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Barry Marshall

Interview: Barry Marshall
Nobel Prize in Medicine

May 23, 1998
Jackson Hole, Wyoming

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We understand you grew up in Western Australia. What was that like when you were growing up?

Barry Marshall: I was born in Kalgoorlie, which is really like the mining areas in Colorado. It's 300 miles from the coast of Western Australia. My father was a tradesman on the mines, and my mother was a nurse. Maybe that's the medical connection coming out there.

We moved to Perth when I was about eight years old. It was a bit difficult coming from a country school, where I was one of the top students, to a city school where I was just one of many, many students. It was a bit of a shock to me, I suppose. Perth was probably half a million people then, and we didn't have TV until I was about ten years old, didn't have a phone for many years, didn't have a car for many years. So one thing I thought about thinking back on my childhood is that there were so many times when I had a lot of boredom, with nothing to do. It's just so lucky these days that children have all these other things that they can do: communication things, electronics, television. So I'm never one of these people that downplays the role of television, because there's nothing worse than boredom, as far as I can tell.

Did your family enjoy reading? Did you have books around?

Barry Marshall: Oh, yeah. I used to read a lot. I suppose early on I read all the Sir Walter Scotts. I remember at school we used to have a chemistry series which was probably Time magazine or Disney, or something. I was always very interested in chemistry. I was the oldest of four children, I had two younger brothers and a younger sister.

Our father, because he was a tradesman, he always had lots of tools -- oxyacetylene, welding, arc welders -- and we used to buy chemicals and make gunpowder and explosives and fireworks. All kinds of interesting boy-type of projects. I could have grown up to be a Unabomber, I know. So it was an exciting childhood. I think maybe people can't afford to let their children get up to stuff like that nowadays, it's really too dangerous.

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You still have all of your digits.

Barry Marshall: I came close a couple of times though, I can tell you. But it was an interesting childhood. I was always interested in science. We always had the opportunity to have a go at making something, because we had all the tools there. My father did a trade in a railway shop. Then he became an engineer on a whale chaser. In Western Australia, the boats chasing the whales in those days were actually refurbished ex-World War II PT boats. He did correspondence courses in diesel engineering and refrigeration, so there were always interesting technical books around the place that I could read.

Did you ever go out on one of the whale chasers?

Barry Marshall: We used to ride them when they came back from the season. They would go from the coast, on the river, from where it met the sea, up to Perth City, which is about eight miles. It was a pretty exciting time.

When people say, is there something that got me into medicine? My grandmother used to have condensed Reader's Digest novels and biographies. I remember early on reading The Mayo Brothers. There were the two brothers, it was approximately 1910, I think. I think their dad was a surgeon. There was this interesting story of their puppy developed a bowel obstruction or something and dad was away and the two kids chloroformed the dog and opened him up, did a laparotomy and fixed the puppy. That really captured my imagination. I was always interested in medicine.

Did you think about doing something similar?

Barry Marshall: I actually did operate on my dog many years later, when I was actually a qualified doctor. The dog survived, you'll be pleased to know.

It sounds like you had an intrinsic curiosity.

Barry Marshall: I was always curious and very interested in science, and always enjoyed school. Each year I would always be thinking, "Wow! Next year at school, or at college, I'll be able to do chemistry, or geometry that I can't do now." Or in medical school it was, "Wow! Next year I'll be able to do anatomy!" Cutting up dead bodies was my big goal in first-year medicine, and so it went on. Every year there was something exciting and wonderful that I was looking forward to the next year. Medicine is like that, just so varied that even after I graduated I thought I only wanted to be a general practitioner. But every single sub-specialty I did in my internship, I'd come home from the first week and I'd say to my wife, "I want to be a neurosurgeon. This is great!" Or, "I want to be a hematologist," or cancer specialist. Everything fascinated me, and it was really only because I got involved in this little project with the bacteria in the stomach that I ended up going into gastroenterology. Because any specialty would have made me perfectly happy.

Was your mother an influence on your interest in medicine?

Barry Marshall: Yes, she probably was an influence. She always had medical books around and nursing books. I was interested in anatomy and physiology, but you didn't have the intensive exposure to science that you have nowadays. I was also interested in engineering and electronics. I suppose I've been successful in some ways because of integrating practical approaches to medical problems, to diagnosis or treatment. For many years I told her I wouldn't be a doctor, because I felt that I'd be pressured into it. Finally, when I'd graduated and had my college applications there, I said, "Okay, I'm going to do medicine." And she said, "Oh, this is wonderful!" Everybody wants their son to be a doctor, I suppose.

Did she ever pressure you?

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Barry Marshall: No, she didn't. After I went into med school, she went back and finished her nursing career. So it's been satisfying for me to be successful in medicine, because I know she'd get such pleasure out of it. There's not a lot of room left on my mantelpiece, and some of those awards, I can take them over to Mom's place and she puts them on her mantelpiece. That gives me a lot of pleasure to see that.

Did you get the sense that your father felt the same way?

Barry Marshall: My father always encouraged me. He was a tradesman and he probably left school a little earlier. He always had difficulty, I think, with engineering concepts, with mathematics and engineering. I think he always had an inferiority complex in that he didn't have the higher engineering degree, coming in through the trades. Really, it was very weird to have engineering or electronics degrees or anything like that in Western Australia when he went through. So he went about as far as he could go with what he had. I have to say that my father used to drink a few beers, and he would come home, and he was usually fairly a non-emotional kind of guy, a bit like me. But after he'd had a few drinks on Friday night, and I'd be there studying away at my anatomy, he'd come up and pat me on the shoulder and say, "You know, Barry, we're so proud of you, going through medical school," and have a tear in his eye. And I used to say, "Okay. Yeah, Dad. Okay. Off to bed now," and tuck him in. He's still a lot like that. It's kind of like the advertisement where the father and son are fishing and the father says, "I love you, son." And the son says, "You're not getting my Bud Lite."

Did you play a particular role in the family, in relation to your younger siblings?

Barry Marshall: I think I was given a lot of responsibility very early on, because my parents were struggling to make ends meet, looking after a family, buying a new house. We were on the very, very edge of civilization in Perth. Now there's miles and miles of suburbia, after where we were. But in those days there was a house, there was forest at the back of the block, and there were snakes and spiders and things around. My mother used to have to walk to the shop, so I would baby-sit the younger ones and change their diapers. I suppose it's a role that naturally comes to an eldest daughter, looking after the youngest children. But maybe because she was a nurse, it seemed quite natural for me to help out in all those different things. It gave me a lot of responsibility and honesty, I suppose. It also gave me a bit of pressure.

When I got up towards med school I knew that I might only get one chance. If I didn't make it through med school each year, perhaps I'd have a fine life, but really, I didn't consider that I'd have any backup and a chance to have another go at it. So I always felt that the pressure was on, and that I needed to make the most of this opportunity that I had.

So when you decided to become a doctor, you didn't know what specialty you would end up in?

Barry Marshall: No. In the early '70s, most doctors were just general practitioners. The specialties were there, but when you went into medical school you mainly just went in to be a doctor. My mother still wishes that I was a real doctor. In other words, a general practitioner, because she's always trying to hit me up for a course of antibiotics, or write her a prescription. I try to fight back. I try to make her go to her own doctor, but it seems so convenient to have me around who can do it for her.

If I was going to be a specialist, she wanted me to be an ophthalmologist, because even when you're examining the patients, you don't have to touch them. You still wear a suit, and you look at them through a lens from a distance. I did have an eye condition when I was about eight years of age, and I used to see this specialist in the city. All he would do is look at my eyes with a lens for about two seconds and prescribe some eye drops, and off I went. That seemed to be the pinnacle of medicine as far as she was concerned. But I think gastroenterology is interesting.

How did you come to specialize in gastroenterology?

Barry Marshall: As I said, when I was doing my training every specialty was interesting to me. I even liked geriatrics. Just the challenge of having older people, who are lovely patients, and very grateful when you're helping them. But many of them have five different diseases, instead of just one, and the interaction of all those diseases and drugs! I needed a rest, because I'd had a busy term in internal medicine.

I did gastroenterology. It was just interesting that there was so much going on in those days, because ulcers were very common and patients were coming in. Every single night we'd have a patient with a major bleed. They'd be getting blood transfusions and going to surgery. It was just an interesting thing to find those little bacteria in the stomach. Actually, I had a colleague, Dr. Warren, who was a pathologist. He's very obsessional, a little eccentric, and it was difficult for him to get any of his colleagues to take this seriously. He sort of gave me a tutorial on them one afternoon, and it was just wonderful to me to see these bacteria that weren't in the medical books. I like to do things a little differently, buck the authority, try something out of the box. Thinking out of the box, as it's been said. And the idea that bacteria could survive in the stomach, when the medical books said they couldn't survive in the stomach, that's what made me so curious about it.

Could you tell us about Robin Warren and his impact on you, the partnership that you had? Was he a mentor?

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Barry Marshall: We didn't actually have parallel careers, we just crossed paths when I was doing a gastroenterology fellowship. He had collected about 20 patients with these bacteria, but he didn't have the clinical correlation. He could see the biopsies and the inflammation, but needed somebody else to go and talk to the patients and find out what they felt like, whether there was any relationship between their disease and these little bacteria on the biopsy. He taught me a lot about microbiology and pathology. And then, from what he had told me, I would then go and read the medical books and try and find out what was in the books. And every single pathologist in the whole world who wrote a book described gastritis totally differently. In other words, they didn't understand it.

I'd actually worked this out when I was a student in college, that if I went to a lecture and came out of the lecture thinking, "I don't understand that," it was because it was a bad lecture, and the lecturer didn't know his stuff. Because when I had a good teacher, I would always know exactly what he was talking about and I'd never have to refresh it. I would just understand it. And that's actually something that I've taken into my teaching career, is that if I know the subject and know my stuff, I don't have to get nervous about getting up in front of hundreds of people and giving a lecture, and they'll say it was a good lecture. And so, it's the preparation you put into it, and you have to know your stuff to be able to teach it to others.

The fact that all those pathologists had different interpretations of the same material meant to me that they didn't understand it. So I'm thinking, maybe these bacteria play a role in there.

One of the things that happened with me is that I was interested in computers, even in 1980 with e-mail, but it was really teletypes in those days. Our library had just got a line to the National Library of Medicine. So I came in and started doing literature searches, because I was interested in computers and it was fun for me. But I started trying to track these bacteria. And I found various, very widespread, dispersed references to things in the stomach, which seemed to be related to the bacteria, going back nearly 100 years. So that we could then develop a hypothesis that these bacteria were causing some problem in the stomach, and maybe that was leading to ulcers. And then, instead of having to do 20 years of research checking out all those different angles, the research was done, but it was never connected up. And so, with the literature searching, as it became available, we were able to pick out the research that was already there and put together this coherent pattern, which linked bacteria and ulcers. It didn't happen overnight. We actually thought about it for two years before we were reasonably confident. It was really quite a few years before we were absolutely water-tight.

So you did some of your important research through searching existing literature. But you had to test this hypothesis in the lab. That was a different challenge, wasn't it?

Barry Marshall: That's true. We started off being very successful with patients when we first started treating them. They would tell us that this new treatment was much better than what they had been taking.

One of my little discoveries was I discovered that these bacteria were killed by Pepto-Bismol. We started giving a combination of a Pepto-Bismol type drug with an antibiotic, and about 1994 we had a 75 percent cure rate. So we were able to say, "Okay, if these bacteria are causing trouble, let's eradicate them," and the patients felt better. But everybody has a treatment which supposedly works, and until you've done the double-blind studies, the medical fraternity are very skeptical. So I didn't expect that to be accepted.

You presented this in Belgium, didn't you?

Barry Marshall: I presented that in Belgium, but I'd actually submitted it to the gastroenterology meeting in Australia first.

What did they do?

Barry Marshall: Well,

They said, "Dear Dr. Marshall, we're so sorry that we couldn't accept your abstract. It was such a high standard this year, we had 67 applications and we could only accept 64." So mine was in the bottom 10 percent. Looking back at it I can say it was pushing it a bit to try and get it accepted, but it's fun to have the rejection letter after all these years. My boss knew about the conference in Brussels, so he said, "Don't be downhearted, I still think it's good. You go to Belgium." The hospital paid my airfare, and I connected up with some researchers in Belgium, and made phone calls and whatever, and presented it in Belgium, and that's when it sort of hit the news.

Some of your colleagues thought the way you presented it was a little crass, didn't they?

Barry Marshall: Well, I was fairly confident at that stage, and I was sticking my neck out.

I knew there'd be a lot of Americans there. And we were then challenging for the America's Cup. And so, in fact, I got up and I really threw down the gauntlet. My first slide was a photo of Perth in Western Australia, lovely river and sea, and a yacht. And I said, "This is Perth, Western Australia, and this is the yacht that's going to win the America's Cup in 19..." I think it was '86 or '87. And everybody, "Ahh!" You know, paper balls were being thrown at me. And then I went on to present the new bacteria. I wasn't totally alone though, because I had connected up with the head bacteriologist in England who was interested in that species or that type of bacteria. I'd visited with him for a couple of days before the conference and he had kind of given me a little more confidence than usual, and backed me up on it. As he introduced me, he said, "Well, this is Barry Marshall. He's got this wonderful, interesting new bacteria." So although people were skeptical, and they all went home with the aim of trying to prove me wrong, that's how science moves forward. Someone has a hypothesis and you say, "Okay, if I can prove it wrong, I can publish a paper saying he's wrong." Gradually, over the next few years, one by one, these people trying to prove me wrong fell by the wayside and actually converted over to my side, and became experts in their own right, in helicobacter.

It's often said that science is a matter of study, waiting, careful observation, but sometimes there are instances of happenstance, luck, serendipity. Didn't you have a lucky break when you were trying to grow the bacteria?

Barry Marshall: That's correct.

We were persistent. We were reading the literature, and as far as we could tell this was similar to some bacteria that had been grown from mice, spiral bacteria. So we were using the same media and the same atmosphere and sending biopsies down, looking under the microscope for bacteria there. I'd come down to the lab a few days later and I'd say, "Did it grow?" "No, sorry, it didn't grow." So this went for about six months, and then I did some biopsies just before Easter. We have a very long Easter break, a four day holiday, in Australia. Luckily, there's no separation of church and state in Australia, because you wouldn't have had this holiday in the U.S. Anyway, we took biopsies on a Thursday and they were in the incubator Friday and Saturday. The technologist was so busy on Saturday morning, he left the research material there and just looked after the important, human, normal, routine biopsies. So he didn't look at these biopsies from Thursday until Tuesday morning, and then I got a phone call, "Barry, come down to the lab! We think we've grown these bacteria." I came down and I was talking to them and I said, "Why didn't we grow them before?" And they said, "We routinely throw the plates out after two days if nothing is showing up." And of course, helicobacters need at least three -- usually four -- days to show up on the plates.

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E-coli grows overnight, and people are just used to these kinds of bacteria. You get something a big sluggish, like helicobacter, and you really have to wait the four days. We had probably been growing them with the correct method for about three months. Of course, they would usually give my work to the lowest technologist in the lab to do, after everything else. He'd been throwing them in the trash after two days. I was like, "How can I cope with this?" So maybe a little lesson, that I needed to be carefully involved in everything after that. But that was the breakthrough, because after that we could identify that those bacteria were definitely abnormal and not normally present. They grew under certain conditions, and could be killed by certain antibiotics.

You had all of these people working to test the theory and some of them actually trying to puncture it, but you were continuing at the same time to further research all of this, and were trying to get the bacteria to grow in animals. Why were you taking the animal route?

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Barry Marshall: To prove a new infectious agent is actually the cause of a disease, you have to do what's called Koch's Postulates. Robert Koch was a German microbiologist. He did most of his famous work in the 1880s. He actually promulgated and published his Koch's Postulates for tuberculosis in 1884. It was 100 years later that I did my famous experiment, which I'll tell you about later. But Robert Koch had the problem that half the people walking around in the streets in Frankfurt, the poor people, were coughing up tuberculosis bacteria, but didn't necessarily have active TB, or weren't particularly sick. So a lot of skeptics believed that his Koch's bacillus was just a harmless bacteria that lived in sputum. So Robert Koch said, "Let's do this experiment." You have to get the bacteria and grow it in a culture. Then you get part of the culture and you inoculate that into the animal. Show that the animal then develops the same disease that the human had, and then show that you can once more isolate the bacterium from the disease. Usually you do this experiment, in animals, to fulfill Koch's Postulates.

We had an experiment that was funded where we would have little baby piglets and we would give them some helicobacter each week. Then, a week later, we would do an endoscopy on them to see if the bacteria were causing any inflation in the stomach. Now piglets grow like you wouldn't believe. In the Midwest, people know how quickly they grow. So after three months of this experiment, I had 70-pound pigs that I was wrestling each week trying to do an endoscopy on, and it was a big mess, and the bacteria didn't take. Whenever I presented my work, the skeptics would get up and say, "Well, Dr. Marshall, that's all very nice, but let's face it. You know, people with ulcers have got such a disturbed physiology in their stomach, and these bacteria are so common, that they must just be harmless, and they're just colonizing the people with the ulcers." So I had to prove that the bacteria could infect a normal, healthy animal, cause the disease. Then I had to fish the bacteria up afterwards.

Is it frustrating when you're at that point in your research and things are not going your way and people are weighing in with those kinds of dismissive remarks?

Barry Marshall: I'm a lot more mature now, and I know that this is how science works. You've got to be pretty thick-skinned and ready to take the blows. In those days, it used to really cut me to the quick when people -- even my boss -- would get up and criticize my work this way. I was a... "brash young man" is a term that came out of the Reader's Digest article many years ago. "Zealot" was another of the names that I was given. I read the history of the zealots, and you know, I was exactly like that.

It was a campaign, everyone was against me. But I knew I was right, because I actually had done a couple of years' work at that point. I had a few backers. And when I was criticized by gastroenterologists, I knew that they were mostly making their living doing endoscopies on ulcer patients. So I'm going to show you guys. A few years from now you'll be saying, "Hey! Where did all those endoscopies go to?" And it will be because I was treating ulcers with antibiotics.

Do you think there was an economic motive that made some people unwilling to consider this?

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Barry Marshall: That's true. The livelihood of gastroenterologists and many of the drug companies depended on these drugs that were worth billions of dollars, treating millions of people with ulcers. And the thing about ulcers is they come back every second year, that's why they're always thought to be constitutional, or emotional, or caused by stress, because the patient's lifestyle would stay the same and maybe each winter he would get his ulcer back. Gastroenterologists, it seemed to me, only need a few hundred patients. They would do the same endoscopy on the patient each year. He would come back with ulcer symptoms, they'd put the scope down and say, "Yes, you've got an ulcer again. Try this other ulcer medication." There was always a new one to try on the patients in the '80s. And I would say, "Hang on a minute. There's something wrong here. When you see an ulcer, you give the patient Tagamet. And if the patient doesn't have an ulcer, you give the patient Tagamet. Why are we doing this endoscopy when they all get Tagamet?" That was the big drug in those days. I was a little skeptical of that diagnosis of being neurotic or a little stressful. If we didn't find anything there, particularly in women, we would say, "You're under a lot of stress, my dear. You haven't really got anything wrong with yourself. We'll give you an antidepressant." I used to see this happening so often in women whose biopsies were very, very inflamed with these bacteria.

How did you balance your strong feelings with working in the field professionally, and having to deal with the consequences?

Barry Marshall: Looking back on it, I'm sure I could have been diplomatic and progressed more rapidly. I was probably doing the wrong thing in a number of circumstances, in a number of relationships with my peers, or my senior colleagues. I think it happens to a lot of researchers that are in a new field, or with a new discovery, because you want to keep it for yourself. You love it more than anybody else, and people outside the story who don't understand it all cannot see where you're coming from. You're just in different dimensions all of a sudden. I had connections very early on with people who were the top specialists in the world.

One of the top ulcer specialists in the world was in Amsterdam, and in 1983 I visited him, just a young guy with a few ideas. He had hinted that there were some funny things going on in the ulcer treatment story that didn't add up to the fact it was all caused by acid. There was something else there. So I knew he'd be receptive. I explained it to him and he was very receptive to it. So instead of my bosses in gastroenterology in Australia, it didn't matter what they said, because I knew that the person who wrote the textbook that they were reading actually thought there was some credence to my work. I visited Stanford in 1984, and Dallas, really epicenters, if you like, of the ulcer business. Although they were very skeptical, they did go out and start testing the hypothesis.

What did you do at that point?

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Barry Marshall: Well, you know, there is a tradition in medicine of medical researchers testing out their own new discovery on themselves. So, I'd heard about this. There was a book called The Brother Surgeons, about John Hunter and his brother. Famous surgeons way back. Lucky I didn't do his experiment. He infected himself with syphilis. He subsequently died by syphilis years later, when he was an old professor, from his own experiment probably. So, this tradition of dangerous experiments exists. I didn't think my experiment was particularly dangerous. I had to get past this hurdle of fulfilling Koch's Postulates. I studied the literature, and there were a few subtle hints that people would have no symptoms when they had this infection. When I spoke to ulcer patients, they couldn't tell me about any illness they had had. They were perfectly fine, and then they developed an ulcer. So I didn't think I would become unwell. I had treated a few patients with antibiotics successfully at that point, so I thought I could probably cure it. I was a bit overconfident in retrospect. I wanted to make sure that it did take, because I didn't know whether I'd have the guts to do this every week.

We mixed up a complete flourishing growth of bacteria from a petri dish -- we calculated out later that it was a thousand million bacteria -- and mixed it up, and I said, "Well, here it goes, down the hatch." And my lab technician, who was fairly conventional, he was horrified. He was waiting for me to drop dead, but I said, "Well, I'm feeling all right. Okay, let's press on." You know, go and do ward rounds. So, off I went and I kind of forgot about the experiment.

The plan was, a week or so later I was going to have an endoscopy. I already had one at baseline to show I didn't have any bacteria and I was normal, and a week later I planned to have another endoscopy. The subsequent week, I noticed in the evening when I was eating a meal -- like Chinese, which I always love -- it would just sit on my stomach like a lump of lead. I'd be, "Boy, I feel so full!" And I would take little sips of water after dinner, trying to wash it down. I've seen a lot of patients with this symptom.

About the fifth or the sixth day I'd wake up at the crack of dawn and say, "I'm going to be sick." I'd run into the bathroom and I would vomit. But I wouldn't vomit up a meal, I would vomit up just this clear, watery liquid. And I said, "Well gee, that's weird. I don't do that very often." I did it about three mornings in a row and I noticed on the third morning there was no acid in the vomit, and just copious amounts -- maybe a pint -- of just watery stuff would come up. And I went, "Wow, this is weird." And my mother told me that weekend that I had bad breath. Only your mother would tell you such a thing is what I always say. She said, "Barry, are you constipated? How come you've got a bad breath?" I said, "Oh, you silly old nurse, what would you know?" My friends in the lab weeks later told me about this. And I said, "Well, why didn't you tell me I had bad breath?" Because that was interesting in itself. And they said, "Well, we didn't like to say, you know. It's impolite." So the poor fellows, they had to work with me in the lab all this week. I had an endoscopy on the eighth day and I was very, very sick with that endoscopy. Usually I can tolerate the tube pretty easily, with just a little gagging, but it was very uncomfortable. They took several biopsies from my stomach, and the biopsies showed severe damage to the lining, the mucosa. The bacteria all sticking all over the cells, and some of the cells were sloughing off, and the basement membrane was exposed, which is the layer that they sit on. The mucous layer was very, very thin. And so, great experiment!

I had a publication at that point, and I said, 'Well, this is great. We'll do another endoscopy next week and see what it's like then."

Towards the end of the 14 days, I sort of mentioned to my wife that I'd done this experiment. Because she was saying, "Barry, there's something wrong with you. All night you're hot and cold. You're breaking out in a sweat. You're not eating your meals. You've got dark rings under your eyes. You look terrible." And I said, "Well you know, I took this bacteria and now I've got the infection." She said, "What?" She was, "You'll give it to the children! You get rid of it immediately! Take antibiotics or you're out of the house. You're staying in an apartment," as far as she was concerned. And so, after two weeks I went and had my second endoscopy and started antibiotics that day. So that was the end of the experiment. And subsequently, I've been found that I don't have the bacteria. Everything's back to normal.

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But I'd identified this syndrome where you catch the bug. A few days later, you start feeling a bit squeamish. Funny things happen. You start vomiting. There's no acid in the vomit. So this was the syndrome. Then I started to do detective work to find out. How come nobody knew about this syndrome?

Would you do something that risky today?

Barry Marshall: I'm not sure that I would. I would definitely study all the different angles of it further before I'd do it on myself. Actually, I do have some future experiments planned along those lines, but not quite as dramatic. We'll be a lot more careful. We know how to get rid of this bacteria now.

Would you tell your spouse before you did it again?

Barry Marshall: Yes. I'll probably have to move out of home for a week. No way does she want to have this thing.

It sounds like you've had a real passion for your work. Is that still what keeps you going?

Barry Marshall: I think the passion's died down a little, but I still love it. In those days, every single day we would get a new idea. With these new bacteria, ten of them would fall by the wayside, but one out of ten maybe would be successful and we'd have a new treatment, a new diagnostic test. We'd see something different happening in the patients. We'd find antibodies in the blood. It was just a wonderful discovery. It was exactly like one of these archaeologists telling us the story of how he discovered this new Egyptian tomb. He was crawling through this little dusky corridor and then, bingo! The door was opened and there was this incredible chamber with all these Egyptian relics in it. It was actually like that with helicobacter.

Once I'd done that experiment and realized that there were all these other things happening with the infection, and studied the literature, it was then revealed to me, if you like, that lo and behold, lots of doctors over the years had described this exact syndrome. But it was many years between the initial infection, where you vomited, and the ulcer. You might have got this initial one when you were five years old, and your mother said, "Well, a stomach virus." A few days later, you're better. But the bug sits there in your stomach, working away, causing damage. And then 20 or 30 years later, when you're doing all those things -- drinking coffee, going to college and having a really hectic life -- your acid level builds up a little bit. Bingo, you've got an ulcer. So I connected up these two widely dispersed episodes and I published a hypothesis, which everyone said, "Wow. This is a great hypothesis, because we can test it." And they checked it out and they couldn't prove it wrong.

Was the course of treatment basically what you had suggested?

Barry Marshall: The years after that were still somewhat difficult, in that we didn't have a very good treatment. The treatment we had had side effects, and the patients could tell which treatment they were on by the color of the tablets and everything. So it was hard to do a double-blind study. After 1990, new combinations of antibiotics were tried by hundreds of different people, until we had a cure for about 80 percent. It was just antibiotics and simple drugs that you could put into a placebo, or an active drug trial. The study that really clinched it for the skeptics was published in The New England Journal in 1993 by Henschel from Austria, where he just uses antibiotics versus placebo in people with ulcers and showed that he got exactly the same results as Dr. Marshall had got five years before. So, that is what proves something in medicine. Someone who isn't you gets the same result and says, "Hey, he must be right." Convincing the skeptics is tough and it does take time.

You're Australian, and you were working against a pretty strong North American medical group. Did that play into it?

Barry Marshall Interview Photo
Barry Marshall: Yes, and no. If I'd discovered the initial findings in the United States, I might have just discounted them. There's a very structured and very conventional gastroenterology program in the United States. If your head's just full of that conventional learning (50 percent of which is incorrect), it's very difficult to get a new concept in. So it's wonderful in some ways if you don't know everything. If the field is not well understood, maybe it's better to find your way into it and take the leads as they come, rather than saying, "Here's the body of knowledge. I'm going to study this bit, and advance that bit of knowledge." Maybe you just need to be lateral. The second thing about Western Australia is that it's a little incubation chamber. I was able to work there for a couple of years and be rather eccentric and brash and do weird experiments, all the things that I wanted to do, without too much exposure, with a few mentors that were trying to dampen down this enthusiasm. My wife obviously had a major impact on that. She's got more tact than me and probably saved me from some tough situations. "You can't write that letter," to the medical superintendent, whoever I was writing a letter to at that particular time. It turned out to be a very nice combination. And I did connect up with the right people. By the time I connected up with people in the United States I knew I was right. I thought it would only take two years before everyone believed it. But I knew that an idea which is so useful and so beneficial would definitely find favor anywhere, if it was allowed to just float. I wasn't supported by the big drug companies. There was plenty of money going into ulcer research, but not into these bacteria. Although I wasn't supported by them, I knew that eventually they would either go down or they'd change camp. And a bit of both happened.

Can you tell us a bit about the other areas you're starting to explore?

Barry Marshall Interview Photo
Barry Marshall: Well, we found that we had a tiger by the tail with this bacteria. Not only did ulcer patients have it. That's pretty simple -- they wanted treatment with antibiotics -- but more than half the people in the world are infected with helicobacter. Now, in the U.S. it's 30 percent. It's more likely to be older people who might have picked it up in the Second World War, in the trenches, or in some poor conditions that they were living in, some hollow in West Virginia where they didn't have running water and the toilet wasn't properly connected or whatever. So people who are older and were alive before the Second World War can have it. Younger people born in the U.S. probably wouldn't have it, but people who were born outside the U.S. that immigrated in, more than half of them would probably have the bacteria. So this sort of interesting combination is going on, and these people would still get ulcers and they're susceptible to stomach cancer. That's the U.S. scene.

In India or Africa, China, Russia, where conditions have been very poor over the last 50 years, more than half the population has the bacteria. It's not terribly expensive, but they can't afford to spend $50 on an antibiotic treatment for their stomach complaint. Many of them, in fact, have no symptoms. It may be that if you catch it when you're very, very young, two years of age, your acid level is dampened and you never get enough acid to get symptoms or ulcers, and it festers away there. You may get a very marginal form of malnutrition. In England, children with helicobacter were found to be slightly shorter, about a centimeter shorter than the control group. Maybe it sets you up to be more susceptible to other infections that could kill you, such as cholera, and there's some literature on that.

Barry Marshall Interview Photo
So in some ways, helicobacter is kind of like dandruff on the stomach. It's abnormal, it causes an irritation, but many people would go out and fulfill their normal lives and not even know about it. However, it does set you up for ulcer, or possibly a one percent chance of stomach cancer. So I'm in favor of treating everybody and wiping the whole thing out. But of course, we don't have the tools to do that now. We don't have simple diagnostic tests. We don't have a free antibiotic therapy. The concept of treating half the world with antibiotics is pretty horrific to most doctors, because of these resistant bacteria that would develop. The only possible solution is a vaccine. So many companies now are looking at vaccine ideas, and putting millions of dollars into a vaccine. But it's not going to be very profitable, because the patients will only take it once. And the people who need it can only afford to spend a couple of dollars on it, so World Health won't buy it. So, in some ways it's going to be a long haul I think to finish the helicobacter story.

Of course, the other side of it is the ecological or evolutionary aspect of it. How long has mankind had helicobacter? Supposedly, they found some helicobacter genes in pre-Columbian mummies in Latin America. I've spoken to an Egyptologist, and he's going to try and get me some Egyptian mummy stomachs, we can cut up to see if we can find the bugs.

So you're not finished?

Barry Marshall: No. There's a lifetime of work in it. There are literally thousands of scientists now in the helicobacter business.

I've got a lucky combination of a team of scientists working with me on interesting questions that I'm curious about. I also have some connections with industry, so if we have a good idea for new treatment or a new test, we can try it out on the patients, who are always very, very willing to take part in my research. They say, "Well, he did it on himself, so we can trust him, I suppose."

We bring products into the mainstream medical treatment very quickly, in a year or so, we hope.

Are there ever any moments where you think, there's something totally unrelated that I'd love to do?

Barry Marshall: Well, basically I'd like to be Mick Jagger. But since I can't be Mick Jagger -- you know. Obviously there are things like that that I would like to do.

One of the things my wife says is that she actually has five children. She's got the four children and me, and that I never grew up. A lot of doctors seem to be in this category, in that they have always got this childish curiosity, and they go into med school because they can't face life, and they know it will be seven years before they actually have to make a real life decision. And then if you stay in medicine and train further for a specialty, you can postpone this real life event, if you like. And then if you can go into research... Well, actually you never have to finish. I think that's the ideal choice.

But I have other interests. I'm very interested in computers, information. I've always had that as a hobby. I have a research foundation and a helicobacter web site where you can see pictures of helicobacters and people from America Online can send me e-mails night and day. So it gets a big hectic at times, but it's a lot of fun.

Do you think you've got a lock on the Nobel Prize?

Barry Marshall: If I say that, that's one sure way of not getting it. So I've just canceled that off the agenda.

Does it matter?

Barry Marshall: No. I'd have to say that really the pinnacle of anything I ever received was the Lasker Prize. This is very, very close, this weekend here at Jackson Hole. It's amazing the people that I've met here. But the Lasker, there were about 100 Nobel laureates at the ceremony. The fellow who won it at the same time with me was Dr. Peter Doherty and Rolf Zinkernagel, who won the Nobel Prize the year after they won the Lasker. If I never win any more prizes I'll be perfectly happy. I've far exceeded anything that I would have expected out of my research career.

I'm not all that young now, and my kids are partially grown up, but I've got these years ahead of me and so what am I going to do to top this? Well, I think I'd get a lot of satisfaction out of being useful and creating some jobs and training new scientists, and being a positive influence on people who might be interested in getting into medical research. They are concerned, you know. "Everything's already been discovered. There's no hope for me." And I'd just like to say, "It's so wide open and so wonderful at the moment with all this biotechnology going on." I can see that in the future everybody will be a lot healthier and happier, because of the things that are happening now, in my lifetime.

Thank you so much, Dr. Marshall. It's been a real pleasure talking with you.




This page last revised on Sep 23, 2010 16:34 EDT