Harald zur Hausen

Harald zur Hausen
zur Hausen in 2010
Harald zur Hausen
Born	11 3, 1936
Birthplace	Gelsenkirchen, Westphalia, Germany
Died	Template:Death date and age Heidelberg, Baden-Württemberg, Germany
Nationality	German
Occupation	Virologist, physician, academic
Employer	German Cancer Research Center (DKFZ)
Known for	Discovery that human papillomavirus (HPV) causes cervical cancer
Education	University of Bonn (MD), University of Düsseldorf (DSc)
Awards	Nobel Prize in Physiology or Medicine (2008), Canada Gairdner International Award (2008)
Website	[https://www.nobelprize.org/laureate/823 Official site]

Harald zur Hausen (11 March 1936 – 28 May 2023) was a German virologist and physician whose discovery that human papillomavirus (HPV) can cause cervical cancer fundamentally changed the understanding of cancer etiology and ultimately led to the development of vaccines that have saved countless lives worldwide. For this work, he was awarded the Nobel Prize in Physiology or Medicine in 2008, sharing the prize with Françoise Barré-Sinoussi and Luc Montagnier, who were recognized for their discovery of HIV. Zur Hausen served for two decades as chairman of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg, one of the world's foremost cancer research institutions. His persistence in pursuing the viral origins of cervical cancer, at a time when most of the scientific community was skeptical, established a new paradigm in oncology and opened the door to preventive cancer vaccination. He was widely published, deeply influential in the field of tumor virology, and remained active in research into the links between infectious agents and cancer well into the final years of his life.

Early Life

Harald zur Hausen was born on 11 March 1936 in Gelsenkirchen, an industrial city in the Ruhr area of western Germany. He grew up during the turbulent years of the Nazi era and World War II, coming of age in postwar Germany. As a young man, zur Hausen developed an interest in biology and medicine, which would guide his subsequent academic pursues.

Details of zur Hausen's childhood and family background are limited in publicly available sources, though his upbringing in the industrial Ruhr region during a period of immense social upheaval in Germany shaped his generation profoundly. The postwar reconstruction of Germany, including the rebuilding of its scientific and medical institutions, provided the backdrop for his decision to pursue a career in medicine and scientific research.

Education

Zur Hausen studied medicine at the University of Bonn, the University of Hamburg, and the University of Düsseldorf, ultimately earning his medical degree (MD) from the University of Düsseldorf. He also later received a Doctor of Science (DSc) degree. His medical training provided a strong foundation in both clinical medicine and laboratory science, and during his studies he became interested in microbiology and virology — fields that were undergoing rapid transformation in the 1950s and 1960s with new discoveries about the molecular basis of infectious diseases and their relationship to cancer.

After completing his medical education, zur Hausen worked at the Institute of Microbiology at the University of Düsseldorf, where he began his early research career. He subsequently spent a formative period at the Children's Hospital of Philadelphia in the United States, working in the laboratory of Werner and Gertrude Henle, who were pioneers in the study of the Epstein–Barr virus (EBV). This experience was instrumental in shaping zur Hausen's interest in the role of viruses in human cancer, a theme that would define his entire career.

Career

Early Research and the Epstein–Barr Virus

Zur Hausen's research career began with the study of the Epstein–Barr virus (EBV) and its relationship to human cancers. Working in the laboratory of Werner and Gertrude Henle at the Children's Hospital of Philadelphia, he contributed to the growing understanding that certain viruses could be causatively linked to specific human malignancies. The Henles had played a key role in establishing the connection between EBV and Burkitt's lymphoma, and zur Hausen's work in their laboratory deepened his conviction that viruses were responsible for more human cancers than was commonly accepted at the time.

Upon returning to Germany, zur Hausen continued to investigate the links between viruses and cancer. He held positions at several German universities, including the University of Würzburg and the University of Erlangen-Nuremberg, before being appointed professor and chairman of the Institute of Virology at the University of Freiburg in 1972. During these years, he began to shift his focus from EBV toward a different family of viruses — the papillomaviruses — and their possible role in cervical cancer, a line of inquiry that would consume the next several decades of his career and ultimately lead to his Nobel Prize.

Hypothesis Linking HPV to Cervical Cancer

In the early 1970s, zur Hausen proposed a hypothesis that was at odds with the prevailing scientific consensus. At the time, many researchers believed that herpes simplex virus type 2 (HSV-2) was the likely viral cause of cervical cancer. Zur Hausen, however, suspected that human papillomavirus (HPV), which was known to cause common warts but was not generally considered a serious pathogen, was in fact the infectious agent responsible for cervical cancer.

This hypothesis was initially met with significant skepticism. Many in the scientific community dismissed the idea that a common, seemingly harmless virus could be responsible for one of the most lethal cancers affecting women worldwide. Zur Hausen persisted in his research despite this resistance, spending more than a decade working to isolate and characterize the specific HPV types present in cervical cancer tissue.

Discovery of HPV16 and HPV18

The breakthrough came in the early 1980s. In 1983 and 1984, zur Hausen and his research team at the University of Freiburg succeeded in molecularly cloning the genomes of two previously unknown types of human papillomavirus from cervical cancer biopsies: HPV16 and HPV18. These two HPV types were found to be present in approximately 70 percent of cervical cancer cases worldwide, establishing a definitive link between HPV infection and cervical carcinoma.

The identification of HPV16 and HPV18 was a watershed moment in cancer biology. Zur Hausen demonstrated that the viral DNA was integrated into the genome of cervical cancer cells and that specific viral genes — particularly the E6 and E7 oncogenes — were responsible for the transformation of normal cells into cancerous ones. This work provided the molecular mechanism by which HPV caused cancer, transforming the field's understanding of viral oncogenesis.

The discovery was not merely of academic interest; it had immediate and profound implications for public health. By identifying the specific viral agents responsible for cervical cancer, zur Hausen's research laid the scientific groundwork for the development of diagnostic tests to detect HPV infection and, eventually, for the creation of prophylactic vaccines against the virus.

Leadership of the German Cancer Research Center

In 1983, zur Hausen was appointed chairman (Scientific Director) of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg, a position he held for twenty years, until 2003. Under his leadership, the DKFZ grew into one of the largest and most productive biomedical research centers in the world, with a particular emphasis on understanding the causes and mechanisms of cancer.

During his tenure at the DKFZ, zur Hausen oversaw the expansion of research programs in molecular biology, genetics, epidemiology, and clinical cancer research. He also held a professorship at the University of Heidelberg. His leadership helped establish the DKFZ as a center of excellence in the study of infection-related cancers, and the institute's work during this period contributed to numerous advances in understanding how viruses, bacteria, and other infectious agents contribute to carcinogenesis.

Impact on HPV Vaccine Development

Although zur Hausen did not personally develop the HPV vaccine, his discovery of the causal link between HPV and cervical cancer was the essential scientific foundation upon which the vaccines were built. In the years following his identification of HPV16 and HPV18, other researchers — including Ian Frazer and Jian Zhou — used zur Hausen's findings to develop virus-like particle (VLP) technology that formed the basis of prophylactic HPV vaccines.

The first HPV vaccines, Gardasil (manufactured by Merck & Co.) and Cervarix (manufactured by GlaxoSmithKline), were approved for use in the mid-2000s. These vaccines target HPV16 and HPV18 — the two types identified by zur Hausen — along with other HPV strains in the case of later vaccine formulations. The vaccines have been shown to be highly effective in preventing HPV infection and the subsequent development of cervical cancer, and they have been incorporated into national immunization programs in dozens of countries around the world.

The World Health Organization has estimated that cervical cancer claims the lives of hundreds of thousands of women annually, with the vast majority of cases occurring in low- and middle-income countries. The HPV vaccine has the potential to dramatically reduce this burden, and in 2020, the WHO launched a global strategy aimed at eliminating cervical cancer as a public health problem through vaccination, screening, and treatment. Zur Hausen's discovery is the cornerstone of this global effort.

Later Research: Infectious Agents and Cancer

Even after his retirement from the DKFZ chairmanship in 2003, zur Hausen remained scientifically active. He continued to investigate the relationship between infectious agents and cancer, broadening his focus beyond HPV. In his later years, he pursued research into a possible link between certain bovine infectious agents — found in dairy cattle and beef — and the development of colorectal cancer and other malignancies in humans.

Zur Hausen hypothesized that novel bovine infectious factors, which he termed "bovine meat and milk factors" (BMMFs), might play a role in colorectal and breast cancer. He proposed that early childhood exposure to these agents through dairy products or undercooked beef might increase cancer risk later in life. This research was controversial and remained the subject of ongoing scientific investigation at the time of his death.

Personal Life

Harald zur Hausen was married to Ethel-Michele de Villiers, a fellow virologist who also worked at the DKFZ and contributed significantly to research on papillomaviruses and their role in human disease. The couple collaborated on scientific projects throughout their careers.

Zur Hausen died on 28 May 2023 in Heidelberg, Baden-Württemberg, Germany, at the age of 87. His death was mourned by the global scientific community, with tributes from institutions including the DKFZ, the International Agency for Research on Cancer (IARC), the American Association for Cancer Research (AACR), and numerous universities and research organizations worldwide.

Zur Hausen was described by colleagues as a persistent and methodical scientist who was willing to challenge established dogma when the evidence led him to conclusions that contradicted prevailing views. His decades-long pursuit of the HPV–cervical cancer hypothesis, in the face of widespread skepticism, has been cited as an exemplary case of scientific tenacity and intellectual courage.

Recognition

Zur Hausen received numerous awards and honors over the course of his career, reflecting the significance of his contributions to medicine and cancer research.

His most prominent recognition was the Nobel Prize in Physiology or Medicine in 2008, which he shared with Françoise Barré-Sinoussi and Luc Montagnier. The Nobel Committee cited zur Hausen's discovery that human papillomaviruses cause cervical cancer, noting that his work had "gone against current dogma" and led to an understanding of the mechanisms of HPV-induced carcinogenesis as well as the development of prophylactic vaccines.

In 2008, he also received the Canada Gairdner International Award, one of the most prestigious prizes in biomedical research, for his "discovery and characterization of the human papillomaviruses that cause cervical cancer."

Among his many other honors, zur Hausen was elected as a member of multiple national and international scientific academies, including the National Academy of Sciences (NAS) of the United States, the European Academy of Sciences and Arts (EASA), and the American Philosophical Society (APS). He was also elected as a foreign member of the Slovenian Academy of Sciences and Arts. He was named a Fellow of the AACR Academy by the American Association for Cancer Research.

Throughout his career, zur Hausen received the Robert Koch Prize, the Johann Georg Zimmermann Prize, the Prince Mahidol Award, the Coley Award, and the German Cancer Prize, among many other accolades.

Legacy

Harald zur Hausen's legacy in medical science is defined by his central role in establishing the causal connection between viral infection and human cancer, and by the public health revolution that followed from this discovery. His identification of HPV16 and HPV18 as the primary causative agents of cervical cancer transformed the field of oncology, providing definitive evidence that cancer could be caused by a sexually transmitted virus and that prevention through vaccination was feasible.

The HPV vaccine, which emerged directly from zur Hausen's research, has been described as one of the most significant advances in cancer prevention in history. Countries that have implemented widespread HPV vaccination programs have already seen dramatic declines in HPV infection rates and in the incidence of precancerous cervical lesions. The WHO's global strategy to eliminate cervical cancer, launched in 2020, is built upon the scientific foundation that zur Hausen established.

Beyond the specific impact on cervical cancer, zur Hausen's work helped legitimize the broader field of infection-related cancer research. His success in demonstrating the HPV–cancer link encouraged other researchers to investigate the roles of infectious agents in various malignancies, contributing to a more comprehensive understanding of cancer etiology. His later research into bovine infectious factors and their potential role in colorectal cancer continued this tradition of investigating unconventional hypotheses about the origins of cancer.

The International Agency for Research on Cancer noted upon his passing that zur Hausen's "scientific discoveries have had a lasting impact on public health globally" and that his work "paved the way for the development of preventive vaccines against HPV, which have the potential to save millions of lives." The AACR described him as a "pioneer" whose "groundbreaking discoveries changed the course of cancer research and prevention."

The Proceedings of the National Academy of Sciences, in a memorial tribute published in 2024, characterized zur Hausen as "a physician scientist and true pioneer" whose molecular cloning of the HPV16 and HPV18 genomes represented a landmark achievement in biomedical research.