Germ of an idea
A pair of mavericks who battled the medical establishment have had their work acknowledged with a Nobel prize, report Victoria Laurie and Amanda Banks
05oct05
ONE evening more than 20 years ago, a young doctor stood in his laboratory at Fremantle Hospital and took a big swig of some foul-tasting bacteria. He then sat back and waited for flu-like signs of peptic ulcers to emerge.
Within a few days Barry Marshall was doubled over in pain with clinical gastritis, a precursor to stomach ulcers. It also made him feel empathetic for patients who had suffered for years with the pain of stomach ulcers.
"After about three days I started vomiting, I was waking up in the middle of the night, I couldn't eat well, I was having night sweats," he says. "I had the endoscopy after a week and it showed the bacteria had taken hold."
His results were like all the other biopsies he'd seen of stomach ulcer patients. Corkscrew-shaped bacteria had burrowed into Marshall's stomach lining and were wreaking havoc.
Marshall's radical plan to make himself sick proved what he and his pathologist co-researcher Robin Warren discovered in 1982: that a germ, not stress and diet, caused stomach ulcers. The discovery eventually led to the pair being awarded the Nobel Prize for Medicine on Monday night.
The men jokingly describe themselves as "bacterial friends" who have worked together like a husband and wife team. But their 20-year partnership has required dogged research and determination in the face of a sceptical, even hostile, science community.
Yesterday the pair were smiling through their hangovers. "We were in the right place at the right time," says Marshall, the more vocal of the pair, who describes himself as a lucky optimist.
Warren is the quiet one, described as a dogged genius with an "obsessional nature". As a team, they proved a winning scientific combination. Their work together began in 1981 when a young Marshall met Warren, a Royal Perth Hospital pathologist with an interest in gastritis.
The pair set out to investigate a possible connection between a microbe - later called Helicobacter pylori - and ulcers. They studied biopsies from 100 patients and cultivated the bacteria after many failed attempts.
If stress and frustration were the cause of stomach ulcers, Marshall and Warren would have been prime candidates. They were disbelieved, even ridiculed, for a decade after making their breakthrough.
"People believed we were somewhat eccentric," says Marshall, 54, a University of Western Australia professor who graduated from UWA in 1974 and runs its molecular microbiology laboratory. The father of four remains the dynamic, even brash, half of the partnership. The eldest son of a welder and a nurse, Marshall grew up in the remote gold town of Kalgoorlie. The lessons in bush self-sufficiency he learned in childhood showed in Marshall's early medical career; he once strapped test tubes to his kitchen ceiling fan for a makeshift centrifuge to separate blood cells.
BUG IN THE SYSTEM
* A peptic ulcer is an area of the lining of the stomach or the duodenum that has become inflamed and eroded by the body's digestive juices.
* About 506,000 Australians are thought to have some form of gastrointestinal ulcer.
* Ulcers occur when the protective lining, which prevents digestive juices attacking the stomach or duodenal wall, fails.
* It used to be thought that stress and poor diet caused ulcers but infection with the bacterium Helicobacter pylori is the most important cause.
* Symptoms include a burning or gnawing pain often one to two hours after meals, in the middle of the night or early morning when the stomach is empty.
* Often people are not aware they have an ulcer until they experience a complication, such as a haemorrhage.
* No single antibiotic is effective against H.pylori so combination therapy is often given, usually at least three drugs. Combination therapy, with acid-suppressing drugs, has a success rate of 80per cent to 90 per cent.
– Adam Cresswell
Adelaide-born Warren, 68, a father of five, is the quiet achiever whose wife was one of the early ulcer patients cured of her condition by antibiotics.
Marshall believes that achievers follow their hearts and their instincts. So in 1984 he went through the drama of making himself ill to prove the pair's theory that a bacterium was the cause of ulcers.
The pair found reports of the bacteria in medical books of the past 100 years. "Everyone had forgotten about these observations," Marshall says.
In the wake of antibiotics, which cured most infectious disease, he says scientists had stopped looking for bacteria.
"We found reports where they had their electron microscope turned up to such a big power they were looking between the bacteria," he says. "There were bacteria everywhere and they would move the microscope around until they could see a clear area between the bacteria and study that. We said: 'Hang on, let's get back a bit and just look down the ordinary old microscope', and we can see these bugs everywhere."
Their research led them to believe that the culprit was a corkscrew-shaped bacterium that they had found in the stomachs of many ulcer patients.
Frustrated that the scientific community would not listen, Marshall took the radical step of downing a glass of bacterial brew. The damage done by the bacteria was temporary as Marshall's immune system fought off the infection. But at home, his wife's anger was not quite so readily calmed.
"I said to my wife: 'We were right.' I said I took the bacteria, I've got the illness and she said: 'You did what? Here we are, trying to manage with all these little children and the chaos in our lives and you make yourself sick.'
"I was then threatened with eviction. These days that would have been the appropriate thing because we now know [the bacteria] is somewhat infectious . . . I could have given it to family members."
Would he do it again? "If there was an important scientific question that had to be solved in humans. I am not the only one who has done this."
Warren says he was never funded for his bacteria research. "All the work that I did I did in my own time, usually after hours," he says. "I became a scientist because I saw something in gastric biopsies that we had ... but I was only a part-time scientist."
Yet for years the medical world remained hostile or unconvinced by the Australians' bold claim. Ulcers were caused by weak stomach linings, gastric acid and awful diets, it was argued, and bacteria could not survive the acid bath of the stomach.
But Warren's painstaking research showed the bacterium could, in fact, survive and even form a protective alkaline layer around itself. He and Marshall argued that conventional treatments such as antacids could kill the pain and heal the ulcer, but without killing the bacteria, the ulcer was doomed to return.
Marshall moved to the US for a decade and conducted more research, but the Australian's brash assertions and alleged lack of conclusive trials left many refusing to let go of traditional ulcer treatment.
In the best traditions of science, it was the meticulous research of other curious scientists that tested, then endorsed, the visionary findings of Marshall and Warren.
In 1994, the US National Institutes of Health endorsed antibiotics as standard treatment for stomach ulcers. Yet it took until 1996 before their discovery was properly applied in GPs' surgeries across Australia. Today, Marshall says, doctors routinely treat patients' ulcers with a short regime of antibiotics, "and they don't think anything about it".
Research is now focused on finding a vaccine aimed at eradicating the culprit bacteria, which have been found to cause more than 90 per cent of duodenal ulcers and up to 80 per cent of gastric ulcers.
The Nobel pair's legacy is that being diagnosed with an ulcer is no longer a sentence to suffer chronic, crippling pain. It also reduces pain in the federal health budget, saving an estimated $200 million a year.
The doubting Thomases have disappeared. The only voices heard these days are laudatory ones.
The Nobel prize comes on top of a plethora of awards for both men, including the inaugural Florey Medal in 1998 for medical research. In the same year, Marshall was awarded a five-year scholarship, worth $1.25 million, that has since led to the invention of a simple oral test - similar to a driver's breath test - that can detect ulcers. It is being used across the world.
The pair will fly to Stockholm for an award ceremony on December 10 when they will receive their gold medals, a diploma and a cheque for $1.7 million.
"It is nice; Robin will be able to upgrade his computer and he won't have to spend four days wandering around looking for the best mail-order value from fly-by-night companies," Marshall says.
http://www.theaustralian.news.com.au...816505,00.html
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