REGENERATION AND TISSUE EQUILIBRIUM 285 



isms through the tissues, which are the carriers of finely graded organismal 

 differentials. 



In the highest organisms, the adult mammal, the same factors which are 

 active in the lower organisms play a role in the maintenance of the equilibrium 

 which makes possible the existence of an individual. But in contradistinction 

 to the findings in more primitive organisms, this equilibrium is an autogenous 

 one. The various tissues composing the individual must have the same in- 

 dividuality differential, otherwise disturbances take place. In addition, also 

 mechanical factors, like cuts, the presence of foreign bodies, may lead to dis- 

 equilibrations in these organisms, which are, however, usually readily re- 

 paired. Only under certain conditions of sensitization may mechanical factors 

 lead to furthergoing growth processes, such as the formation of placentomata. 

 But even without the action of mechanical factors the autogenous equilibrium 

 may be disturbed if growth stimuli act on adjoining tissues of a different 

 kind ; thus, changes connected with transplantation of pigmented skin into 

 defects in white skin in the guinea pig may give to the pigmented skin, or 

 some of its constituents, a growth momentum which causes it to invade the 

 adjoining white epidermis. Similarly, if in the vagina-cervix-uterus sex tract 

 a marked and long-continued stimulation of the surface epithelium is pro- 

 duced by the injection of estrogen, the growth momentum of the epithelium 

 of the cervix, which has the power to produce squamous epithelium, is in- 

 creased more than that of the cylindrical epithelium of the uterus, and in 

 consequence of this disequilibrium the squamous epithelium may invade and 

 replace the cylindrical epithelium over long distances. The equilibrium in 

 the normal individual depends, therefore, also upon the maintenance of the 

 mutual normal growth momentum of adjoining tissues. A long-continued dis- 

 turbance of this equilibrium by a variety of factors may ultimately lead to the 

 initiation of localized cancerous growth. 



In general, we may then conclude that a finely equilibrated state exists be- 

 tween neighboring tissues, the disturbance of which may lead to growth proc- 

 esses which, in some cases, succeed in restoring the same, or, in other cases, 

 a new stable equilibrium. Transplantation prevents regeneration when it 

 supplies the missing regulatory factors, which in the higher organisms are of 

 an autogenous character ; but in principle, conditions are the same in this re- 

 spect in the furthest differentiated adult organisms as in the more primitive 

 and embryonal ones. In the latter, regeneration can be prevented by tissues 

 which differ within a certain range in their organismal differentials, and which 

 also may differ in their tissue differentials. We can here distinguish ( 1 ) a 

 specific inhibition exerted by tissues of the same kind, such as, for instance, 

 medulla restraining adjoining medulla, or chorda restraining chorda, in their 

 respective regenerative tendencies (isoregulation), and (2) an inhibition by 

 tissues of another kind, such as gill tissues inhibiting leg growth, or skin pre- 

 venting the growth of a tail or limb (alloregulation). It is necessary, besides, 

 that transplant and host, or adjoining tissues in general, should be in close 

 contact if the specific interactions between neighboring tissues are to become 

 effective; otherwise these interactions are interfered with and growth and 



