History of SV40 Contamination of Polio Vaccines History of SV40 Contamination of Polio Vaccines The discovery of the polyomavirus SV40, as well as its introduction as a pathogen into the human population, was tied to the development and worldwide distribution of early forms of the polio vaccine (13, 95, 111, 123). Inactivated (Salk) and early live attenuated (Sabin) forms of polio vaccines were inadvertently contaminated with SV40 (95, 97, 111). In addition, different adenovirus vaccines distributed to some U.S. military personnel from 1961 to 1965 also contained SV40 (64). The viral contamination occurred because these early vaccines were prepared in primary cultures of kidney cells derived from rhesus monkeys, which are often naturally infected with SV40 (13, 95, 111). Infectious SV40 survived the vaccine inactivation treatments, and conservative estimates indicate that up to 30 million people (children and adults) in the United States may have been exposed to live SV40 from 1955 through 1963 when administered potentially contaminated polio vaccines (95, 111). Millions of people worldwide were also potentially exposed to SV40 because contaminated polio vaccines were distributed and used in many countries (85, 123). These data led the Institute of Medicine to conclude that “the biological evidence is of moderate strength that SV40 exposure from the polio vaccine is related to SV40 infection in humans” (111). Shortly after its discovery, SV40 was shown to be a potent oncogenic DNA virus (13). In animal models, the neoplasias induced by SV40 included primary brain cancers, malignant mesotheliomas, bone tumors, and systemic lymphomas (13). Subsequently, many in vitro studies established that the oncogenic capacity of SV40 reflects the disruption of critical cell cycle control pathways (9, 96, 116). During the last decade, numerous published studies from independent laboratories, using different molecular biology techniques, have demonstrated SV40 large tumor antigen (T-ag) or DNA in primary human brain and bone cancers and malignant mesothelioma (1, 13, 39, 50, 123). More recently, studies have demonstrated that SV40 T-ag sequences are significantly associated with non-Hodgkin's lymphoma (NHL) (102, 124, 125). Therefore, the major types of tumors induced by SV40 in laboratory animals are the same as those human malignancies found to contain SV40 markers. A recent meta-analysis (122) of the molecular evidence conclusively established a significant excess risk of SV40 with those selected human cancers. It is noteworthy that SV40 has been detected in malignancies from children and young adults not exposed to contaminated polio vaccines, as well as in older adults (5, 18, 71, 73, 76, 117, 124, 125, 129, 132, 133). The detection of viral markers in young persons, by using molecular techniques, coupled with the isolation of infectious SV40 from tumors (62) and from nonneoplastic specimens (66, 67), suggests that SV40 continues to cause infections in the human population today. In contrast, some retrospective epidemiological studies have failed to demonstrate an increased cancer risk in populations which had a high likelihood of having received potentially contaminated polio vaccine (20, 82, 95, 112, 114). However, the epidemiological data available are recognized to be inconclusive and limited (95, 111, 123), and the Institute of Medicine found that the epidemiological data for cancer rates in people potentially exposed to SV40-contaminated vaccines are inadequate to evaluate a causal relationship (111). This conclusion is based on the lack of data on which individuals actually received contaminated vaccines, the unknown dosage of infectious SV40 present in particular lots of vaccine, the failure to know who among the exposed were successfully infected with SV40, the inability to know if the vaccine “unexposed” cohorts may have been exposed to SV40 from other sources, and the difficulty of monitoring a large population for cancer development for years after virus exposure. These important limiting factors led the Institute of Medicine to “not recommend additional epidemiological studies of people potentially exposed to contaminated polio vaccine.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC452549/