Robin Warren, pathologist who rewrote the science on ulcers, dies at 87

The long-held medical view was that stress caused ulcers. Dr. Warren and fellow Australian Barry Marshall, who shared a Nobel Prize, showed it was a bacteria.

Robin Warren, an Australian pathologist who shared a Nobel Prize for rewriting medical views on gut health with research that included his partner drinking a bacteria-laced brew to show how microbes can cause ulcers, died July 23 in Perth, Australia. He was 87.

The death was announced by the University of Western Australia, where Dr. Warren was a professor emeritus. The statement gave no other details.

The discoveries by Dr. Warren and Barry Marshall at Royal Perth Hospital completely upended long-standing medical assumptions that the stomach’s gastric fluids would kill any invasive bacteria. Yet, for more than a decade, the two researchers confronted a medical community slow to accept their theories and acknowledge their findings.

As Marshall once put it, “To gastroenterologists, the concept of a germ causing ulcers was like saying that the Earth is flat.”

For patients, there are now antibiotic treatments for peptic ulcers — once considered a chronic condition — as well as a noninvasive breath test to diagnose ulcers and avoid possible biopsies. In wider medical research, the work by Dr. Warren and Marshall also introduced theories about possible bacterial factors in ailments caused by inflammation, such as Crohn’s disease and ulcerative colitis, and as potential triggers for cancers.

Until the studies by Dr. Warren and Marshall, the medical consensus was that ulcers and other gastric troubles were often attributed to stress or lifestyle choices such as eating spicy foods or drinking alcohol.

“With tenacity and a prepared mind [they] challenged prevailing dogmas,” said a statement from the Nobel committee when Dr. Warren and Marshall received the prize for medicine in 2005.

The journey began with a glance in 1979 at a biopsy sample at the Royal Perth Hospital, where Dr. Warren was a chief pathologist. He noticed bacteria on tissue from a patient with ulcers. Dr. Warren had long mulled over an alternative “germ theory” for ulcers, but he had scant evidence to bolster his ideas and almost no supporters.

“Bacteria had been seen before, but these findings had been disregarded as some odd curiosities or just contaminations,” said Swedish microbiologist Staffan Normark at the Nobel Prize announcement in Stockholm.

Marshall, as a young clinical researcher, watched the eyerolls at Dr. Warren during medical conferences. “He would mention these bacteria and the surgeons would be saying ‘ha ha ha, Robin’s talking about his bacteria again,’” recalled Marshall in an interview with the Medical Republic, an Australian health and science site.

The biopsy sample spotted by Dr. Warren gave him a tangible lead. He recruited Marshall, and they began studying tissue from patients with ulcers and other digestive problems. Nearly all the samples showed the presence of the same bacteria. They dubbed it Helicobacter pylori, or H. pylori: “helico,” as in helicopter, for its spiral shape, and “pylori” for the pylorus valve at the bottom of the stomach.

They announced their findings in a series of papers, including in the British journal the Lancet, in the early 1980s. The medical community remained skeptical.

“For about 100 years, or 1,000 years, the standard teaching in medicine was that the stomach was sterile and nothing grew there because of corrosive gastric juices,” Dr. Warren said. “So everybody believed there were no bacteria in the stomach. When I said they were there, no one believed it.”

Robin Warren, right, and Barry Marshall during a meeting with Swedish students at the Nobel Forum in Stockholm on Dec. 7, 2005.

(Jonas Ekstromer/Associated Press)

In July 1984, Marshall turned himself into a lab subject. He swilled down a bacterial broth in an attempt to draw conclusive links between H. pylori and ulcers. Test animals such as pigs and rats were immune to the bacteria. Dr. Warren already had an H. pylori infection, and they feared he could have built an immunity.

“So, Barry, I think it has to be you,” Marshall recalled Dr. Warren telling him.

After about three days, Marshall became sick. “I started vomiting. I was waking up in the middle of the night, I couldn’t eat well, I was having night sweats,” he told the Australian, a newspaper based near Sydney, in 2005. “I had the endoscopy after a week and it showed the bacteria had taken hold.”

The test revealed H. pylori around an inflamed part of his stomach. He was better after a course of antibiotics, further advancing their findings toward a cure.

About two-thirds of the world population has been infected with H. pylori, often during childhood, but the bacteria leads to health problems in a relatively small number of people, according to the Centers for Disease Control and Prevention. Infections can also bring an increased risk of gastric cancers or a lymphoma known as mucosal associated-lymphoid-type, or MALT, the CDC says.

The precise reason H. pylori becomes aggressive in some people is not fully understood. But when it happens, the bacteria can cause ulcers by damaging the stomach lining and making it more vulnerable to digestive fluids. H. pylori causes more than 90 percent of duodenal stomach ulcers and 80 percent of upper-intestinal ulcers, the Nobel committee said. Other causes are overuse of some drugs that can compromise the stomach lining.

“The idea of stress and things like that was just so entrenched nobody could really believe that it was bacteria,” Dr. Warren once said. “It had to come from some weird place like Perth, Western Australia, because I think nobody else would have even considered it.”

Robin Warren, left, and Barry Marshall walk to a news conference at the University of Western Australia in Perth on Oct. 4, 2005.

(Tony Ashby/AFP/Getty Images)

‘10,000 unusual things’

John Robin Warren was born on June 11, 1937, in Adelaide, Australia. His father was a winemaker. His mother was a nurse.

“I cannot remember my mother ever pressuring me to study medicine, but somehow this always seemed to be my aim,” Dr. Warren wrote in his biographical essay for the Nobel committee.

Months after receiving a university scholarship to study medicine, he had his first grand mal seizure and was diagnosed with epilepsy. He was prescribed drugs that helped control the seizures, but he could not receive a driver’s license and used his bicycle for appointments and classes. His family had discussions — without Robin’s knowledge — about whether to demand that he pass up medical school because of his condition.

“It was only years later that I came to appreciate just how much my mother had gone through to support my independence. … Apparently, mother was worried sick, but she never said a word about it,” he wrote.

After receiving a degree in medicine from the University of Adelaide in 1961, he trained in clinical pathology at the Royal Adelaide Hospital.

Dr. Warren sought a position in Papua New Guinea, then under Australian control, in hopes of studying more “exotic and usual diseases.”

Instead, he was recruited by the Royal Perth Hospital in 1968 as a staff specialist in pathology, which included an affiliation with the University of Western Australia. He retired from the hospital in 1999 and was named a professor emeritus at the university in 2005.

In 2007, he was appointed a Companion of the Order of Australia, the country’s highest civilian honor.

During the early 1980s, Dr. Warren said, he and Marshall felt almost like outcasts with their bacteria research. “Otherwise,” Dr. Warren said, “it seemed that only our wives stood beside us.”

He married the former Winifred Theresa Williams in 1962, and they had five children. She died in 1997. Complete information on survivors was not immediately available.

In an interview with the Australian Academy of Science, Dr. Warren said that pathologists often encounter oddities in research. The challenge, he noted, is to decide which enigma holds a mystery worth cracking.

“When you look down the microscope at pieces of tissue … it’s not unusual to find something unexpected, because there are so many unusual things,” he said. “And if there are 10,000 unusual things, you find one of them every now and again.”

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