December 22, 1922] 



SCIENCE 



721 



individuals were exceptional in this respect, the 

 average time being about twenty days. 



These results are of significance for several 

 reasons : 1. The experiment is clear cut and ad- 

 mits of but one interpretation, i. e., that it is 

 the iodine within the tyrosine molecule that is 

 essential for Anuran metamorphosis, because 

 tyrosine without the two atoms of iodine is 

 in'oapable of inducing metamorphosis.^ 



2. Thyroidless and pituitarjdess frog larva; 

 do not metamorphose unless fed thyroid sub- 

 stance or very large quantities of elemental 

 iodine. Such larvae have no thjToid mechanism 

 fior the manufacture of 'the thyroid hormone, 

 yet apparently are able to utilize inorganic 

 iodine when administered in very large quanti- 

 ties along with normal food. The substitution 

 of the two iodine atoms for two hydi'ogens of 

 the tyrosine molecule transforms the tyrosine 

 into a highly active metamorphosis-inducing 

 agent far superior to any quantity of ele- 

 mental iodine in its rate of action and second 

 only to the thyroid hormone itself. It seems 

 clear that in tadpoles metamorphosis depends 

 upon an organic iodine complex of some sort, 

 and that the iodine to be effective does ncit need 

 to undergo transfonnation within the thyroid 

 gland. It is evident that when thyroidless 

 larvas metamorphose when fed quantities of 

 inorganic iodine, the latter to be active must 

 e niter into organic combination with either the 

 body proteins of the larva or the algse fed 

 with it. 



3. Iodized proteins and aminojaeids have 

 been employed by several investigators in the 

 treatment of various disorders of the thyroid 

 in cases of human hypoithyroidism, but the 



1 Large asolotls seven inolies long were thy- 

 roideotomised and kept five months following the 

 operation and then twice injected with iodotyro- 

 sine. Metamorphosis resulted within seventeen 

 days following the first iajeotion. Similar ani- 

 iQiEtls injected with tyrosine and ' dibromtyrosine 

 did nat transform. Partially thyroideetomized 

 axalotls (two thirds of the gland excised) were 

 kept five months and then twice injected with 

 iodo-serum globulin. Metamorphosis occurred 

 within sixteen days. Uhlemhuth's claim that 

 Urodele larvs difcer from Anurans in regard to 

 metamorphosis and iodine is not sustained. 



writer has never heard that such products can 

 eompiletely take the place of the thyroid hor- 

 mone. Yet in thyroidless Anuran tadpoles 

 iodo-tyrosine to all intents and purposes is as 

 good as the thyroid secretion in transforming 

 the individual, i. e., it completely takes the 

 place of the gland seci-etion in so far as meta- 

 morphosis is concerned. 



Metamorphosis in Anurans is dependent 

 upon a peculiar property of the iodine atom 

 when organically combined in a certain way 

 and it seems that mammals and Anurans are 

 not to be compared in regard to their reactions 

 to iodine. Thyi"oidless tadpoles promptly 

 metamorphose when fed iodized amino-acids or 

 large quantities of elemental iodine, but thy- 

 roidless mammals and individuals with atro- 

 phied and very degenerate glands can not 

 utilize elemental iodine at all, and the same is 

 probably true of iodized amino acids. Voegthlin 

 and Strouse ('09, Journal Pharm. and Exp. 

 Therap.) observed that iodized amino-acid fails 

 to replace the thyroid function in pathological 

 cases of hypothyroidism, i. e., myxedematous' 

 and cretinous mammals, nor was the nitrogen 

 metabolism or blood pressure of dogs influ- 

 enced by administration of this substance. 

 Furthermore, Miura ('22, Jour. Lab. and Clin- 

 ical Med., Vol. 7) has made the interesting ob- 

 servation that di-iodotyrosine gives no protec- 

 tion to mice against lethal doses of aeetonitrile, 

 whereas thyroid tissue protects these animals 

 against the poison. 



It is clear that in so far as the metamor- 

 phosis of thyroidless and pituitaryless tadpoles 

 is concerned iodo-tyrosine is practically as 

 good as the thyroid hormone but this same 

 substance in mammals can not be substituted 

 for the glandular tissue itself. 



4. The suggestion of some recent writers that 

 bromine if it could be substituted for the iodine 

 of the thyroid might prove just as active physi- 

 ologically, is not borne out by these experi- 

 ments. Bromine has no influence upon Anuran 

 transformation and can not be substituted for 

 iodine. 



W. W. Swingle 



OsBOEsr Zoological Lacobatokt, 

 Yale IIniveesitt, 

 October 5. 1922 



