440 THE BIOLOGICAL BASIS OF INDIVIDUALITY 



then the same in tumors and in the normal tissues in which the tumors 

 originate and these differentials are among those substances which may func- 

 tion as antigens and call forth immune processes against transplanted tumors. 

 This interpretation is not invalidated by the recent experiments of L. Gross in 

 which it has been shown that, if in the inbred strain C3H after transplantation 

 of a tumor originating in another mouse belonging to this strain, this tumor 

 undergoes complete regression, after a preliminary period of growth, the 

 inoculated mouse has acquired thereby, at least in a number of cases, an 

 immunity against a second transplanted tumor of the same type. 



Inasmuch as Gross assumes in accordance with the widely prevalent opinion 

 that in strain C3H all individuals are genetically homozygous, he concludes 

 that tissue constituents as such of one mouse, if inoculated into another in- 

 dividual belonging to this strain, are not able to call forth immune processes in 

 this mouse and that the immunity demonstrated under these conditions must 

 be due to factors other than constituents which normal tissues and tumors 

 have in common. However actually a fully homozygous condition has not 

 been achieved in any of these closely inbred strains and the genetic constitu- 

 tion of all the different C3H individuals is therefore not identical ; and inas- 

 much as the method used by Gross makes possible the demonstration of very 

 fine degrees of immunity, it might be expected that in a number of mice 

 belonging to this inbred strain an immunity can be shown to exist under the 

 conditions of these experiments. If the interpretation of Gross were correct, 

 it should be possible by similar means to call forth an immunity against an 

 autogenous tumor, in the mouse in which the tumor originated. But even if 

 such an experiment should succeed, which is not very probable, it would not 

 be permissible to conclude on this basis that the individuality differentials can- 

 not function as antigens in such instances, but it would indicate merely that 

 under these experimental conditions constituents of the tumor cells other 

 than the individuality differentials which they have in common with normal 

 tissues, acted as antigens. 



We believe that the organismal differentials in tumors and in normal tissues 

 from which they have developed are identical, or at least very similar, and 

 that the transformation of normal tissues into tumors does not depend 

 upon changes in the genes which determine the organismal differentials, 

 but upon conditions which are comparable to changes in organ and tissue 

 differentials, although they are not necessarily identical with these. The dif- 

 ferences between various tumors, arising in different individuals and in dif- 

 ferent organs, depend upon the original differences in the organismal and 

 organ differentials of the individuals and of the tissues in which they develop, 

 and in addition, upon certain changes of a special character, among which 

 the production of specific intrinsic growth factors or the invasion of cells by 

 extrinsic agents or viruses may play a role. Additional alterations may take 

 place during the life of a tumor, and in particular during serial transplanta- 

 tions, such as variations in growth energy or adaptations to the constitution of 

 new hosts. Future investigations must determine more accurately wherein 

 these changes of a chemical nature, which occur during the transformation of 



