Turning Medical Dogma on Its Head: Nobel Prize Winner Barry Marshall, MBBS

Marc Gozlan, MD

Disclosures

October 10, 2005

In This Article

Breaking the Dogma

Barry Marshall, MBBS

Photo courtesy of Dr. Marshall.

When did you first become interested in Helicobacter pylori? Was it in 1981, when you were a gastroenterology fellow looking for a research project?

Yes, that is correct. I first met up with Robin Warren, a pathologist, in August of 1981.

Why did you decide to work with him on the bacteria he observed in the stomach of some people with gastritis?

Well, I guess it is not a very exciting topic, but it was interesting for me because the stomach is supposed to be sterile. And it was interesting to be studying a bacterium that had not been described in the textbooks and which, in fact, should not have been there because the stomach is sterile. All the medical books at that time said that acid kills bacteria, and so the gastric juice was sterile.

A second reason might have related to the fact that my father was the engineer at a chicken factory in Perth. His factory used to make all the chickens for Kentucky Fried Chicken, and chickens were known to have these bacteria called Campylobacter. It was curious to me because I thought maybe we had a new kind of Campylobacter, and then maybe something like eating chickens would have caused it to be common.

It is often said that Dr. Warren was convinced that these bacteria somehow played a role in gastric disease, but that he had not told anyone in the scientific community about his findings. Is that right, and if so, why?

Well, Robin Warren was able to look at the histology and see that the bacteria were associated with gastritis. But actually, he did discuss it with various people, including his boss at the time. I suppose that eventually somebody would have taken an interest. It just so happens that I was the first one who came along to take an interest.

Also, most gastroenterologists doing endoscopies in those days would only take a biopsy if the patient had a peptic ulcer of the stomach, in which case they were interested in whether or not it was cancerous. They would not normally biopsy a red stomach and they would never biopsy people who were normal.

So, if you only ever took a biopsy from a cancer, then you would not be able to tell what normal people were like. And, similarly, since nearly everybody with ulcers has gastritis, and most of them have the bacteria, you could not really tell whether the bacteria were common also in healthy people or whether they were only present in people with ulcers or gastritis.

What was your first job in which you worked with H pylori?

I reviewed the clinical records of 25 patients in whom Warren had found the bacteria in gastric biopsies. I described what diseases they had or did not have. In that group of patients, there did not seem to be anything obvious. They seemed to have stomach pains, so they were having an endoscopy, but not all of them had ulcers and not all of them had cancer. So, it was hard to see a pattern just in those 25.

Of course, you didn't have a normal group to compare with those 25.

Exactly. To solve that problem, I wrote a protocol and had an ethics approval at the end of that year to do a study on 100 patients having endoscopy in which we would do a questionnaire before the patient had the endoscopy. So we were unbiased. Then, an independent gastroenterologist would do the endoscopy, and we would take the biopsies and study them in the laboratory. We did that from January to May of 1982. It was not until the end of that year -- the end of 1982 -- that I discovered the connection with ulcers. It was all blinded, so it was several months before we had the data back from analysis.

Can you talk about the first patient you treated for H pylori?

Among the 25 first patients, we saw an aged man of Russian origin. We did not have a protocol approved to treat a lot of patients -- that was in 1981 -- and we had this patient who had chronic abdominal pain. Robin Warren was impressed by the severity of the gastritis in this man. Without any other obvious known cause, it seemed that treatment with antibiotics would be worth a try, and because of our knowledge of Campylobacter, we thought a reasonable broad-spectrum antibiotic would be tetracycline. So we gave him a course of tetracycline.

Outside a research protocol, it was difficult to make conclusions, and he did not speak very good English, but he told us that he felt much better. At follow-up, I think the bacteria was suppressed or completely absent, and the gastritis had healed. But we probably followed him up too soon. In other words, we followed him up after only 2 weeks of treatment, whereas we now know that the gastritis would probably take a month or more to really heal completely. So he was the first patient, in fact, deliberately treated for H pylori.

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