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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[MUST READ] Coca-Cola’s secret influence on medical and science journalists

Please read this article from the British Medical Journal: http://www.bmj.com/content/357/bmj.j1638

 

This is a very important argument, and it is essential for healthcare professionals, journalists and politicians alike to make a concerted and aggressive effort to kick these sugar-peddling companies out of the sphere of academic influence.

The more overt “More Doctors smoke…” advertisements of yesteryear are thankfully a thing of the past, but the covert influence of sugar-saturated food companies is no less a threat to our health. Aaron and Siegel (1) report that from 2011 to 2015, the Coca-Cola Company and PepsiCo were found to sponsor 95 national health organizations, many medical and public health institutions amongst them. They also lobbied against 29 public health bills intended to reduce soda consumption or improve nutrition.

The British Nutrition Foundation, for example, lists amongst “Sustaining Members” Coca-Cola, PepsiCo, Kellogg, Nestle, Tate & Lyle and has “Corporate Members” British Sugar plc, Mars UK, KP Snacks, McDonalds, United Biscuits, Weetabix, Ocean Spray and many more. Although it is open to companies and corporations from a variety of backgrounds including healthcare and fitness, the actual members who have provided support read as a Who’s Who of Sugar Salesmen (2), making their promise of a “a focus on objective nutrition science interpretation and delivery” open to scrutiny. The American Society for Nutrition is no different, with an almost-identical list of names cropping up (3) for this group, which publishes the Journal of Nutrition.

Indeed, the editorial boards of top nutrition journals are littered by corporate affiliations with sweetie companies – The American Journal of Clinical Nutrition, for example, lists the likes of Mars, Coca-Cola, PepsiCo, Nestle, McDonald’s  and Ferrero amongst companies who have a relationship with members of their board (4). The ambassador’s reception may also be overflowing with hazelnut-and-wafer spherical treats at many other nutrition journals, who often  home of the Journal of Nutrition Education and Behavior, who have eight “corporate patron friends” and four “corporate sustaining friends.  (5)

It would be interesting to note how these journals consider submissions which report a detriment to health from these companies’ products, but when some of the largest nutrition journals display such a conflict of interest it must become clear to all that the Honey Pot relationship between “Big Food” and academia is poisonous and needs to be dealt with.

References:

(1) Sponsorship of National Health Organizations by Two Major Soda Companies. Aaron, Daniel G. et al. American Journal of Preventive Medicine , Volume 52 , Issue 1 , 20 – 30

(2) “Member Organisations – British Nutrition Foundation”. Nutrition.org.uk. N.p., 2017. Web. 10 Apr. 2017.

(3) “American Society For Nutrition – Our Sustaining Partners”. Nutrition.org. N.p., 2017. Web. 10 Apr. 2017.

(4) AJCN Editor Conflict of Interest Statement. (2017). Ajcn.nutrition.org. http://ajcn.nutrition.org/site/misc/EditorCOI.xhtml Web, 10 April. 2017.

(5) Nestle, Marion. Food Politics. 1st ed. Berkeley, Calif.: University of California Press, 2013. P112. Print.

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3D Organon VR Anatomy Atlas – As good as Gray’s Anatomy?

Very detailed Anatomy Atlas (gets your textbook and transplants it into an interactive virtual reality cadaver). The detail is fantastic, which is probably why it costs quite a lot, but some of the structures are a bit too small and the user-friendliness of the application probably needs to evolve over time. My feeling is that most people will still stick to their Gray’s Anatomy in 2017 to see how the leg bone’s connected to the… hip bone, but it’s good to see things like this being developed as this may change in the near future!

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The Body VR – A virtual reality version of the film “Fantastic Voyage” for schoolchildren

This Virtual Reality Human Body Educational Experience (think a virtual reality version of the film Fantastic Voyage) is geared towards schoolchildren. It is quite short, but as a free experience it is hard to criticise something which is aiming to combine education with some entertainment for kids, particularly given that there aren’t that many similar experiences. The same team is releasing an Anatomy Viewer as well, a Beta of which is included in this application.

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Dying with Indignity in Iran

Published on: https://iranwire.com/en/blogs/693/4344

In this guest blog, Dr Nima Ghadiri describes the harrowing experience of the end-of-life care his grandmother received in an Iranian hospital, and the betrayal of the principles of bioethics, which were first identified many centuries ago by Iranian polymaths, including Avicenna and Razi.

Avicenna (left) and Razi (right), Persian physicians and polymaths who helped define the principles of bioethics, used by healthcare professionals to this day

My beloved grandmother and closest friend Batool Sepassi died in an Iranian Hospital ICU (Intensive Care Unit) following a short illness.

During the course of a viral illness, she became increasingly short of breath and had to be admitted to a local private hospital. She had a chest infection and was taken to the intensive care unit accompanied by close family. At this point the family had separated to go to the payment desk, and my grandmother was taken to ICU, though no medical history was taken nor treatment started until payment was organized (the privilege of private healthcare).

There were some major flaws in treatment. Having been admitted with a chest problem, it took 30 hours for a chest consultant to see my grandmother, though not without a battle — we were told “this patient is not on my list” — and a serviceable X-ray was only taken the following day.

My family was only allowed an hour a day to visit my grandmother, which was extremely hard given that she thrived on closeness to family and friends. My close relatives stayed outside all day the ICU to be able to glance at my grandmother from a distance and hear her calling out for them. This was a traumatic experience, particularly when they heard the expressions “Saaket” or “Khafeh Sho” (“Shut up”) from my grandmother when she was undergoing procedures. My grandmother loved to communicate and form bonds with people, and appreciated having her close ones hold her hand during medical procedures. During all of her stay, her arm was outstretched to hold someone’s hand, but there was no one there and her hands were eventually fastened to the bed.

The course of the disease was unpredictable, and ultimately a poor prognosis was given, i.e. the chances of my grandmother’s survival diminished. During this period, interactions with nurses and doctors were punctuated by disregard and dismissal. For example, when one relative noticed that the nebulisers were inserted in my grandmother’s eyes rather than her nostrils (where they belong), this fact was dismissed with a “oh, her oxygen was high”. There were a few good doctors and nurses, but they were conspicuously outnumbered by the poor ones. When my cousin objected against intubation (insertion of a tube into the lungs) for the last few hours of life, instead of explaining the rationale, the doctor shouted at her “Do you want to kill your grandmother?” It took a lot of pressure to prevent the ICU team from doing a completely needless invasive procedure (kidney dialysis) with just a few hours of life remaining and kidney test results that had been unchanged for years.

Nevertheless, simple measures such as giving my grandmother something to drink were considered a luxury. When my grandmother was deteriorating, no provision was made to allow her to be close to loved ones. She and her family did not want her to be in an intensive care unit, and not only was she kept there against her will during the treatment phase, but she was kept there when she was about to die.

I asked my cousin to connect her to me by video call before her death during the one-hour visiting period. Her eyes were initially closed, but as soon as she heard my voice, they opened wide. Her mouth was entirely bandaged apart from a tube coming out of it, but I could see the outline of her lips moving briskly underneath all the bandages. She wanted to say something, and had never been stopped from talking to me before. She started vigorously shaking her tied arms in an attempt to communicate with me, but then realized her efforts were fruitless and her eyes started welling up with tears. In all my years of knowing her, I don’t remember her crying. She died just over an hour later, curtains drawn and no loved ones around her.

Nothing could have prepared me for this image, which remains traumatically imprinted in my mind. It will be a memory I will never forget. I keep wondering what she wanted to say – was she saying goodbye to me, or asking me to convey a message: to look after my mother, my brother, or help someone desperately in need? Finding the answer to this is a futile quest, but it is a rumination that will, sadly, remain.

Dying alone, with family not allowed to be with her is one thing, but my family were also denied the chance to see her after death. Only after begging were they able to get a brief glimpse of her in the corridor prior to entering the mortuary after challenging the comment, “She’s gone, why don’t you just go now”.

Passing away is an inevitable part of people’s existence, but the environment for this chapter of life is so important. As a doctor who works in the United Kingdom’s National Health Service, I have been well-versed in the importance of dignity in death. But in Iran, a country whose polymaths helped define the early principles of bioethics, it is unfathomable that core bioethical values were denied for such a sweet soul as my grandmother, and potentially for others. These principles include Non-Maleficence — not performing unnecessary procedures that serve just to prolong the patient’s life and often cause distress and pain to the patient — and Autonomy – respect for the desires and values of the patient, including how they want to be treated and how they want to die.

In my grandmother’s case this was with her family around her and without fruitless procedures. Denying someone’s spirit and character so manifestly in their final days and hours is criminal. These sentiments were shared by my family, and indeed being able to spend time with a loved one before and after their death to say goodbye should be a basic right, rather than just being able to observe this sorrowful moment from a distance. It should not be such as Sisyphean effort to spend time with a loved one and find out what happened during a hospital stay, hampered at all stages by a lack of sympathy and empathy alongside a degree of ageism against someone who is perceived as just a bed number rather than a human being.

A photo of Nima Ghadiri’s grandmother holding a pomegranate on Shab-e Yalda (An ancient Persian festival commemorating the Winter Solstice), three weeks before she died

I remain always indebted to my grandmother for looking after me as a child in the United Kingdom and being someone I could talk to and share my life with for so much of my existence. Even at her age, she had the spirit of someone many decades younger, was full of life and brought joy to so many. She shared all she had with charity and those less fortunate than herself. Strangers often commented on how sweet and bright she was and I used to talk to her about films, technology and current affairs. She remained a fountain of wisdom and I could not have dreamt of a better grandmother. Her grandchildren remain traumatized by the manner in which she has gone, and the suffering and abuse that she endured. Because she was such a positive and life-loving soul, I do not want the final page of her life to be negative. I am not sure how yet, but I know that I would be happy if the discussion arises for Iran, the country of Avicenna, Razi and numerous others, to re-discover what care, particularly at the end of life, means. Perhaps in the future, I will open a palliative care institute in her name.

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