On 9th Nov 2016, Nanyang Technological University’s Lee Kong Chian School of Medicine had the honour of hosting a lecture by Nobel Laureate Dr Barry J. Marshall, Professor of Clinical Microbiology at University of Western Australia. Titled “Man vs Helicobacter: The past 50,000 years & The next 50”, Dr Marshall shared his experiences about his studies on Helicobacter Pylori, a bacteria known for causing gastrointestinal ulcers, and how it transformed the medical landscape of gastroenterology.
In the 1970s, many Australians suffered from gastric pains that responded poorly to conventional medicine, eventually developing peptic ulcers which run the fatality of internal bleeding. While physicians were baffled by this mysterious disease, they continued to believe that nothing could survive the harsh acidic conditions of the stomach. Therefore, patients would still receive blanket diagnoses that blamed stress as the main culprit.
Dr Marshall affirmed that the ulcers are caused by harmful microorganisms, but there was little evidence to prove his claim then. The mystery started to unravel in 1979, when Dr Marshall learned of Dr Robin Warren’s discovery of an unknown spiral-shaped bacteria living within ulcer biopsies. Together, the duo begun studying this mysterious strain (later known as H. pylori).
However, attempts to cultivate Helicobacter in a laboratory were unsuccessful. The failing streak ended when some bacterial samples were left over the long Easter weekend, and as if riding on Alexander Fleming’s luck, the world’s first successful lab cultivation of H. pylori happened by accident in 1982.
Despite having concrete evidence, Marshall and Warren failed to address Koch’s Postulates, the 4 infallible criteria for explaining the relationship between disease and pathogen. (See infograph below) As such, their claims of Helicobacter causing gastric ulcers were readily dismissed by the scientific community.
The Gastroenterological Society of Australia also rejected their research papers for presentation, of which 56 papers were accepted out of 67 submissions. While Dr Marshall continued to believe in the legitimacy of his discovery, his reputation was already hurt from the devastating blow. Following these incidents, Dr Marshall became increasingly sceptical of prevalent scientific dogmas, which he lamented as “the illusion of knowledge” which restricted the progress of potentially ground-breaking research.
To fulfil all 4 Koch’s Postulates, it was necessary to obtain data from suitable animal models. Since Helicobacter targets primates as their susceptible hosts, Marshall and Warren repeatedly failed to infect mice or piglets for antibiotic studies. With human trials being prohibited, Dr Marshall took the ultimate wager in 1984, when he experimented a bacterial cocktail on the only viable subject: himself. He threw up and suffered from severe stomach inflammation for about two weeks.
He recalled with a grimace, “I always feel bloated and I’m throwing up acid every night. My wife was terrified of me passing (it onto) the kids.”
Dr Marshall’s recovery from antibiotics was only the first piece of good news. With Koch’s Postulates fulfilled (at least for gastritis), his hard-earned findings were published in the New England Journal of Medicine, the world’s leading medical journal. Much research interest was generated in the US community, and Dr Marshall’s leap of faith was immortalised by the comic Ulcer Tales.
This was the turning point which laid the bedrock for future Helicobacter research in the following decades and won Marshall and Warren many accolades, including the coveted Nobel Prize in Physiology or Medicine (2005).
When presented with foreign situations, even experts could succumb to bias and fallacy. Like how facts remain true even if they are ignored, Dr Marshall’s lifelong devotion to H. pylori demonstrated a cardinal level of tenacity and integrity which we as learned individuals of science, should aspire to achieve through our works.