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Week of Oct. 8, 2005; Vol. 168, No. 15 , p. 229

Nobel prizes: The power of original thinking

Awards honor a gutsy move, optical brilliance, and chemical crossovers
Nathan Seppa, Peter Weiss, and Aimee Cunningham

Two Australian scientists who showed that bacteria can cause stomach ulcers have won the 2005 Nobel Prize for Physiology or Medicine.

The researchers made their discovery 23 years ago, at a time when ulcers were thought to result mainly from excess stomach acid brought on by stress and spicy food. In 1979, J. Robin Warren, a pathologist at the Royal Perth Hospital, noticed a curved bacterium in stomach-tissue samples from a patient. A few years later, a gastroenterologist at the hospital, Barry J. Marshall, cultured the microbe—ultimately named Helicobacter pylori. The two scientists then found H. pylori in nearly all patients with ulcers and also in most patients with gastritis, an inflammation of the stomach lining.


TOUGH CUSTOMER. Scientists had thought that no microbe could live in the acidic stomach, but Helicobacter pylori proved them wrong.
Nobel Committee for Physiology or Medicine

Despite the duo's string of confirming reports in the 1980s, the scientific community demurred for a decade before adopting the notion that a pathogen could cause stomach ulcers. Today, gastroenterologists estimate that H. pylori causes 80 to 90 percent of ulcers. Antibiotics plus acid-blocking drugs routinely cure the disease.

"The award is well deserved," says Martin J. Blaser, an infectious-disease physician at New York University School of Medicine. Over the past decade, treatment has made H. pylori "an endangered species in the stomach," he says.

However, Blaser recalls a 1983 scientific meeting in Brussels at which Marshall presented his early findings. "Marshall said they had discovered a new bacterium," says Blaser. "That data looked good." But when Marshall claimed that the microbe was the cause of stomach ulcers, "people were skeptical, because quack theories arise all the time," Blaser adds.

The following year, a frustrated Marshall took an extreme step: He swilled a vial of live H. pylori. Within a week, he developed raging gastritis. Treatment with an antibiotic and bismuth, which had shown some efficacy against ulcers, eradicated the microbe. But Marshall's stunt still didn't appease all his critics.

Finally, large-scale trials in the early 1990s established that antibiotics coupled with acid-blocking drugs or bismuth indeed knock out the microbe and cure ulcers.

Warren has since retired, and Marshall is now at the University of Western Australia in Nedlands. They will share the $1.3 million award.

The discovery of H. pylori "represents a paradigm shift" in the study of human diseases, says gastroenterologist Richard M. Peek Jr. of Vanderbilt University School of Medicine in Nashville. With their work, Peek says, Warren and Marshall showed that H. pylori infections can lead to dangerous inflammation. Other researchers have since linked inflammation of various origins to malignancies.

For example, they've tied chronic inflammation in the intestines to colon cancer and linked inflammatory infections by hepatitis B and C viruses to liver cancer. In some cases, H. pylori infection itself can predispose a person to stomach cancer, Peek notes.

H. pylori infects half the world's population, but only a fraction of those people get ulcers. Scientists are now examining genetic variations in people that might explain why only some are vulnerable to the microbe.

—N. Seppa


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