348 THE BIOLOGICAL BASIS OF INDIVIDUALITY 



of normal tissues we found that the degree of species-relationship between 

 host and donor may influence to some extent the result of heterotransplanta- 

 tion. Furthermore, especially those tumors which grow rapidly after homoio- 

 transplantation may be expected to grow actively also after heterotransplan- 

 tation ; therefore, a rapidly growing sarcoma may be especially well suited for 

 heterotransplantation. There may perhaps be in addition some special condi- 

 tions which may enable cancer tissues to overcome more readily than normal 

 tissues the unfavorable effects of heterogenous transplantation. 



However, in general, the injurious effects which take place in strange 

 species are cumulative and lead gradually to the death of the transplant. 

 By re-transplanting the tumor into an individual belonging to the species in 

 which it originated, such a cumulative action may be prevented, or at least 

 delayed, and the tumor given a chance to recover to some extent from the 

 injury received by the hetero toxins. After such a recovery has taken place, it 

 may be possible to transplant the tumor again into the strange species, and 

 this process may be repeated a number of times. Such a procedure was used 

 by Ehrlich in heterotransplantation of mouse tumor to rat and he called it 

 zigzag transplantation. The conditions are here, to a certain extent, com- 

 parable to those prevailing after injuring the tumor by exposure to graded 

 degrees of heat; then, also, a recovery may take place after transplantation 

 into a new host. But there are indications that even after transplantation into 

 relatively nearly related species a gradual and slowly cumulative injury does, 

 as a rule, take place eventually; while after transplantation into more dis- 

 tantly related species, as for instance, from mouse to guinea pig, a repeated 

 heterotransplantation, with intermediate recovery periods, in the original 

 species would in all probability be impossible. 



However, it is not only the cumulative action of the preformed heterotoxins 

 which prevents the continued growth of a tumor in a strange species, but in 

 addition, it is the active immunity developing in the host against the heterog- 

 enous differential which helps to injure and destroy the transplant. Such an 

 immunity against heterogenous tissues can be elicited much more readily and 

 effectively than against homoiogenous tissues, and when it is well established, 

 the critical period sets in. It might therefore be expected that if the injurious 

 action of these immune heterotoxins were avoided by re-transplantation of 

 the heterogenous tissue into a new, not yet immunized individual of the 

 strange species, the results might be improved, provided we had to deal with 

 relatively resistant and rapidly growing tumors. Such a condition apparently 

 has been realized in more recent experiments by Ito in transplantation into 

 rats of a squamous cell tar carcinoma experimentally produced in a mouse. 

 This mouse carcinoma could be transplanted for many generations into rats 

 if a re-transplantation into a new host was carried out every five or six days. 

 But if the transplant was allowed to remain as long as ten days in the 

 heterogenous host, it became entirely necrotic. It must be assumed either that 

 an increased growth momentum, acquired during their transformation into 

 cancer, made it possible for these cells to overcome the injurious action of 

 the natural heterotoxins better than normal tissues, or that a diminished sensi- 



