Dr Barry Marshall, a young Australian gastroenterologist, was sure peptic ulcers were caused by infection, but he couldn’t prove it. That is, until a long 4-day Easter weekend led to a fateful change in the lab.
It was 1982, and the conventional wisdom of the time was that peptic and duodenal ulcers were caused by stress and spicy food. Throughout the 1900s, treatment focused on reducing the acid level in the stomach (a remarkably acidic environment, with a pH of 2 – about the same acidity as lemon juice and vinegar). Milk diets were tried in the 1920s. Bland diets were standard, and often surgical removal of part of the stomach was required for those who didn’t respond to bland diets. Antacids like Tagamet and Zantac were not developed until the 1980s.
Five to ten percent of us will get an ulcer at some point in our lives. Now there are good treatments, and ulcers are rarely life-threatening. That did not used to be the case. Prior to current treatments, ulcers were not just painful; they were dangerous. Ulcers could erode the lining of the stomach. If that happened near a blood vessel patients could suddenly hemorrhage, which could be fatal. Ulcers could erode and create a hole in the stomach, leaking acid into the abdomen, which can also be life-threatening. In fact, death from ulcers was not uncommon in the 1800s and 1900s; James Joyce died after stomach surgery for ulcers. Rudyard Kipling died from a perforated duodenal ulcer. My husband’s grandfather died from ulcer hemorrhage as a relatively young man.
So, for young doctor Marshall in 1981, the cause of ulcers was a burning (pardon the pun) question. He and a pathologist, Dr Robin Warren, had noticed some odd spiral shaped bacteria in the biopsies they took when performing endoscopies on their ulcer patients. However, everyone knew that no bacteria could live in the hostile, acidic environment of the stomach, so these bacteria were felt to be just an artifact and not significant. But, Dr Marshall kept seeing them and soon had a series of well over one hundred ulcer patients in whom he had found this bacterium. And Marshall, always inquisitive, liked to quote social historian Daniel J. Boorstin, “The greatest obstacle to discovery is not ignorance—it is the illusion of knowledge.” Because everyone knew stomach acid would kill germs, and they knew stress and poor diet caused ulcers, their minds were not open to other ideas. Marshall kept plugging away.
The first thirty-four samples, kept in the lab to grow this new germ, grew nothing. Then came the fateful weekend of Easter 1982. It was a long holiday weekend, so the petri dishes stayed in the incubator for 5 days, instead of the usual two, and something grew! He was able to isolate and identify the bacterium, initially named Campylobacter pylori.
He presented a paper at a medical conference in Brussels in 1983, and other gastroenterologists began looking and found these spiral bacteria as well. The following year, Marshall and Warren reported in the well-known medical journal The Lancet the presence of the curved bacteria in 77% of their patients with gastric ulcer and in 100% of their patients with duodenal ulcer. It was not well received. Most people thought Marshall was an eccentric. Antacids were among the best-selling drugs in the world and the medical and pharmaceutical establishment were loath to embrace this unproven assertion of a bacterial infection as the cause of ulcers. And just the presence of this new bacterium was not proof it caused ulcers.
There’s something called Koch’s Postulates; criteria that must be satisfied in order to prove a certain bacterium causes a specific disease. Developed by famous microbiologist Dr Robert Koch in the 19th century, they are: the identified organism must (1) be present in all cases of the disease; (2) be isolated from diseased patients; (3) cause disease when reintroduced to a healthy susceptible animal model; and (4) then be isolated again from the new host.
Marshall spent six months with piglets, feeding them a human diet with plenty of this new bacterium (later re-named Helicobacter pylori). However, he gave up when he realized the natural environment of pigs included so many bacteria that the H pylori would never take hold. Impatient, he decided to experiment on himself! In 1984, he had an endoscopy; his stomach was normal. He then drank a bottle of broth full of H. pylori extracted from a patient suffering from gastric ulceration. His lab technicians were horrified. As he had hoped and expected, Marshall soon developed painful gastritis. He endured two weeks of vomiting, appetite loss, and heartburn, during which time two endoscopies confirmed both his infection and the ulcerative damage to his stomach mucosa. A course of antibiotics eventually set everything right. Koch’s Postulates satisfied!
He then was able to get research funding to try a course of antibiotics on ulcer patients who had tested positive for H pylori. Things progressed steadily from there. Within ten years, the National Institutes of Health published a consensus statement agreeing that treatment of H pylori was crucial for proper ulcer care. In 1997 the CDC launched a campaign to educate doctors and the public about treatment of ulcers with antibiotics.
Marshall and Warren went on to receive the Nobel Prize in 2005 for their discovery. All because of some determination, perseverance, and a long Easter weekend.