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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SpringWatch — The blossoms are out!

Although blossom season isn’t as big an event in the UK as it is in East Asia, it is still enjoyed by many around the country. This bank holiday (the archaic British term for public holiday which originates from when the Bank of England closed) has been the warmest recorded which means that many families have been enjoying the blossoms and the many other delights of Spring. I don’t think I’ve ever seen so many families, young and old people, dogs enjoying early May as much as over the last few days.

British blossoms are delightful, though they do not have the symbolic meaning that they have elsewhere. In Japanese culture, cherry blossoms (Sakura) are a symbol of the transient nature of life, and are a cultural feature in art, literature and film. The way they bloom en masse, like clouds, conjures classic iconic images of Japan. There is even a hierarchy for work trips to hanami (“looking at flowers”) picnics. Its definitely on my wish list to travel to Japan for cherry blossom season, but for now I have to make do with the UK’s version, which isn’t shoddy at all (I hope you agree):

Lots of shades of colour on this street’s blossoming trees.

I like the juxtaposition of the pink blossom and the blue sky (which can be a rarity for this time of the year in the UK)

Here I am under a particularly blooming tree, taken with an old iphone camera.

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Seeing Things

An Art Exhibition inspired by the hallucinations of Charles Bonnet Syndrome

Visual Hallucinations

It was a pleasure to attend the first day of the Seeing Things interactive art exhibition, which is taking place at the lovely Forum in Norwich over the next two weeks.

Charles Bonnet Syndrome is a type of visual hallucination which people can experience after sight loss. In comparison with other types of hallucination, those who experience these know that they are just a creation of the brain as a reaction to visual loss.

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Fascinating paintings depicting some of these hallucinations. Source: Own photo


The Art of Charles Bonnet

This art exhibition, set up by the NNAB, features art from people who suffer from the syndrome, as well as other visual artists who have been inspired from speaking to those who experience these vivid hallucinations, which have their own unique attributes in comparison with other types of hallucinations.

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To the left – a bear statue in front of some upside-down cupcakes. Strange faces can also be a feature of the condition. Source: Own photo


Experiences

Dominic Ffytche, a world expert in the condition, gave a fantastic lecture about the Syndrome, and it was indeed fascinating to listen to the experienced of sufferers from the condition. The audience comprised of people who suffered from the condition, people who had not previously heard of the syndrome and clinicians, such as myself, who are aware about the condition but want to understand more and gain perspective.

I was particularly intrigued by the number of people who experience hallucinations of old period clothing from different eras, which seems to be a consistent feature of the syndrome. Interestingly, even when the syndrome was first described 250 years ago — the literature describes sufferers talking about people wearing period dress of the time. Perhaps 18th century formal-wear has a hallucinatory quality to it?

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Dr Dominic Ffytche, an expert in the condition, shows images of certain visual hallucinations that people experience. Source: own photo


Gaps

Even though Charles Bonnet Syndrome was first described 250 years ago, by a Swiss philosopher who was writing about his grandfather’s experiences having lost his sight to cataracts, we still do not know why exactly it happens. Certainly, we suspect that the brain fills in the gaps generated from visual loss by producing new fantastic pictures or old images which it might have stored. For many people, these hallucinations are not a problem but for some they can, understandably, be distressing. Certainly, it helps to understand these hallucinations and it is useful for both sufferers, the public and clinicians (such as yours truly) to be aware and understand this fascinating condition.

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An interesting hallucination — bear and inverse cupcakes. Source: own photo

To this end, it is fantastic to have an art exhibition which both raises awareness and bewitches us, humbling us as clinicians into realising there is still so much about the eyes and the brain that we don’t yet understand. Do you have any experience of this condition? Please feel free to comment below.

Links:
Royal National Institute of Blind People
Norfolk and Norwich Association for the Blind
NHS Charles Bonnet Syndrome Information

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Mary and the Witch’s Flower Spoiler-Free Review: The Birth of Studio Ponoc

Last week I caught a preview screening for the debut feature from Ghibli heir Studio Ponoc at the fantastic Cinema City Picturehouse cinema in Norwich, UK. I had consciously avoided any review of this film, apart from chancing upon a somewhat disappointing missive a few weeks before.

The cinema was packed to the rafters with cinephiles, and it was a rare pleasure to witness flawless etiquette amongst the audience (which spanned all ages). The only test for the latter was a slightly overlong, nevertheless interesting, behind-the-scenes documentary which preceded the film itself, explaining the birth of Studio Ponoc. Founder Yoshiaki Nishimura was brutally honest in his statement that the creation of a new studio was deemed necessary for several Ghibli staffers after Hayao Miyazaki’s announcement that he would not be making any more feature films. “We have young families” stated Nishimura in his explanation of the rationale behind the new studio.

Studio Ponoc

Studio Ponoc was founded in April 2015, and Nishimura brought several other Ghibli members of a similar age to himself, with the goal being the birth of a new Japanese animation dynasty. Indeed, Ponoc is a Serbo-Croatian word which means midnight or the beginning of a new day. The pedigree of Ponoc’s crew is not in doubt — its lead director, Hiromasa Yonebayashi, has already been a key animator of Spirited Away and Ponyo, before taking the reins completely for The Secret World of Arrietty and When Marnie Was There. Other animators have had roles in a number of Studio Ghibli’s masterpieces over the years.

Mary and the Witch’s Flower is the debut feature for the studio, and is scheduled for a UK-wide release on the 4th May 2018. It is based on “The Little Broomstick”, a children’s novel written by Mary Stewart in 1971. The version I saw was in Japanese, with English subtitles. The dubbed version features some stellar voice cast including the likes of Jim Broadbent and Kate Winslet. However, my personal experience is that there is always some magic lost in the dubbed versions of japanese animated films.

Film Synopsis (No Spoilers apart from those already in the Trailer)

The film starts with a bang, with a chaotic battle scene which only reveals its significance towards the end of the film. We meet Mary, a well fleshed-out young red-haired girl who does not like her hair and is inquisitive about the world. She gets annoyed easily, particularly at her own quirks, but she is caring and empathetic in her interactions with others. As a lead character, she is excellent and deserves to be the early symbol for Studio Ponoc in the same way that Totoro has been for Studio Ghibli. Indeed, our empathy for her transcends some of the finest Ghibli protagonists: Kiki, San, perhaps even Spirited Away’s Chihiro.

Mary’s world is upended following a visit into the woods, which is clearly inspired by the studio’s heritage, and the rest of the story has a magical theme (as implicated by the title) with segments which do resemble Ghibli’s classic Kiki’s Delivery Service. Mary meets a Headmistress who appears inspired by Zeniba from Spirited Away, enters a world of the arcane arts and encounters a perilous situation which threatens all that she loves. The plot is somewhat formulaic and, perhaps, lacks the flights of whimsy and depth from Ghibli’s finest works which could elevate it to a true masterpiece. However, the formula is, like a perfect witch’s potion, brewed perfectly and did not feel derivative.

Visuals

The film is mainly set in Rural England, and the behind-the-scenes featurette described how the animators travelled to England and made sketches of the countryside. Their meticulous research has paid dividends in some breathtaking English scenery, from forests filled with mist to verdant countryside. Later scenes have a psychedelic appearance which seem inspired by The Beatles’ Yellow Submarine, and have so much detail that it is impossible to appreciate them in just one viewing. To put it simply, the beauty of this film rivals anything that Studio Ghibli has done.

BBFC Age Rating

The film is rated “U” for very mild threat. Whilst I agree that the feature warrants a U rating for children to have the optimum chance to be bewitched by this film, it does actually have some intense moments, including emotive scenes involving animals.

Overall

The spirit of Ghibli permeates this film, and a tight plot is complemented by stunning visuals which rival any of the works of the studio’s progenitor. Despite a fantastical narrative, the magical whimsy of Ghibli’s finest works doesn’t quite make it over to Ponoc’s debut to forge a true masterpiece. However it is an immensely strong debut feature which Ghibliholics, fantasy fans and many more will wolf down faster than Spirited Away’s No-Face.

This kind of film needs to be championed, as a world without the beauty of Miyazaki’s legacy, would be a dark world indeed.

My rating: 4 stars out of 5.

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EGX Rezzed 2018 Review

I just attended the Rezzed games event in London for the first time. This is a spin-off from the main EGX (originally, the Eurogamer Expo) with a primary focus on indie games. It also seeks to attract young budding games-makers and journalists to the industry. The weekend had a very relaxed theme and people were immensely friendly. The location in London’s Tobacco Dock was also well-ventilated (very important when there are lots of gamers), there wasn’t much queuing required (often none), and it made for a thoroughly pleasant experience for a Spring weekend.

There were a number of games that I enjoyed both playing, and looking at. Here are some of my highlights:

Onrush

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Codemasters.com

There were, of course, smatterings of “triple A” titles, and the one which I enjoyed the most was a racing game developed by Codemasters called Onrush. This was a fast-based arcade-style racing game with various types of vehicles on a hilly terrain and it was setup as a 6vs6 competition in the expo. It reminded me of the Excitetruck remake on Nintendo Wii and MotorStorm on Playstation. The gameplay was very crisp, and it was obvious that the makers have put a lot of time testing the game to make sure it plays beautifully. The soundtrack was outstanding too. The release date is 5th June 2018.

Homo Machina

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http://www.homomachina-game.com/

This gorgeous 2D exploration game from Darjeeling Productions is inspired by the medical illustrations of Dr Fritz Kahn. Think of the concept of the Pixar film “Inside Out” with tiny little humanoids controlling your actions. I just wanted to watch the game, can’t wait for it to come out on mobile and tablet formats.

Bad North

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https://www.badnorth.com/

This game caught my eye in the Nintendo Switch section (though it will be released on all formats) – a compact little real-time strategy game on rotatable islands inhabited by humble island dwellers who are under attack from Vikings. It may look simplistic but the minimalist charm and movements (e.g. the way the arrows and rain drop) were zen bliss.

Phogs

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Image: Bitloomgames.com

This was such a wacky offering from Bitloom Games – you and a friend control a double-ended dog as you solve puzzles on various floating islands, with the aim being to feed a giant worm with either an acorn or a globe-shaped light bulb (!) The cooperative mechanic (both players sharing one controller) was amongst the finest I have every played, and the lovely pastel colours were joyful to look at. Loved it!

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Me sitting on some Phogs-theme upholstery

Strange Brigade

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Image: Strangebrigade.com

This cooperative third-person shooter by Rebellion Developments had an exuberant 1930s theme to it, I played a level as one of four diverse heroes fighting hordes of mythic beings in some kind of Egyptian setting. The visuals were stunning and the gameplay mechanics felt great, but the main attraction of the game was the over-the-top British pulp style narration.

Knights and Bikes

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http://foamswordgames.com/

This hand-painted game set on a British island seemed to have an ET/Stranger Things/Super8 style theme to it, with an 80s feel and coming-of-age theme. In the small part that I watched, there was a clear emotional underpinning to the game which suggests a lot of heart has been put into the writing and design.

The Leftfield Collection

There were some awesome little indie games in the Leftfield Room – the ones which stood out for me were Wobble Garden: a spring and light based installation which provided a sensory experience unlike any other game I’d played before. Haiku Adventure had a beautiful Japanese ukiyo-e inspired landscape scene in a puzzle game which seemed to involve using Haiku to chill out a flock of assorted wildfowl.

Other Comments

The show also had some very nice retro games, and also had a few multiplayer units for games which had already been released. I particularly enjoyed re-awakening my old puzzling skills in Sega’s Puyo Puyo Tetris. My younger brother Sina The Doc, who first suggesting we attend this expo, also enjoyed meeting some of his podcasting heroes and had a go on a game which appears inspired by the classic Theme Hospital, Two Point Hospital:

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My younger Brother on the left, Sina The Doc

A nice weekend, maybe I’ll come again next year!

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