IODINE AND AMPHIBIAN METAMORPHOSIS. 249 



is due to the iodine in the molecule, in the former group the meta- 

 bolic response depends upon something else, i.e., the CO-NH 

 group within the thyroxin molecule. This brings us to the consid- 

 eration of another point, i.e., the possibility of substituting other 

 halogens for iodine and obtaining the same effects upon meta- 

 morphosis. 



Kendall ('18) as a result of his investigations of the unique 

 effects of thyroxin upon the metabolic rate of mammals, was led 

 to conclude that insofar as the physiologic effect upon mammals 

 is concerned, possibly other halogens could be substituted for 

 the iodine of the thyroxin molecule without greatly changing the 

 physiological properties of the thyroxin. His conclusion follows: 

 "In regard to the relation of iodine to the activity of thyroxin, 

 the presence of iodine in the compound must exert some influence, 

 and it seems not improbable that the presence of iodine renders 

 the active groups more reactive. In the absence of iodine it 

 would take a greater working pressure to bring about its reaction. 

 The substitution of iodine by hydrogen or chlorine or bromine 

 would undoubtedly be followed by an alteration in the degree of 

 reactivity of the substance but its gross chemical nature and 

 properites would not be altered thereby." 



Whether or not other halogens can or cannot be substituted for 

 the iodine of the thyroxin molecule and this substance still retain 

 its physiological activity in mammals is an open question, at any 

 rate there are no experimental data tending to answer the ques- 

 tion one way or the other except possibly the work of Ostwald 

 and von Cyon who observed that thyreoglobulin containing no 

 iodine was physiologically inert, whereas this substance gives all 

 the physiological effects of thyroid tissue when iodine is present. 

 However, this may be, it is clear that insofar as amphibian meta- 

 morphosis is concerned other halogens such as bromine can not 

 be substituted for iodine. The experiments upon thyroidless 

 axolotls and anuran larvae where 3-5 dibromtyrosine was em- 

 ployed, demonstrates the futility of endeavoring to substitute 

 bromine for iodine with hope of affecting metamorphosis. It is 

 merely quibbling to say that bromine would probably be just as 

 effective as iodine providing the organism possessed a mechanism 

 for utilizing this halogen in the way the thyroid utilizes iodine to 

 elaborate its hormone, because in our experiments the animals 



