A Solid Working Hypothesis, Endurance, and Some Disregards of Your Peers as Trailblazers for Serendipitous Observations


Harald zur Hausen

Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280,
69120 Heidelberg, Germany

 

During my scientific career a major theme was the potential role of infectious events in human carcinogenesis. During my first 3 years working in an Institute of Microbiology in Düsseldorf I had a lot of freedom to work on questions of my interest, but almost no advise. During this period I felt increasingly frustrated and looked for a different position which I found in Philadelphia, USA. Looking back at my first 3 years I changed my view of this period since it provided me with a chance to acquire a broader perspective for my future work. Profoundly influenced by the modification in pathogenicity of certain bacteria after becoming lysogenic for specific phages, I started to work on the concept that human cancers should be due to a similar mode of infection by specific viruses. During the years in Philadelphia and subsequently after moving to Würzburg in Germany I could prove this concept for Epstein-Barr virus, by demonstrating viral DNA latency and reactivation in Burkitt’s lymphoma cells and its latency in epithelial cancer cells of nasopharyngeal carcinomas. Thereafter my group worked on the role of papillomaviruses in cancer of the cervix. This was in part ridiculed by some of my former peers, since “everyone knows that wart viruses are harmless”. This changed after 1983/1984 when we identified after more than 10 years of work the HPV types responsible for most cervical cancers. During the last 3 decades of the past century we made several serendipitous observations. The discovery of reactivation of latent Epstein-Barr virus infections by tumor-promoting phorbol esters was one of them. This was followed by the identification and characterization of a novel B-lymphotropic polyomavirus, closely related to the recently identified human polyomavirus type 9, the identification and characterization of a novel adeno-associated virus (AAV) with a specific affinity for respiratory epithelia. It is now labeled as AAV-5 and frequently used as vector system. Moreover we found a novel African green monkey Epstein-Barr virus and our group isolated a number of novel human papillomavirus and torque Teno virus (TTV) genotypes. During the past decade we concentrate our efforts on the characterization of virus-like bovine small single-stranded circular DNA molecules and their potential role in colon and breast cancers and in human neurodegenerative diseases.







 

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