PROLIFERATIVE DISEASES 



inoculation in pure strains of mice. Neither genetically pure 

 strains nor any close analogy to intraperitoneal inoculation 

 exists in nature. Results must therefore be very carefully 

 examined before any conclusions are transferred to the human 

 field. Two topics call for some discussion: {a) whether the 

 evidence for indirect production of leukaemia eliminates the 

 general idea of somatic mutation, and {b) the implication of 

 transmission by non-cellular ('viral') agents. 



{a) Kaplan ( 1 954) maintains that the effect of irradiation 

 in producing lymphomata in the thymus and leukaemia in 

 G57 B I mice is an indirect one, and not due to the induction 

 of somatic mutation in some of the irradiated cells. In his 

 view the thymus atrophy following irradiation is mainly in- 

 direct, hormonal changes inducing extensive cellular destruc- 

 tion. During the process of regeneration, which is itself under 

 hormonal control, opportunities are offered for cells to escape 

 control and become malignant. Kaplan believes that somatic 

 mutation plays no part and, by imphcation, that any con- 

 sideration along clonal lines would be inappropriate. 



This is an important current point of difference amongst 

 those concerned with the more academic aspects of cancer 

 research. Our approach would be that the essential feature 

 is that finally a population of cells emerges which can be 

 shown to be genetically different from normal lympho- 

 cytes by their capacity to produce disease in isologous hosts. 

 We know of no way by which genetic change can occur other 

 than by somatic mutation, and we therefore postulate that in 

 these mice somatic mutation has occurred at some point in 

 the ancestry of the eventual leukaemic cells. 



We do not exclude the possibihty that in certain strains of 

 mice mutation to a potentially leukaemic character may be 

 of universal occurrence, so that the thymus will always con- 

 tain a few cells less susceptible to control than their con- 

 geners. Irrespective of whether these mutant forms were 

 pre-existent or induced by X-ray, it seems hkely that the 

 process leading to the emergence of the malignant potentiality 



172 



