Monday, November 06, 2006

A Cure for Cancer: the 2005 Nobel Prize winners for medicine.

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.


Anonymous Maxine said...

Spot on, Clare! Really fascinating post, even though I knew the story you have a way to grip the reader to the end.

yes, it is interesting how there are almost two hurdles on these medical science discoveries -- first getting the thing accepted by/published in the scientific literature, and then educating the medical profession to change their prescription habits.

Mind you, it should not be forgotten that there are a lot of cranks about too -- so we need checks and balances, but not closed-mindedness. Tough one.

I really did love reading your post. Thanks for writing it.

Mon Nov 06, 08:40:00 pm  
Anonymous marly said...

Another in your cross-discipline category of the deserving who are not sufficiently seen or understood...

Tue Nov 07, 02:15:00 am  
Anonymous Robin Warren said...

The story is nicely told. I wish my wife could see it.

Tue Nov 07, 09:40:00 am  
Blogger kimbofo said...

Thanks for this, Clare. It's a great post. Makes me proud to be Australian!

Tue Nov 07, 09:21:00 pm  
Anonymous clare said...

Maxine: Yes cranks...they worry me. I shy away but then sometimes I think who am I to say who is a crank and who is a genius? And don't the cranks sometimes have an essential role - needling and challenging the accepted view which one day, in some way, may turn out to be dogma? Just my thoughts. I'm probably wrong about that. Thank you very much for reading Maxine, and your comment.

Marly: Yes, I am getting quite a list - there are so many worthy people out there who I should know more about.

Wed Nov 08, 08:14:00 am  
Anonymous clare said...

Robin Warren: Thank you so much for for visiting. I am absolutely delighted you've read this and many congratulations on the prize.

Wed Nov 08, 08:15:00 am  
Anonymous clare said...

Hello Kimbofo. I'm glad you liked it - yes - it would make me proud to be Australian too.

Wed Nov 08, 08:16:00 am  
Anonymous Maxine said...

I agree with your sentiments on "cranks", Clare, and did not mean to sound harsh. However, there is a difference between the questioning mind and the reflex "this is an opportunity to wheel out my insight that relativity/evolution is wrong/perpetual motion/homeopathy/fermat's last theorem solution" etc.

I have just read too many of these types of article over the years, I am afraid -- most of them not coming from any context of what knowledge has previously gone before (Newton: "standing on the shoulders of giants") but springing, fully-fledged, out of the person's brain with no reference to the rest of the world of science.

But I am sure we don't disagree on the need for imaginative, daring questioning and the need for open-mindedness of scientific enquiry.

On a slightly different point, how lovely that Robin Warren has commented on your article.

Wed Nov 08, 09:29:00 am  
Anonymous clare said...

Oh you didn't sound harsh, Maxine!

It is just something that bothers me - that I might have laughed at Wegener and his drifting continents - and I am worried that I wouldn't recognise genius because I think it would scare me. Genius often comes along with a certain strangeness, I think -- an aggressively different way of seeing things -- which would make me edge away.

I am sure there are far more cranks than geniuses in the world submitting papers.

Your second paragraph about springing fully fledged from Newton's shoulders made me laugh. Thank you very much for that!

Wed Nov 08, 09:49:00 am  
Blogger Jonathan said...

Very interesting Clare. It made me think about that man who is supposed to eat all sorts of things like bicycles and such. Does he actually dissolve all the bits with his stomach acid, or do they just pass straight through? And if you drink coke, which is also acidic, does it make the digesting power of the stomach even stronger? I suppose it must. Is there actually anything preventative you can eat which stops these bacteria? Apart from bicycles that is.

Thu Nov 09, 10:59:00 pm  
Anonymous clare said...

Jonathan: What interesting thoughts! I really have little idea except I guess some parts could well dissolve, or at least start to dissolve.

I shouldn't think ingesting coke would make the digestive power of the stomach stronger though. The main component is phosphoric acid which although is a 'strong' acid (in the chemical sense) is quite dilute - so I would not expect the pH of the stomach to change.

I expect if you significantly change the pH of the stomach - say by taking a indigestion remedy - then the bacteria wouldn't thrive since presumably their enzymes only work at a specific (low) pH. I think this was the old method of controlling ulcers. However once the indigestion remedy is cleared from the system and more acid is made, the bacteria could flourish and the inflamation would return.

It's quite a few years since I thought about this sort of stuff. It reminds me how much I loved it. Thank you, Jonathan.

Fri Nov 10, 10:00:00 pm  

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