EXPERIMENTAL LEUKAEMIA 



of these cells takes place when the irradiated or grafted 

 tissue is regenerating under difficulties. It is quite probable 

 that from the point of view of whether and when leukaemia 

 develops, the indirect hormonal conditions are the dominant 

 factors, but the difference in the behaviour of the cells from 

 the normal lymphocytes is based on somatic mutation. The 

 only criterion of mutation is that it occurs at random through 

 a cell population and produces descendants that, in the same 

 test environment, are clearly distinguishable from cells of the 

 unmodified parental clone. There is the further point that if 

 a cell line is, by virtue of a minor mutational change plus 

 appropriate environmental conditions (usually hormonal), 

 allowed a marked selective advantage, new opportunities for 

 mutation within the line are provided. It is well accepted 

 that in general a conditioned neoplasm is far more likely to 

 give rise to an unconditioned malignant tumour than is 

 normal tissue. In the case of the regenerating thymus cells 

 in the inhospitable environment of an irradiated host, we 

 can readily conceive that a mutant form would have an 

 advantage over normal cells which it would lack if the en- 

 vironment were brought back to normal by bone-marrow 

 injection or its equivalent. The possibility would then emerge 

 of a secondary mutation to a form with an advantage over 

 the normal, even in a normal environment. 



A final possibility is that a mutant character provoked in 

 a surviving irradiated cell {A) of the host might be trans- 

 duced to a regenerating cell (B) of the grafted thymus. Under 

 the complex local and hormonal conditions of the situation, 

 cell B and its descendants might break away from control 

 more effectively than A and emerge into dominance as the 

 leukaemic strain. 



(b) No virus could conceivably survive in nature if it were 

 limited to genetically homozygous hosts, and the ' operational 

 viruses ' concerned in this field seem to have only two possible 

 interpretations: (i) They are casual viruses which in most 

 strains produce no symptoms but which in somatically un- 



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