HEREDITY AND TRANSPLANTATION OF TUMORS 365 



The transition from the ordinary strains of animals to closely inbred, homo- 

 zygous strains is a gradual one ; it takes place step by step. The guinea pigs 

 and rats which we used at first in our transplantations of normal tissues did 

 not belong to inbred strains. We determined the organismal differentials by 

 comparing the effects of auto-, various kinds of syngenesio-, homoio- and 

 heterotransplantations. Because we did not have to deal with closely inbred 

 strains, variability in the results within certain limits in the syngenesious- 

 homoiogenous range of the spectrum of relationships may therefore be ex- 

 pected, and this was actually observed. But this difficulty could be over- 

 come by increasing the number of experiments in which we tested the effects 

 of relationship on the fate of the transplants. The greater the number of un- 

 known factors, the greater must be the number of equations. The conclu- 

 sions reached in these earlier experiments concerning the significance of the 

 relations between organismal differentials of host and transplant on the fate 

 of the latter were confirmed in our subsequent investigations with closely in- 

 bred strains of guinea pigs and rats. However, a fully homozygous condition 

 had not yet been reached in the case of the inbred guinea pigs ; in the case of 

 the rats, the heterozygous condition had only very slightly been diminished 

 after as many as forty generations of' close sister-brother inbreeding. As 

 stated, our early observations on the transplantation and spontaneous develop- 

 ment of tumors in mice were made in partly inbred strains. The same limita- 

 tions applied here as in the earlier transplantations of normal tissues in 

 guinea pigs and rats. In both instances, the difficulties due to the larger num- 

 ber of variable factors present made necessary a larger number of experi- 

 ments. Likewise, in the case of tumor transplantations subsequent experiments 

 by various investigators and also by ourselves with more fully homozygous 

 strains confirmed essentially the earlier conclusions. It must, however, be 

 emphasized that even these closely inbred strains had, in all probability, 

 not yet reached a completely homozygous condition. There is therefore only 

 a quantitative difference in the nature of the strains used in the earlier and 

 in the later investigations, and both lead to the same results provided a suffi- 

 cient number of experiments are made. 



All these observations and experiments point to the conclusion that the 

 transplantability of tumors depends largely on the relations between the 

 genetic constitutions of host and donor and the character of the organismal 

 differentials, which is the expression of these constitutions. But there is one 

 finding which seems contradictory to these conclusions. Rous and Long dis- 

 covered that their third chicken sarcoma, which had originated in a Leghorn, 

 grew, on the average, better after transplantation into Plymouth Rock chickens 

 than in Leghorns. Presumably factors of a secondary character complicated 

 the relationship between tumor and host in this case, or this condition may 

 possibly have been due to peculiarities of the agent present in these tumors 

 rather than to those of the tumor cells. But before entering into a further 

 discussion of genetic factors in the transplanted tumors, we must again con- 

 sider the difficulty which we experience if we analyze tumor growth by means 

 of transplantation of the ordinary transplantable tumors. 



