Fire In The Belly

The Weird & Wonderful Story of Marshall & Warren & the Discovery of H. Pylori

© Photo by Dani Bregman

BH came to see me for one of the most common complaints in primary care: “stomach issues”. Bloating and burping. A burning, gnawing feeling in his abdomen, especially between meals. Heartburn at night, and sometimes nausea, leading to a loss of appetite which only made his symptoms worse. 

I suspected that he had an ulcer, or at least gastritis, and sent off a few tests, including a breath test for Helicobacter Pylori, the small, spiral-shaped bacteria now known to be the main cause of peptic ulcers. In the meantime, I started him on anti-acid medication along with some lifestyle recommendations.

Sure enough, the H. Pylori test came back positive, and after a two week course of treatment, he felt better than he had in years. Score one for me as far as BH was concerned - and who was I to argue? - but I knew who really deserved the credit: Barry Marshall and Robin Warren, two Australian doctors who discovered H. Pylori back in the early 1980’s.

It used to be thought that ulcers were caused by stress, spicy food, and too much acid. But mostly stress. Who thought this? Pretty much everyone - think of the expression, “you're giving me an ulcer!”, which we still use today. Pharmaceutical companies also promoted this view, and made fortunes from the anti-acid medications that were the mainstay of treatment.

Comes along Dr. Robin Warren, a pathologist who noticed small, helical bacteria in the stomach lining of patients with ulcers, and thought the two might be related. He teamed up with Dr. Barry Marshall, a young internist, and together they came up with the hypothesis that the cause of peptic ulcers was not stress after all, but rather a bacterial infection.

Unfortunately for them, this hypothesis was not so easy to prove. First, no one believed that bacteria could grow in the highly acidic, inhospitable environment of the stomach. Second, and perhaps related, H. Pylori turned out to be extremely difficult to culture in vitro, and didn’t have quite the same clinical effects on animal models in vivo. Third, pharmaceutical companies were distinctly uninterested in a cure for ulcers that could kill their cash cow. Fourth, and definitely related, journals and reviewers refused to publish their findings.

Finally, out of frustration, Dr. Marshall took a drastic step. By then the pair had managed to culture H. Pylori in a kind of bacterial soup, and Marshall, a perfectly healthy guy, at least from a gastrointestinal perspective, raised a beaker of broth teeming with H.Pylori, gave a bawdy toast (at least I like to think he did), and drank it.

Soon enough Marshall developed all the signs and symptoms of a gastric ulcer: nausea, discomfort, bloating - all the complaints BH had when he came to me. A biopsy showed that Marshall had indeed given himself H. Pylori and an ulcer to go with it, thereby vindicating their theory. 

In 1985, Marshall and Warren published their findings in the Medical Journal of Australia, in a paper called “Unidentified curved bacilli in the stomachs of patients with gastritis and ulceration.” It still took years for their theory to become adopted by the medical community at large, but eventually it did, and in 2005, the pair won the Nobel Prize in Physiology and Medicine, for their ground-breaking work.

Marshall and Warren and the discovery of H. Pylori is one of my favorite stories in medicine. I’ve been thinking about why I love it so much, and I came up with three reasons - three lessons, really, that it teaches, that resonate with me.

One, put your money where your mouth is. Literally. When Marshall and Warren encountered obstacles to their great idea, they didn’t give up, or back down, or cop out by putting others at risk. Marshall proved their theory of disease by making himself sick.  Actually, to be honest, they did consider using volunteers - but eventually decided not to partly out of ethical concerns, so good for them - be honorable, moral, and bold - be your own guinea pig!

Two, the truth will out. If the stress theory of ulcers was wrong, then that would eventually become known. If not from Marshall and Warren, then from somewhere else, no matter how long it took, no matter how anyone felt about it, no matter how many vested interests it went up against. It’s hard to practice medicine without a belief in objective truth, and in science as a means of teasing it out.

If that seems obvious to you, well, what can I say? Maybe you didn’t grow up in the liberal arts, like I did, where concepts like objectivity, truth, and progress can be blithely dismissed. Maybe that’s why I like the occasional reminder that reality exists, and sometimes even matters!

Three, the whole world can be wrong. I was a History major in college, so why should I have to learn this basic fact over and over again? After all, there would be no History without it. If the whole world, with its ideas and notions, were finally right, that would mean the end of History, as Francis Fukuyama indeed believed about the supposed ideological triumph of liberal democracy. 

And yet, it seems that I do have to constantly relearn this lesson, and since I do, who better to teach it than Marshall and Warren? They were right, and everyone was wrong. They stood on one side of the river, while everyone else stood on the other. They proved not only that the world can be wrong, but that in their case, it actually was. Or, to generalize their lesson: if you have to ask, “can the whole world really be wrong?” rest assured, it probably is.