STIMULUS FOR REGENERATION 241 



velopment the normal stimulus is usually a sperm, but we may substitute a 

 whole variety of chemical agents. The development of the primitive nervous 

 system also requires a stimulus for differentiation, and this is provided by the 

 roof of the archenteron. Here again, a variety of chemical agents could be 

 substituted for the roof of the archenteron. In an experiment based on this 

 idea of stimulation, regeneration was obtained in the limb of the frog, in 

 which normally regeneration never occurs. The frog limb after amputation 

 normally heals without the formation of a blastema and without any re- 

 generation. If the cut surface is stimulated by treatment with saline solu- 

 tions, however, the limb then forms a blastema and this blastema will begin 

 to differentiate into the missing part. A number of other treatments have 

 been applied to the frog limb with the result that the limb can regenerate 

 perfectly well, provided an additional stimulus is applied. The normal stimu- 

 lus of simply cutting through the tissue, as in the amputation of the limb, is 

 not sufficient. Probably in the amputated stump of a frog limb regeneration is 

 blocked in some way. Such a block is not present in .a salamander limb, which 

 normally does regenerate after amputation. 



We have some idea of the nature of this block. In a salamander limb, if 

 a clean cut is made regeneration always follows. If, however, the skin is 

 pulled over the cut surface, no regeneration occurs. In other words, if the 

 wound is covered with skin immediately after the amputation is made, re- 

 generation is blocked. Normally in an animal like the frog both the epi- 

 dermal and dermal layers of the skin close over the wound rapidly during 

 healing. The function of the treatment with salt solution seems to be simply 

 to prevent the dermal layer from migrating over the wound, and under these 

 conditions regeneration will occur. The treatment may also stimulate the 

 epidermal layer. At any rate, when both layers of the skin cover the wound 

 no regeneration occurs. When only the epidermal layer migrates over the cut 

 surface regeneration takes place. 



Thus it appears that the ability of organisms to regenerate is not lost as 

 such, but there may be conditions of healing which create a block to the 

 proliferation and growth of cells. If this block can be removed by chemical 

 treatment, regeneration may be expected in those forms which normally do 

 not regenerate. This interpretation is more reasonable than the assumption 

 that animals lose the powers of regeneration, and it encourages experimenta- 

 tion with mammalian limbs. 



This brings us to the end of a task which we set out to do in the early part 



