In the early 1980s, patients presenting with stomach pain would undergo endoscopy or X-ray to look for an ulcer. When one was found, patients would be treated with agents to lower the levels of stomach acids -- antacids into the late 1970s followed by histamine2 receptor antagonists. More potent proton pump inhibitors wouldn't arrive until the U.S. Food and Drug Administration approved omeprazole (Prilosec) in 1989.
Ulcers would heal, but ultimately return.
"We could control the ulcer, but not cure the ulcer," Peterson said.
According to Dr. David Graham of Baylor College of Medicine in Houston, "It was a bad existence. [It was] very expensive, you had to frequently go to doctors and you had lots of X-ray examinations, or later, endoscopic examinations to show if an ulcer was present or not."
Serious complications, such as gastrointestinal hemorrhage, strictures, and perforations, occurred in about 25 percent of patients, many requiring surgery. About 10 percent of those died, Graham said.
Like Peterson, Graham doubted Warren and Marshall's findings.
"Dr. Marshall, when he first presented this, was young, a resident, and didn't know how the system worked," Graham said in an interview. "And he believed that just because you could show people and it all made sense that they would believe it. But you just need to do the studies to get the proof and show that if you eradicate the infection that the ulcer disease is also cured, and that takes time."
Studies did confirm the causal role of H. pylori, and Graham and Peterson eventually accepted the idea. They both became leading U.S. experts studying the bacteria and how to treat it.
Peterson couldn't identify a tipping point for when acceptance of a causal role for H. pylori started to gain traction. He said it came after researchers from around the world started to confirm the Australians' findings and show that treating the infection cured the ulcers.
Graham said official acceptance of the idea came at a 1994 National Institutes of Health consensus conference that concluded that there was a strong link between H. pylori and peptic ulcer disease -- and that patients with ulcers and infection with the bacteria required treatment with antibiotics and antisecretory drugs.
"I had been waiting for 10 years for this day, and I felt a combination of relief and satisfaction that I had achieved what I set out to do," Marshall wrote.
But still, clinicians were slow to accept H. pylori.
In a 1997 study in Archives of Internal Medicine, researchers found that, in 1995, about three-quarters of ulcers were still being treated primarily with antisecretory medications. Only 5 percent of patients received antibiotics.
It wasn't until 1996 that the FDA approved the first antimicrobial treatment for peptic ulcers -- a combination of the antibiotic clarithromycin (Biaxin) and the proton pump inhibitor omeprazole.
In 1997, responding to the clinical inertia preventing the widespread use of antibiotics to treat ulcer disease, the CDC launched a national campaign to spread the word through public service announcements on television and radio.
Around the end of the 20th century, Graham said, the idea finally took hold.
This process "probably happened slower than it should have, but about as fast as new ideas travel through medicine."
Now, the proportion of ulcers attributed to H. pylori is declining, although it varies depending on location.