THE PHYSIOLOGY OF DEVELOPMENT 209 



developed limbs and the tail persists into the adult stage. 

 The nature of the physiological change which initiates this 

 series of events is the same in either case. 



The first experiment which threw any light on this was 

 the discovery of Babak (191 1) that the axolotl larva of the 

 Mexican salamander {Amhlystoma tigrinu7n ) which is nor- 

 mally neotenous, can be induced to undergo transformation 

 into the adult form by thyroid administration. Gudernatsch 

 (19 1 2- 14) showed that this was true of frog tadpoles. If 

 tadpoles are fed on diets of various tissues, ovary, liver, thymus, 

 brain, pancreas, spleen, pituitary, and thyroid — those fed on 

 thyroid gland develop limbs and lose their tails long before 

 the others. Thus in Rana catesbana (Swingle), a species 

 which normally requires three seasons to attain to the stage 

 at which metamorphosis occurs in nature, the six- weeks-old 

 tadpole will transform into a pigmy frog if fed on ox thyroid. 

 These observations received abundant confirmation both as 

 regards urodele larvae and anuran tadpoles (Morse, Barthelemez, 

 Jensen, Huxley and Hogben, Uhlenhuth). 



Bennet Allen (19 16- 18) succeeded in overcoming the 

 manipulative difficulties of extirpating the thyroid gland in 

 tadpoles of the toad. The thyroidectomised tadpoles behave 

 in a perfectly normal manner until the limb-buds develop, 

 when transformation should occur. Instead of undergoing 

 metamorphosis at this stage they remain permanently in the 

 larval state, attaining as age advances dimensions far exceeding 

 those of a normal tadpole. They can, however, be induced, as 

 Swingle (19 18) showed, to develop into normal frogs if fed 

 on thyroid tissue. Later E. R. and M. M. Hoskins confirmed 

 the work of Allen by similar experiments on frogs and others 

 on urodele larvae. 



Thus both inAnura andUrodeles it is certain (i) that the 

 removal of the thryoid normally prevents metamorphosis ; 

 (2) the administration of thyroid substance (or implantation 

 of thyroid tissue) accelerates normal metamorphosis and 

 initiates metamorphosis in thyroidless individuals. It has 

 long been known that the thyroid gland is essential to normal 

 growth in mammals, that it contains a high percentage of 



