CAN ORGANISMAL DIFFERENTIALS BE CHANGED? 583 



strange epidermis is in more direct contact with the host tissues and is better 

 supplied with blood by the underlying capillaries ; this might possibly improve 

 the chances of survival, (c) There is another possibility which has been 

 suggested by Bytinski-Salz. Various kinds of amphibian skin contain glands 

 which secrete poisonous substances. By cultivating the skin in vitro, the 

 poisons may have been extracted to a large extent previous to transplantation, 

 or perhaps a depression in the gland activity and a corresponding diminution 

 in the production of the toxic substances following transplantation may have 

 been brought about. Still, there remains the possibility that cultivation in 

 vitro may have induced a change in metabolism of the skin, which enhanced 

 its transplantability. This change may have been either of a non-specific or 

 of a specific character, dependent upon the kind of plasma in which the skin 

 had previously been cultivated. Similar successful experiments with human 

 skin have more recently been reported by Stone and others ; other surgeons, 

 however, did not notice an improvement in the results of homoiotransplanta- 

 tion through a preceding cultivation of the tissue jn vitro. 



3. More recently, experiments have been made by Lumsden, in which the 

 temporary growth of a mouse tumor in a rat, or of a rat tumor in a mouse, 

 changed the tolerance of tumor tissues in vitro to the corresponding heterog- 

 enous sera, in which they were subsequently immersed, in such a way as to 

 suggest that by the growth in the heterogenous species they had apparently 

 lost their own organismal differentials and assumed the characteristics of the 

 foreign species. Thus a mouse tumor, after growing in a rat, had become 

 resistant to serum from a rat which had been immunized against mouse 

 tumor, but at the same time it had become susceptible to the serum of a 

 mouse immunized against rat tissue. However, after transplantation of such 

 tumor cells into rat and mouse, they grew only in the latter ; they still be- 

 haved therefore as mouse cells and had not really changed their organismal dif- 

 ferential. It must then be assumed that changes of a secondary nature in some 

 unknown manner had reversed the reactions towards immune sera. Of a 

 somewhat similar nature are the experiments of Kimura, in which also 

 growth in vitro seemed to induce a change in tissues, but in this instance 

 the change became manifest even in the living organism. However, the 

 experiments of Albert Fischer indicate that no real change in organismal 

 differentials occurs in tissues growing in strange media in tissue culture. 



4. The growth energy of tumors undergoes various adaptations in the 

 course of serial transplantations. As a rule, it increases gradually following 

 the first few transplantations, until finally a tumor may grow successfully 

 in hosts in which at first negative results had been obtained, sometimes even 

 in heterogenous hosts. It has been made very probable that the antigenic 

 properties of cells from spontaneous tumors (Dmochowski) and of leukemic 

 cells from spontaneous cases (MacDowell) may change within certain limits 

 in the course of serial transplantations, and that they may thus differ in 

 their reactions, in certain respects, from analogous cells which had not been 

 subjected to such treatment. 



If we consider all these experiments together, there is no necessity for 



