Barry Marshall and Robin Warren, Nobel Prize in Physiology or Medicine 2005: Official interview

Doctors Warren and Marshall, welcome to Stockholm and I want to congratulate you on your prize. I know each of you have arrived on different days. You've been here a few days now and it's not your first visit. How's it been? Give us a glimpse of Stockholm this time through your eyes. It's a strange place because you're getting up in the dark and when it's daylight it seems to be only just daylight at the moment. And then when you're wandering around suddenly you start thinking it's tea time and you realize it's only three o'clock and it's dark again. So it's a real Swedish experience, that's all I can say. I've never had anything like it. So you've never been here during the winter time before but you have visited Stockholm before? Always in the summer. And what do you usually do in Stockholm in the summer? You've been more than once before. Well we usually have a conference or something but in my days off I wander around the shops and the seaside and watch people doing things on Sunday. Last time I was here they were all having a fun run. I don't know what it was but they were all running through the streets with t-shirts on. It was a great day. And this time is your fun run for both of you? I guess so. Okay, we know that you're both sharing this award but when did you first meet and how did you begin collaborating together? Tell Rob, you can tell that Rob. We first met in 1981. We basically began collaborating because I was working on these bacteria in the laboratory and I was bound, I was sort of fenced in by the laboratory and I couldn't get to the clinical world to spread my work at all. And Barry was in the clinical work looking for some work to do. So he came down to see if he could help me. Anyway, he wanted to know what I was doing and he was sort of vaguely interested and agreed to send me some extra biopsies, the sort that I wanted from different patients which I hadn't been able to get before. And he became very interested and actually the whole thing expanded to include the clinical area as well as my pathology work. So in collaboration with Barry the whole work expanded to an area which was big enough I think to produce really good results that we could publish which I wouldn't have been able to do on my own. But when was the first positive development, the first breakthrough if you will? I think the first breakthrough was when I saw them. That's true. Robin had, I wasn't aware of the fact that Robin had really been trying to get people interested in them for about 18 months before I turned up. And I was in the stage of my career where you were supposed to do some kind of research project and I'm a bit cynical but I thought most of the people doing research projects were doing pretty boring stuff. And so when I had the opportunity of investigating a possible new bacteria in the stomach and as Robin showed it to me it was, I couldn't really figure out why other people were not interested because the medical book said the bacteria couldn't live in the stomach and Robin spent all afternoon showing me all these cases. And quite clearly it was the same bacteria and these things were thriving in the stomach. So it was just a totally different thing from what you would normally expect to find. And I thought then, I didn't have very monstrous ambitions or anything, but I was thinking wouldn't it be great if Robin let me be co-author and we described a new bacterium. So I was sort of interested in trying to culture it straight away and everything and it took off after that didn't it? And it was great. I think the main thing was our main study the next year. Actually I knew Robin before that because I was in gastroenterology and well we didn't know each other but I used to go to presentations where he would be showing the biopsy reports to the gastroenterologists each, maybe it was a Thursday afternoon or something. And occasionally I remember Robin would make some comment about the fact there was bacteria on the biopsies. But of course nobody appreciated the implications of this. Did you appreciate it at the time when you heard? Well I'm not sure whether I was there before we actually got working on the bacteria. I'm not sure whether he'd mentioned it before then. But I remember after that he used to rile the surgeons a bit because they would chop out somebody's stomach for ulcers. And then Robin would show the biopsies and say, good work boys you've chopped out the bacteria. Which was a bit of sarcasm. It was obviously you don't treat bacteria with surgery, you treat them with antibiotics. So tell me why is it that only you could see this bacteria and that it took actually having to point it out to people? You know one of the main arguments against my findings by the clinicians was that Dr Warren, if those bacteria really are there, why haven't they been described before? And all I could say was that I didn't know why they hadn't been described before. They had of course actually been described before but I didn't know that. Neither did anyone else seem to know it. And also I didn't know why I hadn't seen them before. Because really once you've seen them they're quite easy to see. So how did you first see them? I just saw them. One day they weren't there and the next day they were. Well it's not that one day they weren't there and the next day they weren't. It was just that one biopsy I was looking at I just happened to find them. And once I started you know I saw some there and I followed and looked at the higher power to see what I was looking at. And then I sort of found that you know with the very highest power magnification on the microscope and Christ they actually are bacteria I'm sure they are you know. So I got special, I tried to convince my colleagues and they couldn't see them so I got a special stand-in that I'd been playing around with and it showed them extremely well so that nobody really, at least in my department, nobody could argue about it. Everyone else did. And the name Helicobacter pylori, is that how it's pronounced? Yeah. Why is it called that? This describes the shape and the position of them. Okay why isn't it named after you? Don't scientists name bacteria? After people die I think. Okay. Yeah I put this rule I don't think you should name anything after people that are still alive because you know what if they start being disreputable or something and you say oh no we've named it after him what are we going to do? You'll find you'll have a disreputable bacteria. There's kind of a joke about that is that early on we found that Helicobacter's were more common in people with sexually transmitted diseases so that at one point there was this little theory that I was talking about that maybe they're sexually transmitted somehow. So you know if it was going to be a venereal disease did you really want it to be named after you? So I say okay we'll call it Warren bacteria and he said no we call it Marshall bacteria so we just cut our losses and called it Helicobacter. Okay after the shape and that. Helicobacter. Well Helicobacter. It used to be called Campylobacter pyloribus. Campylo means curved it's it's Greek I guess classical Greek. Campylo means curved and bacta means rod so curved rod but it wasn't just curved you know like a like a cholera bug or vibrio as we call it. Oh the Campylobacter's either of it. That's true. It's sort of double curved. So it's like a corkscrew and it's a very short corkscrew with one and a half turns but other Helicobacter's it's got lots of relatives now in cats and dogs especially and they have maybe 10 turns so that the helical is a good explanation for it. Helicobacter. The discovery was quite some time ago now 15. I discovered them in 1979. 1979 and when did they become recognized by the scientific world? Really recognized as an actual cause of duodenal ulcers 1990. Okay. That was when they were officially recognized to be treated by the general profession and I think most people actually sort of recognized the existence of them and probably that that's what they did quite some time before but they didn't have an official sort of conference and decide that officially that they were you know now textbook stuff until 1990. So this has basically been your life's work would you say that? Well it became so more or less yes I suppose I mean during that 11 years that I mean just before that conference I read an article in one of the most prestigious medical journals the New England Journal of Medicine which basically said I think the same things that we'd been saying in our own papers you know six and six years before and a couple of years before our two main ones then but it just practically repeated what we'd said but I thought you know since it was a major American article that was saying all the things that we'd said that it would suddenly sort of end up by saying you know that they agreed with Warren and Marshall and that no the treatment for duodenal ulcers is is should now be include treating these bacteria but the bloody thing ended up just the last couple of lines is saying yes but of course this work is still just research. So what was your response to that isn't there isn't there a formal response that one can make towards it? You can bang your head against a brick wall so many times you know and I think you've just got to have faith that you you know what you're talking about because in the end well in the end it worked out. In the end you've gotten the ultimate recognition it's come you know just this year you found out just two months ago that you're being being awarded this this prize but how has how's it affected your your lives since then both personally and and professionally? What the prize? The recognition through the prize. Well the main thing that's affected I retired eight years ago actually I'm you know I'm a retired gentleman these days but you know just doing my own thing and enjoying myself and now suddenly I've been swamped by everybody around the world wanting me to do things for them and I finally just decided to take Barry Marshall's offer and handed over my the major part of this sort of thing to a university secretary that they've appointed to look after us otherwise I you know I'm just not any good at that sort of thing anyway at the best of times so she'll fix I hope she'll sort of sort all the things out and just let us know the important things that we have to do. And what about you Dr Marshall? I had a I think I was working at approximately two jobs and now I've got three. What's the third one? Well the third one's the Nobel the first one was the academic the second one was business commercial things and then now the third one's Nobel so Robin is right the University of Western Australia has supported us and have funded a lady who's going to be the Nobel secretary and when when someone I typically it's impractical someone asks you to give a lecture in say it's Thailand and you would say okay well it takes me a day to get to Thailand a day to give the lecture and day to get back and so you would allocate three days of your time to do it but then in fact it takes you four days to write the lecture and nothing gets done while you're away so it takes you two or three days just to catch up with your mail plus you're dog tired so you really can't do an international lecture in in three days it really takes you at hard work and so that by having a Nobel manager she can allocate our time and say well you can't go there because you've got this and this activity on each end of it and if you want to kill yourself that would be a way to get there pretty quickly is trying to do too many of these lectures and the many many of them are quite important lectures but you just can't do everything it is better to have somebody else making these decisions for us because we would try to accept everything and in the end we would I don't know burn out or something we'd get sick of it but I think done properly we I think we can enjoy it at the moment it's a it's you know I think we're coping with it fairly well at this stage now that we've been in this we get to find out what happened I don't know how you've been doing it but actually most of these requests to go and lectures I've just been the mainly come by email and I've just been emailing them back telling them to get in touch with me next year so suddenly next year probably this is all going to start again I'm going to get all these buddy emails but at least now I can forward the emails to to our secretary at the university and she can decide what I think that's she's good at this sort of thing I think she can go into them work out which ones are really important and which ones we should do and which ones we can do if we want to which ones we can forget about and send nice letters to the whole lot it might be a blessing in disguise then that you already retired when when when the when the prize came about I wondered do actually don't worry I'm when I say retired I've retired from from ordinary work but I've started I've been able to do some of the things I've wanted to do for many years tell me a little bit about those things well I started off by trying to catch up with my hobbies photography and I've got a whole backlog of stuff at home that I haven't been able to to keep up with and and I'm and I've been getting um back on big getting used to computer work and so on as well using computers I used to be quite good at but I've let it lapse a bit in the last 10 years or so um because these days the computer photography is so good and digital photography and computer programs and printing and the sort so I thought maybe I can get my old pictures and scan them into the computer and make do my own prints again I used to do all my own printing when I was you know using black and white but career-wise do you think it would have made a difference to you in terms of sheer motivation in terms of funding perhaps if you've got if you've gotten the nobel prize a little bit earlier in your career well it would have had to have been eight years ago earlier than that that would have been marvellous in the fact because my my wife was still alive then and she was she actually thought I'd get it you know she kept telling one of the last things she told me before we before she died was that you know make sure you get my you know when you get the nobel prize dr you know Robin you know I've forgotten what she said but uh yeah she was right behind she was one person who was right behind us all the time and when she died that's when I retired actually I just you know been looking after her for a few months and I just thought well what the hell and why go back again but I mean I didn't do the photography for very long but that's something one of the things I'd really like to do because after that I suddenly decided several people were at me from different places to get all my old work together and and get that in a form that could be put in libraries and so on and you know digitize all our old you know all my old pictures and so on and papers and and all you know all the work that I've done before and that I thought you know all right I'll just scan a few things into the computer it won't take very long that that was the silliest mistake I ever made because I think someone kept telling me that I'm a perfectionist and well a lot of people have told me that but I fiddle around with things and and I don't like getting on to the next thing until the last thing is done perfectly and what I find is that as I get better and better at doing it all the times I did it before are no longer good enough so I have to go back and do those again and actually I just got to the stage where I was doing these old papers and pictures and so on illustrations everything else from my old from all my old work there's a hell of a lot of stuff there and and this came up and now all that's been left behind somewhere and you know when I get the time I'm going to have to start all over again on that and because you've really got to keep at it you know to keep the you know all the different things in the computer the illustrations and and type recognition programs into the scanning you know text and so on I mean it's all very tricky and and and you can't do it fast unless you really got it at your fingertips and and you've got to be at least I've got to be doing it all the time to to be in that position and you want to be thorough about it as well well I can't help it I am for that sort of thing if it's not right it's not good enough and I Understandable and uh Dr Marshall your family's reaction close friends were there any surprising you expect people to say congratulations and be really happy for you? My family's reaction was to drink a lot of alcohol as quick as possible they sound quite swedish actually so the first night Robin and I were doing interviews for several hours and as we as the evening went on this noisy party got louder and louder just behind us and in the end I had to drive everyone home they weren't sober enough to drive their home cars home we were the only two that hadn't had anything to drink or maybe just one oh well turns out that we we you can't be having a hangover every second day if you've won the Nobel Prize there's stuff to do next morning unfortunately but you did have your own private celebration at some point where you yeah we actually we had a some pretty good uh little parties you know just the relatives around and my parents Adrian's parents are still alive and the the kids uh so and then there were some big parties at the government house ballroom and for Western Australia and the university some of them quite good some of them were just politicians I think but I think uh I appreciate that uh everybody wishes us the best and actually we have been doing this research for 20 years so literally thousands of people have been experimented on during that time in Western Australia particularly and uh so they all would have helped us in different ways and they are all having a great time coming to these parties and slapping us on the back I mean I uh Robin you you might uh do you remember uh Dot Hayes that was the gastroenterology nurse in with well um the nurse that was doing gastroenterology with us in in Royal Perth in 1982 really Dot Hayes her name was she was doing ceramics at the time a ceramics course and she baked this little plate with a picture of helicobacter pylori on it and she had written around the edge of it the nobelly prize so she was the first one that decided that it was worth the nobel prize years before we heard it from anybody else I think or there was going to happen indeed well she was probably a fortune teller she knew it was important um you pointed out that you know while while most sufferers in in first world countries have basically been cured and you don't you you're getting the prevalence in in third world countries is this to do with simply accessible accessibility to to medication for well there's more of it in developing countries because the the hygiene is not up to 20th century standard in a lot of countries and you can't do much about H. pylori if everybody is poor and they don't have a clean water supply so you know there's really nothing you can do at the moment in Peru because if you treat people for their H. pylori there's a 30 chance they'll catch it back again just by drinking the water so it means that you would only treat the really serious ulcer patients and you'd have to keep an eye on them because quite a few of them would get it back okay so alleviation has to start with proper clean water supply it's not totally understood how you catch it as well so I would say that there's plenty of fruitful research projects in countries where the helicobacter varies in different ways Malaysia is an interesting one because the different racial groups the Muslims have a rather low prevalence of H. pylori the Chinese are much more and so that you look at diet ethnic things different customs different hygiene practices in their families and you might have some clues as to what keeps helicobacter away is this anything that you're working on at the moment or will be involved in well we have done a bit of this work we've recently done a survey in indigenous communities in Australia where there's quite high levels of helicobacter but we think it's just a developing country issue but in a specific person it's hard to identify exactly what caused them to catch it I mean Robin's got his own personal story there well you used to have H. pylori didn't you but do you think you ever remember when you caught it well I mean I think the work that Dick McAllen did just shows pretty conclusively that people probably had it from childhood that's right so you were a kid in Adelaide or somewhere yeah so but about I mean in Australia about a third of the population's got it and I don't know if that third a lot of them you know I mean what percentage do you reckon one percent gets peptic ulcer disease I reckon 20 percent get peptic ulcer in their lifetime and that would that would translate into a lifetime in the whole incidence in the whole population of 10 percent so that that was the number that people used to quite so it must be about 20 chance of having an ulcer if you have H. pylori so if we go back to your situation Robin you lived in the city your dad was a professional person well yeah winemaker and did you have like masses of brothers sisters a couple of younger ones yeah so you didn't really have any reason to have helicobacter except in those days things were not particularly clean people did not did you always have a clean actually did you have a flushing toilet or did you ever live in the house with no I think we're just as clean then as it was a generation so you might have caught it what about your dad did he have ulcers and you and your family have ulcers I wouldn't be surprised if the old man did have them he behaved like it sometimes but I don't know so it's hard to track it down but obviously in a western country you'd have to catch it off someone in your family and possibly you can catch it from your partner your spouse but even you know it's not horribly infectious so you wouldn't catch it in the first well from my own experience of families the people who put the funniest things in their mouths are the you know one-year-olds and two-year-olds they crawl around on the floor and just about eat anything and I think one the best theory I could think of is that it's got something to do with that and if this helicobacter being up you know when they get sort of fecal material in their nappies and so on I mean it all goes into everybody else's mouths at some stage so clearly there's a there's there is there's a well obviously little toddlers can't you know don't have the level of hygiene if you've got three little children together in the same room well one vomits they all experience a bit of vomitus in the environment if we could move on to to something else I've noticed that Australia seems to have bred a number of Nobel Prize winners in just medicine and or physiology you seem to be overweight in that field of Nobel Prize winners than any other field do you think there's anything special behind this is there especially nurturing environment in this field I'd like to say so but I don't know I mean actually I know Flory for instance went to the same school and medical school as I did never mind the same country and um there was another Nobel Prize winner that went to them too I don't remember his name Clegg or Clegg physics good physics prize back in the early 1900s brag brag brag that's right so I mean that's three of us just from one from one school oh yeah there's only one school in Adelaide isn't there well people that went to that school say so yeah and then and then the same university although you know I mean Flory and myself went to the same medical school never mind the university so but I mean coming back to the the issue of education how how strong of a role do you think it plays in shaping people with the constitution to to face the sheer number of frustrations that you for example have faced over the years uh in in research I mean do you think that well what do you think is about education that that fosters scientists and their determination to succeed well I think in my case it's just my nature I'm if people try and push me I'd push back if I think I'm right well I think Robin um I mean if you think you're right and someone tells you you're wrong you say well he wouldn't know what he's talking about I'm right you know there's I suppose there are people who are quite influenced by what other people think of them or say about them and maybe Robin and I are not like that and we we don't we don't care if you think what we're doing is dumb we think it's interesting we'll say well you know it doesn't really make any difference to us what someone else thinks and of course once we got into it we were we knew that we were the ultimate experts in this particular area of gastric research if you like nobody was doing the same work and obviously we knew much more about it than anybody so once it started you it was irrelevant that if that other people said that we didn't they didn't think these bacteria caused ulcers because they didn't know as much about them as we did I think one of the things about it was that we had very good evidence what we're doing was was correct I've had people come along and ask me about you know when do we sort of encourage people to with new ideas to and well I think you encourage people with new ideas all the time but one thing they should have is some sort of evidence to back up their ideas and even with the extremely good evidence I could just show you a picture and say there are the bacteria there's the mucosa that's what they're doing you know so you could see that anyone here could anybody could see them it's black and white it's you know there's no doubt about it but even in that case I still had half my colleagues trying to prove that the bacteria weren't even there you know but but I mean I wouldn't have argued so much if I hadn't had some way of arguing with people but I could show them the things you know I could project slides on the wall and say look there are the bacteria on them you know there's the inflammation underneath well one of the other arguments they had was that and this I mean I managed we managed to prove this was wrong later on but but that you know Dr. Warren the bacteria probably just secondary to the inflammation and but I didn't think they were and the way the bacteria were arranged on the surface of the the mucosa and so on looked as if they were causing the inflammation but you can't really argue like that you've got to get some better evidence and this is where for me it was very good that Barry came in and helped me because he could get the the extra evidence he could see the patients and and so on he knew what was going on with the patients that I didn't I mean I think in in certain circumstances a lot of students of of science probably molecular molecular biology or microbiology would would say you've been lucky you know that that you've had your findings and confirmed to yourselves pretty early but what about the sheer frustration of doing experiment after experiment I mean what would you advise young students in the sciences how how would you advise them to to go on what should they what should be the key what should they be aiming for eventually I think it depends what they're doing and but I think they should be aiming at getting some good evidence for their ideas and that's not always so easy I mean with the luck that we had was the luck in finding something that there was pretty when we pretty easily found pretty good evidence for us well there's been anyone who really was interested and wanted to to look you know only had to look but most people didn't want to look I mean we were doing I mean I was trying to convince people that something was there that everyone knew wasn't there it wasn't like a slight change or an improvement on something you know a variation or you know I mean there are very few bacteria appear in the small intestine that do anything much but people are always wanting to find an organism that's causing some some disease in the small intestine and they're you know they're always asking you know are giardia there you know it's a type of protozoan and we used to see it about you know once every two or three years but the gastroenterologist had asked us every damn biopsy from the small bowel you know are there giardia there and and I mean if we found something else there but you know if we had and sort of managed to show that whatever else we found there was causing the symptoms that patients were having that'd be only too pleased to hear about it but to find these in the stomach like that when bacteria just simply were not supposed to be in the stomach it was a total change it was I mean one of the ways I put it sometimes is that you know everybody knows that the earth is flat and the fact you know as far as I'm concerned that if you look over there you can't see a mountain that's just over the horizon over there it's because it's because the earth isn't flat it goes around well maybe the light's curved there's a process of constantly learning and being open to to to challenges but it's it's a complete change from being the earth being flat to you being someone saying that the earth is round and you know what the hell are you talking about the earth can't be round we'd walk around but and going around the sun you know what do you mean going around the sun we're floating around in mid-air we're not you know we're standing on the ground that's this sort of thing you know and you've got to be able to look at things from further away and see the big picture I suppose it's a bit like a religion and as the years went by I think we both realized that it was no the process wasn't going to happen if we fought harder or argued more it was just time that was going to solve all our problems arguing and being controversial and everything and it took 10 years so that when we started off the people who were the senior professors who were criticizing our work or being conservative about it they had then started to retire and the the hot young guns of our age were now the professors and they had all kind of grown up a little bit with a bit of exposure to helicobacter and had played around with it and so that by 19 in the by the 90s it was easy to find lots of professors who were fine doing the same thing who agreed so that the controversy kind of aged and fizzled out there's still little aspects of it but there was by the 90s there's not this argument of whether helicobacters existed or whether most people had them or whether they were harmful those things were out of the way the things were argued and you know should you treat people with this antibiotic or that antibiotic rather than whether you should treat them at all that wasn't on the agenda anymore well have any of the non-believers come forward and actually shake your hand shaking your hand and said well done well that really happened a few years ago didn't it robin yeah i've had a number of them doing i've actually heard people come out come out of the woodwork in the last few months actually who said that rather guiltily that they they were sort of naysaying behind our backs well never mind the drug company i've had a number of surgeons come along and you know tell me that you know that work you did it's really it really took away a lot of our business yeah not just the drug i mean the drug companies didn't like as much either because they were they had actually produced some really good drugs for peptic ulcer disease the main trouble with them was that they didn't actually cure the disease they just um relieved so that the ulcers could heal and then they'd take the drugs away and the patients that were all right for a few weeks and then the bad this isn't a really bad patient and they get it again and so in effect actually these patients weren't really much better off than they had been even though they could take the drugs and relieve it they were sort of permanently taking drugs they couldn't eat food they wanted to and they're getting repeated attacks of pain and i mean i've had patients right with this type writing letters to me and they as far as they were concerned they didn't seem to be any better off than they had been even though they had these really good drugs that while they were taking them they actually could heal and relieve the the disease and actually this is i think what put the surgeons out of business i don't think we did well that's that's probably one one good reason to stay within research instead of working for a commercial drug company which is a a question that a number of our science students in sweden face today there's a dilemma dilemma of wanting to work you know should i go work for a drug company or should i go work for work in research stay in academia um and especially as sweden is trying to grow this biotechnology sector at the moment of the number of drug development companies there's so much money needed for this sort of thing that i think you've got a bit of both yeah it's good to have both and i think the united states have got both and i think sweden you have got both uh but in australia it's there's a bit of a scarcity of commercial uh biotech people actually in the business who employ scientists and so that it just worries you that there is good scientists coming out of the university with degrees and apart from teaching students there's not really a job for them at the end of it and so they're all going to the four corners of the earth this is what generally happens then to australian scientists that's right but they have to follow the money and the money right now well take one area of stem cell research it's all in california they just funded three billion dollars of stem cell work over the next three years out of private subscriptions so obviously if you're in stem cell research you'd be looking at the wanted ads from california and so that's what we unfortunately have come to the end of our time so i'm going to have to say thank you so much for being here it was lovely meeting the both of you good luck with the rest of the week i know it's going to be exhausting for the two of you i i hope there's some enjoyment in it for your families and the rest of the entourage that you brought with you it's great to meet you