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April 17, 2012

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The Mike Hogg Award and Lecture – Harald zur Hausen, M.D., Nobel Laureate and Oncovirus Hunter 

On Tuesday, March 27, 2012, Harald zur Hausen, M.D., presented a lecture on his suspicion that infectious agents are a component of colorectal cancers and hematopoietic malignancies. Zur Hausen is the 44th recipient of the Mike Hogg Award, which is supported by the Mike Hogg Fund and is hosted by MD Anderson’s Alumni and Faculty Association, a part of Trainee & Alumni Affairs. Each year, a Nobel Laureate who continues to participate in research is chosen to give the lecture and receive what is considered one of MD Anderson’s most prestigious awards. Zur Hausen was the Scientific Director of the German Cancer Research Center (DKFZ) from 1983 until 2003. DKFZ is one of Global Academic Programs’ Sister Institutions.

Twenty-five years before Harald zur Hausen was born, Francis Peyton Rous, M.D., at the Rockefeller Institute, showed that filtered, cell-free samples from chicken tumors could infect healthy chickens. The Rous sarcoma virus (RSV) is the first known virus capable of inducing cancer. Rous’ seminal 1911 work, however, did not gain much support among his colleagues and it would be 1966 before the effort was rewarded with the Nobel Prize. In the intervening 55 years, Harald zur Hausen would survive WWII, complete medical school and start his life as a researcher.

Unlike many scientists who venture into a field based on availability or inspiration from a mentor, zur Hausen knew what he wanted to pursue while still in medical school. By 1960, several important studies had taken place suggesting the role of viruses in cancer – zur Hausen wanted to be part of that kind of work. Beginning his career as a laboratory assistant at the Institute for Microbiology at the University of Düsseldorf, zur Hausen married his first wife. With their first son in tow, they headed for Philadelphia and he worked at the lab of Werner and Gertrude Henle.

The Henles had devised vaccines for influenza and mumps while working at The Children’s Hospital of Philadelphia as well as developing the first method to prevent hepatitis. When zur Hausen began working in the Henle’s lab at the start of 1966 the entire group was focused on the Epstein-Barr virus, which had recently been discovered by Michael Anthony Epstein, Ph.D., a pathologist at the University of Bristol and Yvonne Barr, Ph.D., a virologist working on her Ph.D. The Henle’s lab was able to draw the connection between the Epstein-Barr virus, infectious mononucleosis and Burkitt’s lymphoma, a cancer common in parts of Africa. This marked the discovery of the first virus responsible for human cancers. Zur Hausen’s contribution to this effort was illustrating by electron microscope that Epstein-Barr virus particles were inside Burkitt’s lymphoma cells.

Soon after, zur Hausen and his family returned to Germany and the Institute for Virology at the University of Würzburg. The focus of his work was in proving that Epstein-Barr virus DNA is latent in every Burkitt’s lymphoma cell but the virus does not cause a persistent infection. He did and this was the first illustration of a persistent tumor virus in human tumors. During this time zur Hausen also showed the virus existed in epithelial cells of nasopharyngeal cancer. Taking a new position at the Institute of Clinical Virology in Erlangen-Nürnberg changed the course of his research.

After reading clinical reports that repeatedly recounted genital warts becoming squamous cell carcinomas and knowing research had shown genital warts contained papilloma-virus particles, zur Hausen believed the papillomavirus was the cause of cervical cancer and set out to prove it. At the close of the 1970’s, and following a move to the University of Freiburg’s Institute of Virology, zur Hausen’s second wife, Ethel-Michele de Villiers, Ph.D. and Lutz Gissman, Ph.D., isolated and cloned HPV-6 from genital warts, but they could not find it in cervical cancer. After isolating HPV-11, however, they were able to show that type of human papilloma virus existed in one cervical cancer biopsy. Continued research isolated HPV-16 and 18 DNA, which we now know cause the vast majority of cervical cancers.

Zur Hausen and his colleagues had shown the connection between the virus and cervical cancer and went on to show how two of the virus’ genes, E6 and E7, were almost always transcribed in the cancer cells as well as the pre-cancerous lesions. Getting a vaccine created would prove nearly as daunting a task as isolating the cause of the cancer. Market analysis by the pharmaceutical companies that zur Hausen initially approached said there would not be enough of a market. After a decade of work, zur Hausen and his colleagues had drawn the HPV connection to cervical cancer in 1984. It would be 2006 before a vaccine was approved by the Federal Drug Administration.

The next 20 years of zur Hausen’s career were spent as the scientific director of the German Cancer Research Center (DKFZ) where he was tasked with a reorganization of the institution but managed to keep his hand in laboratory research. In 2003 he left the role of scientific director, but continued to conduct research in his laboratory in DKFZ’s virus building. Zur Hausen’s current work, and the subject of his lecture at MD Anderson, is in the potential infectious agents in red meat that might be necessary to cause colon cancer.

While studying the epidemiological record, zur Hausen has keyed into four areas where he sees patterns with cancer development: cancers with an increased frequency when there is immunosuppression; cancers where there is an immunosuppressive protection effect, or a decrease in cancer; cancers incidence increased as a result of infection; and cancers potentially linked to animal-human transmission. Each of these areas are intriguing but it is perhaps the connection between cancer and red meat zur Hausen poses that has garnered the most recent attention. Zur Hausen hypothesizes that an undiscovered virus is being passed through red meat that could play a role in colon cancer and possibly lung and breast cancer as well.

As a research field, oncoviruses have shed light on many of the complexities and intriguing nature of cancer. The researchers who have helped elucidate the role oncoviruses play in causing cancer have provided the framework for how cancer is viewed and the development of research to better understand the disease. In all oncoviruses, the virus alone is not enough. There must be another factor that propels the changes to enable cancer development.  Understanding how viruses and those factors interact will allow for an even greater understanding of not only the disease but how we can combat it. For Harald zur Hausen, that is the point of his life long investigation of oncoviruses – to allow for more effective prevention, timely diagnosis and beneficial treatment. He, de Villiers and the other members of his lab have no plans to stop contributing to the ever-increasing understanding of cancer and how to help patients with the disease.

Calendar of Events

GAP Annual Conference
Oslo, Norway
May 14-16, 2012

DKFZ Stem Cell Symposium
Heidelberg, Germany
Oct. 14-16, 2012

Yonsei Joint Symposium
Seoul, Korea
Oct. 18-19, 2012


Yonsei Cancer Center Joint Symposium and EAB Meetings

On October 18- 19, 2012, Yonsei Cancer Center in Seoul, Korea will host its 7th External Advisory Board (EAB) Meeting and joint symposium. Each year, Waun Ki Hong, M.D., head of the Division of Cancer Medicine, chairs the meeting. Other members of the EAB from MD Anderson include Thomas Buchholz, M.D. and Timothy Thompson, Ph.D., both professors in the Department of Genitourinary Medical Oncology; and George Chang, M.D., associate professor in the Department of Surgical Oncology. Hong obtained his M.D. from Yonsei University’s School of Medicine before completing his medical oncology fellowship at Memorial Sloan-Kettering Cancer Center in New York. His research has made strides in larynx preservation, chemoprevention and treatment of head, neck and lung cancer, as well as personalized cancer therapy. Yonsei Cancer Center, founded in 1969, is a joint effort between the Korean government and Yonsei Medical Center, which is also home to the Yonsei University School of Medicine.

Network News

DKFZ Hosts Symposium on Stem Cells and Cancer

The 7th International Heinrich F.C. Behr Symposium on Stem Cells and Cancer will be held October 14-16, 2012 at the German Cancer Research Center (DKFZ) in Heidelberg. Stem cells are integral to repair in response to injury and infection but genetic changes can lead to the creation of cancer stem cells that foster tumor development. The intent of the symposium is to discuss the latest information surrounding stem cells and their contribution to cancer.

The symposium is a joint effort between DKFZ, the National Cancer Institute (NCI) in Bethesda, Maryland and the German Academy of Sciences Leopoldina. More than 300 students and scientists are expected to attend and engage in the discussion with leading researchers from across Europe and the United States. The symposium will focus on leukemic, brain and solid tumor stem cells as well as possibilities for reprogramming cancer stem cells.

Be sure to register by September 14, 2012 and contact the conference organizers if you have any questions.

Brain Tumors 2012 - From Biology to Therapy

The Nencki Institute of Experimental Biology and The Neurobiology Committee of Polish Academy Sciences will host Brain Tumors 2012 in Warsaw, Poland from May 28-30, 2012. The conference will gather experts from a variety of institutions, including Memorial Sloan-Kettering Cancer Center, The International Agency for Research on Cancer in France, Uppsala University in Sweden and Cleveland Clinic. MD Anderson will be represented by Amy Heimberger, M.D., an associate professor in the Department of Neurosurgery; Waldemar Priebe, Ph.D., professor in the Department of Experimental Therapeutics; and Konrad Gabrusiewicz, Ph.D., a postdoctoral fellow in the Department of Neuro-Oncology.