Number of words: 858

For centuries, gastritis had rather vaguely been attributed to stress and neuroses. (In popular use, the term dyspeptic still refers to an irritable and fragile psychological state.) By extension, then, cancer of the stomach was cancer unleashed by neurotic stress, in essence a modern variant of the theory of clogged melancholia proposed by Galen.

But Warren had convinced himself that the true cause of gastritis was a yet unknown species of bacteria, an organism that, according to dogma, could not even exist in the inhospitable acidic lumen of the stomach. “Since the early days of medical bacteriology, over one hundred years ago,” Warren wrote, “it was taught that bacteria do not grow in the stomach. When I was a student, this was taken as so obvious as to barely rate a mention. It was a ‘known fact,’ like ‘everyone knows that the earth is flat.’”

But the flat-earth theory of stomach inflammation made little sense to Warren. When he examined biopsies of men and women with gastritis or gastric ulcers, he found a hazy, blue layer overlying the craterlike depressions of the ulcers in the stomach. When he looked even harder at that bluish layer, he inevitably saw spiral organisms teeming within it.

Or had he imagined it? Warren was convinced that these organisms represented a new species of bacterium that caused gastritis and peptic ulcers. But he could not isolate the bacteria in any form on a plate, dish, or culture. Others could not see the organism; Warren could not grow it; the whole theory, with its blue haze of alien organisms growing above craters in the stomach, smacked of science fiction.

Barry Marshall, in contrast, had no pet theory to test or disprove. The son of a Kalgoorlie boilermaker and a nurse, he had trained in medicine in Perth and was an unwhetted junior investigator looking for a project. Intrigued by Warren’s data (although skeptical of the link with an unknown, phantasmic bacteria), he started to collect brushings from patients with ulcers and spread out the material on petri dishes, hoping to grow a bacterium. But as with Warren, no bacteria grew out. Week after week, Marshall’s dishes piled up in the incubator and were discarded in large stacks after a few days of examination.

But then serendipity intervened: over an unexpectedly busy Easter weekend in 1982, with the hospital overflowing with medical admissions, Marshall forgot to examine his plates and left them in the incubator. When he remembered and returned to examine them, he found tiny, translucent pearls of bacterial colonies growing on the agar. The long incubation period had been critical. Under the microscope, the bacterium growing on the plate was a minuscule, slow-growing, fragile organism with a helical tail, a species that had never been described by microbiologists. Warren and Marshall called it Helicobacter pylori—helicobacter for its appearance, and pylorus from the Latin for “gatekeeper,” for its location near the outlet valve of the stomach.

But the mere existence of the bacteria, or even its association with ulcers, was not proof enough that it caused gastritis. Koch’s third postulate stipulated that to be classified as a bona fide causal element for a disease, an organism needed to re-create the disease when introduced into a naive host. Marshall and Warren inoculated pigs with the bacteria and performed serial endoscopies. But the pigs—seventy pounds of porcine weight that did not take kindly to weekly endoscopies—did not sprout any ulcers. And testing the theory on humans was ethically impossible: how could one justify infecting a human with a new, uncharacterized species of bacteria to prove that it caused gastritis and predisposed to cancer?

In July 1984, with his experiments stalled and his grant applications in jeopardy, Marshall performed the ultimate experiment: “On the morning of the experiment, I omitted my breakfast. . . . Two hours later, Neil Noakes scraped a heavily inoculated 4 day culture plate of Helicobacter and dispersed the bacteria in alkaline peptone water (a kind of meat broth used to keep bacteria alive). I fasted until 10 am when Neil handed me a 200 ml beaker about one quarter full of the cloudy brown liquid. I drank it down in one gulp then fasted for the rest of the day. A few stomach gurgles occurred. Was it the bacteria or was I just hungry?”

Marshall was not “just hungry.” Within a few days of swallowing the turbid bacterial culture, he was violently ill, with nausea, vomiting, night sweats, and chills. He persuaded a colleague to perform serial biopsies to document the pathological changes, and he was diagnosed with highly active gastritis, with a dense overlay of bacteria in his stomach and ulcerating craters beneath—precisely what Warren had found in his patients. In late July, with Warren as coauthor, Marshall submitted his own case report to the Medical Journal of Australia for publication (“a normal volunteer [has] swallowed a pure culture of the organism,” he wrote). The critics had at last been silenced. Helicobacter pylori was indisputably the cause of gastric inflammation.

Excerpted from pages 281-283 of ‘The Emperor of All Maladies: A biography of Cancer’ by Siddharth Mukherjee