The Titration of Viruses in Baby Mice

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Abstract
This paper describes efforts to determine the LD50for mice, 24–48 hr. old, of pools of four strains ofHerpes simplexvirus, using the intraperitoneal route of inoculation.The results have been analysed in an attempt to account for the very irregular relationship between dose of virus and mortality which was observed.It is clear that, in addition to those difficulties which beset the interpretation of the results of any biological assay, titrations in very young animals raise difficulties of their own. The principal sources of difficulty are the high and uncertain non-specific mortality, the tendency of the mothers to eat their babies and individual variation between the litters. The latter, it is suggested, is mainly a reflexion of differences between the mothers, at least when a closely inbred strain of test animals is used.Interesting and unexpected correlations were observed between the dose of virus and the proportion of mice eaten by the mothers and between the strain of virus and the proportion of mice eaten by the mothers.It is emphasized that the results of titrations in very young animals must be interpreted with the greatest care and that in carrying out titrations the litter rather than the individual baby mouse should be regarded as the unit. Mice eaten by the mothers are probably best ignored altogether, although there are grave theoretical objections to doing this.I should like to thank Professor H. R. Dean for his advice and encouragement. It is a pleasure to acknowledge the technical help which I have received throughout this investigation from Miss D. Sutton. I am also indebted to Dr M. G. P. Stoker for advice and for making available facilities in his laboratory; to Dr W. L. Smith and Mr T. H. Hollingsworth of the Department of Human Ecology, Cambridge, for advice on some of the statistical problems raised; to Miss M. E. Skinner and her staff on the ‘Animal Floor’ of this department, without whose help it would not have been possible to ensure that the large number of litters used were available when required; and to those of my colleagues who have been good enough to offer advice and criticism, especially Mr Douglas Annear.
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