At a news briefing on 12 February 2002, then US Defence Secretary Donald Rumsfeld made the statement for which he is renowned: “As we know, there are known knowns; there are things we know we know. We also know there are known unknowns; that is to say, we know there are some things we do not know. But there are also unknown unknowns – the ones we don’t know we don’t know.”
To which we might add that there are things we know we know but, as it turns out, are completely wrong.
For example, for most of the 20th century it was known with certainty that stress and lifestyle caused stomach ulcers, a widespread, painful, often-debilitating condition for which treatment ranged from diet modification to surgery.
But then, in 1979, Robin Warren, a pathologist at Royal Perth Hospital in Western Australia, observed spiral-shaped bacteria in a biopsy of the stomach lining from a patient – and continued gathering samples from other patients.
An article in The Lancet describes the “historic discovery – that gastric biopsy samples from patients with gastritis had an unexpected burden of [these] curved bacteria”.
“As far as I was concerned, the way they were arranged, they were associated with the gastritis. But trying to convince other people of that was impossible,” it quotes Warren as saying. “Every time I spoke to a clinician they would say, Robin, if these bacteria are causing it as you say, why hasn’t it been described before?”
Orthodox medical teaching at the time, The Lancet notes, was that bacteria did not grow in a normal stomach.
One person who didn’t need to be convinced was Barry Marshall, a trainee doctor at Royal Perth who became interested in Warren’s findings and in 1981 asked to join in his research.
They initiated a study of biopsies from 100 patients and, as an article published by the Nobel Prize Committee explains, they found that the organism was present in almost all patients with gastric inflammation, duodenal ulcer or gastric ulcer.
Warren, born in Adelaide, South Australia, on 11 June 1937, is described in The Lancet as “a reserved man whose colleagues talk about his quiet persistence, thoughtfulness, and careful observation”, while Marshall, born on 30 September 1951 in Kalgoorlie, Western Australia, was said to be “brash”. They made “a good team”.
Marshall’s brashness came to the fore in 1984 when the pair had presented their findings at conferences and in publication, including in the 16 June edition of The Lancet, with a paper titled “Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration”.
Although they found microbiologists to be largely supportive of their analysis, the attitude in much of the medical community was “patronising and negative”, Marshall says. “I was out there fighting battles with the gastroenterologists.”
“Marshall grew desperate”, according to a 2010 Discover magazine profile of the scientist, headlined “The doctor who drank infectious broth, gave himself an ulcer, and solved a medical mystery”.
“He ran an experiment on the only human patient he could ethically recruit: himself.” He took some of the bacteria from the gut of an ailing patient, stirred it into a broth, and drank it.
He developed gastritis, the precursor to an ulcer. In the lab, he biopsied his own gut, culturing a hitherto unknown bacterial species, later denoted Helicobacter pylori, “and proving unequivocally that bacteria were the underlying cause of ulcers”.
In awarding the pair the 2005 Nobel Prize in Physiology or Medicine, the prize committee recognised their “remarkable and unexpected discovery that inflammation in the stomach (gastritis), as well as ulceration of the stomach or duodenum (peptic ulcer disease) is the result of an infection of the stomach caused by the bacterium Helicobacter pylori.
“Thanks to the pioneering discovery by Marshall and Warren, peptic ulcer disease is no longer a chronic, frequently disabling condition, but a disease that can be cured by a short regimen of antibiotics and acid secretion inhibitors.”
Jeff Glorfeld is a former senior editor of The Age newspaper in Australia, and is now a freelance journalist based in California, US.
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