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A triumph for scientific freedom
This week’s Nobel Prize winners in medicine—Australians Barry J. Marshall and J. Robin Warren— toppled the conventional wisdom in more ways than one. They proved that most ulcers were caused by a lowly bacterium, which was an outrageous idea at the time. But they also showed that if science is to advance, scientists need the freedom and the funding to let their imaginations roam.
Let’s start with the Nobel pair’s gut instincts. In the late 1970s, the accepted medical theory was that ulcers were caused by stress, smoking, and alcohol. But when pathologist Warren cranked up his microscope to a higher-than-usual magnification, he was surprised to find S-shaped bacteria in specimens taken from patients with gastritis. By 1982, Marshall, only 30 years old and still in training at Australia’s Royal Perth Hospital, and Warren, the more seasoned physician to whom he was assigned, were convinced that the bacteria were living brazenly in a sterile, acidic zone—the stomach—that medical texts had declared uninhabitable.
Marshall and Warren’s attempts to culture the bacteria repeatedly failed. But then they caught a lucky breaker rather, outbreak. Drug-resistant staph was sweeping through the hospital. Preoccupied with the infections, lab techs left Marshall’s and Warren’s petri dishes to languish in a dark, humid incubator over the long Easter holiday. Those five days were enough time to grow a crop of strange, translucent microbes.
Marshall later demonstrated that ulcer-afflicted patients harbored the same strain of bacteria. In 1983, he began successfully treating these sufferers with antibiotics and bismuth (the active ingredient in Pepto-Bismol). That same year, at an infectious disease conference in Belgium, a questioner in the audience asked Marshall if he thought bacteria caused at least some stomach ulcers. Marshall shot back that he believed bacteria caused all stomach ulcers.
Those were fighting words. The young physician from Perth was telling the field’s academically pedigreed experts that they had it all wrong. "It was impossible to displace the dogma," Marshall explained to me in a jaunty, wide-ranging conversation several years ago. "Their agenda was to shut me up and get me out of gastroenterology and into general practice in the outback."
At first, Marshall couldn’t produce the crowning scientific proof of his claim: inducing ulcers in animals by feeding them the bacterium. So in 1984, as he later reported in the Medical Journal of Australia. "a 32-year-old man, a light smoker and social drinker who had no known gastrointestinal disease or family history of peptic ulceration"—a superb test subject, in other words—" swallowed the growth from’ a flourishing three-day culture of the isolate."
The volunteer was Marshall himself, Five days later, and for seven mornings in a row, he experienced the classic and unpretty symptoms of severe gastritis.
Helicobacter pylori have since been blamed not only for the seething inflammation ,of ulcers but also for virtually all stomach cancer. Marshall’s antibiotic treatment has replaced surgery as standard care. And the wise guy booed off the stage at scientific meetings has just won the Nobel Prize.
What does all this have to do with scientific freedom Today, US government funding favors "hypothesis-driven" rather than "hypothesis-generating" research. In the former, a scientist starts with a safe supposition and conducts the experiment to prove or disprove the idea. "If you want to get research funding; you better make sure that you’ve got the experiment half done," Marshall told me. "You have to prove it works before they’ll fund you to test it out."
By contrast, in hypothesis-generating research, the scientist inches forward by hunch, gathering clues and speculating on their meaning. The payoff is never clear. With today’s crimped science budgets and intense competition for grants, such risky research rarely gets funded. Proceeding on intuition, Mar- shall told me, "is a luxury that not many researchers have."
It helps, he added, to be an outsider. "The people who have got a stake in the old technology arc never the ones to embrace the new technology. It’s always someone a bit on the periphery--who hasn’t got anything to gain by the status quo—who is interested in changing it." In hypothesis-driven research, the scientist inches forward by hunch, gathering clues and speculating on their meaning.