Il. 223. BIOLOGICAL VARIABLES In the following paragraphs (223-289) the biological variables affecting the lLife-shortening response to irradiation are reviewed. The data refer to the genetic constitution of the animal species or strain, which appears to be a major determinant of the response; to the effects of age at irradiation, both in the intra- and in the extra-uterine life; and to the differntial effect on male and female animals, because special physiological conditions or the expression of peculiar diseases in the two sexes may result in a variable amount of lifeshortening induced by a given dose. The effect of partial versus whole-body irradiation is considered in paragraphs 314-324 with other modifying biological conditions. A. 2oh, GENETIC BACKGROUND Among the genetic variables, the inter-species and intra-species dif- ferences should be considered separately. In the first case, the objective of the analysis is to establish a scale of sensitivity with respect to life-shortening between various mammals, analogous to that repeatedly attempted for short-term survival (for an extensive discussion of these problems in rela- tion to the acute radiation syndromes, see [B18]. In this connection the pro- blem of data extrapolation to other species may naturally be discussed. In the case of intra-species comparisons, the problem is that of analysing the character and the amount of life-shortening in genetically different strains of the same species, in order to correlate the degree of radiation effect with some vital characteristics of the strain, such as longevity, age-specific rate of death and spectrum of spontaneous diseases. These experiments have been carried out so far in the mouse for the availability of inbred animals in large numbers and the relative easiness of obtaining crosses of inbred genotypes. Before discussing long-term effects, it should be recalled that in respect to early radiation death the susceptibility of inbred strains differs by less than a factor of two and that resistance to early death is generally associated with physiological vigour. Also, a short life-span, when it is due to a high incidence of leukaemia, does not seem to influence the response to the acute radiation syndrome [V7] while it does, as it will be seen, for the longer-term survival.