The first research article reporting the use of a genetically engineered OV was published by Martuza and colleagues in 1991 (16), in which the authors showed that infection with a thymidine kinase (tk) gene-deleted herpes simplex virus (HSV) led to the death of multiple human glioma cell lines, as well as, primary cultures of human glioma cells. The gene discussed is TKT; the disease is central nervous system cancer.