**3.2. Carcinogens of biological origins (Oncogenic viruses/bacteria/parasites)**

The hypothesis that cancer can originate from a virus comes from Danish scientists Oluf Bang (1881-1937) and Vilhelm Ellerman (1871-1924), who was the first to show, in 1908, that avian er‐ ythroblastosis (chicken leukaemia) can be transmitted by cell-free extracts. In 1911, Francis Pey‐ ton Rous (1879-1970), American pathologist, described a solid cancer, sarcoma, in domestic chickens caused by exposing the healthy bird to a cell-free filtrate containing retrovirus later be‐ came known as the *Rous sarcoma virus* [42]. Abbie Lathrop (1868-1918) and Leo Loeb (1869-1959) described breast cancer in mice caused by a transmissible agent as early as in 1915 [43]. Since then several oncoviruses have been linked to different types of cancer [44]. In 1933 Richard Ed‐ win Shope (1901-1966) discovered the first mammalian tumour caused in cottontail rabbit by fi‐ broma virus and papilloma virus (*Shope papilloma virus*). Shortly later, in 1936, a geneticist and cancer biologists John Joseph Bittner (1904-1961) discovered a mouse mammary tumour virus (MMTV), the so-called Bittner virus, causing a breast cancer, which is a promoter in models of human breast cancer [45]. In 1957, Sarah Elizabeth Stewart (1905-1976) and Berenice E. Eddy (1903-1989), pioneers in the field of viral oncology research, discovered the Stewart-Eddy poly‐ oma virus, which produced several types of cancer in a variety of small mammals [46]. John J. Trentin (1908-2005) and others were the first to report of cancer (sarcoma) produced in animals (hamsters) by inoculation of virus of human origin (*Adenovirus*) [47]. Michael Anthony Ep‐ stein, Bert Achong (1928-1996) and Yvonne Barr identified the first human cancer virus (Ep‐ stein-Barr Virus or EBV) from Burkitt lymphoma cells in 1964 [48]. Baruch Blumberg (1925-2011) isolated Hepatitis B virus (HBV), a cause of hepatitis, and suggested that it contrib‐ uted to liver cancer hepatocellular carcinoma. It was confirmed to be an oncovirus in the 1980s. Hepatitis C virus (HCV) was shown to be a major contributor to liver cancer (hepatocellular carcinoma) by Michael Houghton and Daniel W. Bradley in 1987. The first human retroviruses, Human T-lymphotropic virus 1 (HTLV I) and 2 (HTLV 2), linked to T-cell lymphoma/T-cell leu‐ kaemia and Hairy-cell leukaemia, respectively, were discovered by Bernard J. Poiesz, Robert Charles Gallo and Mistuaki Yoshida. In 1984 Harald zur Hausen and Lutz Gissman discovered that the human papillomaviruses HPV16 and HPV18 were responsible for approximately 70% of cervical cancers, while Alan Storey, Kit Osborn and Lionel Crawford in 1990 indicated that HPV types 6 and 11 were responsible for 90% of genital warts. Valerie Beral, Thomas A. Peter‐ man, Harold W. Jaffe related Kaposi's sarcoma-associated herpesvirus (KSHV) with AIDS [49], which prompted Patrick S. Moore, Yuan Chang, Frank Lee and Ethel Cesarman to isolate Kapo‐ si sarcoma-associated herpesvirus (KSHV or HHV8) in 1994 [50]. Very recently in 2008, Chang and Moore developed a new method to identify oncoviruses called digital transcriptome sub‐ traction (DTS) and isolated DNA fragments of Merkel cell polyomavirus from a Merkel cell car‐ cinoma, considered to be responsible for 70–80% of these cancers [51].

There is also evidence of a link between the bacteria Helicobacter pylori (HP) responsible for development of gastric and duodenal ulcers and cancer risk [52,53]. The human oncogenic viruses, which include HBV, HCV, HIV, HPVs, EBV, KSHV, HTLV-I and HTLV-II and HP are associated with nearly 20% of the human cancer cases. The elimination of these pathogens would decrease by 23.6% the cases of cancer in developing countries and by 7.7% in developed countries [54]. The commonly omitted advantage of the discovery of oncoviruses was the possibility of transplantation of carcinogen-induced tumour systems in mice, which delivered models for the studies on anticancer drugs.

Rare source of cancer are also parasitic diseases caused by *Clonorchis sinensis* (Japan, Korea, Vietnam) and *Opisthorchis viverrini* (Thailand, Laos, and Malaysia) or *Schistosomas species* (Africa, Asia). All of them are known to be carcinogenic and linked with biliary tract cancer (cholangiocarcinoma) and bladder cancer, respectively [55]. Most of the biological carcinogens are classified as group 1 agents in IARC classification [3].
