The Nobel Prize in Physiology or Medicine 2008
Harald zur Hausen, Françoise Barré-Sinoussi, Luc Montagnier
"I hope indeed, that this Nobel Prize will of course create more awareness of the role of infectious agents in human cancer"
Telephone interview with Harald zur Hausen immediately following the announcement of the 2008 Nobel Prize in Physiology or Medicine, 6 October 2008. The interviewer is Adam Smith, Editor-in-Chief of Nobelprize.org.
[Harald zur Hausen] zur Hausen.
[Adam Smith] Oh hello, Professor zur Hausen.
[AS] This is Adam Smith from the web site of the Nobel Foundation ... Hello. Would you mind if we recorded a very brief telephone interview with you?
[HzH] No, it's fine.
[AS] Thank you.
[HzH] I was informed that this would come through.
[AS] Thank you very much. Well first of all, of course, many congratulations on the award of the Nobel Prize.
[HzH] Well, thank you very much. I'm of course totally surprised. And it's of course a great pleasure for me.
[AS] Where were you when you received the news?
[HzH] Here in the Institute, in my office.
[AS] This is in the DKFZ?
[HzH] In the DKFZ, indeed. Well I am an Emeritus as you may know, but I still kept my office. I'm still Editor-in-Chief of the International Journal of Cancer, and also keep a laboratory here.
[AS] Yes, yes indeed. So, if we may turn to the discovery. When you first suggested that human papilloma virus caused cervical cancer, the prevailing view was that it was herpes simplex virus.
[AS] So how was your suggestion at first received?
[HzH] Well it was not very welcome, let's say it this way. Because in the early phase indeed, quite a number of scientists believed that herpes simplex type 2 would do it. There were a number of reports which seemed to confirm that there are increased antibody titres to herpes simplex type 2 in cervical cancer patients. And I reported it for the first time in public in 1974 at a meeting in Key Biscayne in Florida, when there was a meeting which was specifically scheduled for herpes simplex type 2 in cervical cancer. And at that time I reported our negative results in trying to find herpes simplex type 2 DNA in cervical cancer cells. And at the same time I stated that it would be very worthwhile to look rather into genital papilloma viruses, because the reasoning for me was that I had surveyed the literature and found a number of anecdotal reports on malignant conversion of genital warts.
[AS] So I imagine, since the meeting was organised around herpes simplex virus, you were the unwelcome guest on that occasion.
[HzH] Almost. You are almost exactly stating it in the right way because my statements were not well received, and I felt as a lonely voice in that meeting.
[AS] And it took about 10 years before you discovered the main disease-causing genotypes, HPV16 and 18.
[HzH] Well it's true, let's say in the meantime, between – I started to work on papilloma viruses in 1972 myself – but in the meantime we could identify the, individual ... excuse me, I'm still a little bit nervous at the moment.
[AS] Understandable, yes.
[HzH] Well, we could demonstrate that there exists a plurality of papilloma virus types. So there was not, as initially assumed, only one single papilloma virus type, but a multitude of different types, which was also confirmed by the group of Gérard Orth in Paris. And, but we concentrated ourselves on trying to isolate the viruses from genital warts because initially we suspected that that virus may be responsible for cervical cancer development. In 1979/1980 we could finally – it was mainly in collaboration with my co-worker Lutz Gissmann – that we could identify HPV6, and Ethel-Michele de Villiers was cloning it subsequently, with Gissmann. And subsequently we could identify another one – that was HPV11, which was also in genital warts and laryngeal papillomatosis. In fact, in the subsequent period, we were initially disappointed not to find HPV6 and 11 in cervical cancer, without one rare exception. But, the probes helped us to identify HPV16 and 18 subsequently. In 1983 and 1984 this was published, by two of my students, Mattias Dürst and Michael Boshart. And, so that was in a way for us a breakthrough because at that time period, of course, interest was awakening very substantially, and quite a large number of groups were collaborating there, and starting to work on papilloma viruses, and ask us for the probes, so we dispersed them very freely throughout the world.
[AS] Yes, I understand that you gave them to anybody who asked ...
[AS] ... and indeed then others went on and claimed patents on some of them, but that's another story, perhaps.
[AS] It's perhaps surprising that vaccine development didn't immediately follow your discoveries.
[HzH] Well, I mentioned it some time ago – in Stockholm, even – that, I tried to contact very early the German, particularly German pharmaceutical companies. And one of the companies, the Behring company in Marburg, became quite interested in it initially, and so they even funded our research for a certain period of time, with the expectation that we could collaborate on the development of vaccines. But then they did, at the same time, a market analysis and according to this market analysis there would be no market for such a vaccine. And then they stopped the funding. And it stopped for a certain period of time, indeed, at our place, intention to work on vaccines.
[AS] It shows how wrong market analysis can be.
[HzH] Well, it was totally wrong of course, as seen today. But, I mean, there's a little bit of an excuse for these companies, because at that time the PCR technology was developed, and many people started to work with this technology, and there was – quite a wide variation in data had been obtained in this time period. And, so they ... from 0–100% in supposedly negative tissues turned out to be positive, and so on. So this confused industry too.
[HzH] And, in addition...
[AS] And, so what eventually changed?
[HzH] Well, eventually it changed basically as the continuation of some molecular studies, which demonstrated indeed that the virus must be closely involved, but also the epidemiology studies, which in the end clarified the situation in demonstrating that HPV16 and 18 were so-called high-risk viruses, and indeed major risk factors for the development of cervical cancer.
[AS] And the results of the vaccination trials that have so far been reported have been enormously promising. Do you think that vaccination programmes should be widened now?
[HzH] Yes. From my viewpoint, yes, clearly so. I think the vaccination is extremely successful. It is presently – the major disadvantage at this stage is that it is too expensive for those parts of the world which most badly need the vaccine; namely, the developing world. And so the prices have to go down in the future in order to enable those people to receive the vaccine. From my personal experience, what I hear is that, in Africa, for instance, and also other parts of the developing world, the willingness to be vaccinated is remarkably high, so it's more a question of how do we get it to those people and how do we get a drastic reduction of the present price.
[AS] One final scientific question. Do you think that in general we're going to see more link between infectious disease and cancer in the future?
[HzH] Well, if you ask me this way, yes. My personal feeling is, yes, we will see more links. One came up this year only – the so-called Merkel cell carcinoma polyoma virus, which – the virus is called Merkel cell polyoma virus – which has been found in Merkel cell carcinomas, and every evidence at this stage points to the fact that this is indeed aetiologically involved. I think it's, I hope indeed, that this Nobel Prize will of course create more awareness of the role of infectious agents in human cancer, and I'm so pleased that the HIV part is also awarded.
[AS] Yes, it's a fascinating linkage. What do you think gave you the dedication to stay with the studies of HPV's link with cervical cancer for so long?
[HzH] Well, my personal conviction that there must be ... first of all there must be an infectious aetiology of this type of malignant disease, but secondly also I was in-between always encouraged – in spite of the fact that we didn't find directly this virus – by the fact that I saw how many questions there remained open in the papilloma virus field. But, maybe I should mention it; I was not from the beginning mainly interested in papilloma virus, I was mainly interested in infectious agents in human cancer. So papilloma viruses came up as the most likely candidate from my viewpoint.
[AS] But yes, infectious agents had been the lifelong pursuit.
[HzH] Yes, indeed. Indeed.
[AS] So I shouldn't keep you on the telephone for too long, you have many other things to do, but may I just ask you if you have any plans for how you might celebrate this?
[HzH] I don't know yet. It was so surprising I really have to sleep about it for one night or so before I make any decisions.
[AS] I fear the chances of getting any sleep for the next little while may be rather small.
[HzH] Yes, there's a risk indeed. Alright ...
[AS] Anyway, my congratulations ...
[HzH] Thank you once again.
[AS] Thank you for talking to us.
[HzH] Thank you. Bye bye.
[AS] Bye bye.
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