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A discovery that turned into a life-saving vaccine

When the Nobel Prize in Physiology or Medicine 2008 was awarded, Harald zur Hausen invited 13 of his family members with him to Sweden to celebrate. And there were many reasons to celebrate. Only recently, his discovery that human papilloma viruses cause cervical cancer has lead to one of the first cancer vaccines in the world.

Over 200,000 women die from cervical cancer each year, and it is the second most common form of cancer in women. Infection often occurs between ages 15 and 22, and the cancer typically occurs at ages 40 to 45. In many countries, screening programs are conducted routinely with the purpose of discovering the cancer at an early stage and starting treatment in time. For example, every 3 years, all women in Sweden between ages 23 and 49 are called in for a PAP smear. Women between the ages of 50 and 60 are called in every 5 years. However, screening programs are not as common in developing countries and the mortality rate is much higher. With a vaccine against cervical cancer now out on the market, hopefully thousands of lives can be saved every year. The man behind the discovery leading to the vaccine, Harald zur Hausen, was working in front of his computer when the Nobel Prize in Physiology or Medicine was announced last year.

“I was very surprised. There had been some rumors in 2007 but this year I did not expect it at all. It is really a great honor,” he says.

A conviction

Today, Harald zur Hausen is an Emeritus Professor but remains very much involved in research, in particular into viruses that cause cancer. His interest in this field began a long time ago, when he was a student doctor in the 1950s.

“I was fascinated with bacteria being able to take up DNA from viruses and change their characteristics, and I speculated as to whether this could be similar to the way cancer forms, that is, if the cancer cells took up viral DNA,” he says.

As Assistant Professor in the Virus Laboratories of the Children’s Hospital in Philadelphia, Harald zur Hausen started to study the Epstein-Barr virus, which is linked to the tumor disease, Burkitt’s lymphoma. He continued this area of study when he returned to Germany and the Institute of Virology in Wurzburg, and there he achieved one of his greatest accomplishments as a researcher. He was able to prove that viruses can persist in human tumor cells as genomes and are associated with tumor growth. In other words, he proved for the first time how viruses cause cancer. In 1972, Harald zur Hausen was appointed Professor of Virology at the University of Erlangen-Nuremberg in Bavaria, where he started investigating the viral candidates responsible for cervical cancer. The general belief at the time was that it was caused by a Herpes simplex virus, but Harald zur Hausen doubted this. So when he presented his findings that Herpes simplex virus was not present in this form of cancer, many researchers were skeptical and dismissed his results.

“But I never distrusted my findings and not everybody was skeptical. We were also well supported financially here in Europe so we carried on with the research. We believed we were on the right track,” he says.

For example, he studied the human papilloma virus (HPV) that causes skin warts and he was able to extract DNA from the virus particles. Harald zur Hausen and his co-workers discovered that two papilloma types HPV 16 and HPV 18 were present in more than 70% of cervical cancers. He also found that part of the HPV genome was integrated in the human DNA in cervical cells that gave rise to cancer, leading to new ways of treating the disease.

In 1983, the same year as his findings on HPV 16 and HPV 18 were published in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS), he became Scientific Director of the German Cancer Research Center in Heidelberg. During his time at the center, apart from doing important research, he introduced many positive changes in the organization of the center. For example, he encouraged researchers to work more closely with clinicians in order to study human material and less on mouse models, introduced peer review and broke down barriers between research institutions.

The long road towards a vaccine

In 1984, a year after his initial findings, Harald zur Hausen sent a request to a number of pharmaceutical companies that they start working on an HPV vaccine. At the time, the pharmaceutical industry did not see any market for a vaccine and it was regarded as too expensive to develop. In 2003, Harald zur Hausen retired as Director of the Cancer Center but he continued his research and kept hoping for a vaccine. In 2005–2006, more than 20 years after his discovery, the life science industry succeeded in developing an HPV vaccine to prevent cervical cancer. It was one of the first vaccines against cancer.

There are currently [2009] two vaccines available, Gardasil from Merck and Cervarix from GlaxoSmithKline, but Harald zur Hausen thinks, and hopes, that it is just a matter of time before more vaccines are available, and at a much lower price. Today, the price of vaccination is very high (approximately USD 400).

“It’s too expensive for both developed and developing countries. Prices need to be negotiated with the distributers. But I think it is just a matter of time before Indian or Chinese companies will start distributing the vaccine at a better price.”

The vaccine is now being administered to increasing numbers of young women all over the world. For example, from 2010, all girls in grades 5 and 6 in Sweden will be offered vaccination. Other countries such as Denmark, the United Kingdom and Australia have already carried out vaccination programs.

In recent years, several new viruses that cause cancer and other incurable diseases have been discovered. With the cervical cancer vaccine now out on the market; are there more vaccines on the way?

“It depends on the type of virus of course, for example, work on the polyoma virus may lead to a vaccine but Hepatitis C and AIDS are more difficult. It depends on the agent,” says Harald zur Hausen.

His current research focuses on how viruses cause leukemia in children for example, and he does not appear to want to stop doing research anytime soon.

“In order to be a successful scientist, you need to work hard and be persistent, and avoid to believe too much in dogmas,” Harald zur Hausen concludes.

This article was originally published i NLS magazine No 01 2009, out February 2009

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