Spiral bacteria

An accidental collaboration of two unlikely researchers in an unexpected place led to one of the most radical changes in medical thinking and practice in history. It resulted in the disappearance of stomach ulcers and a spectacular Nobel prize for Medicine.

The City of Perth on the west coast of Australia and its port, Fremantle, are not really the first choices on this planet where you would expect huge scientific discoveries in biomedicine to take place. Such breakthroughs usually occur within very large and wealthy urban conglomerates, to which entire networks of the world’s leading universities gravitate, and where the associated and supporting giants of the pharmaceutical and biotechnological industries have their research divisions — a sector which employs tens of thousands of the most educated people around the world.

That being said, Perth, along with Fremantle, is a real metropolis when compared to Kalgoorlie, a mining town a few hundred miles east of Perth, in Western Australia, where Barry James Marshall was born back in 1951. According to him, “all of these miners owed a lot of money and drank a lot of beer.” So, his mother, who was a nurse, decided that they needed to move before they acquire those same characteristics. His family moved to Perth when he was 8 years old, so Barry went to school there. In high school, he didn’t excel all that much, collecting solid, but mainly average marks. However, at his entrance exam and his interview to attend the Medical School of the University of Western Australia in Perth, he left a great impression, so in 1974 he successfully completed his education there. He wanted to practice family medicine.

At that point in his life, he couldn’t have known that his life would take him in an entirely different direction and that his name would be remembered in the history of medicine, most often mentioned together with another doctor who was fourteen years his senior — John Robin Warren. Dr Warren was born in Adelaide. He was already a very experienced pathologist at the time when Marshall acquired his medical degree. After years of work in Adelaide and then in Melbourne, in 1967, John Robin Warren was elected to the Royal College of Pathologists of Australia and Asia, becoming a senior pathologist at the Royal Hospital in Perth. Indeed, Perth was the place where he went on to spend the majority of his career. With Warren’s move from Melbourne to Perth, the life paths of these two doctors — whose collaboration would become one of the most famous collaborations in the history of medicine — had already come quite close, at least from a geographical point of view.

Among all of the diseases that can attack a person, and there are more than sixteen thousand of them according to the international classification of diseases, Barry Marshall was most interested in stomach ulcers. One in ten adults at the time suffered from so-called stomach ulcer disease. Drugs to reduce gastric acid secretion were among the most heavily prescribed in the entire world. Those who struggled with this particular disease suffered extremely uncomfortable pain. At the bottom of their stomach, or on the duodenum that continued from the stomach towards the intestines, they would have an open ulcer. The bottom of the ulcer was not protected from acid produced in the stomach by acid-resistant mucosa, but rather openly exposed to it. When acid made contact with an ulcer, sufferers would feel dull pain that was tremendously difficult to tolerate.

Food ingested with each meal would neutralise, move away, or flush out that acid, so eating reduced the pain. But as soon as the digested food continued its path through the digestive system and moved towards the gut, the acid production would continue and the same terrible pain would return. There was also a continuous danger that the ulcer would completely penetrate through the mucosa. The acid would then begin to leak into the abdominal cavity, causing life-threatening inflammation of the peritoneum.

Until the end of the 19th century, stomach ulcers were treated with various baths and treatments that weren’t scientifically based. Then, in the 1880s, a surgical approach was introduced. To remove the pain and prevent the unwanted perforation of the digestive tract, part of the stomach would be surgically removed. The rest of the stomach would be connected directly to the small intestine. This was a difficult operation associated with the threat of massive bleeding, so it was life-threatening. However, medical professionals soon realised that even such radical surgery would not always cure the problem. Although about half of those who were surgically treated would feel better after the procedure, for the rest the ulcer would return. About a quarter of those operated on would become the so-called “people with gastric disability”. They would lose a feeling of a healthy appetite and would, therefore, never feel entirely healthy again. These problems were so prevalent in the whole population that even the famous Mayo Clinic in the United States was practically developed to a substantial extent from the revenues from stomach surgeries. In addition, gastric cancer was the most common malignancy in the early 20th century and it was known to be associated with gastritis and stomach ulcers, although the nature of this association wasn’t clear.

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In this case, it is important to understand how the thinking about the causes of gastric ulcers has developed. For decades, the medical dogma was that the stomach ulcer was a so-called “psychosomatic illness”, where psychological stress leads to the increased secretion of gastric acid. The presence of too much acid was then presumed to upset the natural balance in the stomach. It gradually destroys the gastric mucosa at the site of the least resistance. This seemed like a logical explanation of how ulcers develop initially. It was assumed that spicy foods could also play a role through a similar mechanism. However, this disease was not easy to scientifically investigate, because it was necessary to unequivocally prove the physical existence of an ulcer in the digestive system. That was simply not possible until surprisingly recent times. Only large X-ray machines, together with a contrast liquid which the patient had to drink, made it possible to show the change in the continuity of the gastric mucosa caused by the ulcer. However, these X-ray machines were housed in the hospitals of the world’s largest cities, whose doctors at the time studied these ulcers mainly in various businessmen. Their patients often smoked a lot of cigarettes and had high blood pressure, so it was easy for researchers to assume that stress was the main cause of this disease. Ulcers in the rural population, which were also common, were not studied at all.

Some groups of scientists took a different approach: they tried to cause ulcers in rats. They would tie them up and lower them into the icy water to cause them stress, and as such — a stomach ulcer. They then wanted to demonstrate that rats can be protected from developing such ulcers by receiving drugs that prevent the secretion of stomach acid. From this, they concluded that stress causes the increased secretion of stomach acid and consequently the ulcers through a direct, causal mechanism. However, when the design of these studies in rats is more carefully scrutinized, this should not have been unequivocally concluded from the results of these experiments.

The implementation of these so-called “double-blind” experiments, which are in standard application today when it comes to proving a cause-and-effect relationship between a risk and a disease, were not yet required as key evidence at the time. The results of the research carried out on rats coincided with what everyone already believed to be true. That is why they were accepted very quickly in the research community, without further rigorous experimental verification.

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In 1979, Barry Marshall was admitted to specialise in internal medicine at the Royal Hospital in Perth. In his third year, he had to perform some scientific research as a part of his training. He started looking for pathologist Robin Warren and this was how the two of them first met. Warren told Marshall that he has an interesting problem that they could study. In samples of the gastric mucosa of patients with ulcers and stomach cancer, which he would obtain from surgeons and then studied under a microscope, he occasionally noticed an unusual microorganism. It was a bacterium that had a spiral shape — or the shape of the letter “S”. Moreover, he had also seen this bacterium in about twenty patients who had no ulcer or stomach cancer, but they did have a significant inflammation of the mucosa. This is what he found potentially interesting: he noticed that whenever he saw this unusual bacteria, the signs of inflammation were also present on the gastric mucosa. Warren asked Marshall to study the medical records of patients with this bacteria in their stomach in a little more detail. He wanted to know if there was anything common to them all, that would catch his eye.

Marshall remembered one of those patients because he had admitted her to the hospital himself. She was experiencing nausea and chronic abdominal pain, but her tests were all normal. She was eventually referred to a psychiatrist, where she was given antidepressant medication. An even more interesting patient was an elderly Russian man. He reported to the hospital with severe stomach pain. In the absence of a clear diagnosis, doctors hypothesised that there his intestinal arteries must be narrowing, occasionally leading to pain, just as the atherosclerosis of the arteries of the heart causes chest pain. However, the doctors wanted to also account for the possibility of unrecognised inflammation somewhere along the intestines. This is why they prescribed him an antibiotic, just in case. The 80-year-old returned for a check-up two weeks later, but this time he was fully recovered, he even had a spring in his step. His stomach pain seemed to have been cured by the antibiotics he was prescribed. That was a rather unexpected turn of events.

As Marshall still had his fourth year of training ahead of him, and he was intrigued by the aforementioned cases, he decided to conduct a small clinical study. Among the hundred patients admitted to the hospital for stomach pain, he looked for signs of infection of the digestive system caused by an unusual spiral-shaped bacterium, which Warren had previously identified as potentially intriguing. Their joint research began in the spring of 1982. It was a very unusual research avenue to choose. The medical community believed that the whole purpose of the human stomach — and its incredibly acidic interior — was to break down food into digestible parts. Gastric acid was supposed to destroy all of the bacteria that could possibly be residing in food. This would protect the digestive tract from dangerous infections and poisoning. No one imagined that there may be a form of life that could possibly survive the insanely high acidity in the stomach. That’s why the Marshall and Warren project was similar to conducting a study of bacteria living in the crater of a volcano, or in Arctic ice. Everyone’s first thought at the time was that there simply can’t be any bacteria in the stomach, so any study of it would be considered a pointless exercise.

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The presence of bacteria in any tissue of the human body can be confirmed by taking a swab, or a small sample of that tissue, which is then planted on a nutrient medium. The bacteria should then start to quickly multiply. The nutrient medium is located at the bottom of a round glass jar, in so-called Petri dishes. Marshall took a sample of the gastric mucosa from all of his patients suspected of having an ulcer or gastric cancer. He did this through a tube, which he would lower into their stomachs through their mouths and down through their oesophagus. He would then ask the hospital’s microbiology lab staff to plant the sample on a nutrient medium. He was wondering if any strain of bacteria would start to grow. According to the expectations of the time, the medium should remain unchanged because there simply shouldn’t be any bacteria in the stomach. But if anything was to grow, that would be a very interesting finding indeed.

Much to the disappointment of Marshall and Warren, no bacteria grew on the first thirty samples planted on nutrient media. However, according to the standard procedure, the technicians in the laboratory threw the cultures away after only a couple of days. They did so with all of the samples they received for analysis because most of them were swabs from children’s throats and tonsils. After two days, a number of other microorganisms that are constantly present in the mouth, but which don’t cause a sore throat, would begin to grow en masse. At that point, the culture in the medium ceases to be useful for making a diagnosis. However, there shouldn’t have been any other bacteria present in the stomach. So, the technicians could have waited longer, but they didn’t. They simply followed their standard protocol which was designed mainly for throat infections in children.

However, over the Easter holidays, samples taken from the stomachs of the 34th and 35th patients remained in the hospital from Thursday until Tuesday. When the technicians returned to the lab, they found a significantly grown culture of spiral bacteria in Petri dishes. This unusual bacterium grew very slowly and took several days to develop into a noticeable colony. Along with it, no other bacteria grew on the nutrient medium, confirming that the cultures of samples from the stomach were not “contaminated” by some other bacteria, too. In the next thirteen patients, the research team allowed the cultures to grow for a significantly longer period of time. They all had spiral bacteria in their stomachs, but nothing else. Whatever this bacterium was, stomach acid obviously didn’t manage to kill it. Warren called it Campylobacter pyloridis, believing that it belonged to the Campylobacter bacterial family. Only later on did it come to light that it is a member of another bacterial family, and the spiral bacterium would be given the name by which the entire medical world knows it today — Helicobacter pylori. Whatever its final name was to become, Marshall and Warren knew then that they might be onto something extremely important.

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In that very same year, 1983, they sent a scientific paper with a summary of their previous results to the scientific journal of the Australian Association of Gastroenterologists. Anonymous reviewers, who received their work for evaluation, rejected it and rated it as one of the worst 10 per cents of the research articles received that year.

While waiting for that crushing response from the journal, Marshall and Warren continued with their research. From gastric and duodenal ulcers, where they now found the bacterium with certainty in the large majority of their patients, they extended the study to patients with gastritis and stomach cancer. They observed that all patients with gastric cancer develop the malignant disease with the background of prolonged inflammation and irritation of the gastric mucosa. If there were no spiral bacteria present, then there was no inflammation there, either. Thus, the spiral bacterium appeared to be an important cause of the chronic inflammation of the gastric mucosa. Consequently, it seemed to be an underlying factor in gastric cancer, too. Therefore, Marshall and Warren concluded that the spiral bacterium could be among the causes of stomach cancer. However, medicine at the time considered malignant growths to be non-communicable diseases and didn’t link them to bacterial contagions at all.

Marshall then presented his paper on the association between spiral bacteria, inflammation of gastric mucosa and gastric cancer at the annual congress of the Royal Australian College of Physicians in Perth. According to his own statements, it was then that he first experienced what it felt like to tell hundreds of colleagues about something that seemed very important and exciting to him, only to be greeted by a wall of silence and total scepticism. He knew that he had respected all of the scientific methods, and he expected his work to be accepted with enthusiasm. However, it was then that he realised that his idea was far too radical for anyone to admit to actually taking it seriously.

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As he began to gather more respondents, he started to expand his research. Still, because he was still a very young doctor, Marshall began to write to pharmaceutical companies. He asked them for small donations to purchase a personal computer, on which he could store his data. It was 1983, and personal computers were still not cheap, nor were they widely available. He received an answer from all of the pharmaceutical companies. They all wrote that the economic situation was difficult and that times were uncertain, so they could not sponsor scientific research. This didn’t leave much of an impression on him, because he knew that these companies earned about a billion dollars per year at the time on the sales of ranitidine (“Zantac”), which blocked the secretion of stomach acid, and another billion per year for cimetidine (“Tagamet”) — amounts that would be much higher today due to inflation.

Why were these two drugs so widely prescribed? Reducing acid secretion would significantly reduce pain, as the ulcer would no longer come into contact with as much gastric acid. In addition, most patients would no longer be threatened by the perforation of the gastric mucosa through excess acid production, and thus by gastric surgery, which always carried some risk of significant bleeding and death. These pharmaceutical effects alone were, apparently, worth about 100 dollars per month per drug user to the health care systems. In North America in the 1980s, one in every 30 citizens carried cimetidine tablets in their pockets. So, hardly anyone had much interest vested in changing such a situation, least of all the pharmaceutical industry.

Marshall, however, received a new impetus for his struggle — and it came right from within the circles of the pharmaceutical industry. One company developed a product which they named Denel and it contained bismuth. This is a chemical element whose compounds, such as carbonates and salicylates, have historically been used in medicine to disinfect, to treat diarrhoea and even syphilis, because it killed bacteria. It was similar to Pepto-Bismol, a popular product that was already being sold in the U.S. to control the symptoms of stomach ulcers. The company’s researchers turned to Marshall because they showed, in their clinical trials, that Denel seemingly treated stomach ulcers just as successfully as the mass-prescribed cimetidine.

This surprised them because Denel, unlike cimetidine, should have no effect on gastric acid secretion. They concluded that the control of acid secretion may not be the most important thing in the treatment of ulcers. They were particularly surprised that, in about a third of those treated with Denel, stomach ulcers wouldn’t return after they stopped the drug treatment. With the mass-prescribed ranitidine and cimetidine, i.e., the stomach acid blockers, the ulcer would return over time in practically all patients within just one year.

Scientists from the company that contacted Marshall realised, based on these experiments, that there must be some underlying problem with the stomach ulcer their drug works on — but it could not have been the acid secretion. Marshall requested photos of their examinations of the gastric mucosa “before” and “after” the administration of bismuth. He was excited when he spotted spiral bacteria in the first set of images, while they disappeared in the second set. It seemed that this new drug, Denel, might cure the ulcer by somehow removing the presence of spiral bacteria.

Marshall then descended to the lab where he grew cultures of that spiral bacteria. He added Denel to the glass jars with a nutrient medium. Denel killed all of the bacteria that were growing in the jar. Marshall thus obtained the first evidence that a drug that kills spiral bacteria also cures stomach ulcers. It did so even better than acid blockers, where the ulcer still returned despite treatment. Delighted by this discovery, the producers of Denel organised a presentation for Marshall at an international conference of microbiologists in Brussels. This was a good move because the microbiologists would have shown significantly less resistance towards such results than the gastroenterologists. Encouraged, Marshall and Warren wrote a scientific paper on this discovery in 1983. But wherever they tried to publish it, gastroenterologists among the reviewers flatly rejected their results, expressing utter scepticism.

It should not be forgotten that they tried to publish the discovery that could have undermined an industry worth more than a whopping 2 billion US dollars at the time — which would be worth many times more today. However, it was more than the interests of the pharmaceutical industry that it ‘’toyed’’ with. Big pharma generously supported research projects of physicians in hospitals. It was also heavily present in the entire field of gastroenterology, especially in regard to endoscopic examinations. At the time, every gastroenterologist examined at least twenty patients with suspected stomach ulcers each week. In every fourth patient, an ulcer would indeed be detected. As long as the ulcer was treated by reducing the secretion of the stomach acid, it remained a disease that would keep forcing the patients to come back. This ensured a constant influx of patients into the hospital wards. If Marshall and Warren turned out to be right, these gastroenterology patients would have to be moved to the infectious diseases department, where they would be simply, cheaply, and permanently treated with antibiotics. Gastroenterologists would be left without a large number of their patients, while the pharmaceutical industry would lose its best-selling drugs. Only then did Marshall and Warren begin to realise the potential impact of their discovery would be on real-world medicine and how difficult it would be to change things from where they were at the time.

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However, despite the remarkable obstacles they faced, they didn’t give up. They understood that, in their further steps, they would need to gather much stronger, experimental evidence. Up to that point, they only managed to demonstrate that this unusual bacterium was almost always located where the ulcer was present. In scientific circles, this still didn’t carry enough weight. Correlation does not imply causation. As an example, both the disease and the bacteria could, in some way, depend on stomach acid. Admittedly, the effect of bismuth was the first hint of the possible cause-and-effect relationship between spiral bacteria and ulcers, but this only seemed to be relevant to about a third of all patients.

Marshall knew that he needed stronger evidence to convince his colleagues. He tried to infect various animals with the spiral bacterium: pigs, mice and rats. He was surprised to find that the spiral bacterium was adapted only to humans. It was necessary, therefore, to perform an experiment on humans. He would need to infect healthy people with spiral bacteria. He should then wait and check how many would develop gastritis or a stomach ulcer. Once they do, they then had to be completely cured with an antibiotic. Afterwards, an examination of the stomach should prove that the bacteria were no longer present. A study that could demonstrate all this would seem like solid evidence and it would surely generate attention. But no ethics committee would grant a permit for such an experiment to take place, where healthy people would intentionally be infected with a spiral bacterium to develop a disease. Marshall was faced with a really difficult task. In the world of biomedical research, his proposed research would be ethical if it were to be tested out on laboratory animals. Unfortunately for his plans, the spiral bacterium that he and Warren identified seemed to be adapted only to humans. At this point, Marshall seemed to have reached a brick wall. His journey was brought to a stop and he could go no further.

Marshall was increasingly troubled by his acquired knowledge. It was not easy anymore seeing the patients at his hospital who were suffering from stomach ulcers. Some of them even died from stomach acid seeping through their stomach wall, or from complications of the surgery, while he believed that they could have been cured by antibiotics. This made him increasingly determined. When he encountered his next patient with severe gastritis, Marshall took a sample from his stomach, cultured it on a nutrient medium in the lab and grew strains of spiral bacteria in several glass jars. Then, he examined which antibiotic would destroy it the most effectively. The combination of metronidazole and bismuth removed the entire colony of spiral bacteria.

He then applied this treatment to the patient. It worked really well. He then examined the patient’s gastric mucosa with an endoscope. There were no further signs of the disease present.

After that, he took the spiral bacteria from the glass jar in which he had grown them. He mixed them into some soup.

Then, he sat down and ate the soup.

He didn’t think anything was going to happen quickly, knowing that the spiral bacterium grew at a relatively slow pace. But his stomach began to gurgle more frequently in the coming days. After five days, he started waking up in the morning feeling severely nauseous. He would then need to run to the bathroom and vomit. He was still going to work, although he felt very tired and slept poorly. He also developed rotten-smelling breath from his mouth, which was noticed by his mother. After about ten days, he asked his colleagues to examine him endoscopically. Spiral bacteria were present everywhere in his stomach, and inflammation of his stomach wall had also developed.

He then decided to tell his wife what he had done. She panicked, telling him that he had to stop the experiment urgently and take some antibiotics. She feared that both she and the children would be infected. She was particularly worried that everyone would get ulcers which could then progress into stomach cancer. Once Marshall experienced the first encounter of the stomach with a spiral bacterium himself, he realised that many people probably become infected at an early age, when they roam around with dirty hands and put everything inside their mouths. Indeed, many babies and young children tend to vomit for no apparent reason. One such episode could easily signify that spiral bacteria was first introduced to the stomach. This is why it can be found in the stomachs of so many people, but in most cases it doesn’t cause any noticeable symptoms. Inflammation of the stomach wall or ulcer occurs only in a small proportion of people, who obviously have some additional, special predisposition or may be exposed to additional risks.

A synthesis of the research done by Marshall and Warren was published in The Medical Journal of Australia in 1985. They gathered evidence that Helicobacter pylori causes up to 80% of gastric ulcers and 90% of duodenal ulcers. They suggested that the treatment with acid blockers works only temporarily because the bacteria survive and continue to support the inflammation, which then leads to the development of ulcers, and also certain forms of cancer. They showed how antibiotics cure most stomach and duodenal ulcers. They concluded that working at a somewhat remote academic location helped them in this discovery because they could develop their hypotheses and test them without the interference of the prevailing biomedical beliefs of the time. Thanks to Marshall and Warren, stomach ulcers are no longer a chronic, disabling disease, but can be cured with antibiotics.

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Following the publication of their paper, many would expect mass campaigns to introduce a new approach to the treatment of gastric ulcers, which would also prevent gastric cancer. Instead, almost nothing happened. The description of their work continued to exist on the pages of this Australian scientific journal for another decade. The news about the effectiveness of antibiotic treatment spread primarily among patients with stomach ulcers by word of mouth. This was because the knowledge of an effective treatment meant the most to them. But their gastroenterologists still weren’t treating them with antibiotics. Meanwhile, Marshall was perfecting approaches to treatment. By the end of 1985, he was able to cure almost all of the patients who entered his hospital with a stomach ulcer or with inflammation of the stomach wall. Some patients came to him secretly, from all parts of Australia, such as highly skilled workers and executives who didn’t want their employers to know they were suffering from a stomach ulcer and wanted to be cured quickly.

How did Marshall and Warren eventually manage to convince the medical community of the importance of their discovery? This didn’t happen in a straightforward way and, yet again, it required little luck. Marshall temporarily went to work in the USA, which proved to be a good move. There, due to a combination of circumstances, he noticed that Procter & Gamble, the huge corporation that produced Pepto-Bismol, was also the largest client of the well-known company Hill & Knowlton, which specialises in public relations. When Marshall moved to the US, these channels showed interest in airing the news of his discoveries during his work back in Australia. The stories had deliberately bombastic headlines, such as: “A guinea pig doctor experimented on himself to cure his stomach ulcer” and they were published by magazines with the widest audience — Reader’s Digest and the National Enquirer. They may not have had a positive impact on Marshall’s credibility among other scientists, but they created interest in his discoveries among a very large number of stomach ulcer patients across the United States. Public pressure began to mount on the U.S. National Institutes of Health, as well as their Food and Drug Administration, to test and approve stomach ulcer and gastritis treatment with antibiotics. Both agencies responded positively, primarily because antibiotics were already licensed and were thought of as very safe drugs, so this new approach to treating ulcers and gastric inflammation didn’t pose a risk to patients. From that point, a change in medical practice began to spread quite quickly and the results were very positive and satisfactory for the patients.

Therefore, between 1993 and 1996, the U.S. medical community concluded that antibiotic treatment of spiral bacteria in patients with gastric ulcers was superior to all previous approaches.

Still, let us remember that spiral bacteria caused the most stomach and duodenal ulcers, but it wasn’t responsible for all cases. Therefore, a diagnostic test for the presence of the bacterium in the stomach had to be performed, so that antibiotics were used only in patients infected with the Helicobacter pylori. Fortunately, Helicobacter had the property of the decomposition of the urea to produce ammonia. Based on that knowledge, Marshall and Warren developed a test for the presence of 14C-urea in exhaled air. The discovery was patented, sold to a pharmaceutical company, and is now being applied around the world. This helped to eventually make this exceptional pair of scientists very well off through their research.

Thanks to the scientific collaboration of Marshall and Warren, stomach ulcers are now treated with antibiotics. Gastric cancer, one of the most common forms of malignant tumours, has meanwhile almost disappeared from the high-income countries of the world. The two colleagues are also credited with one of the most radical changes in medical thinking and practice over the past century. They showed that even malignant tumours can have infectious microbes as their primary cause. Barry Marshall received the Alpert Award in 1994; the Australian Medical Association Prize, as well as the extremely prestigious Lasker Prize, which often precedes the Nobel Prize, in 1995; a year later, he was awarded another prize of a similar level of prestige, that of the Gairdner Foundation in Canada. In 1997 he received the Paul Ehrlich and Ludwig Darmstaedter Prize; in 1998, the Heineken Prize for Medicine, the Florey Medal, and the Buchanan Medal of the Royal Society of London. He was elected a Fellow of the Royal Society of London in 1999 and received the Benjamin Franklin Medal for Life Sciences in the same year. In 2002, he received the Keio Award for Medical Sciences. And then, in 2005, Barry James Marshall and John Robin Warren received the Nobel Prize in Physiology or Medicine. A documentary about Warren and Marshall’s work was made in Australia in 2006, entitled “The Winner’s Guide to the Nobel Prize”.

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After this story, some open questions still remain. Do we need, perhaps, fresh views on other diseases whose causes we still don’t understand well enough? The spiral bacterium — Helicobacter pylori — has shown that in diseases, the causes of which remain unexplained, we cannot rule out the action of infectious microbes. In childhood and at a young age, we all contract and get over many infectious diseases, which leave us with some kind of “scars” on our immune systems. The question is whether such scars, with some mechanisms that are still insufficiently known to us, can eventually lead to the development of various chronic diseases much later in life. Perhaps we still don’t understand the exact cause of many late-onset diseases simply because they were caused much earlier in life than we tend to expect and through events that we don’t usually associate with their symptoms.


Declaration: Professor Igor Rudan, FRSE, is the President of the International Society of Global Health; co-Editor-in-Chief of the “Journal of Global Health”; Joint Director of the Centre for Global Health and the WHO Collaborating Centre at the University of Edinburgh, UK.

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