The Scientist

Barry J. Marshall and J. Robin Warren, two Australian researchers who discovered the bacterium Helicobacter pylori and elucidated its role in gastritis and peptic ulcer disease, have been awarded this year's Nobel Prize in Physiology or Medicine.

The Nobel Assembly at the Karolinska Institute said today (October 3) that the pair had been recognized for their "remarkable and unexpected discovery" which showed that gastric inflammation, and ulceration of the stomach or duodenum, was the result of infection with the bacterium.

Warren, a pathologist from Perth, first observed small curved bacteria in the antrum in 1979. He saw the organisms in about 50% of patients from whom biopsies had been taken, and made what the Nobel Assembly said was a crucial observation--that signs of inflammation were always present in the gastric mucosa close to where the bacteria were seen.

"Don't ask me why nobody saw them before," Warren told The Scientist today. "My feeling is that nobody thought they were there. Standard medical teaching at the time was that there were no bacteria in the gut."

Marshall, then a clinical fellow, joined Warren in a study of biopsies from 100 patients and, after several attempts, managed to cultivate the species—subsequently dubbed Helicobacter pylori.

"This was a paradigm-shifting discovery," said Adrian Lee, an H. pylori researcher and now Pro-Vice Chancellor (Education) at the University of New South Wales, Australia. "I gave a lecture just a week ago, using it as an example of the importance of always keeping an open mind if medical science is to progress. So often, one is taught dogma."

At the time of their discovery, it was widely believed that stress and lifestyle were the major causes of peptic ulcer disease. Warren and Marshall overturned that dogma, and it is now clear that H. pylori, a flagellated, gram negative, spiral organism, causes more than 90% of duodenal ulcers and up to 80% of gastric ulcers.

Their findings, however, were met with skepticism by the clinical community and "it took a remarkable length of time for their discovery to become mainstream," Lee told The Scientist.

"They thought we were mad," said Warren. "It was against all the medical teaching, but we had the evidence. We just had to keep pushing it and pushing it."

In 1985, for example, Marshall underwent gastric biopsy to prove he didn't carry the bacterium, then deliberately infected himself to show that it caused acute gastric illness. In a paper published in the Medical Journal of Australia he described developing a mild illness over a course of 14 days, which included histologically proven gastritis.

"This extraordinary act demonstrated outstanding dedication and commitment to his research," said Robert May, president of Britain's Royal Society. In a statement, May said Marshall and Warren's work "produced one of the most radical and important changes in the last 50 years in the perception of a medical condition."

However, "it wasn't until 1991…that it was really accepted by all gastroenterologists worldwide," noted Leif Percival Andersen, president of the European Helicobacter Study Group, from Copenhagen University Hospital, Denmark.

Warren and Marshall's discovery paved the way for peptic ulcers to be cured by eradication of the bacterium with a combination of antibiotics and acid secretion inhibitors. As a result, "peptic ulcer disease is no longer a chronic, frequently disabling condition," the Nobel Assembly said.

"In a country like Denmark, for example, peptic ulcer disease is now really a rare disease," Andersen told The Scientist. That effect can be directly attributed to Marshall and Warren's discovery, he said.

Subsequent studies have shown that H. pylori colonizes the stomach in about 50% of all humans, causing disease in about 10-15% of infected individuals. Severe complications include bleeding and perforation and, in some people, H.pylori infection of the corpus region of the stomach can predispose to stomach cancer.