638 REGENERATION AND GROWTH 7 



A regenerating nerve at first promotes the migration of Schwann cells (p. 641) 

 and later inhibits this (Abercrombie et al., 1949). Only the early stages of regenera- 

 tion are sensitive to the inhibitor, so that self-inhibition is not possible, but re- 

 regeneration is inhibited (Davidson and Berrill, 1948) until the first act is complete, 

 and much of the inhibitor eliminated (Weiss, 1955). Some of the inhibitor proba- 

 bly continues to circulate indefinitely and controls the equilibrium-size of the 

 organ (Weiss, 1955). There is probably an inhibitor, and a promotor, specific to 

 each organ. The specific inhibitor of liver-growth is diluted by simple dilution of 

 the serum which therefore permits resumption of growth (Glinos and Gey, 1952; 

 Warburton, 1955). The circulating inhibitor, like the promotor, is active also on 

 a parabiotic partner (Bucher et al., 1951) and on the homologous organ of the 

 embryo (Rose, 1952). 



A control of subsidiary levels by the most active region of a body-regenerate in 

 planarians may depend, in part at least, on the production of inhibitor by the 

 latter, since it regenerates fastest (Brondsted, 1955). Subsidiary regions, when 

 isolated take longer to recover the ability to re-regenerate than does the dominant 

 region (Brondsted, 1954; Lender, 1954), which indicates that they must first re- 

 cover from this inhibition. The action of a regenerate on normal growth appears 

 to be converse to that on another regenerate, i.e. inhibitory by a young regenerate 

 and promotor by later stages (Przibram, 191 7; Huxley, 1932). The initial inhi- 

 bition of normal growth may be due to simple competition, and the later accelera- 

 tion to rebound, but it is also possible that the promotor is state-specific, and 

 reflects the incompatibility between early regeneration and normal growth. 



Nature of promotor and inhibitor. The release of the wound-factor by any kind of 

 damage implies that it is probably a protein or one of its degradation-products, 

 though masked lipid also may be released in this way, and the wound-factor of 

 some plants has been identified (English et al., 1938) as a dicarboxylic fatty acid. 

 Both water- and fat-soluble promo tors of regeneration in animals have been recog- 

 nized. Loofbourow (1948) found that virtually all of the essential nutrients in an 

 extract of damaged cells, — amino acids, nucleotides, vitamins, etc., contributed to 

 its potency, and Fischer (1948) obtained a similar list for embryo-extracts. Harris 

 (1953) and others also have stressed the heterogeneous nature of the promotors 

 in the latter. At the other extreme Palladina and Gudina (1953) concluded that the 

 activity of extracts of necrotic tissues was dtie merely to (NH4)-,C03, — an end- 

 product of protein-degradation. 



The promotor released later by the regenerating tissues themselves has been 

 identified with a component of the globulins of the serum at that time (Balazs and 

 Holmgren, 1949; Engley et al., 1955). There is an increase in the globulin/albu- 

 min ratio after wounding (Cuthbertson, 1954), and during stress in general (Selye, 

 1948), and the globulin-fraction is more growth-promoting than the albumin 

 (Balazs and Holmgren, 1949). The increased globulin is associated with a non- 

 specific increase in all serological reactions and no specific regeneration-antigens 

 have been detected (Engley et al., 1955). The antibody to normal axolotl-muscle 

 inhibits muscle-regeneration in this animal (Striganova, 1949), indicating no 

 change in muscle-protein during regeneration. Weiss (1952, 1955) also envisages 

 the promotor as a normal typical protein of the tissues in question, possibly capable 



