Nobel winner Harald Zur Hausen on vaccines and the need for basic research

Print 02 March 2015
EJ Lane / FeircePharmaAsia

SINGAPORE--Harald zur Hausen in 1976 published the hypothesis that human papillomavirus plays an important role in the cause of cervical cancer. It took three decades before that groundbreaking work led to approval of a vaccine for cervical cancer.

On the sidelines of Singapore's annual Global Young Scientists Summit, he talked about the path to convincing drug companies he was onto something.

He received the Gairdner Foundation International Award in 2008 for his contributions to medical science. He also shared the 2008 Nobel Prize in Medicine with Luc Montagnier and Françoise Barré-Sinoussi, who discovered the human immunodeficiency virus.

Hausen sat down with FierceVaccines on Jan. 23 to discuss the need for more basic research leading to possible drug discovery and his views on drug development.

FierceVaccines: Your story is particularly interesting as a lesson learned in that pharmaceutical companies took a lot of convincing to evaluate your research. Has that changed since then for the industry generally?

Harald zur Hausen: Not really. I think there are very few companies who work on long-ranging projects between initiating basic research, leading to application and translation into practice. I mean, there have been a few companies in the past who started it, but many of them gave it up. I'm thinking, for instance, of Swiss companies, specifically.

I believe also a few American companies did it, but I'm not so exactly familiar with this division. But right now it seems to be a bit more difficult to do this. And so they claim the only way is a very intense interaction between companies and university research institutions and so on. I think, in my opinion, there's nothing against it as long as the next change in the directorship of the companies does not change the topic completely. And then, again, the money has been mainly lost.

FierceVaccines: So, the actual ability to keep money on one problem at a time is the key?

Harald zur Hausen: Some persistency on the subject is very important. It may not lead eventually to the desired result, but on the sideways, which appear on this type of study, you almost uniformly come up with something which is interesting.

FierceVaccines: Should a drug company do that, do you think?

Harald zur Hausen: I'm not a director fortunately--or maybe unfortunately--of a drug company. So, it's a little bit difficult to advise them. I mean, from my viewpoint as an academic researcher, I would say it would be good if they do it, yes.

FierceVaccines: What is the thinking that should go on behind the vaccines business?

Harald zur Hausen: It is not straightforward. The vaccine for HPV had a very colorful history because initially in 1984 I visited virtually all German, in particular, also some Swiss companies and approached them in order to develop a vaccine for this infection. There was only one company--now the CSL Behring company--in Marburg, which became interested. The former director was a very open-minded person and quite an active director in that sense. He started a program, but one of the directors did a market analysis for the HPV vaccine and also for an analysis of the available data.

And that analysis came out with the statement that there is no market for such a vaccine, mainly because everyone [who's already] infected by this virus is a small child. And both of these statements turned out to be entirely wrong, but it led immediately to ask Behring to stop the sponsorship, which I had to do. And we were left in a way of frustration at that time. And, in my opinion, it delayed the development of the vaccine by probably a period of four to 5 years.

FierceVaccines: The push starts as a public health push then? Advocates for an unmet need?

Harald zur Hausen: The pediatricians are quite active. Some gynecologists are, too, but a number of others are not active at all. At least I have not met any pediatrician who was opposing it. There needs to be more education, training, more advocating being done for the medical personnel, for health officials, in particular also, and also for--what is it--teachers, parents and so on.

FierceVaccines: In Asia, public health programs often choose because of cost between immediate treatments and longer term vaccination efforts. Your thoughts?

Harald zur Hausen: If you develop a nasty view of this old story, it's due to the fact that the physicians--some physicians do not see that as really something which would fit to their own problem in the future. Because if you vaccinate girls against HPV, then the likelihood that, for instance, surgically interventions for precursor lesions will rapidly decline in the forthcoming years. And so that the cancer would be greatly diminished in incidence rates. It's a nasty view. I mean, the other one is just simply that they are not sufficiently interested in the whole story at all and not sufficiently educated about those aspects.

FierceVaccines: So the epidemiology is not well understood?

Harald zur Hausen: The epidemiology isn't relatively clear in many of these instances, no. You know the number of cases in most countries take other types of vaccine like diphtheria vaccine, cholera vaccine and whatever that exist, or mumps and measles vaccines. You know to which extent the vaccine's accepted, to which extent it's not accepted. You can calculate the cases or can see the cases, which are knowns ... even in occurring selectively in the non-vaccinated population and not in the other one. And some instances there are even deadly cases of the infected children.

So, in a way it's a natural choice to use a vaccination. But yet there's a lot of hesitation, and there's even some different types of reasons for this type of hesitation. Some of them are really a religious reasons. Let's say you do not--should not--interfere with the natural course of something, which occurs--it's an unnatural mode of intervention with the biology and so on. This is only part, probably, of the reasons of those people. But it's a disaster if you look at it from a public health viewpoint.

FierceVaccines: The world of biological drugs has attracted a great deal of research because of expensive treatments. Is this an area you are following?

Harald zur Hausen: Yes. There is a lot of concern, I can tell you there's only - of the example of the papilloma virus vaccines because I was traveling throughout the world basically, advocating that the prices are too high. And, of course, complaining also at the companies that something needs to be done. They do it now, I must say. But for quite a while they didn't do it.

Even just as a footnote I was invited by a company to Belgium to visit the facilities where the vaccine's produced in order to demonstrate why it is so expensive. And they invited me on a table where we were sitting with 20 people, and one brought in 20 glasses of champagne glasses. And when he stood behind me, he lost his balance and put all the champagne glasses on me. I said jokingly, "This must be revenge for that I'm advocating lower prices for those vaccinations." But I was soaked in champagne from the shoes up to the top.

And I had to give a lecture and had to fly back on the same day to Frankfurt, and I was probably smelling like a bar.

FierceVaccines: Many companies do now have extensive access programs through GAVI, the Global Alliance for Vaccines and others?

Harald zur Hausen: GAVI does a lot. Also the Gates Foundation, I think, they may even in part support GAVI. I mean, in particular in Ecuador, Africa there's some programs running under the supervision of GAVI and the Gates Foundation, which are clearly very beneficial. I'm talking of the HPV vaccine specifically.

FierceVaccines: Do you think scientists should understand that part?

Harald zur Hausen: Well, they should understand it, yes. They should be aware of how pharmaceutical companies have been getting something licensed. I mean, the vaccine for HPV, for instance, required, of course, a large number of clinical trials prior to the licensing. And, of course, it has been expensive.

FierceVaccines: Finally, tell us where basic research should be looking now.

Harald zur Hausen: What you can do today is define some interesting research topics, but I'm not willing to predict which of these research topics in 10 years from now to which extent they will be applied. Almost all of these types of predictions--at least many of those which I have read--turned out to be wrong in the end. There are some research projects going on, no doubt, about stem cells, about the differentiated somatic cells, I mean, for producing iPS cells into kind of an embryonic state. These are all interesting research areas to which extents have become applied in the practice. It's very difficult to predict in at least in a foreseeable period of the future.

FierceVaccines: Were you thinking about that when you started out?

Harald zur Hausen: No. I was thinking that it's an interesting area. But I know of what we can do, and I think we have focused on a problem, which we also consider is highly important and interesting. So, for those reasons we have to concentrate our work on specific issues. We cannot work in all areas.

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