Historical Perspective

Transmissible agents have a venerable part in the history of cancer research. In 1911, Peyton Rous, often considered to be the father of tumour virology, was the first to demonstrate the acellular transmission of a sarcoma between chickens (the term 'virus' had not yet been coined). The research community was not receptive to the notion that a chronic disease may have an infectious cause and it was to be 55 years before Rous received the Nobel Prize for his seminal discovery. In the 1930s, Shope discovered oncogenic pox viruses and papillomaviruses in rabbits. In 1936, Bittner demonstrated that predisposition to breast cancer in C3H mice was transmitted in breast milk. In 1951, Gross discovered the first murine leukaemia virus and, in 1960, Hilleman identified SV40 virus as a contaminant of polio vaccine grown in monkey kidney cultures. However, the concept that infections might cause chronic diseases, such as cancer, can be traced back even further. For example, in the nineteenth century, the simple epidemiological observation that cancer of the uterine cervix was relatively common in prostitutes, but unknown in celibate nuns, led to the suggestion that the cause might be linked to sexual behaviour and perhaps even be sexually transmitted. In 1905, several years before Rous published his work on chicken sarcomas, Goebel drew attention to 'the occurrence of bladder tumours due to bilharziasis' (shistosomiasis).

In 1964, the first human tumour virus (the Epstein—Barr virus (EBV)) was discovered using electron microscopy, in Burkitt lymphoma cells, by Epstein, Achong and Barr. Later, EBV was also detected in undifferentiated nasopharyngeal carcinoma and subsequently in several other tumours. By the 1970s, cancer viruses were in fashion. President Nixon 'declared war' on cancer (National Cancer Act, 1971) and funding was increased for the National Cancer Institute's 'special virus cancer programme.' Although the 1970s saw many important developments, including the discovery of oncogenes and tumour-suppressor genes (TP53), no new cancer viruses were identified and interest began to wane. This was to change in the early 1980s, with several major discoveries. In 1980, Poiesz, Gallo and colleagues discovered the human T cell leukaemia virus, which is associated with endemic leu-kaemia/lymphoma, particularly in Southern Japan and the Caribbean. In 1981, the large-scale prospective epidemiological studies of Beasley et al., in Tiawan, confirmed the long-suspected causal association between the hepatitis B virus and liver cancer. In 1983, zur Hausen and colleagues isolated HPV 16 from a human cervical cancer specimen, Marshall and Warren identified Helicobacter pylori (later associated with gastric cancer), and the HIV (discovered by Barre-Sinoussi) emerged as an important cause of several cancers. Hepatitis C virus, a cause of liver cancer, was discovered in 1989 and, in 1994, Chang and Moore identified the Kaposi sarcoma-associated herpesvirus (HHV-8).

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