On the Nature of Cancer 123 



specific in their effects. Cancer is only one of the many possible muta- 

 tional responses to injury or other embarrassment of normal functional 

 processes. Haddow has suggested that malignant transformation is 

 an artifact of adaptation, that a carcinogen which cannot be lethal 

 or very virulent provokes an adaptive response in a cell which is 

 selective within its capacity to retain the carcinogen or in its suscepti- 

 bility to interference by the carcinogen. The cell can evade for a 

 long time, but under continued assault or with the passage of time 

 it succumbs to give rise to a race of mutants which lack the ability 

 to mature. The price of survival by mutation is high; the price is 

 the loss of those functional endowments which are presumably pre- 

 empted by carcinogens. The azo dye carcinogens, for example, have 

 been described as depriving liver cells of those proteins required for 

 growth regulation. 10 Thereafter the descendants of the afflicted cells 

 no longer have the wherewithal to differentiate like normal liver cells. 

 Many of the chemical carcinogens are known to behave as mutagens 

 in other biological systems as well. 



It appears reasonable to suppose that those mutagens which incite 

 cancer should exist widely in nature rather than in the laboratory or 

 in highly industrialized surroundings alone. We shall therefore pay 

 particular attention to the naturally occurring tumors, rather than 

 those produced by chemical agents, in tracing the cause of cancer. 



Among the animal tumors the mammary carcinoma of the mouse is 

 of especial interest because it bears more than a superficial resemblance 

 to mammary carcinoma in the human. This disease occurs at random 

 among wild mice, but its incidence is truly devastating among certain 

 highly inbred laboratory strains, occurring in 96% of the Bar Harbor 

 C3H and the Paris R III strains in adult life. Crossbreeding experi- 

 ments once made it appear that the disease was an inherited condition, 

 but on closer scrutiny of the data it became necessary to postulate 

 an extrachromosomal factor in the transmission of this form of cancer. 

 From this postulate emerged one of the significant landmarks of cancer 

 research. By the elegantly simple expedient of foster nursing Bittner 

 in 1936 demonstrated that this extrachromosomal factor was trans- 

 mitted with the milk of the nursing mother. AYhen newly born C3H 

 (high cancer strain) females were foster-nursed on C57 (low cancer 

 strain) foster mothers the incidence of mammary carcinoma in the 

 subsequently matured C3H mice was reduced markedly. Conversely, 

 when the newly born C57-strain females were nursed on C3H foster 

 mothers cancer of the breast appeared in many of them on maturity. 11 



It is significant that in these foster-nursing experiments the C3H 



