2008 NOBEL LAUREATES The Nobel Prize in Physiology or Medicine 2008 “for his discovery of “for their discovery human papilloma of human viruses causing immunodeficiency cervical cancer” virus” ) X X I I P P DKFZ SCAN SCAN AKUTIN/ AGUNIA/ S M DEUTSCHES KREBSFORSCHUNGSZENTRUM ( KREBSFORSCHUNGSZENTRUM DEUTSCHES Harald zur Hausen Françoise Luc Montagnier 1/2 of the prize Barré-Sinoussi 1/4 of the prize 1/4 of the prize Born: 1936 Born: 1932 Birthplace: Germany Born: 1947 Birthplace: France Nationality: German citizen Birthplace: France Nationality: French citizen Current position: Nationality: French citizen Current position: Professor Emeritus and Current position: Professor Emeritus and former Chairman and Professor and Director, Director, World Foundation Scientific Director, German Regulation of Retroviral for AIDS Research and Cancer Research Centre, Infections Unit, Virology Prevention, Paris, France Heidelberg, Germany Department, Institut Pasteur, Paris, France PHYSIOLOGY OR MEDICINE 13 Copyright © Nobel Web AB 2008. Nobelprize.org, Nobel Prize and the Nobel Prize medal design mark are registered trademarks of the Nobel Foundation. 2008 NOBEL LAUREATES Speed read: Finding the culprit identification of the virus associated with AIDS, occurred within just a few months amid a flurry of global research activity directed towards finding the cause of the then-new epidemic. Harald zur Hausen’s suggestion that human papilloma virus (HPV) infection might lie behind cervical cancer flew in the face of general opinion in the early 1970s, which held that another commonly present virus, herpes simplex virus, might be the cause. Realising that there were a multitude of different HPV subtypes, and hypothesising that unknown subtypes might cause the cancer, zur Hausen’s group began a painstaking search for such novel ooking back over the two discoveries rewarded viruses. By the early 1980s they found novel viruses with the 2008 Nobel Prize in Physiology in genital warts. Their subsequent identification of L or Medicine reveals two different timelines two novel HPV subtypes in cervical cancers formed for discovery research. One, Harald zur Hausen’s the essential piece of evidence linking HPV infection realisation that subtypes of a virus that produces to the onset of the disease. harmless warts can also lead to cervical cancer, took a decade of work to prove, initially against a Françoise Barré-Sinoussi and Luc Montagnier’s backdrop of considerable scepticism. The other, discovery of the virus that later came to be known Françoise Barré-Sinoussi and Luc Montagnier’s as human immunodeficiency virus (HIV) occurred zur Hausen identifies two new Harald zur Hausen publishes tumorigenic types of HPV in The first preventive HPV his first report attempting to cervical cancer biopsies – HPV16 vaccine is approved by the find human papilloma virus and HPV18 – and subsequently US Food and Drug Adminis- (HPV) DNA in cervical cancer shows that they are present in tration; two HPV vaccines are and genital wart biopsies the majority of cervical cancers currently on the market 1974 1976 1983–1984 1985 2006 zur Hausen and his zur Hausen demonstrates that parts of the team identify multiple, HPV DNA are integrated into the host genome previously undiscovered, in cervical cancer cell lines, providing an strains of HPV opening to study the role of the transferred viral DNA genes in malignant transformation Timeline: Milestones for the 2008 Nobel Laureate in Physiology or Medicine, Harald zur Hausen. 14 PHYSIOLOGY OR MEDICINE Copyright © Nobel Web AB 2008. Nobelprize.org, Nobel Prize and the Nobel Prize medal design mark are registered trademarks of the Nobel Foundation. 2008 NOBEL LAUREATES just two years after the first reports of cases of what we now know as AIDS. An infective agent was suspected by many to cause the disease, and Barré- Sinoussi and Montagnier decided to test whether it might be a so-called retrovirus. Retroviruses are relatively uncommon among the viruses that infect humans and rely on the host’s cellular machinery to replicate their RNA. The gamble proved correct; their studies revealed retroviral activity in cells taken from a patient’s lymph nodes, and demonstrated that viral particles from these cells could infect and kill white blood cells. Within the year, Barré- Sinoussi and Montagnier had isolated HIV from several patient groups. Soon afterwards several research groups provided convincing evidence that showed HIV to be the cause of AIDS. protection from the two HPV subtypes found in the majority of cervical cancer cases. Barré-Sinoussi Identifying the viral culprits behind two human and Montagnier’s discoveries led to a greater diseases that impact greatly on global health understanding of HIV and the way it interacts with provided crucial insights into the workings of each humans, allowing the development of diagnostic virus, which, in turn, led to the development of tools and a range of antiviral drugs aimed at much-needed treatments. zur Hausen’s discoveries controlling HIV, and with it providing hope that the enabled the development of vaccines that provide disease could eventually become treatable. April: Barré-Sinoussi and Montagnier isolate the virus and show it infects and A serious new medical kills lymphocytes from both diseased syndrome is described in An international virus and healthy patients, and reacts with California and New York, defined taxonomy consortium antibodies from infected patients as Acquired Immune Deficiency names the virus Human Syndrome (AIDS) by the US Jun–Oct: They obtain isolates of the virus Immunodeficiency Virus Centers for Disease Control from several patient groups type 1, or HIV-1 1981–1982 1983 1984 1984–1985 1985 Françoise Barré-Sinoussi and Luc Several research groups Montagnier detect activity from a new publish reports that help to type of retrovirus in cells cultured definitively show that the from the lymph nodes of patients virus causes AIDS showing early symptoms of AIDS Timeline: Milestones for the 2008 Nobel Laureates in Physiology or Medicine, Françoise Barré-Sinoussi and Luc Montagnier. PHYSIOLOGY OR MEDICINE 15 Copyright © Nobel Web AB 2008. Nobelprize.org, Nobel Prize and the Nobel Prize medal design mark are registered trademarks of the Nobel Foundation. 2008 NOBEL LAUREATES In his own words: Harald zur Hausen “I’m of course totally surprised. And it’s of course involved in this cancer, together with the fact that a great pleasure for me.” Sitting in his office at the so many questions remained unanswered about German Cancer Research Center, the news that papilloma viruses. “I was not from the beginning Harald zur Hausen had received the 2008 Nobel mainly interested in papilloma virus, I was mainly Prize in Physiology or Medicine had yet to fully sink in. interested in infectious agents in human cancer. Perhaps surprise is an apt response; for years, few Papilloma viruses came up as the most likely considered zur Hausen’s proposal, that cervical cancer candidate from my viewpoint.” was caused by the same virus that caused skin warts, worthy of serious discussion, let alone a Nobel Prize. The key breakthrough in finding that two subtypes of human papilloma virus, called HPV16 and 18, When zur Hausen first suggested publicly that human are found in most cervical cancer cases wasn’t papilloma virus, or HPV, caused cervical cancer at a automatically followed by the successful development meeting in Key Biscayne, Florida, in 1974, it flew in of vaccines, mainly because companies were the face of the prevailing view that the culprit was unconvinced that this was a worthwhile investment. herpes simplex virus. “It was As zur Hausen recalls, one not very welcome,” recalls zur “My statements were not German company showed some Hausen. “My statements were well received, and I felt as interest, but it pulled the plug not well received, and I felt as a on the project after carrying out lonely voice in that meeting.” a lonely voice” some damning market analysis. “According to this market When asked what gave him the dedication to analysis there would be no market for such a vaccine. persevere for years and eventually prove the link And then they stopped the funding.” between HPV and cervical cancer, zur Hausen responds that it was the combination of a personal Now the opposite appears to be the case; results conviction that there must be an infectious agent from trials on cervical cancer vaccines within the last decade have been enormously promising. zur Hausen sees this as clear evidence that vaccination programmes should be widened; however, he cautions that “The major disadvantage at this stage is that it is too expensive for those parts of the world which most badly need the CIENCE PHOTO LIBRARY CIENCE PHOTO S / vaccine; namely, the developing world.” UCT zur Hausen believes that scientists will discover more links between viruses and cancer, and he TANNARD, TANNARD, S is keen to promote greater interest in this line of research. “I hope, indeed, that this Nobel Prize will of course create more awareness of the role R LINDA R LINDA D of infectious agents in human cancer”. Having spent decades in pursuit of his goal, it is perhaps appropriate that he hadn’t rushed into making any plans for celebrating his Nobel Prize. Coloured transmission electron micrograph of “It was so surprising I really have to sleep about it human papilloma viruses (HPV). for one night or so before I make any decisions.” This article is based on a telephone interview with Harald zur Hausen following the announcement of the 2008 Nobel Prize in Physiology or Medicine. To listen to the interview in full, visit http://nobelprize.org/nobel_prizes/medicine/laureates/2008/hausen-interview.html 16 PHYSIOLOGY OR MEDICINE Copyright © Nobel Web AB 2008. Nobelprize.org, Nobel Prize and the Nobel Prize medal design mark are registered trademarks of the Nobel Foundation. 2008 NOBEL LAUREATES In her own words: Françoise Barré-Sinoussi isiting the Pasteur Institute in Cambodia, Françoise Barré-Sinoussi says she was unaware that she had been awarded the AVASSARD R V L Nobel Prize in Physiology or Medicine until a French radio journalist called her for an interview.