57] RATE OF REGENERATION— ZELENY 57 



the decrease is due to increase in age. The increase from the fourth t& 

 the fifth regeneration may be due to some special characteristic of the 

 stage immediately preceding metamorphosis or it may merely indicate 

 the existence of some uncontrolled external factor such as food or 

 temperature. 



Discussion 



The evidence shows clearly that when the age factor is eliminated 

 there is no decrease in rate of regeneration with successive removal. 

 On the contrary the second regeneration is more rapid than the first 

 up to the period of maximum rate. The second regeneration however 

 passes its maximum sooner than does the first and after the tenth day 

 the latter therefore catches up to the former in total amount regener- 

 ated. There is no striking difference between the second and the third 

 regenerations but in each comparison the third has a slight advantage. 



When the successive regenerations in single individuals are com- 

 pared, the rate decreases w T ith successive removal. This decrease is 

 undoubtedly due to the age factor. 



The possibility has suggested itself that the second regeneration 

 starts out at a more rapid rate than the first because the cells at the 

 cut surface were undergoing regenerative changes at the time of the 

 new operation and can therefore start the process much faster than 

 can the old cells at the first surface of regeneration. Following a first 

 removal there is a considerable degree of reorganization of the cells 

 at the cut surface, accompanied by active migration. During this 

 period, which in Rana clamitans lasts two or three days, there is little 

 or no mitotic cell division. Then follows a division period which 

 reaches its maximum at seven to ten days. Its decline is associated 

 with the oncoming of tissue differentiation (Sutherland 1915, Metcalf 

 1915). 



A special study has been made of the relative rates of second 

 regenerations from old cells following a cut inside of the first removal 

 level and from new cells following a cut outside of the first level. This 

 comparison shows only a very slight difference in favor of the new 

 cells and this is largely confined to the early stages, the period of cell 

 migration. 



The period of increase in rate is the period of active cell multipli- 

 cation and the decline in rate is associated with cell differentiation. 

 The second regeneration therefore reaches the period of differentiation 

 slightly in advance of the first regeneration. 



Apart from the slowing due to age there is no indication of a 

 limitation of the amount of new material that may be produced by 

 regeneration. The actual limitation comes not from the using up of 



