Two Australian scientists won the Nobel Prize in Physiology or Medicine yesterday for discovering that a common bacterium -- not stress -- causes most ulcers.
The "remarkable and unexpected" 1982 discovery by J. Robin Warren and Barry J. Marshall, who infected himself to prove their theory, overthrew the existing scientific dogma and opened up a new area of research into whether infectious microbes cause a host of diseases, the Nobel Prize committee said.
"The discovery that one of the most common diseases of mankind, peptic ulcer disease, has a microbial cause has stimulated the search for microbes as possible cause of other chronic inflammatory conditions," wrote the committee, which cited the pair's "tenacity" in the face of deep skepticism.
Warren, 68, and Marshall, 54, learned of their honor while having a drink together in a pub in Perth as part of a tradition they started years ago to make light of whether they would ever win the prize.
"Robin and I often have a beer down by the riverside this time of year," said Marshall, now of the University of Western Australia in Nedlands. "But it's more of a joke. . . . We would always dream about winning the Nobel but never really thought [we would]."
"It's only just starting to sink in," added Warren, now retired, who will share the $1.3 million prize.
Warren was the catalyst for the pair's work. In 1979, while a pathologist at the Royal Perth Hospital in western Australia, he noticed small, curved bacteria in biopsies of the lower part of the stomachs of about half of the patients he examined.
The scientific establishment dismissed Warren's findings, but Marshall, a gastroenterologist, was intrigued. They joined forces three years later and began trying to grow and identify the organism. After many frustrating attempts, Marshall succeeded only when he inadvertently left slides unattended over the Easter holiday in 1982 and returned to find thriving colonies of the microbe, enabling him to identify it as a previously unknown spiral-shaped bacteria, subsequently dubbed Helicobacter pylori.
The pair went on to show that the organism was present in virtually all patients with ulcers and gastritis, an inflammation of the stomach that sets the stage for ulcers, leading them to propose that the infection was the cause. Their claim was met by deep skepticism, in part because no one thought bacteria could survive in the harsh, acidic environment in the digestive system.
"One of the standard teachings in medicine was nothing grew in the stomach," Warren said. "That was something that was being taught to students for 100 years."
The prevailing wisdom was that ulcers, which are painful, sometimes debilitating sores in the lining of the stomach and intestines, were caused primarily by lifestyle factors, such as spicy food, and emotions, particularly stress.
"It was thought at the time that stress and lifestyle were the causes of peptic ulcer disease," Staffan Normark, a member of the Nobel Assembly, said at a news conference at the Karolinska Institute in Stockholm.
Marshall finally decided to try to prove their case with a dramatic test -- he swallowed a mixture containing the bacterium. A week later, he became violently ill. Lab tests and biopsies showed that he had been infected by the organism and that he had developed gastritis.
"At the time there were no animals that were susceptible to this bacteria. So Barry Marshall instead drank a culture of Helicobacter pylori," Normark said. "He could in this experiment show the bacteria was causing gastritis in the stomach, as evidenced by an inflammation."
Marshall then ingested a combination of bismuth and antibiotics, which eradicated the infection and set the stage for a series of experiments demonstrating that antibiotics could treat gastritis.
The bacterium is now known to cause 80 to 90 percent of all ulcers, which can now be quickly cured in most cases.
"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 committee said.
Other experts agreed.
"This discovery has revolutionized our understanding of ulcer disease," said American Gastroenterological Association President David A. Peura. "Defining the role of H. pylori in the development of ulcers and stomach inflammation has not only allowed gastroenterologists to offer more effective treatments to patients, but it has also allowed for the development of more targeted, effective therapies."
Scientists have since deciphered how the bacteria causes disease and found that it can also increase the risk of stomach cancer, a major killer in many parts of the world.
"This cancer has decreased in incidence in many countries during the last half-century but still ranks as number two in the world in terms of cancer deaths," the Nobel committee wrote.
The discovery spurred interest in whether other microbes cause diseases that are due to chronic inflammation, such as Crohn's disease, ulcerative colitis, rheumatoid arthritis and heart disease.
"Even though no definite answers are at hand, recent data clearly suggest that a dysfunction in the recognition of microbial products by the human immune system can result in disease development," the committee wrote. "The discovery of Helicobacter pylori has led to an increased understanding of the connection between chronic infection, inflammation and cancer."
Elias A. Zerhouni, director of the National Institutes of Health, said: "I think this is a perfect example of how excellent science triumphed over conventional dogma. The prize affirms that we must keep true to our scientific principles of exploration, and continually question our assumptions."