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What Barry Marshall Knew In His Gut


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WHAT BARRY MARSHALL KNEW IN HIS GUT

It took a decade, but Dr. Barry J. Marshall has launched a medical revolution. As an obscure Australian doctor, Marshall startled his profession in 1983 by contending that ulcers and other stomach ills were caused not by stress but by a mysterious, spiral-shaped bacterium. "The idea was considered completely crazy," says David Alpers, chief of gastroenterology at Washington University in St. Louis--in part because Marshall and his colleague J. Robin Warren, a pathologist at Australia's Royal Perth Hospital, could show only that people with ulcers harbored the bacteria, not that the germs actually caused disease. By June, 1984, Marshall was so desperate to prove his point that he acted as his own guinea pig: He swallowed a foul-tasting concoction containing the microbe and came down with a roaring case of stomach inflammation, or gastritis, the precursor to ulcers.

The experiment "certainly got people's attention," says Dr. Walter L. Peterson, a gastroenterologist at the University of Texas Southwestern Medical School in Dallas. It fed Marshall's reputation as a scientific rebel. And it helped stimulate new research that has recently accumulated overwhelming evidence for the link between bacteria and ulcers. New studies at Stanford and other universities also provide strong evidence that the germ, H. pylori, is a major factor in causing stomach cancer. Nowadays, "people who don't accept the idea that this bacterium causes disease are either stubborn or uninformed," says Dr. Martin J. Blaser, a professor of medicine at Vanderbilt University School of Medicine.

In fact, the latest results threaten to transform a lucrative corner of medicine, the $6 billion-a-year world market for ulcer drugs. In the U.S. alone, at least four million people buy such remedies, which reduce acid levels and let stomach and intestinal sores heal. Once treatment is stopped, as many as 80% of ulcers recur, forcing patients to keep taking medicine to control their ailment.

Now, however, thousands of doctors across the country--although still a minority--are starting to treat ulcers and gastritis with antibiotics instead of such traditional drugs as SmithKline Beecham's Tagamet. Eventually, "the maintenance market for ulcer drugs will disappear," Marshall predicts. Executives at pharmaceutical companies such as Britain's Glaxo Holdings and Sweden's Astra doubt that. But they're racing to augment their existing ulcer drugs with ones that kill the bacterium. Work on the germ is also helping scientists home in on the causes of stomach and intestinal diseases. One new theory is that infection with the microbe in childhood could prevent the stomach from developing normal adult levels of acid, increasing the risk of gastric cancer. When infection occurs later in life, some researchers believe, toxins and enzymes produced by the microbe increase the chances of gastritis and ulcers.

`I WAS A NOBODY.' Such theories are sweet vindication for Marshall, 40, who used to be widely criticized both for the evangelical fervor with which he pitched the bacterium-ulcer theory and for his counterattacks on skeptics. Gastroenterologist Nicholas J. Talley of the Mayo Clinic recalls that Marshall's sweeping assertions and combative style alienated the very experts he wanted to persuade. "He didn't need to claim that the bacteria caused every stomach and intestinal disease known to man," says Talley. "Many people were skeptical because of the way he presented it."

Marshall says he had little choice if he wanted to make sure his views were heard. "I was a nobody," he says. "If you have something out of the blue, you have to promote it a bit." Now professor of gastroenterology at the University of Virginia, he has toned down his broadsides. "He has mellowed," says the University of Texas' Peterson. "I guess that's the confidence that comes from being right."

Still, Marshall has not completely lost his touch for controversy. These days, the medical debate over ulcers centers on at what stage sufferers should be treated for the germ. Marshall advocates giving all patients a two- or three-week regimen of antibiotics and bismuth, a substance found in such over-the-counter products as Pepto-Bismol. This, he contends, is the best way to cure not only ulcers but also gastritis and many types of indigestion.

New research seems to back him up: Scientists at Baylor College of Medicine in Houston announced on May 1 that H. pylori disappeared in 55 of 62 ulcer patients treated with antibiotics and that they suffered no relapses for a year. By contrast, three-quarters of the 47 patients given just Zantac, Glaxo's drug, had relapses. On July 27, the National Institutes of Health held a meeting to discuss what further research was needed. Still, most stomach specialists don't use antibiotics for routine ulcers, since they have unpleasant side effects, such as diarrhea. While eradicating the microbe might be advisable in severe cases, declares Alpers, treating everyone this way is "overkill."

LUSH FAUNA. Drug companies insist that Marshall is wrong, but their research divisions don't act like it. Sweden's Astra has reported tantalizing if inconsistent results with a treatment combining its acid-reducing drug, Losec, with antibiotics. Glaxo is performing full-scale clinical trials with a drug made up of Zantac and bismuth. "We are continuing to look for new therapies," says Dr. Duane D. Webb, head of Glaxo's gastroenterology clinical research. Indeed, proprietary treatments to kill H. pylori could be a boon to SmithKline and Glaxo, since patents on their current ulcer drugs expire in 1994 and 2002, respectively. "The financial rewards for companies are great," says Talley.

Even if wiping out H. pylori becomes the standard treatment for ulcers, Marshall won't be entirely satisfied. Scientists have now shown that the microbe is amazingly widespread. Some 25% of all Americans harbor thriving colonies of it--and 50% will have it by age 50. The rates are even higher for people in developing countries. To many scientists, this suggests that, for most of the time, H. pylori is just another innocent member of the human gut's lush microbial fauna.

Marshall, however, has a more dramatic and worrisome theory. Fully half of those infected will come down with stomach or intestinal diseases, he predicts. If he's right, eradicating the germ in apparently healthy people would prevent millions of cases of ulcers, gastritis, and maybe even stomach cancer--the No. 2 cancer killer in the world.

To his critics, such a bold pronouncement is vintage Marshall: both premature and unscientific. "We need to wait before treating everybody," says the Mayo Clinic's Talley. "We don't know yet if only some people need treatment." Marshall counters that waiting for unequivocal proof doesn't help patients. What's important "is having people get better, not how scientific you are," he declares. Once again, he's ahead of the science. But he was right once, so no one's ready to count him out this time.John Carey in Charlottesville, Va.


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