25 Years in Peptic Ulcers: From Chronic to Curable

In 1984, 33-year-old Barry Marshall, frustrated by responses to his work, ingested Helicobacter pylori, and soon developed stomach pain, nausea, and vomiting -- all signs of the gastritis he had intended to induce.

"I didn't actually expect to become as ill as I did," he wrote in an autobiography about one of the defining moments of his research, which ultimately led to winning the 2005 Nobel Prize with his now-retired colleague, Robin Warren.

The event followed the publication of two papers in The Lancet in 1983 and 1984. In those articles, Warren and Marshall, now at the University of Western Australia in Perth, described an association between a new bacterium that would eventually be named H. pylori and peptic ulcers, both duodenal and gastric.

Warren and Marshall had become convinced that the bacteria, successfully cultured after being left out inadvertently over a long holiday weekend, were causing the ulcers. But Marshall had met stiff resistance from gastroenterologists around the world when he broached the idea.

Conventional thinking at the time was that ulcers were caused by excess acid in the stomach and that no living organism could live in such an acidic environment. As it turns out, H. pylori produces ammonia to neutralize the area around it.

Dr. Walter Peterson, now a clinical professor at the University of Colorado Denver, was a member of the skeptical majority. He said Marshall called him and his colleagues the "Acid Mafia."

"Barry Marshall came across as a zealot, as opposed to a scientist," he told MedPage Today, describing Marshall as a good friend now.

Marshall wrote in his Nobel Prize autobiography, "I was met with constant criticism that my conclusions were premature and not well supported. When the work was presented, my results were disputed and disbelieved, not on the basis of science but because they simply could not be true."

But a conviction that he was right and a sense of urgency surrounding the importance of reducing the burden of ulcers -- which affected about 10 percent of Americans at some point in life -- led him to famously use himself as an animal model.

"If I was right, then treatment for ulcer disease would be revolutionized. It would be simple, cheap, and it would be a cure," he wrote, using a word often considered taboo when discussing medical research.

After fighting through years of ridicule, Marshall's overzealousness paid off.

"We were wrong, he was right," Peterson said. "And so I couldn't agree more that he got the Nobel Prize."

It's now well established that H. pylori is a major cause of peptic ulcers, with use of non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin, indomethacin, and the non-selective COX inhibitors footing some of the blame.

"Nowadays, we know that most ulcers are caused by disruption in mucosal defense and not by excess acid," Peterson said.

Warren and Marshall's discovery revolutionized the management of peptic ulcer disease, which had been a chronic condition requiring continuous use of medications believed to be induced by poor diet and stress.

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