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A cure for cancer within reach

Harald Zur Hausen

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Matt Smith:

Welcome to the La Trobe University Podcast. My name is Matt Smith and with me today is Professor Harald Zur Hausen. Would you call yourself a virologist?

Harald Zur Hausen:

You know I have a basic training as a physician and subsequently I went into indeed virology and then into cancer research. So, my major interest throughout my academic career was a question on the involvement of infectious agents in human cancer. But I'm really a cancer researcher, I should say, yes that's probably true. For 20 years, I was Scientific Director of German Cancer Research Centre in Hiedelberg. So, I have had to be exposed to a number of different fields in cancer research as well. But for my personal intense of interest, I was really interested into question of involvement of infectious agents in cancer.

Matt Smith:

You contributed to finding, for the first time, that a virus can transform healthy cells into cancer cells.

Harald Zur Hausen:

Indeed. I think the major work, at that time, for me, was really to demonstrate that the genetic material of a virus is continuously present in certain types of human cells and that was, at that time, if you wish to say so, some way of beginning of molecular biology of infectious agents in human cancer.

Matt Smith:

So, it was back in the 1960's.

Harald Zur Hausen:

Yes, end of the 1960's, beginning of the 1970's.

Matt Smith:

What was the understanding of cancer back then?

Harald Zur Hausen:

Well, there was quite a number of people who doubted it completely as that infectious agents play a role, particularly strong viruses even from Australia. I'm even against it. I was quite intrigued by the fact already the early stage of my career that some viruses infecting bacteria leaves a genetic material in most bacteria and modifies its properties of these bacteria, like diphtheria.

Bacteria for instance become toxic under the circumstances. And as a student, I was in a way, elaborates the idea that this must be also cause of cancer; that some viral infection leaves some traces of its genetic material in the human cells and all its traces may lead eventually, somehow, to cancer. And, however, from that point on, I started to work on this question.

Matt Smith:

So, from that point, if you look at a cancer cell, can you work your way back and find out what virus is causing the cancer? It sounds like a fingerprint.

Harald Zur Hausen:

Let's say this way, yes. In a way it's true but we know today it's now about 21% of human cancers are link to infections in a global scale. Of those, these are not only viral infections; these are also bacterial infections in gastric cancer, for instance, and also parasites and bladder cancer and then some kinds of liver cancer, particularly in Thailand and China.

But the viruses play, indeed, a major role in this kind of condition. And indeed, we understand today, at least, to some extent why it was so difficult to discover them into early days because between the infection and the cancer development usually something like 10, 20 but more commonly 30, 40 or 50 years lapse before cancer appears. And so that was difficult to understand in the old days.

But today, we at least partially understand this because in the many of these instances some cellular genes have to be modified in the course of this new latency period, as well, prior to the development of cancer. And for instance in cervical cancer, we can identify at least in part, those signalling cascades of cellular genes, which need to be modified in order to permit some viral genes to express themselves fully leading eventually to cancer.

Matt Smith:

You just name dropped cervical cancer there. You were a joint winner of a Nobel Prize for that, two years ago in 2008. Can you tell me a bit about that? It was working with finding out that papilloma virus plays a big role in cervical cancer.

Harald Zur Hausen:

We suspected it, since again, in the end of 1960's, beginning of the 1970's. And indeed when I moved at that time from a German station in Wurzburg to another university along, I started a new program on papilloma viruses in cancer, suspecting that they might play a role in genital cancer, in cervical cancer.

And the reason was that I found a lot of literature, some anecdotal reports really but it's scattered all over 100 years, which describes the malignant conversion of genital warts. It's a rare event but it has been described repeatedly.

It was known at that time already and I saw it myself in the electron microscope that these warts contain particles, viral particles, which corresponded to the papilloma viruses. So it was obvious to look for human papilloma viruses whether at the site of the cervix might be more carcinogenic then its final involvement of external genital such.

And so, for quite some time, we intensively tried to analyze and purify the human wart virus and it turns out that it is not human wart virus but plenty of human wart viruses, which we saw quite quickly over the 1974. Today, more than 150 different types of human wart viruses are known. It took us quite a while before we got a hold of the genital wart viruses, which are quite different from other sites of the body, and then the first disappointment came because when we tested those viruses, which we isolated as a genetic material for those viruses in cervical cancer material. We didn't find it. So, the original hypothesis did not turn out to be right. But in view of the fact of the existence of related sequences to these genital wart viruses, which that time two of my students got the task to isolate it, to characterize it.

We were lucky and picked up relatively quickly in '83 and '84. HPV 16, the human papilloma virus type 16 and HPV 18 and characterized and so quickly that the specific genetic activity in the cancer cells versus genomes. And today we know that their responsible even resorted already, in the early days. The 70% of the human cancer's link to these cervical cancers are linked to these two types of infections.

So, in a way, it was passive breakthrough and in addition, we could demonstrate the DNAs becomes integrated into also chromosomes and persist there but the virus usually is no longer able to produce infectious progeny after those processes. It's, as we say, defective. It's one of the interesting features right now, that in many instances where you find viruses in human cancers

They are defectives. They can no longer produce an infectious progeny. If you wish to say so the virus in human cancer is a dead-end road for the virus and, of course, it's a dead-end road for the host, as well, frequently. That's unnecessarily for the prospective cell because that starts to proliferate, unlimited in a way, if it would be permitted to do so.

Matt Smith:

So, you said that 70% of cervical cancer was caused by this virus.

Harald Zur Hausen:

By these two types of viruses.

Matt Smith:

By these two types of viruses.

Harald Zur Hausen:

Especially today, almost 100% of these cancers are linked to the same virus family. There're a couple of additional types, which are isolated and part viral groups and part also viral group.

And to which bring up these the number positive samples almost to 100%. So that's a virus which is almost uniformly found in cervical cancer cells and we do know from experiments, which in partly also done in our laboratory.

If you block the genetic functions of the virus in the cancer cells by some type of genetic engineering, which you can do to sequential or by grafting these cells into susceptible animals which form tumours under all circumstances. The cells are no longer tumour cells. So we can demonstrate directly that viral genome functions are responsible for the cancer growths.

Matt Smith:

That sounds like a lot of prevention then for cancer involved making sure that there's a cure for the viruses, treatment for the virus whether it doesn't have an effect.

Harald Zur Hausen:

Well, it's just right but unfortunately we cannot yet block the viral functions selectively in the cancer cells and a lot of work is going on in all those lines right now. But what could be done is of course is to prevent infection by these agents by vaccination. In fact, in '84, I approached a German company, at that time, to prepare a vaccine and they were initially interested and they funded our research but only for a couple of months.

And then back at the analysis, which they performed, came out telling them that there was no market, there would be no market for the vaccine, which was of course grave mistake, at that time. And so they gave it up and stopped the project, immediately, to my great frustration, I must say.

Matt Smith:

So how much is known about the causes of cancer now? How much do we understand, not just cervical, but how much of the cancer causes is related to viruses?

Harald Zur Hausen:

All we know right now that approximately 21% of the global cancer incidences linked to infections. Out of this all 21%, 35% linked to bacterial infections and go backed to pylori and gastric cancer, about close to 1% to parasites, benign cells, as far some liver flukes and Thailand and some of China. And about the remaining 64% are viruses.

The viruses are the most important players. And we have, right now, for two of these viruses, which are causative agents for two very common human cancers named hepatitis B linked liver cancer, and also the high risk papilloma virus type 16 and 18 vaccines available which are obviously preventive.

For liver cancer, we can already state, right now, due to publications, which appeared last year, that indeed if the vaccination occurs, at the early perinatal period of the new born babies. Then this is clearly a cancer-preventive vaccine because this has been conducted in Taiwan since in 1984.

At the last scale and right now the first data come out that shows that indeed those vaccinated ones develops 70% less cancer cells than the other ones. They are still a few are that infections that or few other reasons developing liver cancer but 70% protection is given in this country.

For human papilloma virus, the suggestion is in so far slightly different because the latency period between the infection and the development of cancer in the odd of 15 to 25 to 30 years somewhere in this range. And the vaccine, which is now available started to be tested eight or nine years ago.

So what is possible to demonstrate already today, is that the essential precursor lesions of this cancer are being prevented. But so far not cancer itself and we will have to wait for something around 20 years or 25 years before we see also a reduction of cancer but we no doubts in the view of the prevention of the essential precursor lesions of this cancer will be also prevented.

Matt Smith:

Good news for that. I wanted to know at this point, can I ask you about the research you're doing?

Harald Zur Hausen:

So, we work presently on, particularly for Australian interesting topic on colon cancer. Because colon cancer rate is here in Australia, as in Western Europe and also in United States, also in America, particular in Argentina and southern part of Brazil. It is a very frequent cancer about to 20% of these cancers.

And for quite a long time it was suspected that this cancer is due to the consumption of red meat and that of the barbeque, grilling, chemical carcinogens are arising. There's also a chronological explanation. The problem, we can be aware of is really that if you are looking to roasting barbequing and consuming chicken or even if you do it for fish , the same kind of chemical carcinogens arise under those circumstances.

And the countries with high consumption of beef have a very high rate of colon cancer, like Australia as too where as lowest population which consume mainly poultry or living on fish, they don't have it.

We started with the processes that it might be due to the infectious agent, which is relatively somewhat resistant for higher temperatures. Possibly even in interaction with the chemical compounds produced in the barbeque process would lead to this type of cancer development.

And just as a theory behind that, really, so I started the geography carefully of colon cancer and it's interesting to know that in India, for instance, the beef is virtually not eaten. The Indians, basically, extremely low rate of colon cancer.

If you look into Japan, it is a country, which almost eating fish mainly for long, long periods, historic periods of time. Since 1975, the colon cancer rate rapidly increased, it's now virtually as high as here and some other countries, so that happened in Japan.

In Korea, it started about 20 years later, and what happened is, really, that after the war, the Americans introduced large quantities of beef to Japan, as it did after the Korean War, in Korea as well. And if you see how the beef is consumed in Japan, I was three times this year in Japan, and I saw that every occasion.

Beef is added to any type of meal, right now. So it seems to be some kind of interesting correlation between consumption of undercooked beef on one end in the appearance of colon cancer. Countries where mainly mutton is consumed, which is once in an occasion in an Arabian countries, the rate of colon cancer is relatively rare, it's not absent but it's relatively rare.

In China, for instance, mainly pork is being eaten as main source of meat but they also eat some beef but the rate is much lower than most of the other countries of the Western world here and then in Japan. So this points really to rather specific factor in beef. And if it so, I think we need to do something against it and either cook the meat very well, it'd probably kills those potential agents.

And secondly, we might be even be able to bread if it's a virus, cattle which is free of that particular type of agent. So in a way, it's important to know the reason and to investigate it.

Matt Smith:

In all your years of researching about cancer, is there anything that you do or not do anymore? For example, do you order beef still?

Harald Zur Hausen:

The reasoning is that I'm old enough, since I ate a lot of beef in the past, that'd probably doesn't mean anymore. But in a way, no, I would certainly recommend, right now, even based on what is known. If one eats beef, it's probably better to cook it well. It may not taste as good anymore but I think one can recommend, and I don't want to foil the beef industry and do something which would harm them, but on the other end we have to find out the truth.

That's really the problem. I mean, what important for humans to know is that really the case of what I'm saying is that we need to document it and to try to avoid it as much as we can.

Matt Smith:

Professor Harald Zur Hausen. Thank you for your time today.

Harald Zur Hausen:

You're welcome.