"STAMP OF APPROVAL"
Australian duo's stunning and controversial discovery that H. pylori causes stomach ulcers earns for them the Nobel Prize for Medicine 20 years after
STOCKHOLM
Two Australians won this year's Nobel Prize for Medicine for pioneering research on stomach ulcers, overturning conventional wisdom to prove they are caused by bacteria and best treated with antibiotics.
Barry J. Marshall and J. Robin Warren "made the remarkable and unexpected discovery" in 1982 that gastritis and peptic-ulcer disease are the result of an infection caused by the Helicobacter pylori bacterium, the Nobel jury said.
They faced an uphill struggle to prove the theory to a doubting world, but determined to prove their case, Marshall in 1985 went so far as to swallow a solution containing the bug and became dreadfully ill.
He thus made his point to a skeptical medical community that had believed bacteria could not survive in the acidic environment of the stomach, instead blaming ulcers on a weak lining, spicy food, and stress.
The two men, who no longer work together, were sitting down to an annual dinner together in Perth when Warren received the Nobel Committee's call on his cell phone.
"I'm amazed and a bit shocked to tell you the truth after all these years," Warren told Australian Associated Press. "For me the main thing is that it finally puts the seal of approval on my work and people can't argue about it any more," he said.
Marshall said his decision to swallow the bacteria was a natural choice.
"Any new discovery is going to be controversial and initially most people won't believe it because you are going to be knocking over some kind of dogma, and that's where we were," he recalled.
Now curable
"Thanks to the pioneering discovery by Marshall and Warren, peptic-ulcer disease is no longer a chronic, frequently disabling condition, but a disease that can be cured by a short regimen of antibiotics and acid-secretion inhibitors," the jury said.
Before the discovery of the bacterium in 1982, stress and lifestyle were considered the major causes of ulcers. But it has now been firmly established that H. pylori causes more than 90 percent of duodenal ulcers and up to 80 percent of gastric ulcers.
In a tribute, Lord May of Oxford, president of Britain's Royal Society, said: "The work by Barry Marshall and Robin Warren produced one of the most radical and important changes in the last 50 years in the perception of a medical condition."
Marshall's deliberate self-infection was an "extraordinary act [that] demonstrated outstanding dedication and commitment to his research."
Francis Megraud, bacteriology professor at Bordeaux University, said "this is one of the greatest discoveries of the past century. There are not many medical discoveries with this kind of impact on people's lives."
In rich countries, infection with the bacterium is less common than in the developing world "where virtually everyone may be infected," the Nobel citation said. The infection is typically contracted in early childhood, frequently by transmission from mother to child, and the bacteria may remain in the stomach for the rest of the person's life. In severe cases, bleeding and perforation may occur, or even stomach cancer, which is the world's number-two killer among cancers.
"Stamp of approval"
The two are the first Australians to win a Nobel Medicine Prize since 1996, when Peter C. Doherty won with Rolf M. Zinkernagel of Switzerland for their discovery of how the immune system recognizes virus-infected cells.
"For me it means they're putting the official stamp of approval on all the work that I did. All the trouble I had and all the disbelief--no one believed what I said, even though I could show them," said Warren, now a retired pathologist. "I had thought by now that we never would get it because I don't think bacteria in the stomach have got the same sort of romance as the double-helix of DNA or that type of thing. But when they rang me from Stockholm suddenly the blood ran down from my head. I could feel it!"
Contrary to popular medical opinion that stress causes ulcers, both men believed the spiral bacterium H. pylori was the real culprit after Warren noticed the bacteria in stomach biopsies while working as a pathologist at Western Australia's Royal Perth Hospital.
But mainstream medical opinion refused to believe bacteria played a role in ulcers and gastritis so Marshall eventually drank a solution containing the bacteria in an attempt to validate their work.
"I didn't think about it very much. Probably I wouldn't have done it if I really thought it through," Marshall said. "In 1984 I presented some of our early findings about gastritis and this link with the bacteria and nobody believed me. It was like I was talking a foreign language. I had been trying to infect some pigs with this bacteria and getting nowhere so I thought: Well, the proof is going to be if we can infect a human and develop this gastritis or inflammation of the stomach."
Within three days Marshall became sick and an endoscopy revealed he had inflammation in his stomach.
"It really threw down the gauntlet to all the skeptics at that point. We had the data and they had to prove us wrong," he said.
But even that evidence had to be tempered, with both men at first fearing further ridicule if the scientific community learned what they had done.
"We didn't publish this stuff straight away--at the time everyone thought we were a little bit crazy because the whole thing was so way out in terms of normal medical teaching in those days," said Warren.
Both men were awarded honorary doctorates by the University of Western Australia in 1997 in recognition of their work.
Marshall now runs a molecular biology laboratory in Perth, and still studies H. pylori.
Warren, who has retired, apart from some part-time teaching, had some advice for aspiring researchers: "If anyone finds a reason why there's something wrong with a sacred cow what they should do is find some really good proof that there is something wrong with it and then publish it and make sure they know what they're talking about first."
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