The drugs worked well, and acidity was thought to be central to the condition - patients had previously been advised to drink milk and take antacids. But Warren, the more retiring of the duo, had noticed the presence of spiral-shaped bacteria in biopsy samples from ulcered stomachs, and saw that they were always accompanied by signs of inflammation.
Warren recruited the young medical intern Marshall to work with him at the Royal Perth Hospital, in an attempt to isolate and culture the bacteria. The bacteria looked like Campylobacter , a newly discovered family known to cause gut infection in poultry.
Marshall's repeated attempts to culture it early in failed, however - until the Easter holidays, when the culture plates were accidentally left in the incubator over a four-day break. This did the trick. The problem, it turned out, was that H. The bacteria was then shown not to be Campylobacter at all, but an entirely new genus.
Marshall and Warren went on to show that patients with ulcers could be successfully treated with antibiotics. And unlike patients treated with acid-suppressing drugs, their ulcers did not return. Fellow gastroenterologists nevertheless continued to resist the idea. Even some bacteriologists were at first suspicious - the highly acidic stomach seemed too hostile an environment to host bugs.
Typically at dawn I would wake up, run to the toilet and vomit. And it was a clear liquid, as if you had drunk a pint of water and regurgitated it straight back. Not only that, there was no acid in it. I knew there was something unusual about vomiting and not having acid. There was not really pain, but each evening I was feeling very full after the evening meal.
I was starting to take sips of water halfway through my meal to help get it down. I noted that, but it was a very vague kind of a symptom. Finally, after 10 days, I had the biopsy, had another endoscopy — and the bacteria were everywhere. In the lining of my stomach there were absolute millions of the white cells that we call pus cells, polymorphs. There was no acid being produced by my stomach. So I had done that; I had developed the disease gastritis and cultured the bacteria from myself.
They were fulfilled 10 years later, using a gerbil, an animal rather like a big mouse. Gerbils get human diseases, and if you infect them with the human bacterium Helicobacter , 50 per cent of them will develop a stomach ulcer in six months. And about 20 per cent get stomach cancer after, say, a year.
Working toward vindication, and beyond. I remember the days when you still had eminent gastroenterologists opposing you. How did you reach the point where your finding was accepted? A big battle was still going on.
We needed people in the United States to take the treatment which we had developed. Well, to convince people in other countries you have to duplicate the study and get the same data. So in the US they tried research products and played around a bit, as we had done. And after four years they had a treatment they could use there. Then they did a double-blind study and got exactly the same results as we had in Australia — in fact, better. It could still be said that this was a psychosomatic illness, that the patient could get positive vibes from the doctor and know that he was getting the best treatment.
Of course his ulcer would heal, because he would be happier. That trial was done in Austria and was then published in America, in the New England Journal [of Medicine] , which would have the most stringent criteria for medical research. The implication, once you say that in the United States and the NIH [National Institutes of Health] or somebody like that puts a document out and everyone accepts it, is that you have to follow it.
In there were thousands of professors and scientists in the US making a living off Helicobacter. I was the same! I was well and truly on the bandwagon. I had been on the lecture circuit for a few years, and having this same argument in debates at medical conferences for years. Now we were pushing the envelope — testing out new treatments, new cultures, finding out how the bacteria could live in acid, evaluating blood tests. I had invented a breath test, and we were working with a pharmaceutical company in the US to bring that to market so that when the GPs started treated Helicobacter they could do a simple test on the patients and not need to have endoscopy every time.
The breath test was crucial. So I worked on the development of the breath test, plus being a professor at the university and whatever else. I worked in the US for 10 years. Well, it was good to see the two systems. In Australia you could do all kinds of research for free, so things could happen quickly in an embryonic stage. If you can do it for free, you can start it next week, provided your mates are doing you a favour.
In the US you could not do any research unless there was money changing hands, because the pathologist had to pay salaries and he had to run his department at a profit. Ideally, you want to be doing about 30 per cent clinic, because then you can test out your research on your patients. And you do only as much research as you have funding for. I saw a breath test for something else, for malabsorption — you can basically give a chemical and see something coming out in the breath.
By then I had a urease test on Helicobacter. We knew that probably the bacteria survived in the stomach by making lots of ammonia, which neutralises the acid. But, on the other side of the equation, it makes bicarbonate and CO2. As I recall it, the first person we did the breath test on was one of the nuclear medicine physicians, Agatha van der Schaaf.
She was the first guinea pig, and I think she was negative. But I tested a few gastroenterologists and they were all positive.
And, of course, that made sense. In medicine, the correct treatment, the correct strategy and the most efficient strategy will eventually win, whatever happens — but it may be delayed. In the year when I arrived in the US there were hardly any papers on Helicobacter. The second thing was that my paper on the diagnosis was being rejected.
The medical journal was just about to send it back to me with a rejection letter. But I happened to be sitting at the bar with a guy who turned out to be the editor of that journal, and telling him about it over a beer.
It did. The personal stuff was usually said behind my back, and my wife used to catch a bit of it. For example, I was at a conference, presenting our work. What are you going to do next? And my wife would be on the bus tour with all the other wives, sitting in behind some of them. They had that guy from Australia talking about bacteria in the stomach. What a load of rubbish.
So things like that used to go on behind the scenes. By then I was pretty thick-skinned. In fact, the worst day in the whole lot of it was the day we had a rejection letter from the Australian gastroenterologists. Robin and I were keen to submit a paper at the Australian meeting of gastroenterology which was held in Perth that year. But it was rejected. This is a hot subject. So my wife and I went to Europe, where it was the top presentation at the whole meeting.
After that we came back very thick-skinned; we had risen above it. Yes, I was an outsider at that point. By the end of that year, Robin and I knew so much about ulcers and we knew the truth; we could see a pattern to it all, so we could make sense of it. And nobody could tell us anything about ulcers, because we had an answer for every single sceptic.
Well, I am a bit. If you look at, maybe, publications listed in my CV, you see that they might include 30 or 40 good ones and 70 that are not so highly rated. And I know that is because they have built up a lab with five scientists who each publish five papers a year. You can easily get your numbers up that way; that is really how you could be a professional researcher of professional standing. It is very hard, and I was never particularly good at it because I was interested in too many other things.
I was interested in patients and interested in diagnostic methods and treatments. It was my mechanical ability that brought me into the diagnosis part of it.
Also, thinking out of the box can be a good idea. That was the day Robin and I suddenly realised that we had discovered ulcers. And that was way back, probably in the first quarter of When we had been cogitating over this for three or four months, I left Royal Perth, went to another hospital and tested out the theory on some new patients.
At that other hospital the ulcer patients had the bacterium as well, and I started treating it and figuring out what the treatment could be. So the secret behind the successful ulcer treatments was that they were also antibiotics. I do one session a week of the endoscopy, which is half a day, and a session of looking after their prescriptions, talking to them on the phone and a few things like that. Can you help? There are thousands of people doing research on this and sure, it causes ulcers and gastric cancer.
But the other side of the coin is that 80 per cent of people with Helicobacter have no symptoms. Helicobacter already does that. It lives in your stomach, and if your white cells become too vigorous it poisons them with a toxin and they all back off a bit, and then everything goes quiet for a while. I developed a theory that the reason you get ulcers is that your immune system is too vigorous and the white cells knock a hole in your stomach and cause the ulcer in the first instance. But the Helicobacter doesn't want you to have an ulcer so it keeps the white cells under control.
Maybe we can use that. There are a lot of such theories. You need to let your kids crawl around on the floor and so on, to get an immunity. I think that if you figured out how many billions of dollars are wasted because all of us are getting sick every few years, just with this really severe illness out of all the diseases in the Australian community, you would say there is a lot of value in making an influenza vaccine.
Are you assuming this would be a mucosal immunisation which would spread to the respiratory tract? If we can make this Helicobacter weaker so that it lasts in your system for only a few weeks, and if we put an influenza vaccine in it, you could be drinking Helicobacter exactly as I did. If we could weaken it a bit, maybe you could drink it, you could have a temporary infection for a few weeks where you were not really sure there was anything going on, and meantime your immune system would become aggravated and fight against the Helicobacter and against the influenza vaccine stuck on the side of it.
How great would that be! Yes, we have to get rid of the Helicobacter. The future of vaccination might be that you would just see the vaccine in the supermarket. Everyone would have it, and not worry about influenza ever again. I have to be honest there. I reckon it will take a couple of years for this to catch on. So he had three anniversaries which, coincidentally, we duplicated years later.
I got the bacteria and cultured them, then worked out which antibiotics could kill his infection in the lab — in this case, bismuth plus metronidazole. I treated the patient and did an endoscopy to make sure his infection was gone. After that I swizzled the organisms around in a cloudy broth and drank it the next morning. Once I got it off my stomach, I would be good enough to go to work, although I was feeling tired and not sleeping so well.
After 10 days I had an endoscopy that showed the bacteria were everywhere. There was all this inflammation, and gastritis had developed. A: I should have recorded it, but the meaning was that I had to stop the experiment and take some antibiotics.
Q: Your personal experience convinced you that Helicobacter infection starts in childhood. Can you explain? Then did people change their thinking?
A: No, it sat there as a hypothesis for another 10 years. Some patients heard about it, but gastroenterologists still would not treat them with antibiotics. Instead, they would focus on the possible complications of antibiotics. After I came to work in the States, publicity would come out. Our credibility might have dropped a bit, but interest in our work built.
People are dying from peptic ulcers. We need to accelerate the process. Between and , the whole country changed color. Q: You have since devised tests for H. How do they work? A: The first diagnostic test, done after a biopsy, detected Helicobacter that broke down urea to form ammonia.
More recently I developed a breath test for Helicobacter based on the same principle. That test was bought by Kimberly-Clark, and they sell it all over the world. That one little discovery set me up for the rest of my career. Q: Is it possible to create a vaccine against Helicobacter? A: After 20 years and a lot of hard work by companies spending millions, we have still been unable to make a vaccine.
So that is my vaccine project, and it is my life at the moment. You just take one sip and three days later the whole surface of your stomach is covered with the modified Helicobacter. Over a few weeks, your immune system starts reacting against it and also sees the influenza proteins stuck on the surface, so it starts creating antibodies against influenza as well. Whereas we are building swine flu vaccine as we speak. We know the sequence of the swine flu virus. You can make the DNA. You can put it in Helicobacter — with a home brew kit, I can make , doses in my bathtub.
Using the same method, a Helicobacter vaccine against malaria would be dirt cheap. You could make million doses in the middle of Africa without a refrigerator.
You could distribute it at the airport through something like a Coke machine. Q: Based on this experience, should we be taking a fresh look at other diseases that do not have well-understood causes? By the s, infectious disease was considered a has-been specialty, and experts were saying everyone with an infectious disease could be cured by antibiotics.
But what about when your kids were 2 years old? Well, you think it is over. It might be gone, but it has put a scar on their immune system. There are hundreds of diseases like this, and no one knows the cause. Today, it has been firmly proven by many researchers world-wide that H. The remaining ulcers are usually a result of regular use of pain medications called non-steroidal anti-inflammatory drugs NSAIDs , which includes aspirin and ibuprofen.
The H. A peptic ulcer is a sore or break in the lining of the digestive tract where gastric juices acid and pepsin are present. Most ulcers occur in the first part of the small intestine duodenal ulcers but they can also form in the stomach gastric ulcers.
When the H. Both the acid and the bacteria irritate the lining and cause a sore, or ulcer, to form. At this time, it is unclear how these bacteria spread from person to person. It is also unknown why only a small percentage of people infected with H.
0コメント