'It was undercutting the basis of gastroenterology...'

Barry Marshall's self-experiment.

Posted by Karen Myers, Curator, on October 31, 2024

Forty years ago, Barry Marshall, FRACP, conducted a famous self-experiment by ingesting a culture of Helicobacter pylori, putting himself on a track to eventually win the Nobel Prize in Physiology or Medicine. The Prize was awarded in 2005 to Marshall and J. Robin Warren, some twenty odd years after they published their initial research in The Lancet and Medical Journal of Australia on the discovery of the link between the bacterium helicobacter pylori and its role in gastritis and peptic ulcer disease.

As is often the case, the discovery of the link involved an element of luck. In the early eighties, Marshall was a young internal medicine trainee who began collaborating with the pathologist Warren, as part of his College-prescribed research project. He had little research experience but brought a curious mind, free of preconceived ideas of what he was about to study:

"At the time, Barry was a registrar on the Royal Australasian College of Physicians training program, which expects its trainees to undertake a small research project and write a paper each year...and Barry had just arrived in the gastroenterology department...they suggested he go and see 'that pathologist who is trying to make gastritis into a bacterial infection'. I, on the other hand, had been missing a link in the story: how my histological and bacteriological findings related to patients".

-- J. Robin Warren

Their journey to the Nobel Prize provides a compelling reason to study the history of medicine and to question what has come before, rather than blindly following the accepted dogma. As with most researchers, it was a long road for Marshall and Warren to have their work recognised and accepted, as it was challenging the long-held belief that stress and diet were the primary causes of gastritis and peptic ulcers.

"In October 1982, I presented the preliminary findings from our study to the local College of Physicians meeting, where it received patronising and mostly negative response".

-- Barry Marshall

An abstract written for the Gastroenterological Society of Australia (GSA) meeting in Perth, 1983, was similarly rejected. However, submissions to The Lancet, published in June 1983 and 1984, garnered some interest, and the Society accepted the abstract in 1984. Nevertheless, there was still more to be done to progress the research:

"In 1983, there was still no collaborative evidence that spiral bacteria were causing either gastritis or peptic alteration, except the association we had seen. Clearly there were two pieces of evidence we needed to obtain. The first of these was to produce the infection in an animal (i.e. fulfil Koch's postulate that bacteria could cause gastritis and peptic ulcer) and secondly, we needed to show that eradication of the organism in the individual led to healing of the gastritis and the associated PUD..."

Thus, Warren undertook the self-experiment and became ill within a week of ingesting the H. pylori broth, providing compelling, if anecdotal, evidence of the bacterium's role in gastritis. The Medical Journal of Australia published the article describing the experiment in 1985 (which has become one of its most cited papers). In 1986, Marshall left Australia to work at the University of Virginia, where he discovered it wasn't just Australian doctors who were sceptical about the research:

"Expecting to find a receptive audience in the USA...I was disappointed. It was to be another eight years before the bacteria was finally accepted there, following the consensus conference held by the National Institute of Health in 1994".

It would be another eleven years before the Nobel Prize was awarded to Marshall and Warren, who joined five other Australian-born Nobel Laureates in Physiology or Medicine: Howard Florey, Hon. FRACP, for his discovery of penicillin (1945), Frank MacFarlane Burnet, FRACP, for immunology (1960), John Carew Eccles, FRACP, for neurophysiology (1963), Peter Doherty, Hon. FRACP, for immunology (1996) and Elizabeth Helen Blackburn (2009).

Robin Warren died on 23rd of July 2024, at the age of 87.

(Blockquotes are taken from Helicobacter pioneers : firsthand accounts from the scientists who discovered helicobacters 1892-1982, edited by Barry Marshall.)