For the longest time, it was widely believed that peptic ulcers and gastritis, which precedes stomach cancer, were attributed to poor lifestyle choices and stress. However, in 1982, two Australian researchers, Barry J. Marshall and Robin Warren, made a groundbreaking discovery by identifying the bacterium Helicobacter pylori as the root cause of gastritis. Here is the story of their discovery and why it took around 2 decades for their discovery to gain widespread acceptance.
In 1979, Dr. Robin Warren, a pathologist at the Royal Perth Hospital in Australia, observed curved spiral bacteria (later named as Helicobacter pylori) in biopsies from gastritis patients and suspected that these bacteria might be responsible for gastritis and stomach ulcers. Even though other medical professionals could see these bacteria under the microscope, they couldn’t accept them as the cause. The prevailing belief was that the stomach was a sterile environment where bacteria could not thrive in its acidic conditions. The medical community and pharmaceutical companies were convinced that the conditions resulted from excess acid due to poor lifestyle and stress. As a result, patients were either referred for surgery or advised to seek psychological treatment for stress. Dr. Warren, while interested in this study, was a pathologist and not a clinician, so he created a patient list and sought a clinician to monitor their diagnoses and progress.
Barry J. Marshall, a medical student at the time, after his graduation joined the Royal Perth Hospital to continue his training in internal medicine. In 1981, Marshall met Warren for his annual research project. Warren shared slides of identical bacteria he had found in the biopsies of ulcer and stomach cancer patients and asked Marshall to work on it. Marshall looked at the last 50 years of published literature to see if anything was documented about this bacteria before. He discovered that the bacterium had been previously identified and reported but had been dismissed as artifacts. In mid-1982, after completing paperwork, Marshall and Warren initiated a clinical trial involving 100 patients to isolate and culture the bacteria from the biopsies. While they found the bacterium in biopsies from nearly all the patients, they initially struggled to culture it. The conventional practice in the microbiology lab was to discard cultures if nothing grew within two days. However, due to the extended Easter holidays, the culture plates were left unattended for a few extra days, and upon return, the bacteria had finally grown. This highlighted the oversight of the lab’s standard practice, which did not account for the slow-growing nature of Helicobacter. The lab’s standard practice of discarding cultures after just two days had overlooked the slow-growing nature of H.pylori, the bacterium they sought. Extending the incubation period, now they could finally culture the bacteria.
In 1983, Marshall presented the connection between peptic ulcers and H. pylori at a meeting of the Royal College of Physicians in Perth, Australia, but his findings were met with skepticism. To gain acceptance, Marshall and Warren needed to develop solid experimental and clinical evidence. Despite their efforts, they could not create an animal model for H. pylori, prompting Marshall to take a daring step. In 1984, he conducted the first human trial on himself. He asked an endoscopist to perform a stomach biopsy, which showed no issues. He then ingested a mixture containing H. pylori and began experiencing symptoms. After ten days, he had another endoscopy, which revealed the presence of the bacterium and gastritis. Marshall then started taking antibiotics and made a full recovery. In 1985, they published their findings in The Medical Journal of Australia, but it remained a hypothesis for another decade. In 1985, Marshall could just cure almost everybody with gastritis or ulcers using antibiotics, but other gastroenterologists just wouldn’t do it..
Marshall eventually moved to the USA and continued his research while advocating for an accelerated acceptance of their findings to save lives affected by peptic ulcers. The National Institutes of Health (NIH) and the FDA eventually recognized the importance of their work and expedited the process. In 1994, the NIH declared that the key to treating gastric and duodenal ulcers was detecting and eradicating H. pylori. Marshall developed a simple breath test to detect the bacterium in the gut, and this test was later approved by the FDA.
In 2005, Barry J. Marshall and Robin Warren were awarded the Nobel Prize in Physiology and Medicine for their discovery of Helicobacter pylori and its role in gastritis and peptic ulcers. When Marshall was asked about his thinking on the process of getting people to accept his idea, he said – “We couldn’t knock down our own hypothesis. That’s the thing, be critical of your own data, and then go with the data. And once you’ve got a pathway, and you’re getting facts, then it doesn’t matter how many people there are out there who don’t believe you. Science is not a democracy.”
Today, extensive research by scientists worldwide has firmly established that H. pylori is responsible for more than 90% of duodenal ulcers and up to 80% of gastric ulcers. Individuals infected with H. pylori are six times more likely to develop stomach cancer compared to those without the infection. Their research has made H. pylori infection one of the most well-studied models of pathogen biology, leading to extensive basic and clinical research, with approximately 25,000 scientific publications to date. To facilitate the extensive response from the scientific and clinical communities, a dedicated journal called ‘Helicobacter’ was established.
Student of Life I Cancer Researcher