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Nobel Aussies a classic tutorial in pioneering science versus group inertia

Those two tough minded ‘Orstrines’ who just won the Nobel in medicine did humanity a great service in proving that stomach ulcers were due to bacteria and could be treated with antibiotics, and not surgery.

They also did science and medicine a great service in bringing to public attention everywhere their story which embodies the fact that even today individuals with Nobel-quality new ideas suffer powerful group rejection.

Every media story on their achievement mentions their years in the wilderness, often with telling detail. It seems possible that this will help more of the public to appreciate that this great problem in modern science is not merely justified prejudice against crackpots, and that one solution has to be to arrange funding separated from peer prejudice against novelty.

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Australians win 2005 Nobel for Medicine

Last Updated Mon, 03 Oct 2005 07:03:30 EDT

CBC News

Australians Barry Marshall and J. Robin Warren have won the 2005 Nobel Prize in physiology or medicine. The researchers discovered the bacterium Helicobacter pylori, and explored its role in gastritis and peptic ulcers.

The bacterium Helicobacter pylori

The prize for medicine is selected in Stockholm, Sweden by the Karolinska Institute. It is the first Nobel to be awarded this year, and will be followed by physics, chemistry, literature, peace and economics.

Two Canadians were believed to be finalists for the prestigious award. Ernest McCulloch and James Till recently won the Albert Lasker Foundation award for basic research for their pioneering work with stem cells.

The process for selecting winners is extremely secretive — nominations are kept sealed for 50 years — though often winners of the Lasker prize go on to receive the Nobel.

Peptic Ulcers – an infectious disease

Helicobacter pylori is a bacterium that appears in the stomach in about 50 per cent of all humans. It is generally thought to be acquired in childhood. Only a minority of infected individuals go on to develop stomach disease.

Until 1982, stress and lifestyle were considered the major causes of peptic ulcer disease. Even though stomach ulcers could be healed by inhibiting gastric acid production, patients frequently relapsed.

Marshall and Warren discovered that the small curved bacteria colonized the lower part of the stomach in almost all patients studied with gastric inflammation, duodenal ulcer or gastric ulcer. They then further showed that patients could only be properly cured of gastric ulcers when H. pylori was eradicated from the stomach.

It is now firmly established that Helicobacter pylori causes more than 90 per cent of duodenal ulcers and up to 80 per cent of gastric ulcers.

Many diseases in humans such as Crohn’s disease, ulcerative colitis, rheumatoid arthritis and atherosclerosis are due to chronic inflammation. The discovery that one of the most common diseases of mankind, peptic ulcer disease, has a microbial cause, has stimulated the search for microbes as possible causes of other chronic inflammatory conditions.

The Nobel prize will be awarded Dec. 10 at a ceremony in Stockholm.

Tue Oct 4, 5:07 AM ET

CANBERRA (Reuters) – An Australian scientist who jointly won the 2005 Nobel prize for medicine said he became a human guinea pig and drank a cocktail of bacteria to prove his theories that ulcers were not caused by stress.

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Australian professor Barry Marshall and Robin Warren were awarded the 2005 Nobel prize for their 1982 discovery that the Helicobacter pylori bacterium, rather than stress, caused stomach ulcers and inflammation.

Marshall, who spent Tuesday fielding calls of congratulations from around the world, said he became a human laboratory rat to convince skeptics that ulcers and stomach inflammation were caused by bacterium.

“I didn’t think about it very much and probably I wouldn’t have done it if I had really thought it through,” Marshall told reporters in the Western Australian capital of Perth.

The discovery by Marshall, now 54, and Warren, 68, led to the development of an antibiotics and drug treatment for most ulcers, overturning the conventional medical thinking of the time and easing the suffering for millions of people each year.

After drinking the bacteria, Marshall suffered nausea, vomiting and stomach pain, but overcame the condition with treatment similar to the regimen of antibiotics and acid secretion inhibitors now commonly prescribed to sufferers.

He said he had no choice but to give himself the condition to convince medical skeptics that the bacterium was the cause and not the symptom of stomach ulcers, which can pre-dispose people to gastric cancer.

SWALLOW YOUR BACTERIA!

“Somebody had to do it, somebody had to swallow those bacteria and develop the disease,” Marshall told the Australian Broadcasting Corp.

“It was the only way you could convince the skeptics.

Warren said the pair were initially reluctant to publish their findings because of the way Marshall had given himself the condition and because their findings were so radical.

“At the time everyone thought we were a bit crazy because the whole thing was so way out in terms of normal medical teaching in those days,” Warren told reporters.

“For me, it (the Nobel prize) means that they are putting the official stamp of approval on all the work that I did and all the trouble that I had and all the disbelief.”

Australian Prime Minister John Howard congratulated the pair on Tuesday, and said their work had bought relief to millions of people around the world.

“The research destroyed a myth, very widely held,” Howard told reporters. “The prize is richly deserved.”

Marshall and Warren, who were working at the royal Perth hospital at the time of their breakthrough, are the first all-Australian team to win the Nobel prize for medicine.

Warren is now retired, but Marshall continues to study the effects of the bacterium on humans and animals.

“I’ve got no imagination. I’m still in the Helicobacter business,” Marshall said. “But these days we’re doing molecular studies, cloning, vaccines and all that kind of stuff.

“You can’t study ulcers in Australia any more, because everyone with an ulcer has been cured, as far as I can tell.”

Here are Barry and Robin celebrating their triumph with the national tipple. As a site that strongly supports soundly based heresy (validated by experiment and in the scientific literature) we think they deserve toasting in champagne rather than beer for their determined climb up the cold and foggy mountain of prejudice they were forced to conquer before finally emerging into the sun of world wide recognition.

What they surmounted was the classic shabby treatment doled out by the authorities and colleagues in every field to pioneers who challenge scripture – scorn, ostracism and other mindless shows of tribalism fueled by vested interests.

Among the details which emerge is the fact that doctors are still prescribing and the drug companies are still selling the very profitable anti-acid medications for ulcers which their discovery outmoded. The door is still a little ajar for marketing those products because not quite all ulcers are caused by the bacteria. Helicobacter pylori causes more than 90 per cent of duodenal ulcers and up to 80 per cent of gastric ulcers.

An anonymous insider writing about “The great Australian Nobel snub” in the October 5 issue of the newsletter Crikey describes the wall of resistance the two met with their unlikely theory.

Rather than welcoming and supporting the work of “local heroes,” many Australian gastroenterologists were highly critical and disbelieving of Marshall and Warren’s (ultimately) Nobel Prize-winning work, and continued for many years to stubbornly deny that Helicobacter pylori had much, or indeed any, role in the pathogenesis of ulcer disease.

Barry Marshall was made to feel quite uncomfortable when he attended specialist conferences – he was regarded by many as a maverick and even a loony, especially when the story of his drinking “swampwater” in order to infect himself got around. Worse still, this lack of acceptance was often blamed on Marshall’s personality (he has been described as “brash”) or justified as a response to him apparently seeking publicity and glory. It certainly didn’t help that he was not a gastroenterologist by training.

Rather surprisingly perhaps their Australian colleagues behaved worse than those in the US and other countries.

Given Marshall and Warren’s pioneering work, Australia should have been the first place in the western world to accept the full H. pylori story. But, shamefully, it was not. Although a Working Party reported to the 1990 World Congress of Gastroenterology (which incidentally was held in Sydney) that H. pylori was definitely an important cause of ulcer disease, many prominent leaders of the gastroenterology specialty in Australia continued to deny its importance, or to claim that it was a cause of only a small minority of cases of ulcer disease, well into the mid-1990s.

(Thus) in 1991, Parke Davis got scant support from local “opinion leaders” when it brought an international speaker (and member of the Working Party) to Australia to discuss H. pylori eradication as an approach to treating ulcer disease.

In a drug company-sponsored 4-page educational publication for GPs published in Australia in 1992, only the last two paragraphs mention H. pylori, and only in the context of how this company’s anti-acid drug might one day have a role – in combination with antibiotics – in eradicating the bacterium. It was only 4-5 years later, when such combinations were shown to be effective in eradication, that education and promotion to GPs about the role of H. pylori in ulcer disease really started to pick up momentum.

Marshall’s work was much more readily accepted internationally than locally, and so he spent what may perhaps have been his most productive years as a researcher overseas.

An earlier piece by Melissa Sweet, a medical journalist, in the Sydney Morning Herald on Saturday, August 2, 1997, two years after Marshall won the Lasker, reports that “everyone knew” they were wrong:

In the early 1980s, Warren, a pathologist at Royal Perth Hospital, had become resigned to unkind jokes from his peers about his theory that an unusual bug he was seeing down his microscope had some role in causing stomach inflammation. No-one had taken much notice because it was such an outlandish notion. Everyone knew that bacteria couldn’t survive in the stomach’s acid environment. They’d been taught so at medical school. Marshall was in the final stages of training to become a physician, having dropped earlier plans to become a GP because, he explains: “When I was in medical school I was given the impression that everything had already been discovered in medicine. It must have been the way it was taught. “So I never thought that medical research would be interesting.

But they were helped by luck in the Fleming manner:

The pair spent several months trying to culture the bugs, succeeding only accidentally when the culture was left longer than usual because of a lack of lab staff over an Easter break. Once able to grow the bug, they could show it was a “new” organism. It was initially thought to belong to the Campylobacter family but was later declared part of a new genus, Helicobacter, which is now known to have members also infecting animals other than humans.

The resistance was great enough that Marshall was driven to experiment on himself in rather a risky manner, which he later said he might not have done if he had thought longer about it.

The establishment was difficult to persuade – everyone accepted that ulcers were caused by acid, stress, spicy foods, and should be treated by drugs blocking acid production. This led to Marshall’s rather dramatic decision to swallow a solution containing the bug to prove it caused disease. About a week later, he started vomiting and suffering other painful symptoms of gastritis, or inflammation of the stomach, which is now recognised as being caused by H pylori. His wife, Adrienne, was not impressed. “That’s a very Barry thing to have done,” she recalls. They had four young children, Marshall was working 14-hour days, seeing patients all day and doing research at night, and now he was “dreadfully ill”. “I told him he had to stop it and get some treatment.” He did. But his point had been made.

Seems that his lack of acceptance didn’t seem to worry the ebullient Marshall too much. “I was very thick skinned. “With his followers he conducted “guerilla warfare” Marshall says. Warren says without his salesmanship they might not have prevailed, and Marshall says it took ten years longer than he had expected.

Dr Tom Borody, a Sydney gastroenterologist who has treated thousands of ulcer patients with antibiotics after becoming an early convert, says: “He was changing the world and the world wasn’t seeing it.” Marshall himself underplays the underdog image. “I used to have a pretty good following. Robin Hood and his merry men – we used to think of it as a guerilla warfare. There were a lot of people who didn’t believe what we said but they couldn’t keep us quiet. I was very thick-skinned.” Robin Warren believes that if Marshall hadn’t tried to push their discovery so hard, “I suspect I’d still be trying to convince people of it. He’s a much better salesman than I am. If you make a big discovery, if you don’t sell it, it’s not going to be heard by anyone else.” But Marshall took at least a decade longer than he expected to persuade colleagues that ulcer patients with H pylori should be treated with antibiotics.

A university professor’s explanation is what sociologists of science know well, that everyone has a vested interest in the conventional wisdom. In this case, there was a highly profitable drug regimen the drug companies were selling. Antibiotics would not be nearly so profitable.

The time-lag reflects, as Professor William Doe of the Australian National University comments, “how difficult it is to change medical paradigms because everyone has a vested interest in the status quo”. The pharmaceutical industry held the biggest vested interest in ulcers. Two of its biggest all-time earners have been the acid suppressing drugs cimetidine (Tagamet) and ranitidine (Zantac), and Astra had just launched the first of a new, even more potent type of acid suppressant. These drugs did not cure ulcers, meaning patients often needed lifelong therapy. The notion that common garden varieties of antibiotics (many of which were out of patent and so did not hold the lure of vast profits) might cure ulcers was, unsurprisingly, not high on the industry’s priorities. The pharmaceutical industry is the main source of information for doctors, which helps explain why Tagamet and Zantac are still big sellers.

There were complications which allowed those with vested interests to argue against their evidence, too, which often happens in pioneering work, which is rarely cut and dried. Even the new drugs now bring side effects. But the two opened an avenue which may lead to vaccines against gastric cancers and possibly similar findings that other chronic diseases are caused by bacteria.

But, to be fair, knowledge rarely advances in a single bound. Many painstaking studies are needed to prove a new hypothesis, especially one so challenging to the previous paradigm. As well, H pylori proved more difficult to eradicate than initially expected, and the drug combinations now recommended often cause side effects. Even so, they have brought great benefit to many thousands. Marshall recalls that during his decade at the University of Virginia, patients came from all over to have their ulcers cured. And H pylori is having ramifications way beyond ulcers. It is now accepted by the World Health Organisation as contributing to many gastric cancers, an enormous problem in many Asian and developing countries, and an international race is under way to develop vaccines against the bug. Professor Doe says the discovery has also contributed to a “renaissance” of interest in the concept that many chronic diseases may be caused by persisting unrecognised infections.

Apparently the field has mushroomed from a scorned idea into an industry.

It’s also been a job creation scheme to make the Employment Minister, Amanda Vanstone, jealous. Dr Neville Hoffman, Marshall’s boss at Sir Charles Gairdner Hospital, says that the discovery has created an industry and the bug has now reached the stage where there are more people living off it than dying from it. Borody notes that there is now an entire journal devoted to Helicobacter, which is the subject of almost 3,000 new scientific papers annually. Stuart Hazell says: “It’s made Barry’s career, it’s made my career, and it’s made plenty of other people’s careers.” NOT surprisingly, whispers about a possible Nobel prize have grown so loud that there are even rumours that the Swedes have asked for Marshall’s US supporters to tone down their lobbying. Borody says: “It is one of the major breakthroughs in this century, basically, and that is why I believe he will end up getting the big prize; they should both get it.”

and prizes accumulated, except in Australia, where the prophets are still without honor.

The discovery has already attracted several lucrative, coveted gongs. The Harvard Medical School gave the two researchers the $US25,000 (about $32,500) Warren Alpert prize, which recognises work that has most benefited clinical practice. This year the pair won Germany’s Paul Ehrlich prize, and Marshall has also received the Lasker prize in the US. But Stuart Hazell says their lack of recognition in Australia is “pathetic” and a comment on the status of Australian science and technology generally. “I was talking to [Federal Science Minister] Peter McGauran the other day, saying it’s about time someone organised for these guys to get an Order of Australia.”

Sweet puts the several morals of the story in a nutshell:

the Barry Marshall story … is compelling at several levels: single discovery sets young WA doctor from not especially privileged background on road to fame, fortune and maybe even a Nobel prize; entrenched attitudes and interests in the health industry impede the march of knowledge and patient care; and why hard slog, serendipity and, perhaps most importantly, salesmanship are so important to science.

All of this was readily apparent earlier in the story, judging from the well informed analysis, Smug as a bug, in the Sydney Morning Herald by medical reporter Sweet, Here is the full report:

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Sydney Morning Herald Features –

Saturday, August 2, 1997

Portrait from SMH

Smug as a bug

He was so sure he was right and conventional medical wisdom wrong about the cause of stomach ulcers that he swallowed bacteria to prove his point. Now once-sceptical peers are talking about a possible Nobel prize. MELISSA SWEET reports.

BARRY is back. He’s burnt out, mellowed out and glad to have some time to just hang out, now that he is home in Perth and far from the frenzy of 10 years in the United States limelight. He may not be a household name in Australia, at least not yet, but there is no doubt that Barry Marshall is a star. In the conservative world of medicine, Marshall has achieved international celebrity status for helping to revolutionise understanding and treatment of ulcers, not traditionally a subject high on sex appeal. Just consider his publication record: he has been splashed by the New Yorker, Time magazine, Reader’s Digest, The New York Times, The Wall Street Journal and The Washington Post, to name just a few. Don’t mention the recent Fortune magazine piece, though. He didn’t like that; didn’t like its theme of Brash Barry As Underdog Wins Out. A shame, because that is one of the many interesting aspects to the Barry Marshall story which is compelling at several levels: single discovery sets young WA doctor from not especially privileged background on road to fame, fortune and maybe even a Nobel prize; entrenched attitudes and interests in the health industry impede the march of knowledge and patient care; and why hard slog, serendipity and, perhaps most importantly, salesmanship are so important to science.

There is no doubt that Marshall, 46, has been one hell of a salesman. That helps explain why he is so well known for a discovery which stemmed from the observations of a colleague, Dr Robin Warren. In the early 1980s, Warren, a pathologist at Royal Perth Hospital, had become resigned to unkind jokes from his peers about his theory that an unusual bug he was seeing down his microscope had some role in causing stomach inflammation. No-one had taken much notice because it was such an outlandish notion. Everyone knew that bacteria couldn’t survive in the stomach’s acid environment. They’d been taught so at medical school. Marshall was in the final stages of training to become a physician, having dropped earlier plans to become a GP because, he explains: “When I was in medical school I was given the impression that everything had already been discovered in medicine. It must have been the way it was taught. “So I never thought that medical research would be interesting, but as I did my internship … I realised there were a lot of people who had things wrong with them that you couldn’t do anything about particularly.” So Marshall, who had not been known at med school as an especially conscientious type, was casting around for a research project to complete his evolution into physician. His boss suggested he check out Warren, who “was always carrying on about seeing bacteria in [stomach] biopsies”. The rest, as they say, is medical history.

The pair spent several months trying to culture the bugs, succeeding only accidentally when the culture was left longer than usual because of a lack of lab staff over an Easter break. Once able to grow the bug, they could show it was a “new” organism. It was initially thought to belong to the Campylobacter family but was later declared part of a new genus, Helicobacter, which is now known to have members also infecting animals other than humans. Most importantly, however, Marshall and Warren began to gather evidence to support their medical heresy that Helicobacter pylori were contributing to many ulcers. The establishment was difficult to persuade – everyone accepted that ulcers were caused by acid, stress, spicy foods, and should be treated by drugs blocking acid production. This led to Marshall’s rather dramatic decision to swallow a solution containing the bug to prove it caused disease. About a week later, he started vomiting and suffering other painful symptoms of gastritis, or inflammation of the stomach, which is now recognised as being caused by H pylori. His wife, Adrienne, was not impressed. “That’s a very Barry thing to have done,” she recalls. They had four young children, Marshall was working 14-hour days, seeing patients all day and doing research at night, and now he was “dreadfully ill”. “I told him he had to stop it and get some treatment.” He did. But his point had been made.

IT WOULD be easy enough to portray Marshall as the poor country lad made good. His father was a boilermaker, his mother a nurse. They lived in Perth until he was about four, then moved north to Carnarvon and a house with a dirt floor and outdoor toilet. A few years later, they moved inland to the tough mining town of Kalgoorlie, of which he remembers tin roofs, night-cart toilets, and their “fridge”, a Coolgardie safe. Then it was back to Perth, where his father worked as a cray fisherman and later ran chicken processing plants for Kentucky Fried. “For many years we didn’t have a car,” says Marshall, the eldest of four children. “We weren’t the first ones in the street to get a TV or any of those things that happened in the ’50s and ’60s. We never had any money but we had a pretty good life.” Engineering was his first love and remains a hobby. His first scientific paper on H pylori was written on a homebuilt word processor. He has to be one of the few professors to have established an Internet site on his field of research (http://www.helico.com/index.html). It includes everything you may ever want to know about ulcers and H pylori, and links to Marshall’s personal home page, complete with pictures of him feeding black swans. Adrienne says Barry has never quite outgrown his love of play. “He’s got a dreadful sense of humour,” she says. “He’s always being stupid, bad jokes, puns, that sort of thing. He really enjoys everything he does. He’s a 150 per cent person; whatever he’s doing he throws himself into. He’s probably a bit more of a boy than a man; a lot of the researchers are like that.”

Marshall studied medicine at the University of Western Australia from 1969-74 and worked on the wheat bins during holidays. He and Adrienne married while still studying (she did psychology) so they could get a Commonwealth scholarship. “We wanted to get away from our parents, basically,” he laughs, “but we used to eat quite a few meals at our parents’ houses because we couldn’t afford food.” Finances are not a problem these days, of course. Marshall doesn’t spell out exactly how much the discovery has earned him – he has shares in a company which makes tests and other products related to H pylori – but notes that all his children have had expensive US college educations. It seems he is in the fortunate position of seeing patients out of choice rather than necessity, with enough funds left over to pursue his research interests. He adds that he has no inclination to be a businessman full-time but is enjoying his lab at Sir Charles Gairdner Hospital and hopes to establish a biotech industry in Perth: “I can now do what I like and I don’t have to do something if I don’t like it.” BUT the road to this point was long and hard, which brings us back to Marshall’s brashness. Associate Professor Stuart Hazell, a microbiologist at the University of NSW, recalls that many medical feathers were ruffled when Marshall first began his campaign to rewrite the textbooks. “When Barry spoke he was very brash, “… that I’ve discovered this and that you people are going to have to relearn all your medicine because we’ve now worked out what is really going on’,” Hazell remembers. “The vast majority of the medical profession, not only in Australia but worldwide, considered Barry to be a quack and really were extremely dismissive for a number of years.” Adrienne says her husband’s aggressiveness in selling his message – unlike many doctors, he has never been media-shy – was simply a reflection of extreme frustration. “It was a tremendous struggle to get his work presented and published,” she says. “It was really tough to hang in there.”

Dr Tom Borody, a Sydney gastroenterologist who has treated thousands of ulcer patients with antibiotics after becoming an early convert, says: “He was changing the world and the world wasn’t seeing it.” Marshall himself underplays the underdog image. “I used to have a pretty good following. Robin Hood and his merry men – we used to think of it as a guerilla warfare. There were a lot of people who didn’t believe what we said but they couldn’t keep us quiet. I was very thick-skinned.” Robin Warren believes that if Marshall hadn’t tried to push their discovery so hard, “I suspect I’d still be trying to convince people of it. He’s a much better salesman than I am. If you make a big discovery, if you don’t sell it, it’s not going to be heard by anyone else.” But Marshall took at least a decade longer than he expected to persuade colleagues that ulcer patients with H pylori should be treated with antibiotics. (This treatment is not recommended for the estimated 15 per cent of peptic ulcers caused by aspirin and other non-steroidal anti-inflammatory drugs). Indeed, Australia only recently licensed the first antibiotic combination therapy for H pylori. The time-lag reflects, as Professor William Doe of the Australian National University comments, “how difficult it is to change medical paradigms because everyone has a vested interest in the status quo”. The pharmaceutical industry held the biggest vested interest in ulcers. Two of its biggest all-time earners have been the acid suppressing drugs cimetidine (Tagamet) and ranitidine (Zantac), and Astra had just launched the first of a new, even more potent type of acid suppressant. These drugs did not cure ulcers, meaning patients often needed lifelong therapy. The notion that common garden varieties of antibiotics (many of which were out of patent and so did not hold the lure of vast profits) might cure ulcers was, unsurprisingly, not high on the industry’s priorities. The pharmaceutical industry is the main source of information for doctors, which helps explain why Tagamet and Zantac are still big sellers. But, to be fair, knowledge rarely advances in a single bound. Many painstaking studies are needed to prove a new hypothesis, especially one so challenging to the previous paradigm. As well, H pylori proved more difficult to eradicate than initially expected, and the drug combinations now recommended often cause side effects. Even so, they have brought great benefit to many thousands. Marshall recalls that during his decade at the University of Virginia, patients came from all over to have their ulcers cured. And H pylori is having ramifications way beyond ulcers. It is now accepted by the World Health Organisation as contributing to many gastric cancers, an enormous problem in many Asian and developing countries, and an international race is under way to develop vaccines against the bug. Professor Doe says the discovery has also contributed to a “renaissance” of interest in the concept that many chronic diseases may be caused by persisting unrecognised infections.

It’s also been a job creation scheme to make the Employment Minister, Amanda Vanstone, jealous. Dr Neville Hoffman, Marshall’s boss at Sir Charles Gairdner Hospital, says that the discovery has created an industry and the bug has now reached the stage where there are more people living off it than dying from it. Borody notes that there is now an entire journal devoted to Helicobacter, which is the subject of almost 3,000 new scientific papers annually. Stuart Hazell says: “It’s made Barry’s career, it’s made my career, and it’s made plenty of other people’s careers.” NOT surprisingly, whispers about a possible Nobel prize have grown so loud that there are even rumours that the Swedes have asked for Marshall’s US supporters to tone down their lobbying. Borody says: “It is one of the major breakthroughs in this century, basically, and that is why I believe he will end up getting the big prize; they should both get it.” The discovery has already attracted several lucrative, coveted gongs. The Harvard Medical School gave the two researchers the $US25,000 (about $32,500) Warren Alpert prize, which recognises work that has most benefited clinical practice. This year the pair won Germany’s Paul Ehrlich prize, and Marshall has also received the Lasker prize in the US. But Stuart Hazell says their lack of recognition in Australia is “pathetic” and a comment on the status of Australian science and technology generally. “I was talking to [Federal Science Minister] Peter McGauran the other day, saying it’s about time someone organised for these guys to get an Order of Australia.”

But you get the feeling that Marshall, who is officially on sabbatical leave from the University of Virginia, is enjoying a break from the jet-setting whirl of conferences and media interviews that had become his lot in the US. After working seven-day weeks for years, he is trying now to have at least one day a week free of H pylori, which his wife describes as “like our fifth child”. “I had my midlife crisis last year, I think,” he laughs. “I’m trying to become less famous for a while and get back into the lab.”

Smug as a bug

Melissa Sweet is the Herald’s Medical Writer.

Madeline Drexler writes an editorial, A Nobel Prize for Intuition, in the International Herald Tribune, saying that the story shows the advantage of being an outsider who has nothing to gain from the status quo who is likely to come up with the new discovery, and how important it is to keep funding available for novel lines of exploration.

Those were fighting words. The young physician from Perth was telling the field’s academically pedigreed experts that they had it all wrong. “It was impossible to displace the dogma,” Marshall explained to me in a jaunty, wide-ranging conversation several years ago. “Their agenda was to shut me up and get me out of gastroenterology and into general practice in the outback.”

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MEDICINE

A Nobel Prize for intuition

Madeline Drexler

SATURDAY, OCTOBER 8, 2005

This week’s Nobel Prize winners in medicine – Australians Barry Marshall and Robin Warren – toppled the conventional wisdom in more ways than one.

They proved that most ulcers were caused by a lowly bacterium, which was an outrageous idea at the time. But they also showed that if science is to advance, scientists need the freedom and the funding to let their imaginations roam.

Let’s start with the Nobel pair’s gut instincts. In the late 1970s, the accepted medical theory was that ulcers were caused by stress, smoking, and alcohol. But when pathologist Warren cranked up his microscope to a higher-than-usual magnification, he was surprised to find S-shaped bacteria in specimens taken from patients with gastritis.

By 1982, Marshall, only 30 years old and still in training at Australia’s Royal Perth Hospital, and Warren, the more seasoned physician to whom he was assigned, were convinced that the bacteria were living brazenly in a sterile, acidic zone – the stomach – that medical texts had declared uninhabitable.

Marshall and Warren’s attempts to culture the bacteria repeatedly failed. But then they caught a lucky break – or rather, outbreak. Drug-resistant staph was sweeping through the hospital.

Preoccupied with the infections, lab techs left Marshall’s and Warren’s petri dishes to languish in a dark, humid incubator over the long Easter holiday. Those five days were enough time to grow a crop of strange, translucent microbes.

Marshall later demonstrated that ulcer-afflicted patients harbored the same strain of bacteria. In 1983, he began successfully treating these sufferers with antibiotics and bismuth (the active ingredient in Pepto-Bismol).

That same year, at an infectious disease conference in Belgium, a questioner in the audience asked Marshall if he thought bacteria caused at least some stomach ulcers. Marshall shot back that he believed bacteria caused all stomach ulcers.

Those were fighting words. The young physician from Perth was telling the field’s academically pedigreed experts that they had it all wrong. “It was impossible to displace the dogma,” Marshall explained to me in a jaunty, wide-ranging conversation several years ago. “Their agenda was to shut me up and get me out of gastroenterology and into general practice in the outback.”

At first, Marshall couldn’t produce the crowning scientific proof of his claim: inducing ulcers in animals by feeding them the bacterium. So in 1984, as he later reported in the Medical Journal of Australia, “a 32-year-old man, a light smoker and social drinker who had no known gastrointestinal disease or family history of peptic ulceration” – a superb test subject, in other words – “swallowed the growth from a flourishing three-day culture of the isolate.”

The volunteer was Marshall himself. Five days later, and for seven mornings in a row, he experienced the classic and unpretty symptoms of severe gastritis.

Helicobacter pylori has since been blamed not only for the seething inflammation of ulcers but also for virtually all stomach cancer. Marshall’s antibiotic treatment has replaced surgery as standard care. And the wise guy booed off the stage at scientific meetings has just won the Nobel Prize.

What does all this have to do with scientific freedom? Today, U.S. government funding favors “hypothesis-driven” rather than “hypothesis-generating” research. In the former, a scientist starts with a safe supposition and conducts the experiment to prove or disprove the idea.

“If you want to get research funding, you better make sure that you’ve got the experiment half done,” Marshall told me. “You have to prove it works before they’ll fund you to test it out.”

By contrast, in hypothesis-generating research, the scientist inches forward by hunch, gathering clues and speculating on their meaning. The payoff is never clear. With today’s crimped science budgets and intense competition for grants, such risky research rarely gets funded. Proceeding on intuition, Marshall told me, “is a luxury that not many researchers have.”

It helps, he added, to be an outsider. “The people who have got a stake in the old technology are never the ones to embrace the new technology. It’s always someone a bit on the periphery – who hasn’t got anything to gain by the status quo – who is interested in changing it.”

Finally, an editorial, Researchers Proved there are No Givens in Medicine, in the Ocala, Florida, Star Banner asks the $64,000 question: “Are there still medical assumptions today that are flat-out wrong? “

This Nobel prize comes long after the two have been vindicated by subsequent research. It is both comforting to see the two get medicine’s highest prize, and unsettling: Are there still medical assumptions today that are flat-out wrong? And are there still some skeptical researchers out there who are willing to do what it takes to prove that they’re right?

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Researchers proved there are no givens in medicine

An Australian medical researcher named Dr. Barry J. Marshall broke a sacred rule in science more than 20 years ago, and thank goodness he did.

Marshall ended up experimenting on himself because nobody else believed his theory. Nobody except fellow researcher J. Robin Warren.

The two are now the latest winners of the Nobel Prize in medicine.

Back when the medical establishment believed that ulcers were caused by stress, these two researchers thought that many ulcers actually could be caused by bacteria known as Heclicobacter pylori (H. pylori for short). The theory brought them ridicule from their peers.

So, Marshall sought to prove his theory – personally. He had biopsies taken of his stomach, and doctors literally peered inside him via a gastroscopic tube. The results showed no ulcers.

Then he swallowed a major dose of H. pylori. A few days later, doctors peered into his stomach once again. Lo and behold, a nasty round of gastratis was in full bloom. He was well on his way to an ulcer – an ulcer that wasn’t caused by stress, but by bacteria that could be thwarted by an antibiotic.

This Nobel prize comes long after the two have been vindicated by subsequent research. It is both comforting to see the two get medicine’s highest prize, and unsettling: Are there still medical assumptions today that are flat-out wrong? And are there still some skeptical researchers out there who are willing to do what it takes to prove that they’re right?

If this is the effect the story of Warren and Marshall is having on the editor of the Ocala Star Banner, perhaps there is hope yet that the story and message of Peter Duesberg and the many expert scientists, journalists and lay scholars who support free discussion in AIDS and a full hearing for this distinguished scientist will get through to the great mass of the public and responsible members of the media, and eventually Washington.

If so, our purpose in this blog is to contribute to the discussion by providing readable guidance and pointers to the scientific literature, trade books and people involved in this affair for newly interested reporters and researchers, including possibly Congressional staff members and other significant parties who wish to look into the matter further.

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