In 1979, Marshall was appointed Registrar in Medicine at the Royal Perth Hospital. He met Dr. Robin Warren, a pathologist interested in gastritis, during internal medicine fellowship training at Royal Perth Hospital in 1981. Together, they both studied the presence of spiral bacteria in association with gastritis. In 1982, they performed the initial culture of H. pylori and developed their hypothesis on the bacterial cause of peptic ulcers and gastric cancer.[9] It has been claimed that the H. pylori theory was ridiculed by established scientists and doctors, who did not believe that any bacteria could live in the acidic environment of the stomach. Marshall was quoted as saying in 1998 that "everyone was against me, but I knew I was right."[12] On the other hand, it has also been argued that medical researchers showed a proper degree of scientific scepticism until the H. pylori hypothesis could be supported by evidence.[13]
In 1982 Marshall and Warren obtained funding for one year of research. The first 30 out of 100 samples showed no support for their hypothesis. However, it was discovered that the lab technicians had been throwing out the cultures after two days. This was standard practice for throat swabs where other organisms in the mouth rendered cultures unusable after two days. Due to other hospital work, the lab technicians did not have time to immediately throw out the 31st test on the second day, and so it stayed from Thursday through to the following Monday. In that sample, they discovered the presence of H. pylori. They later found out that H. pylori grows more slowly than the conventional two days required by other mucosal bacteria, and that stomach cultures were not contaminated by other organisms.[14]
In 1983 they submitted their findings thus far to the Gastroenterological Society of Australia, but the reviewers turned their paper down, rating it in the bottom 10% of those they received that year.[14]
After failed attempts to infect piglets in 1984, Marshall, after having a baseline endoscopy done, drank a broth containing cultured H. pylori, expecting to develop, perhaps years later, an ulcer.[15] He was surprised when, only three days later, he developed vague nausea and halitosis, due to the achlorhydria. There was no acid to kill bacteria in the stomach and their waste products manifested as bad breath, noticed by his wife.[16] On days 5–8, he developed achlorhydric (no acid) vomiting. On day eight, he had a repeat endoscopy, which showed massive inflammation (gastritis), and a biopsy from which H. pylori was cultured, showing it had colonised his stomach. On the fourteenth day after ingestion, a third endoscopy was done, and Marshall began to take antibiotics.[17] Marshall did not develop antibodies to H. pylori, suggesting that innate immunity can sometimes eradicate acute H. pylori infection. Marshall's illness and recovery, based on a culture of organisms extracted from a patient, fulfilled Koch's postulates for H. pylori and gastritis, but not for peptic ulcers. This experiment was published in 1985 in the Medical Journal of Australia[18] and is among the most cited articles from the journal.[19]
After his work at Fremantle Hospital, Marshall did research at Royal Perth Hospital (1985–86) and at the University of Virginia, USA (1986–present), before returning to Australia while remaining on the faculty of the University of Virginia.[2] He held a Burnet Fellowship at the University of Western Australia (UWA) from 1998 to 2003.[20] Marshall continues research related to H. pylori and runs the H. pylori Research Laboratory at UWA.[21]
In 2007, Marshall was appointed Co-Director of The Marshall Centre for Infectious Diseases Research and Training, founded in his honour. In addition to Helicobacter pylori research, the Centre conducted varied research into infectious disease identification and surveillance, diagnostics and drug design, and transformative discovery. His research group expanded to embrace new technologies, including Next-Generation Sequencing and genomic analysis. Marshall also accepted a part-time appointment at the Pennsylvania State University that same year.[22] He established the Noisy Guts Project in 2017 – a research team dedicated to investigating new diagnostics and treatments for Irritable Bowel Syndrome. This resulted in a spin-out company Noisy Guts Pty Ltd[23] which develops functional food products. In August 2020, Marshall, along with Simon J. Thorpe, accepted a position at the scientific advisory board of Brainchip INC, a computer chip company.[24]
Barry Marshall, together with Robin Warren, discovered spiral bacteria in the stomachs of almost all patients with active chronic gastritis, or duodenal or gastric ulcers, and proposed that the bacteria were an important factor in the aetiology of these diseases. In 1985, Marshall showed by self-administration that this bacterium, now called Helicobacter pylori, causes acute gastritis and suggested that chronic colonisation directly leads to peptic ulceration. These results were a major challenge to the prevailing view that gastric disorders had a physiological basis, rather than being infectious diseases. Marshall showed that antibiotic and bismuth salt regimens that killed H. pylori resulted in the cure of duodenal ulcers. The view that gastric disorders are infectious diseases is now firmly established and there is increasing evidence for a role of H. pylori infection in gastric cancers. The work of Marshall has produced one of the most radical and important changes in medical perception in the last 50 years. Barry Marshall was awarded the Albert Lasker Award for Clinical Science in 1995 and the Buchanan Medal in 1998.
^This story is related by Marshall in his Nobel acceptance lecture 8 December 2005, available for viewing on the Nobel website. "Barry J. Marshall – Biographical". Nobelprize.org. Nobel Media AB. Retrieved 1 August 2013.
