When he proposed that the human papillomavirus caused cervical cancer, he was ridiculed. He persevered, and today a vaccine exists.
Dr. Harald zur Hausen, a German virologist who won the Nobel Prize in Medicine in 2008 for his discovery that the seemingly benign human papillomavirus, known for causing warts, also caused cervical cancer, died on May 29 at his home in Heidelberg, Germany. He was 87.
His death was announced by the German Cancer Research Center in Heidelberg, which Dr. zur Hausen led for two decades. Josef Puchta, the center’s former administrative director and a longtime colleague and friend, said Dr. zur Hausen had a stroke in May.
Dr. zur Hausen’s discovery paved the way for vaccines against human papillomavirus, or HPV, a sexually transmitted disease that can also cause other cancers, including of the vagina, vulva, penis, anus and back of the throat.
More than 600,000 people develop an HPV-related cancer every year, according to the National Cancer Institute. Vaccination can prevent as many as 90 percent of those cancers.
Dr. zur Hausen leaves “a huge legacy, “Dr. Margaret Stanley, an HPV researcher at the University of Cambridge said in an interview: a lifesaving vaccine and lifesaving tests to detect the virus.
Colleagues remembered Dr. zur Hausen as courteous, considerate and respectful — not always a given in high-profile research laboratories, they noted — and more than one described him as a “gentleman.”
He was doggedly devoted to his research and could be “unshakable” when he had an idea, said Timo Bund, a scientist at the German Cancer Research Center. Dr. zur Hausen’s hypothesis that HPV caused cervical cancer contradicted the prevailing wisdom of “almost the full scientific world,” Dr. Bund said, and took him a decade to prove.
When he first proposed the notion, in the 1970s, many scientists believed that cervical cancer was caused by the herpes simplex virus. But Dr. zur Hausen could find no sign of herpes in the biopsies of cervical cancer patients. When he presented those results at a scientific conference in 1974, he was “intensively criticized,” he recalled in an autobiographical article in the Annual Review of Virology.
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Dr. zur Hausen had been intrigued by reports that genital warts could, in rare cases, turn into cancer. He began to look for human papillomavirus DNA in cells from cervical cancer patients using a gene probe, a short piece of single-stranded DNA designed to bind to a specific sequence in the HPV genome.
The work proved challenging, in part because it became clear that there were many different types of HPV, each of which has its own genetic sequence and not all of which cause cancer.
Dr. zur Hausen was undeterred. “I think he never doubted in any way that this was correct,” said Michael Boshart, a geneticist at Ludwig-Maximilians-University of Munich who was a Ph.D. student on the research team.
Finally, in 1983, Dr. zur Hausen and his colleagues announced that they had found a new type of HPV in cervical cancer cells. The next year, they reported another. About 70 percent of cervical cancer biopsies, they found, contained one of these two viruses.
Other scientists soon confirmed the findings. “I felt some satisfaction in this situation, because up to this moment several colleagues had ridiculed our research, saying, ‘Everyone knows that warts and papillomaviruses are harmless,’” Dr. zur Hausen wrote in the Annual Review of Virology.
Dr. zur Hausen shared clones of the viral DNA freely with other researchers. “Most scientists are selfish and hang on to their stuff,” Dr. Stanley said. “Because he gave them out to the papillomavirus community, there was an absolute explosion of work.”
That research helped accelerate scientific understanding of the viruses as well as the development of vaccines. The first HPV vaccine was approved in 2006. Dr. zur Hausen won the Nobel Prize in Physiology or Medicine two years later, sharing it with the two French virologists who had discovered H.I.V., Françoise Barré-Sinoussi and Luc Montagnier (who died in February).
He became an ardent advocate for the vaccine, which is highly effective but which many children do not receive. He argued that the vaccine, which was initially promoted primarily for girls, should also be given to boys, which health officials now recommend.
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Harald zur Hausen was born on March 11, 1936, in Gelsenkirchen, Germany, the youngest of Melanie and Eduard zur Hausen’s four children. His father was an officer in the German Army.
The industrial area where he grew up was heavily bombed in World War II. “As a consequence, all schools closed at the beginning of 1943, which was obviously bad for education but welcomed by many of the children,” Dr. zur Hausen recalled. It would be nearly two years before he returned to school.
He decided to study medicine, earned his degree from the University of Düsseldorf in 1960, and became interested in the origins of cancer. His peripatetic research career took him to Children’s Hospital of Philadelphia for several years and then to multiple German universities. In the 1960s and early ’70s, he conducted research on the Epstein-Barr virus and lymphoma.
In 1972, he moved to the University of Erlangen–Nuremberg, where he began his work on cervical cancer. He later continued that work at the University of Freiburg.
It was at the University of Erlangen–Nuremberg that he met the biologist Ethel-Michele de Villiers, who became his wife and his close scientific collaborator.
Nobody “influenced my personal life and my scientific career more,” Dr. zur Hausen wrote in the Annual Review of Virology. “She has repeatedly stated, mockingly, that we two split our activities: She does the work, and I do the talking. Indeed, a large proportion of experimental data obtained during several decades as well as a number of excellent ideas are hers. Looking at her work and her intellectual input and proposals, frequently underestimated by several of her colleagues, I see she has a point in saying this.”
She survives him, as do three sons from a previous marriage, Jan Dirk, Axel and Gerrit. Friends and colleagues said they knew almost nothing about that marriage, noting that Dr. zur Hausen was an intensely private person.
He became the scientific director of the German Cancer Research Center in 1983 and held that position until 2003. But he never stopped conducting research, and in recent years he turned his attention to breast, colon and other cancers.
“He was retired from his directorship,” Dr. Puchta said, “but not from his science.”
Emily Anthes is a reporter for The Times, where she focuses on science and health and covers topics like the coronavirus pandemic, vaccinations, virus testing and Covid in children.
