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The need for a standardised cell substrate for virus vaccine production.

During the last 15 years there have been such enormous advances made in virology, largely due to the development of cell culture techniques, that it is pertinent for us to take stock of the significant milestones and enquire into the future. Fifty years ago the only three virus vaccines used were prepared in or on living animals. Smallpox virus was grown an the skin of animals and the vaccine made from the lymph scraped from the infected tissues. Rabies virus was grown in the brains of susceptible animals and the vaccine consisted of the brain tissue containing the virus which was killed by phenol. Yellow fever virus was grown in fertile eggs from hens and the vaccine made from the infected embryos. No tests were done on the animals or eggs used in the production of these vaccines and indeed little was known about the viruses infecting or inherently endemic in the birds and animals. Although some small modifications have been made in production methods, it is only recently that we are beginning to introduce significant changes. When a vaccine against poliomyelitis was urgently required there was no known easily available susceptible laboratory animal and the production of this vaccine had to await further technical developments. There were two major advances made at about the same time. Enders, Robbins and Weller placed the growth of cell cultures in vitro on a firm footing and showed that poliomyelitis virus could be grown in the tissue on a commercial scale. This was indeed a significant development but it would not have been of such universal application if penicillin, discovered by Fleming, Chain and Florey, had not been so successful in suppressing the bacterial contaminants that had bedevilled tissue culture for so many years. The tissue chosen for poliomyelitis vaccine production was grown from monkey kidneys and the eradication of the disease in many countries is now history. The developments in virology, however, as a result of the opening of new frontiers in tissue cultures have not only shown the presence of hitherto undetected viruses, but they have also shown the effects of both virus/cell and virus/virus interaction. The present findings demand the use of a virus free substrate so that there shall be no possibility of interaction with the vaccine virus. It is also essential to avoid the possibility of an inherent infectious agent in the vaccine escaping detection by our safety tests. The modern trend has been to use cell cultures prepared from tissue of clean animals or birds.Thus, measles virus is grown on chick cell fibroblasts derived from the fertile eggs of chickens known to be free from and continuously monitored for