My grandfather died before I was born. He was a fit man who was careful of his health; an athlete in fact, and one of my earliest memories is staring at the reflection of myself in the polished sides of his trophies on my grandmother's sideboard. He specialised in the long-distance run - today I think he would have been an enthusiastic marathon runner. He was irritatingly enthusiastic about fruit and vegetables, didn't smoke or drink and yet, by his mid-forties he was suffering from the 'indigestion' that would soon kill him at the age of 48.
My brother Huw also suffered with his stomach. His problem was less severe but still painful - a gastric ulcer. He worried a lot and, in accordance with the popular view, I thought that stress and the overproduction of acid in the stomach was to blame. He was treated with the usual medication; which helped - but only while he was taking it. When my other brother, who is a pathologist, heard about this he told him to go for an antibody test; and when this came back positive the resulting course of antibiotics cured the ulcer for good. The reason that my elder brother could guide my younger one in this way was a direct result of the work by Barry J Marshall and J Robin Warren
A link from Petrona
yesterday led me to a variety of sites where I read about how these two Australian doctors won the Nobel Prize for Medicine in 2005
. Through their dogged persistence and belief in an idea (that everyone around them was ridiculing) they found a cure for gastric ulcers and, consequently, the prevention of cases like my grandfather's 'indigestion' or stomach cancer. I find it an extraordinary inspiring tale.
Food is digested in the stomach by hydrochloric acid. I have always found this quite incredible. Hydrochloric acid is what chemists call a 'strong' acid - when concentrated it makes choking fumes in the air; pour it on limestone and the rock immediately fizzes and dissolves - and yet we have this aggressive stuff in our stomachs. For the most part the stomach remains unaffected. As Aydin has explained in Snail'sTales
this is because there is a layer of mucus protecting the cells of stomach walls. The hydrochloric acid is part of the wonderful process of digestion and its job is to chemically attack whatever has been swallowed converting the bulk into molecules which are small enough to be absorbed through the stomach walls into the blood stream. This usually works quite well but sometimes the stomach becomes inflamed (gastritis) or can develop ulcers.
In the 1980s, J Robin Warren, a pathologist, was examining under high magnification a sample of stomach lining from a patient when he noticed something most unexpected: bacteria. When he looked at another sample he found more. In fact he found them in about half of the biopsies. He also observed that wherever there were bacteria the walls of the stomach close-by were inflamed.
When he told the people around him of his find they didn't believe him; the commonly held belief at the time was that the stomach with all that hydrochloric acid was such a hostile environment no bacteria could survive there.
Eventually Warren enlisted the help of a young clinician who was looking for a project, Barry J Marshall; and together they studied biopsies from 100 patients. It sounds like it was a hard slog against much opposition, but they seem to have been encouraged by the way they could actually see
the evidence (Warren used a new stain which clearly identified any colonies of bacteria in the gut), and also by the support of their co-workers and family. In an interview Marshall remember a ceramic plate with 'Nobel Prize' one of their technicians made for them; and Warren remembers his wife (who was also a doctor and mother of five children) encouraging him with her consistent belief that his work would be acknowledged one day with the Nobel prize.
Marshall then went on to cultivate the bacteria they had found in the laboratory (which are the shape of short cigarillos with tentacles at one end. You can see a photograph here
at the bottom of the page). In an interview accessed through the Nobel page
they joke about the naming of the bacteria: they were, they say, reluctant to call it after themselves because there was a suspicion at the time that the bacteria could be sexually transmitted and so they would lend their names to one of the propagators of venereal disease. In the end they plumped for Helicobacter pylori
which describes the shape of the bacteria in Latin.
Marshall had difficulty using animal tests to show that this bacteria grown in vivo
was the agent that actually caused the disease and eventually seems to have come to the private conclusion that the only answer was to infect himself. To the astonishment (and maybe consternation) of his technician he mixed together a few of the cultures to form a bacterial cocktail, gulped it down, and went off to do his ward round. He admits now he probably wouldn't be so reckless, but I suppose then he had that feeling of invulnerability of youth.
For a few days nothing happened, then he describes feeling full, and then eventually vomiting in the morning; but it was another symptom that drew everyone's attention to his ailment and ensured his admission to his family of what he had done: bad breath. His wife demanded that he take a course of antibiotics so that he would not infect his children, and since he had satisfied the third of 'Koch's postulates
' - that the cultured bacteria could cause gasterisis - he did.
Although the idea was not accepted by the Australian medics around them Marshall and Warren did find recognition in the Netherlands. At the time (and this is only in the 1980s) the gastric system was much less understood than it is today and Marshall recalls that there were many different ideas of the processes involved. However the dogma that ulcers are caused by stress was difficult to overthrow - and it is interesting to me that even in the 21st century in the UK my brother was not automatically tested for antibodies by his doctor as soon as he had been diagnosed with an ulcer. It was only because he happened to be related to a doctor that he was saved a couple of months or even years of suffering. According to this Nobel website article
published last year: ' It is now firmly established that Helicobacter pylori
causes more than 90% of duodenal ulcers and up to 80% of gastric ulcers.' So I hope things have now changed.
According to Marshall this change is unlikely in most parts of the world. The bacteria is an infection most likely picked up in childhood and can lurk, inflaming the stomach but not causing any symptoms, for years. Sometimes this is all that happens and the carrier of the bacteria passes through life unaware and symptomless. In the poorer countries with poorer hygiene conditions it is estimated half the population is infected and a large proportion of these people will develop ulcers at some stage and then, if left untreated, maybe cancer. No doubt poor hygiene was the reason my grandfather, whose childhood became impoverished when his father (who was a sailor) was blockaded into a Russian port during the revolution, was infected. Treatment with antibiotics, of course, costs money and so millions in this world are suffering when they could be treated fairly easily. Yet widescale and indiscriminate treatment is also ill-advised; the bacteria is likely to become resistant then so it is better to restrict the use of antibiotics to those who need to be treated.
The best global answer, says Marshall, is vaccination.
Today Warren is retired and pursuing his interest in photography, while Marshall continues his research. I think it is an inspiring story of fighting for an idea against all odds - and one which has an unusually happy ending. Although I do feel it is rather sad that Robin Warren's valiant wife did not live to see her husband's recognition.