Reasons to search for tumorviruses in childhood malignancies and colorectal cancer
Harald zur Hausen was born on March 11, 1936 in Gelsenkirchen-Buer, Germany. He studied Medicine at the Universities of Bonn, Hamburg and Düsseldorf and received his M.D. in 1960. After his internship he worked as a postdoctoral fellow at the Institute of Microbiology in Düsseldorf, and subsequently in the Virus Laboratories of the Children’s Hospital in Philadelphia where he was later appointed as Assistant Professor. After a period of 3 years as a senior scientist at the Institute of Virology of the University of Würzburg, he was appointed in 1972 as Chairman and Professor of Virology at the University of Erlangen-Nürnberg. In 1977 he moved to a similar position at the University of Freiburg. From 1983 until 2003 he held the post of Scientific Director of the Deutsches Krebsforschungszentrum (German Cancer Research Center) in Heidelberg. He retired from this position in 2003.
He has received a number of national and international awards, among them the Robert-Koch-Prize, the Charles S. Mott Prize of the General Motors Cancer Research Foundation, the Federation of the European Cancer Societies Clinical Research Award, the Paul-Ehrlich-Ludwig Darmstädter-Prize, the Jung-Prize, Hamburg, the Charles Rodolphe Brupbacher Prize, Zürich, the Prince Mahidol Award, Bangkok, the Raymond Bourgine Award, Paris, the Coley-Award, New York, the Life Science Achievement Award of the American Association for Cancer Research, San Diego, the German Special Order of Merit with Star, the Tsungming Tu Award and the Nobel-Prize for Medicine, 2008. He has received 25 honorary MD and Ph.D. doctorates from the Universities of Chicago, USA; Umeå, Sweden; Prague, the Czech Republic; Warsaw, Poland; Salford, UK; Helsinki, Finland; Erlangen-Nürnberg and Würzburg (both Germany); Ferrara, Italy; Buenos Aires, Argentina; Melbourne, Australia; Salerno, Italy; Los Angeles, USA; Madrid, Spain; Jerusalem, Israel; Besançon, France; Bucaramanga, Columbia; Valdivia, Chile; Ljubljana, Slovenia; Antwerp, Belgium; Pisa, Italy; New York, USA; Ho-Chi Minh, Vietnam; Ioannina, Greece, and Porto Alegre, Rio Grande do Sul, Brazil. Moreover he has received honorary professorships in Copenhagen, Denmark; Hangzhou, Shenyang, Chengdu, China, and Hanoi; Vietnam. In 2012 he held the TEFAF Oncology Chair.
He is an elected member of various academies (e.g. German National Academy LEOPOLDINA, Heidelberg Academy of Sciences, Polish Academy of Sciences, National Academy of Medicine of Venezuela, American Philosophical Society, Institute of Medicine of the National Academy of Sciences (USA), Foreign member of the US National Academy of Sciences) and research organizations (EMBO, HUGO), and became an Honorary Member of a number of biomedical scientific societies. A large number of Special Lectures and Visiting Professorships, Memberships in Editorial Boards and active involvements in the organization of international meetings complement his curriculum. In April 2013, Harald zur Hausen was elected into the First Class of the Fellows of The American Association for Cancer Research (AACR) of the AACR Academy, Philadelphia, U.S.A.
From January 2000 to December 2009 zur Hausen was Editor-in-Chief of the International Journal of Cancer, and from 2006 to 2010 he was a member of the Board of Directors of the International Union against Cancer (UICC). From 2003 to 2010 he was vice-president of the German National Academy for Natural Sciences and Medicine LEOPOLDINA in Halle. Since 2006 he has been a member of the Scientific Council of the National Science and Technology Development Agency in Bangkok, Thailand and from 2010 to 2012 Chairman of this Council.
Cancer’s discussion began with Nobel Prize Harald zur Hausen. He talked about the danger red meat might represent due to its strong relation with colorectal cancer, with numbers that impressed the audience. However, he also stated that we have all the tools and knowledge to prevent this disease and so many others, focusing on the decrease of alcohol and tobacco consumption.
FRONTAL: We know that your childhood was spent in an area severely attacked during the World War II. What was it like to study under such a climate of war? How did you manage to grow up and find hope in the middle of bombardments?
Harald zur Hausen: Well, that is an interesting question because during that period of time schools were closed. I was six years old when the bombing started. I went to elementary school for only one year and a half and could only go back to school after the War finished, in the end of 1945, and that was a very difficult period. Subsequently, in the post-War period of time, in 1946, I went back to high school (Vechta Gymnasium) and I did not have the background for it, so I had some difficulties during the first year. When I finished the first year, they contemplated carefully whether I could enter the second high school class, but I did.
F: You started by studying the Epstein-Barr Virus, then you switched to Adenovirus and finally you started dedicating yourself to research on HPV. How do you pick a specific virus as an object of study?
HH: In fact, I started to work on Adenovirus and chromosomes changes and Adenovirus helped me a lot to get acquainted with molecular biological techniques. That led me to the Epstein-Barr Virus which, in fact, I started studying in Philadelphia when I spent 3 and a half years in the USA. I became very early interested in the question whether infections could be linked to human cancers and this was mainly based on the observations of bacteria infected by phages (by bacterial viruses), which gained new properties that really resulted from the uptake of genetic material. So at the time I realised – a little bit naïvely – that the same could be true for cancer. In this disease you have a pick-up of viral genes in normal cells and then those turn into cancer cells. Today we know, of course, that this is much more complicated than that simple statement, which was indeed the initiation of my own career in this field. However, the question itself fascinated me and I continued to work on it basically until today.
F: How do you feel when you realise you have dedicated your life to research, making it possible for millions of women today to protect from infection by HPV, and eventually, cervical cancer?
HH: It is obviously very pleasant for us that we have been able to identify those agents that cause cervical cancer, which in the end resulted in the development of a vaccine against the high risk Human Papilloma viral types. Indeed, it is an important aspect that this is a moment when cervical cancer, at least in theory, can be eradicated, probably not only by vaccinating young women, but also by vaccinating boys as well. This is because boys are very active transmitters of the virus and they also acquire later in their lives cancers linked to the same types of viruses like oropharyngeal cancer and anal cancer. In addition, genital warts, which occur relatively frequently in both genders, are very nasty problems. For all those reasons, it is important to get vaccinated and to vaccinate both genders. We have a theoretical chance to eradicate these viral infections completely because they are limited to humans, but only if we vaccinate both genders.
F: You had to struggle against all the skepticism of the scientific community around your discovery – it took you approximately 10 years to affirm it. Did you feel exhausted at some point?
HH: It was a period of time in which it was very difficult to penetrate with your views because it was a strong belief that another agent – Human Herpes Simplex Virus type II – was the responsible for cervical cancer, and we looked into this carefully but did not find it. Therefore, it was one of the triggers to study carefully the Papillomavirus and particularly the fact that genital warts occasionally converted into malignant tumors. Consequently, I thought in the early days that, if the virus can cause cancer in genital warts, it may cause much more active cancer at other sites, namely at the cervix. So in fact, at the end, we were lucky we could isolate those viruses and it was very pleasant.
F: Nowadays, vaccines for HPV are still very expensive, limiting their application to the “rich world”. However, once HPV is associated with sexual risk behaviors, should not there be a greater investment in the “poor world”? How do you feel towards that limitation?
HH: This is indeed a big problem, but it is slightly a lesser problem in these days than it was in the previous years. Right now, companies, as well as some foundations, put a lot of money in support of buying vaccines for the Third World and the companies are reducing the prices quite substantially. The patents for those vaccines are expiring and that anticipates us for further reduced prices so that, in the future, the prices will be pretty low. However, at the moment, the accessibility for the vaccines in many of the developing countries is still rather limited. Only on those places which are preferentially supported by the Bill Gates Foundation and others there is quite a number of girls taking advantage of the vaccination, and this needs to be resolved on a more global level in the future.
F: How do you picture the future of research on HPV? What path do you advise young scientists to follow?
HH: That is a very difficult question. Anyway, I believe that young scientists should try, first of all, to select an original topic to walk on. Secondly, they should not give up quickly, they should be persistent in their work, and even if there are some obstacles they have to face, it may be worth to continue. In many instances original ideas don’t turn out to be the right ones but in some sideways we usually find something which turns out to be quite important for your future career. I think that something else which probably is also important is to not accept the many dogmas that exist today in Medicine. If you look carefully to many of these issues, you will find that there are a lot of open questions still remaining. Take, for instance, the present evaluation of the sequencing of all human genomes or all genomes of cancer cells. Even if you look into individual cancer cells that have been fully sequenced, there are still compartments missing, namely of extra-chromosomal DNA, which exists and may have important biological functions. So, for all those reasons, it is important to get through with your ideas and do not give up too quickly.
F: You need inspiration and imagination in order to pursue a career in research – where did you find yours?
HH: This is another difficult question for me to answer [laughs]. You have to become familiar with the field in which you are working, you have to read a lot and do a lot. If I am, for instance, looking for the role of viruses in human cancers (or infections in human cancers), I need to study the epidemiology of human cancers because without that knowledge, I would not work on certain types of cancers. So you have to be a little bit broad-based and, in some way, I would say it is less inspiration, but rather hard work.
Interviewers: Ana Luísa Pereira, Catarina Cardoso
Writer: Martim Caldeira Henriques