TUMORS AND NORMAL TISSUES 353 



heterogenous tumor, one must use heterogenous tissue of the same species as 

 that in which the tumor originated. For instance, if one wishes to immunize 

 a rat against a mouse carcinoma, the rat must be inoculated with normal 

 mouse tissue, and such an immunization cannot be accomplished by inoculating 

 rat or guinea pig tissues into the rat. Correspondingly, an immunity against 

 a homoiogenous tumor can be attained only by the inoculation of tissues 

 from the same species : a mouse can be actively immunized against a mouse 

 tumor only by means of mouse tissues. Now we know that in the tissues used 

 for heteroimmunization there are present in addition to the heterodifferentials, 

 homoiodifferentials ; but evidently the presence of the heterogenous differen- 

 tials in some way prevents the homoiodifferentials from becoming effective un- 

 der these conditions. We see, then, that the organismal differentials play a role 

 in immunization against heterogenous as well as against homoiogenous tumors. 



The direct action of heterotoxins, and especially of immune heterotoxins — 

 but not of homoiotoxins — on tumor tissue, can also be demonstrated in tissue 

 culture. While, as Lambert and Hanes have found, rat sarcoma grows in 

 vitro as vigorously in plasma from immune rats as in the plasma from normal 

 or tumor-bearing, non-immunized rats, the immune heterogenous serum from 

 guinea pigs immunized against rat sarcoma has a toxic action on this tumor 

 in tissue culture. It also exerts such an effect on rat-embryo skin. Other 

 authors, such as Gussio, Mottram and Rous, likewise were unable to demon- 

 strate the injurious action of homoiotoxins in tissue culture. Furthermore, 

 Rous, and subsequently Kross, did not succeed in demonstrating the existence 

 of homoiotoxins by means of parabiosis, in which substances produced in 

 one animal are supposed to be transferred directly to the circulation and thus 

 to the tissues of its partner. However, as shown in a previous chapter, factors 

 which complicate parabiosis and tissue culture make it necessary to accept 

 negative results obtained by means of these methods with certain reservations. 

 In the case of chicken sarcoma growing in vitro, A. Fischer found that not 

 only plasma from naturally resistant fowl was without any inhibiting effect, 

 but even the serum of geese, ducks and rabbits immunized with chicken 

 sarcoma did not prevent the proliferation of this tissue in vitro. However, 

 the lack of effects of homoiotoxins in tissue cultures may, at least partly, be 

 due to the fact that while in the living vertebrate organism the bodyfluids are 

 constantly circulating and new substances of a specific character are carried 

 to the transplanted tissue, in vitro the amount of such an injurious substance 

 which is able to act on the tissue is very limited, and the tissue can presumably 

 neutralize it to some extent; the results obtained in vitro are, therefore, not 

 comparable in every respect to those obtained in the living animal. 



In a preceding part it could be shown that the homoiotoxins in the blood 

 stream of a homoiogenous animal may injure directly the transplanted normal 

 cells. This is more noticeable in some species than in others, and especially it 

 is noticeable if the difference between the individuality differentials of host 

 and graft is relatively great and if the transplanted tissue is sensitive. There 

 are indications that immune substances may be formed as a result of a first 

 transplantation, which cause an acceleration of the reaction against the 



