Challenging Science’s Status-Quo: The tale of Barry Marshall

He even downed a liquid shot of bacteria to give himself an ulcer… Just to prove the link.

This is a story of perseverance and the“never give up” attitude of a Western Australian by the name of Barry Marshall, who won a Nobel Prize in 2005 for his work linking stomach ulcers with the bacterium Helicobacter Pylori. He had to drink a shot of the bacteria, and rely on a tabloid to champion his research, to get there.

Around 20 years earlier, he was humiliated. His discovery and research linking this spiral-shaped bug with ulcers of the stomach and duodenum received very little attention from the scientific community. He didn’t even make the best 56 of 67 abstracts to be presented at a meeting run by Australia’s Gastroenterological Society:

Barry Marshall receives notification from the Gastroenterological Society in 1983 that his abstract is amongst the bottom 20% for presentation
“To gastroenterologists, the concept of a germ causing ulcers was like saying that the Earth is flat. After that I realized my paper was going to have difficulty being accepted. You think, “It’s science; it’s got to be accepted.” But it’s not an absolute given. The idea was too weird.”

A harsh verdict for Barry Marshall, who ranked in the bottom 20% of submitted abstracts for what he judged to be pioneering work. It wasn’t just his work, of course. The Western Australian was training as a gastroenterology doctor and encountered Dr Robin Warren, a pathologist who was trying to find out the cause of painful stomach ulcers, and had in particularly found a bacteria was present in biopsies of almost every patient who had these: Helicobacter Pylori. Not only stomach ulcers, this same bacteria were also seen on biopsies of stomach cancer patients. 

Marshall was very interested in Warren’s findings, and opened the history books to investigate this spiral bug which was first described in 1893, and even suggested to have a link with ulcers back in 1940. Why had the theory linking it with ulcers disappeared in the forties? The answer is that the doctor who suspected this, again based on patients who had the organism, was encouraged to stop his research because it “wasn’t easy to prove” to the scientific community. The consensus was that bacteria couldn’t survive and thrive in the stomach acid, so would there’s no way that it could contribute to ulcer formation. Imagine if this link had been discovered four decades before.

Ulcers were caused by stress — this was the status quo. Other challengers over the decades came and went. One of these, John Lykoudos, was fined by Greek health authorities when he refused to stop giving people with ulcers antibiotics. 

But Marshall and Warren did not mind being scientific pariahs. They believed that this perception was wrong. Marshall would not give up on the hypothesis that these bacteria cause gastric ulcers, and increase the risk for stomach cancer. 

“If I was right, then treatment for ulcer disease would be revolutionized. It would be simple, cheap and it would be a cure. It seemed to me that for the sake of patients this research had to be fast tracked. The sense of urgency and frustration with the medical community was partly due to my disposition and age. However, the primary reason was a practical one. I was driven to get this theory proven quickly to provide curative treatment for the millions of people suffering with ulcers around the world.”

However, Marshall’s work was met with scepticism wherever he went.

“There was interest and support from a few but most of my work was rejected for publication and even accepted papers were significantly delayed. I was met with constant criticism that my conclusions were premature and not well supported. When the work was presented, my results were disputed and disbelieved, not on the basis of science but because they simply could not be true. It was often said that no one was able to replicate my results. This was untrue but became part of the folklore of the period. I was told that the bacteria were either contaminants or harmless commensals”.

There was, of course, another motivation to the lack of interest with Marshall’s work. 

“I tapped all the drug companies to request research funding for a computer. They all wrote back saying how difficult times were and they didn’t have any research money. But they were making a billion dollars a year for the antacid drug Zantac and another billion for Tagamet. You could make a patient feel better by removing the acid. Treated, most patients didn’t die from their ulcer and didn’t need surgery, so it was worth $100 a month per patient, a hell of a lot of money in those days. In America in the 1980s, 2–4% of the population had Tagamet tablets in their pocket. There was no incentive to find a cure… I had this discovery that could undermine a $3 billion industry, not just the drugs but the entire field of endoscopy. Every gastroenterologist was doing 20 or 30 patients a week who might have ulcers, and 25 percent of them would. Because it was a recurring disease that you could never cure, the patients kept coming back”

These portentous pecuniary walls did not faze Marshall. With immense commitment to his cause, he decided to take things a step further. He stuck to his guns and took a shot of H.Pylori himself, stirring the bug which he took from the gut of a sick patient into a broth. 

“I swizzled the organisms around in a cloudy broth and drank it the next morning”

He did not know what to expect, and was fine for a few days. But then he started vomiting and his breath became awful, and he started feeling exhausted. His wife found out, which didn’t rule out the stress hypothesis, but these were the first time he had experienced stomach inflammation symptoms in his life. He arranged an endoscopic biopsy on himself to confirm the diagnosis, treated himself with antibiotics and was cured with no lasting effects. He was convinced.

But unfortunately, others weren’t. Marshall’s research was on the verge of obscurity. In 1984, Aussie Tabloid The Star caught wind of this. Previously the domain of alien abduction and celebrity gossip, they printed the headline:

“Guinea-pig doctor discovers new cure for ulcers … and the cause”

Amazingly, this headline from a tabloid newspaper piqued the interest of scientists and funding providers, and gradually incepted the idea that this might be something worth looking into. Patients starting hearing about it, and came to Marshall asking to be given antibiotics. It took a few more years for enough other doctors to try out the “charlatan” treatment suggested in the rag and asked for by their patients, and be shocked and swayed by the results. It’s hard to find another example of tabloid health journalism having such a positive long-term impact.

Over ten years after his paper was first rejected, the National Institutes of Health (NIH) held a summit and released a statement to say:

The key to treatment of duodenal and gastric ulcer was detection and eradication of Helicobacter pylori.

Eleven years after that, Marshall and Warren were given a Nobel Prize “for their discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease”. Ulcers were transformed from a chronic and disabling condition to a much more curable one. The standard of care for an ulcer is now treatment with an antibiotic, and stomach cancer is all but eradicated from the Western world. 

Marshall’s figurative middle finger to the scientific community underlined the point that people shouldn’t just reject a theory because it contradicts what was previously believed. If medical journals are gatekeepers for the status quo, maybe something needed to change.

Barry Marshall in 2017. Ever the experimenter, he suffered an injury due to a power saw after a home DIY project. Credit: Picture: Ian Munro/The West Australian

Question everything: Science should be a constant process of curiosity and re-evaluation. Marshall had to drink a shot of spiral-shaped bugs and get picked up by a tabloid paper to show that.

Full rejection letter from the Gastroenterological Society of Australia, 1983
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Maradona (2019) Review

Maradona celebrating the league title with Napoli in 1987. Credit: Meazza Sambucetti/AP

We are in the golden age for documentary films. Netflix has opened a world, hitherto the domain of niche DVD and arthouse theatre releases, to the living room. Even within this glorious era for non-fictional storytelling (long may it last), British director Asif Kapadia has evolved the humble documentary to a truly cinematic experience. Both his Senna and Oscar-winning Amy films have cemented his name as the master of the cinematic portrait.

 
Asif Kapadia’s Senna and Amy.

Both films are outstanding, but can he surpass them with a piece about Argentina’s mercurial and controversial Number. 10 — Diego Armando Maradona? Kapadia has combed through 500 hours of Maradona’s personal archive to tell this story of this seven year period in his turbulent life. Would being granted this seal of approval by Maradona himself render the film too soft on its subject, and gloss over his many flaws and misdemeanours? Questions.

Diego Maradona was a controversial figure on and off the pitch. Source: Getty Images

The film concentrates almost entirely on Maradona’s time in Naples between 1984 and 1991, and is a portrayal of three subjects: (i) The all-too-human Diego, a hugely talented footballer whose dream was to leave Villa Fiorito and buy a house for his parents. (ii) His creation “Maradona” — the only response to the suffocating hero worship he received as a footballer who single-handedly dragged his club and country to improbable trophies, and (iii) The City of Naples — a proud and misunderstood city which was the home to Maradona for 7 years.

Maradona with Carmine Giuliano of the infamous Giuliano clan within the Camorra crime syndicate. Source: http://www.premiumsporthd.it

Seeing Maradona in motion was poetry, from his ballet-like movement on the pitch to the visceral tackles he received by frustrated opponents. His relationships and interactions with his family, friends, fans, media and mafia all make for spellbinding viewing, and this is mainly due to Maradona himself. He’s just a perfect subject — with facial expressions that capture joy anger and sadness beautifully, but are most sublime when reflecting the inner turmoil of his own mistakes and flaws, and those of the people around him.

 
Maradona in the USA World Cup 1994. Some of the more controversial points of Maradona’s career are alluded to in this documentary, though not necessarily described.

The editing of the film into such a tight package is wondrous, early cuts were more than 5 hours long apparently. Chris King has worked with Kapadia for his previous films, and this is clearly a double-act which is going from strength to strength. The soundtrack complements the film very well, with bittersweet original music from Golden Globe nominee Antonio Pinto.

There are only two minor criticisms. Some might consider the sound effect augmentation to stunning video clips a little too obvious. I enjoyed them at first, then they became a little artificial, though never enough for me not to be overwhelmed by the art I was seeing on the pitch. The second point of contention is a little harder to judge. Does Maradona’s seal of approval for Kapadia to use his personal archive render the film less critical of its controversial subject than it could be? Possibly, but at the same time we are able to get a closer portrait than we otherwise might have. And it doesn’t exactly shy away from highlighting his immaturities, his addictions and misdemeanours.

A mural of Maradona by Italian artist Jorit Agoch in the San Giovanni a Teduccio suburb of Naples. Photograph: Cesare Abbate/EPA

Either way, this is a fantastic film and concludes a glorious trilogy of genius figures, alongside Amy and Senna. It is best seen in the cinema, where the 2 hour 10 minute run time leaves the viewer wanting more. I can’t wait to see which subject Asif Kapadia chooses next.

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