Metamorphosis 



651 



periods even the lowest concentrations might 

 be seen to lead to late metamorphic events. 

 This was clearly recognized by Allen, who 

 stated, "this 'threshold of response' is really 

 a question of time of response." 



By following the changes in individual 

 animals continuously for long periods, Etkin 

 found that any effective concentration of thy- 



malities in coordination observed by all 

 earlier workers who gave massive thyroid 

 doses. 



No single concentration of thyroxine was 

 found effective in inducing a normal "time- 

 table" of metamorphic events. Etkin was 

 partly, though not entirely, successful in in- 

 ducing a normal timetable in thyroidec- 



Fig. 227. Abnormal tadpoles metamorphosing under stimulation from strong doses of thyroid (after 



Schreiber, '34a). 



roxine was capable of inducing both early 

 and late metamorphic changes if allowed to 

 operate for a long enough period. The speed 

 of metamorphosis increased with the concen- 

 tration of thyroxine. In low concentrations 

 the first effect observed was an activation of 

 leg growth, and only after the lapse of con- 

 siderable time, during which the legs grew 

 to full size, were late metamorphic events 

 initiated. These later events proceeded in an 

 extremely slow and protracted manner. With 

 low concentrations, therefore, early meta- 

 morphosis is normal in its time relations 

 but the late events of the metamorphic cli- 

 max are unduly protracted. In high concen- 

 trations the events of the metamorphic cli- 

 max were precipitated at their normal rates 

 but not enough time was permitted for early 

 events to undergo their appropriate develop- 

 ment. This is the explanation of the abnor- 



tomized tadpoles by treating them first with 

 low concentrations of thyroxine and subse- 

 quently raising the concentration (Fig. 228). 



It would appear from the above results that 

 the responses of the tissues show the ordinary 

 stoichiometric relations common to many 

 chemical reactions, i.e., the higher the con- 

 centration the faster the reaction proceeds. 

 No true thresholds of response are shown by 

 the tissues. In virodeles the velocity of tissue 

 response is also a function of the concentra- 

 tion of active principle when small doses are 

 used (Zavadovsky, '26). 



According to this interpretation the tem- 

 poral spacing of metamorphic events (Fig. 

 229) depends upon two factors: (1) inher- 

 ent differences in the tissues with respect to 

 rate of response, and (2) the patterns of 

 activation of the thyroid gland. The histo- 

 logical evidence discussed above indicates 



