VIRUSES, PROVIRUStS AND THE CONFLICT OF SYSTEMS 



tliis determinant must have arisen by the creation or mutation of 

 a reproductive particle in the cell. But here we have just (only 

 just) crossed the boundary from heredity to infection: we have a 

 true virus. 



Beyond the milk virus there arc ordinary infectious principles 

 such as those inducing benign epidermal tumours or warts. The 

 only difference between them is that it is difficult to imagine the 

 milk virus arising otherwise than from its host's proteins whereas 

 the wart, owing to its infection, might have done so. 



In this last group the Shope papilloma of the cottontail rabbit, 

 a known nuclcoprotcin, deserves special credit. It serves to bind the 

 whole series together. For on inoculation into the domestic rabbit 

 it loses its capacity for infection and acquires malignancy: it is 

 transmuted from a virus to a plasmagene. 



In this scries we are dealing almost entirely with modified cell 

 proteins of the animals which develop the tumours. We begin with 

 something not inherited through the egg (which it would presum- 

 ably kill) yet as close as possible to a plasmagene. And we end with 

 something infectious without limit and a true virus. In the middle 

 stage we have something half-way between, something with all the 

 properties of a virus save that of natural infection. We have a 

 prouirus. 



The genetic conditions of cancer development can now be 

 provisionally defined. Excessive growth, either new growth or 

 continuance of growth, may be directly determined by the genotype 

 (nuclcus-cum-cytoplasm) of an individual at fertilization, and arise 

 without any somatic mutation. This is true particularly of plants. 

 But the typical development of tumour growth in animals is due, 

 and could only be due, to somatic mutation. This mutation is itself 

 determined by the customary interaction of genotype and environ- 

 ment. Spontaneous tumours are so called because the genotype is 

 the predominant variable in determining the mutation; induced 

 tumours because the environment is predominant. A first class oi 

 these tumours are capable of transplantation only as whole cells. 

 A second class can be transmitted by cell-free filtrates capable of 

 invasion, that is as proviruses. The possibility that nuclear mutation 

 plays a part cannot be excluded in the first class. But all may have 

 arisen, and the second class have certainly arisen, by change in selt- 



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