REGENERATION AND TISSUE EQUILIBRIUM 281 



long as the material entering into these reactions is still plastic, adaptable, and 

 not yet definitely fixed and differentiated, especially in the transplant, there 

 is less likelihood that incompatibilities will develop, than at later stages when 

 differentiation into the more rigid structures has already occurred. 



We find, therefore, very complex interactions between transplant and ad- 

 joining host tissue, and the effects exerted by neighboring tissues upon each 

 other depend not only on the kind of tissues which are brought into contact 

 with each other, but also on the stage of development and differentiation of 

 these interacting tissues. Thus the inhibiting action of a transplant on the 

 regeneration of an extremity is effective only in the first phase of the process 

 of regeneration ; it is ineffective if the transplantation is carried out at a later 

 stage, when regeneration is already under way. On the other hand, if in some 

 manner, as for instance through a purely mechanical factor, we prevent the 

 regeneration from being initiated, all subsequent outgrowth has, by these 

 means, been made impossible. Perhaps the ability to regenerate depends upon 

 the presence and activity of a sensitizing substance, which may be lost or 

 neutralized after a definite time has elapsed. This would represent a condition 

 analogous to that observed in mammalian organisms, where a placentoma can 

 develop only at the stage of the sexual cycle when the sensitizing substance 

 given off by the corpus luteum has become active. The effect of certain contact 

 actions would then perhaps consist in a neutralization of the influence of 

 sensitizing and stimulating substances. 



It follows from our previous discussions that these contact mechanisms 

 between adjoining tissues may consist in the giving-off of various specific 

 substances corresponding to organizers, to sensitizing, or, under some con- 

 ditions, also to inhibiting substances in the place of union. In addition, the 

 physical-chemical structure of the cut surfaces of transplant and host may 

 be of importance, in accordance with Graper's comparison of these surfaces 

 with electro-magnetic fields. 



The importance of contact effects in determining the fate of tissues is 

 indicated also in some experiments of Schaxel with transplantation of ex- 

 tremities in Axolotl. If buds at very early stages of regeneration are trans- 

 planted into a further developed body wall, the transplant is not able to form 

 an extremity through self-differentiation; it is prevented from doing so by 

 the organizer action of the strange surrounding host. Instead, the transplants 

 may form irregular masses, which later disappear; but further differentiated 

 regenerative buds transplanted under the same conditions are able to form 

 extremities. However, if an early regenerating bud is transplanted together 

 with the surrounding skin, then it may differentiate into the typical extremity ; 

 apparently its own skin can supply the needed kind of contact action, which 

 allows it to differentiate normally and to maintain itself after transplantation. 



We can understand the way in which neighboring tissues exert contact 

 actions upon each other, presumably through the giving-off of certain sub- 

 stances, if we consider what happens at certain stages of metamorphosis. In 

 anuran amphibia the gills at definite periods of metamorphosis secrete a sub- 

 stance which dissolves the overlying skin. Also, transplanted gills exercise 



