"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."
