Biography: Barry Marshall
Nobel Prize in Medicine

Barry James Marshall was born in Kalgoorlie, a mining town in the interior of Western Australia. His father was a welder, his mother a nurse. When he was eight years old, the family moved to the outskirts of Perth, the large coastal city that is the capital of Western Australia. The oldest child in the family, he was an irrepressibly curious boy, fascinated by the natural world and all things mechanical. Marshall excelled in school and won a scholarship to study at the University of Western Australia (UWA), where he completed medical studies in 1974. He interned in general medicine at the Queen Elizabeth II Medical Center in Perth, and carried out his residency at Royal Perth Hospital, where he explored a number of specialties, including gastroenterology.

As a resident physician, Marshall saw a great many patients with bleeding stomach ulcers. A staff pathologist at the hospital, Dr. J. Robin Warren, had found mysterious bacteria in the stomachs of many of these patients, near the site of their ulcers. He had found the same organism in patients with chronic inflammation of the stomach lining (gastritis), but could not find it in patients who lacked these symptoms. Warren's observations were anomalous for a number of reasons. Generations of medical scholars had taught that stomach ulcers were caused by an excess of stomach acid generated by stress and dietary factors. It was also believed that bacteria could not survive for any length of time in the acid environment of the human stomach.

Fascinated by the novelty of this mysterious spiral-shaped organism, eventually named Helicobacter pylori, Marshall decided to specialize in gastroenterology, with the specific intent of studying these bacteria, and pursuing the possibility that they were in fact causing the stomach ulcers in his patients. Taking advantage of the body of literature becoming available through the computer networks that were the precursors of the Internet, he found references to this bacteria dating back nearly a century. It was now possible for the first time to compare these unrelated observations and compile a body of data implying a clear correlation between the presence of helicobacter and the occurrence of both gastritis and peptic ulcers. Marshall also found instances of ulcer patients experiencing temporary relief from treatment with the chemical element bismuth, the active ingredient in over-the-counter remedies such as Pepto-Bismol. After initial setbacks, Marshall succeeded in growing helicobacter in the laboratory in 1982, and determined that bismuth could destroy the bacteria in the petri dish. Warren and Marshall published their findings jointly in the British medical journal The Lancet, but their article received little attention. Over the next two years, Marshall's clinical trials of bismuth with human patients enjoyed initial success, but the patients' symptoms invariably returned.

In September 1983, Marshall presented his findings at an international conference in Brussels, Belgium, but his unrestrained enthusiasm, combined with his youthful appearance and informal manner, apparently fed the skepticism of his audience. Marshall's critics contended that the presence of helicobacter in the stomachs of patients with gastric diseases was coincidental, and that the bacteria were probably harmless.

Practitioners of gastroenterology and the pharmaceutical industry were both heavily invested in the theory that peptic ulcers were caused by emotional stress and stomach acids, and could only be treated with repeated courses of antacid medication. While the reduction of stomach acid often alleviated the existing ulcer, inflammation of the stomach lining usually persisted, and most patients found themselves returning in a year or two with another ulcer. Patients were routinely advised to seek psychiatric counseling, find less demanding employment or make other drastic lifestyle changes to address the purported cause of their disease. Volumes were published detailing the alleged psychological causes of gastric ailments, and ulcers remained a frequently cited example of psychosomatic illness.

In this environment, the possibility that the ailment was directly caused by a single microorganism that could be completely eliminated with a two-week course of antibiotics was a threat to the status quo. While many of Marshall's critics had serious scientific questions about his hypothesis, others may have had economic motives in disputing his findings, and Marshall was not shy about saying so. The targets of his criticism soon sought to discredit him and his research. One prominent gastroenterologist dismissed him as "a crazy guy saying crazy things."

Marshall persevered, methodically testing his hypothesis with laboratory animals, but could not cultivate the bacteria in either rats or pigs. By 1984, he had experienced considerable success in treating human ulcer patients with the combination of bismuth and antibiotics, but he had not proved that introducing the helicobacter into a human subject would, in fact, cause gastric illness.

Lacking other human subjects, Marshall resolved to try the experiment on himself. To the horror of his assistant, he ingested a turbid, foul-tasting solution of Helicobacter pylori. After a week, he began to display a number of symptoms, vomiting copious amounts of clear liquid, and appearing increasingly drawn and fatigued. On examination by endoscopy, it was found that the lining of his stomach, previously normal, had become seriously inflamed. Marshall's symptoms soon abated, but he had demonstrated that the bacteria could cause illness in humans. Although he was rebuffed by the Australian medical establishment, interest in his work was spreading. When he was invited to attend a medical conference in Dallas, Texas in 1985, he repeated his assertions of the bacterial cause of gastric illness and challenged the audience of medical scientists to prove him wrong. Before long, experiments in the United States and elsewhere, many designed to refute his hypothesis, were in fact confirming it.

In 1986, Marshall was invited to the United States to serve as a Research Fellow and Professor of Medicine at the University of Virginia. He taught and carried out his research in Virginia for over a decade, establishing the International Research Foundation for Helicobacter and Intestinal Immunology in Charlottesville, Virginia.

By 1994, Marshall's theory of the bacterial cause of peptic ulcers had been largely accepted by the international scientific community and Marshall's work was showered with honors, beginning with the prestigious Warren Alpert Prize. After receiving the Australian Medical Association Award, along with his old colleague, Dr. Warren, Barry Marshall received the most coveted honor in American medicine, the Albert Lasker Clinical Medical Research Award. In the words of the Lasker jury, "Rarely do the discoveries of a single individual change the lives of countless millions within the span of a decade. The revolutionary research of Barry J. Marshall into the causes and treatment of peptic ulcer disease has accomplished just that, and in so doing he has dispelled the darkness surrounding a painful chronic disease and lighted the pathway to a cure." The citation added, "With brilliant insight, personal courage and boundless conviction, Dr. Marshall altered the world's view of peptic ulcer disease."

In 1996, Marshall was named Professor of Research in Internal Medicine at Virginia, and the United States Food and Drug Administration officially approved a course of treatment for peptic ulcer disease consistent with Marshall's findings. The following year, he returned to Australia, accepting an appointment as Clinical Professor of Medicine at the University of Western Australia. In 1999, he was given the added position of Clinical Professor of Microbiology.

Marshall's views had now gained acceptance around the world. In rapid succession, he received Canada's Gairdner International Award, Germany's Paul Ehrlich Prize, the Netherlands' Heineken Prize, Australia's Florey Medal, the Buchanan Medal of Britain's Royal Society, the Benjamin Franklin Medal for Life Sciences and Japan's Keio Medical Science Prize.

For over a decade, Marshall had been mentioned as a contender for the Nobel Prize in Physiology or Medicine. Almost every autumn, around the time of the Nobel announcements, Marshall and his old friend Dr. Warren would meet for a beer at a favorite pub in Perth and joke about winning the Nobel Prize. At the time of his interview with the Academy of Achievement in 1998, Dr. Marshall was already dismissing the possibility of adding the Nobel medal to his honors as a chance that had passed him by, but in the Autumn of 2005 he received word that he and Dr. Warren would indeed share that year's Prize. In the words of the Nobel Committee, they were honored "for their discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease." The Committee added, "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." Barry Marshall accepted this crowning honor with characteristic good humor. As much as his pioneering studies of Helicobacter pylori, he sees his work as an educator of young medical scientists as being among his most important achievements.

Today, Barry Marshall is the National Health Medical Research Council (NHMRC) Senior Principal Research Fellow at the University of Western Australia. In recent years, his research has illuminated the patterns of helicobacter infection in different populations around the world. In more developed countries, with adequate supplies of clean drinking water, the rate of infection is declining, but it persists in less developed countries, and among recent immigrants from those countries. It is probably the most widespread chronic infection in the world, and is nearly universal in the world's poorest countries. Thanks to Dr. Marshall's work, helicobacter is now recognized as a major factor in the development of stomach cancer. Once the most common of cancers, stomach cancer has declined precipitously in the developed world, while remaining prevalent everywhere else. Dr. Marshall hopes to see the insidious corkscrew organism controlled to the point where it can no longer pose a threat to the life and health of men, women and children anywhere in the world. His discoveries have already freed millions from unnecessary suffering.