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Medical Nobel awarded for ulcers

October 3, 2005 By Alison Abbott This article courtesy of Nature News.

Discoverers of Helicobacter pylori earn medicine's highest honour.

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Australian scientists Barry Marshall and Robin Warren have won this year's Nobel Prize in Physiology or Medicine for proving that stomach ulcers are caused by the bacterium Helicobacter pylori. Despite initial resistance from fellow members of the medical community, their discovery has revolutionized the treatment of ulcers.

Plain-speaking Barry Marshall has been a hero for years in his native Perth, in Western Australia. But in the years after his 1982 discovery he was dismissed as a young upstart, pushing a hypothesis that lacked credibility.

It was really hard for people to accept that the disease could be a simple infection.
Francis Mégraud
University of Bordeaux, France
At the time, ulcers were treated with drugs to curb acid secretion in the stomach. The drugs worked well, and acidity was thought to be central to the condition - patients had previously been advised to drink milk and take antacids. But Warren, the more retiring of the duo, had noticed the presence of spiral-shaped bacteria in biopsy samples from ulcered stomachs, and saw that they were always accompanied by signs of inflammation.

Warren recruited the young medical intern Marshall to work with him at the Royal Perth Hospital, in an attempt to isolate and culture the bacteria. The bacteria looked like Campylobacter, a newly discovered family known to cause gut infection in poultry. Marshall's repeated attempts to culture it early in 1982 failed, however - until the Easter holidays, when the culture plates were accidentally left in the incubator over a four-day break. This did the trick.

The problem, it turned out, was that H. pylori grows exceptionally slowly, and earlier attempts had simply been abandoned too early. The bacteria was then shown not to be Campylobacter at all, but an entirely new genus.

Marshall and Warren went on to show that patients with ulcers could be successfully treated with antibiotics. And unlike patients treated with acid-suppressing drugs, their ulcers did not return.

Early resistance

Fellow gastroenterologists nevertheless continued to resist the idea. Francis Mégraud, a bacteriologist at the University of Bordeaux II in France, remembers attending the 1988 Pan American Congress of Gastroenterology and hearing physicians on the bus discussing the idea in tones of outrage. "They seemed insulted, saying, 'We are being asked to treat stomach ulcers with antibiotics, as if it were gonorrhoea!'," he recalls. "It was really hard for them to accept that the disease could be a simple infection."

Drug companies profiting from the lucrative anti-ulcer drug market also resisted the idea, says Mégraud, who is also secretary of the European Helicobacter pylori Study Group. Even some bacteriologists were at first suspicious - the highly acidic stomach seemed too hostile an environment to host bugs.

In frustration, Marshall even undertook the ultimate cause-and-effect experiment. He swallowed a solution containing the bacteria, and a week later suffered an aggressive attack of the kind of gastritis that leads to ulcer.

Final success

Marshall's untiring advocacy and further research with Warren in Perth, which was repeated and extended around the world, eventually won the day. In 1991 a meeting at the Centers for Disease Control and Prevention in Atlanta, Georgia, declared formally the link between H. pylori and gastric disease.

It is now well accepted that as many as 75% of all gastric ulcers are caused by H. pylori, which can be eliminated permanently by a cocktail of antibiotics. The infection is usually acquired in childhood, when the bacterium is transferred between family members via faeces or vomit, but then lies dormant until adulthood. It is also now recognized that untreated cases can lead to gastric cancer.

Marshall and Warren will share the 10-million-kronor (US$1.3-million) prize, which will be presented at a ceremony in Stockholm, Sweden, on 10 December.

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