The 2005 Nobel Prize in Physiology or Medicine

Being, seeing and thinking

As part of the physician training program in the 1980s at Royal Perth Hospital in Western Australia, registrars were encouraged to pursue a research project. In 1981, Marshall found himself in such a position as he commenced a rotation in the hospital’s gastroentero-logy service. His boss, Dr Tom Waters, suggested that he talk to Dr Robin Warren, a pathologist at the hospital, about the mucosal spiral bacteria Warren had observed microscopically in some gastric biopsies. Marshall was intrigued and, on reviewing the endoscopic and clinical details of 25 patients exhibiting these mysterious bacteria, found that they were associated with endoscopic diagnoses of duodenal ulcer (n = 2), gastric ulcer (n = 7), gastritis (n = 12), and erosions and scars (n = 4). But there was no consistent clinical pattern. A literature review revealed that these mucosal organisms had been noted intermittently for at least a hundred years, but there were no clear patholo-gical or clinical patterns.3,4 Marshall and Warren decided to explore the significance of the spiral bacteria by gathering more clinical material and by attempting to culture the organism from gastric mucosa obtained at endoscopy.

Marshall and Warren were at the right place: members of the Royal Perth Hospital gastroenterology service were prepared to provide such specimens and members of the hospital’s microbiology department were willing to freely provide people and resources for the culture quest. It also was the right time. Apart from the happy meeting of an enthusiastic registrar unencumbered by dogma and a more senior person who had an observation waiting to be explored, flexible endoscopy had become a widely used clinical procedure and provided the means to obtain fresh specimens for research. The presence of mucosal gram-negative bacteria (initially thought to be a Campylobacter-like organism3) was soon confirmed, but all attempts at their culture were unsuccessful. On taking stock, in late 1981, Marshall discussed his progress with two senior members of the Royal Perth Hospital gastroenterology service, Tom Waters and Chris Sanderson. The latter, in true Australian (laconic) style, advised: “Barry, you should stop buggerising around and do a proper study!”3

And so, a prospective study of 100 patients, with the investigators blinded, was born, and the next characteristic of revolutionary research satisfied: thinking and addressing what other people presumably had not thought about. Marshall believes his relative inexperience helped him think in an original way about the bugs in the biopsies. “If the dogma is incorrect, it’s better to know nothing about it.” (Marshall, personal communication, October 2005.)

The 100-patient study aimed to pursue the following questions:

• is the organism present in the normal stomach?

• can it be cultured?

• can its presence be correlated with the type and severity of abnormal gastric histology?

• how is it related to patients’ symptoms and disease status?

Marshall and Warren may not have known it, but their journey to Stockholm had begun.