TRANSPLANTATION OF TUMORS 397 



acquired characteristic of tumors which distinguishes them from normal 

 tissues. 



However, there are some indications that also in normal tissues of higher 

 organisms some processes of adaptation may take place. If we stimulate the 

 thyroid gland of the guinea pig by means of iodine or anterior hypophyseal 

 extracts, the stimulating effect ceases after some time and at last, after con- 

 tinued applications of these substances, a refractory state with less than the 

 normal reactivity ensues. It is probable that in this case adaptive changes which 

 occur in the cells exposed to such stimulating substances are responsible, at 

 least in part, for the condition of tolerance attained. Similarly, if a piece of 

 homoiotransplanted cartilage is left for a long time in the host, the reactions on 

 the part of the host tissue against the transplant, instead of increasing or 

 showing a cumulative effect with increasing length of time, seem, as a rule, 

 to diminish in intensity. But, here, it is not certain how far the diminution 

 in reaction is due to adaptive changes in the host or in the transplant. 



Reference has also been made in an earlier chapter to the observations of 

 Rhoda Erdman and Gassul, that a gradual adaptation of anuran amphibian 

 skin to heterogenous amphibian anuran hosts may be accomplished by cultivat- 

 ing the former for some time in vitro in culture media, which were rendered 

 more unsuitable through step-by-step addition of the foreign plasma from the 

 species to which it was desired to adapt the skin. But in these experiments 

 it is not certain that adaptive changes had actually taken place in the trans- 

 planted tissue. 



Somewhat related investigations were carried out subsequently by Kimura, 

 who cultivated chicken tissue in vitro in duck plasma and tissue extract. The 

 chicken tissue thus prepared was used as antigen for the production of 

 precipitins. These precipitins reacted with duck instead of with chicken 

 antigens. Kimura concluded therefore that chicken tissue had assumed the 

 characteristics of duck tissue as a result of adaptive changes taking place in the 

 new heterogenous environment. However, instead of assuming so fargoing a 

 change in the species differential of the chicken tissue within a relatively short 

 period, the possibility may be considered that some duck plasma was admixed 

 to the chicken tissue serving as antigen and that the adhering duck plasma was 

 responsible for the production of the precipitins. That such a transformation 

 of the individuality differential does not actually take place is also indicated 

 by an experiment of A. Fischer, in which he showed that rat fibroblasts, which 

 had been cultivated for more then twenty-three years in chicken plasma, still 

 remained rat cells ; they retained their species differential and cytotoxic im- 

 mune serum directed against rat tissues injured the rat cells that had pre- 

 viously grown in chicken plasma in the same specific way as it injured fresh 

 rat cells. In both the case of tumor tissues and of normal tissues we arrive, 

 therefore, at the conclusion that in all probability definite changes in the species 

 differential do not take place in the course of serial transplantation, and that 

 the adaptive changes occurring in transplanted tumors under certain condi- 

 tions are not due to somatic mutations. 



In the experiments which we have discussed so far, an adaptation of tumor 



