has recommended the same treatment for a young HIV-positive widow he is seeing, and they are now both taking protease inhibitors. Though the virus is still detectable in her blood, her immune-cell count has risen dramatically.

--Reported by Dick Thompson/Washington

KAY JAMISON Using her history of manic-depressive illness to understand and help other victims

She was unusually moody as a child and severely depressed as an adolescent. As a high school senior, she went through the first of what were to be many periods of great energy and feelings of being visionary and important, followed by depressing aftermaths. But it was not until a decade later that Kay Jamison learned the truth.

Shortly after receiving her Ph.D. in psychology from UCLA and accepting a job there as assistant professor of psychiatry, she had a major bout of mania, filled with hallucinations and delusions. Yet despite her academic training, she remained unaware that she was ill until a psychoanalyst she was dating bluntly told her she was manic-depressive and needed to be on lithium.

Jamison was shocked by the revelation. Abandoning her experimental studies of drugs and addiction, she began taking lithium and directing her research toward manic-depressive illness and suicide. She has since become a world authority on the disorder; a top-notch clinician and teacher, first at UCLA and then at Johns Hopkins; and a fellow at Oxford, where she investigated the link between creativity and manic depression.

After completing her 1995 book, An Unquiet Mind, in which she revealed that she was manic-depressive, Jamison stopped seeing patients. "I think patients have a right to come to your office and deal with their own problems, not with your problems or their perceptions of your problems," she explains, although she misses her practice.

Her journey to stability and success has not been easy. Like other manic-depressives, and despite her expertise, she would stop taking lithium, partly because she was addicted to the highs of mild mania. But extreme depression always followed, and after one of the more intense high-and-low cycles characteristic of the disorder, she attempted suicide and went into a coma. "It was very clear to me when I woke up that I wished I hadn't woken up, that I wished I was dead," she says. "But that if I were going to live, I had to stay on lithium."

She has done so, and now leads a tranquil life, working mostly in her Washington home, teaching at Johns Hopkins one day a week and writing a book on youth suicide. As her illness receded, Jamison at first became nostalgic for the highs it once brought on. "I could fly through the star fields and slide along the rings of Saturn," she recalls. Then, as the highs faded away, she remembers feeling only "an acute sadness" whenever she saw a real image of Saturn.

--Reported by Joanna Downer/Washington

MAX AGUILERA-HELLWEG FOR TIME

BARRY MARSHALL Acting as his own guinea pig to discover the true cause of peptic ulcers

I felt an uncomfortable fullness after the evening meal," recalls Dr. Barry Marshall, "and then woke up at 5 a.m., vomiting." During that week in 1984, the Australian physician, then a medical fellow at a hospital in Perth, was suffering for the first time from gastritis, an inflammation of the stomach often associated with peptic ulcers.

But Marshall's discomfort was mixed with elation because he knew the source of his illness: a mixture of bacteria he had taken from the stomach tissue of a patient with a suspected ulcer, carefully cultured and then voluntarily swallowed himself. By acting as his own guinea pig, he had proved to his satisfaction that these bacteria, later called Helicobacter pylori, could bring on ulcers and gastritis.

Others were not convinced. Medical doctrine at the time held that gastritis and ulcers in the stomach or intestines were caused by excess acid, brought on partly by stress or diet. Normal acidic gastric juices were believed to keep the stomach sterile. "No one thought bugs could live there," says Marshall. But he and Robin Warren, the pathologist who discovered the culprit bacterium, had found that the bugs survived by burrowing under the stomach's mucous lining, which shielded them from the acid.

The medical community, skeptical of Marshall's ideas and critical of his unorthodox self-experiment, largely rejected his theory. For a few years, he says, "I was a lone voice." But he began treating ulcer patients with antibiotics and a coating agent and was soon achieving a 75% cure rate. Other doctors then tried variations of Marshall's prescription, got even higher cure rates and helped confirm that, except for cases in which drugs such as aspirin are the culprit, H. pylori is the leading cause of ulcers. That helped Marshall gain worldwide, if belated, recognition.

In 1994 the U.S. National Institutes of Health made that recognition official when it recommended antibiotics for the treatment of ulcer patients who have the bacteria. Marshall has since received several prizes, including the Lasker Award in 1995, and is now a professor at the University of Virginia, where he founded a Helicobacter and intestinal immunology research center. He helped develop tests for H. pylori--which may also be implicated in some stomach cancers--and is now working on formulating simpler tests. Encouraged by the recent deciphering of H. pylori's genome, he is also continuing work on developing a vaccine to combat his favorite bacteria.

--Reported by Sabrina Yohannes/New York

TRAN KHUONG DAN Seeking a durable cure for opium addiction by becoming an addict himself

Tran Khuong Dan, a construction foreman from Hanoi, was shocked when, in 1975, he finally saw his elder brother in Ho Chi Minh City (formerly Saigon) after a 21-year separation prolonged by the Vietnam War. Gaunt and pale, the brother displayed symptoms that were all too familiar to Dan. The brother, like their father, was addicted to opium. "All around me," says Dan, "there were drug addicts." The habit eventually led to his father's death in 1976 and his brother's the following year.

Despite their addiction, both men had practiced traditional herbal medicine and had prescribed remedies for thousands of patients. With the knowledge passed down from his father, Dan built himself a thriving practice in Ho Chi Minh City, eventually accumulating some $75,000. But one question continued to nag him about his brother's and father's deaths: "Why didn't they find a medicine to cure themselves?"

Dan then set out on a cross-Vietnam journey with a single goal: to find a cure for opium addiction. He collected more than 100 herbal potions that villagers substituted for opium when their poppy crops failed and their supplies dwindled. Eventually, he decided on a drastic step: to addict himself to opium and experiment on himself. "I knew from my brother how dangerous this could be," he says, "but I decided this was the only way."

He moved from village to village, smoking opium with tribal chieftains, then returned home and began boiling pots of water and herbs in his kitchen. He tried one herb combination after another, going cold turkey while seeking a remedy. His withdrawal symptoms were "like torture," he recalls, and time after time he went back to his opium pipe for relief.

After six months of self-experimentation, Dan says he finally found a concoction that enabled him to kick his habit, but to test it further he became addicted to heroin--and found his brew cured him of that as well. It was a muddy-brown syrup, later named Heantos, made from the leaves, roots and stems of 13 plants and a splash of alcohol. After he announced his breakthrough in 1989, Dan was immediately besieged by addicts. Since then, he says, some 4,000 patients have been treated, and most of them have been cured.

Now the U.N. is funding a study of Heantos' effectiveness , which will be overseen by the Johns Hopkins medical center. The brew will be analyzed at U.S. labs, and patients using it in Vietnam will be closely monitored. If Dan's elixir is proved effective, it may one day help the world's heroin addicts kick their deadly habit.

--Reported by Tim Larimer/Hanoi

With reporting by NICOLE NOLAN/TORONTO; DICK THOMPSON/WASHINGTON; JOANNA DOWNER/WASHINGTON; TIM LARIMER/HANOI; SABRINA YOHANNES/NEW YORK