384 EXAMPLES OF CHEMICAL CORRELATION 



The active and remedial constituent of the gland is associated with 

 the Iodine which the thyroid contains and which distinguishes it 

 chemically from all other tissues of the body. 1 While the iodine-con- 

 tent of the thyroid varies very much, not only in different species of 

 animals, but in different individuals of the same species, yet the minimal 

 content of iodine which is consistent with normal functioning of the 

 gland is very nearly constant and, on the other hand, the remedial 

 value of a thyroid preparation tends to be proportionate to its iodine- 

 content. The nature of the active iodine compound has been the 

 subject of very many and extensive investigations. The experiments 

 of Oswald showed that the active substance, as it exists in the glandular 

 tissue, is either an iodized protein or closely associated with a protein 

 which he termed Thyreoglobulin. Bauman found, however, that the 

 partial hydrolysis of Oswald's thyreoglobulin by means of sulphuric 

 acid did not destroy its therapeutic activity, but that a fraction of the 

 hydrolytic cleavage -products which he termed lodothyrin retains the 

 original activity of the thyreoglobulin. This substance, according to 

 von Fiirth, is related to the "humin" substances which form in acid 

 hydrolyses of protein in the presence of carbohydrate radicals, and are 

 considered by Gortner and Blish to arise from the Tryptophane groups 

 of the protein molecule. This fact has received peculiar significance 

 as a result of the recent researches of E. C. Kendall who has succeeded 

 in still further fractionating the hydrolytic cleavage-products of 

 thyreoglobulin without destroying its therapeutic activity. By 

 hydrolyzing thyreoglobulin in alkaline alcohol two groups of products 

 are obtained. The one group is insoluble in dilute acids, the other is 

 soluble. The acid-soluble substances are physiologically and thera- 

 peutically inert and they contain very little iodine. The acid-insoluble 

 substances contain a high proportion of iodine, and are physiologically 

 and therapeutically potent. By further fractionation Kendall obtained 

 a white crystalline product containing 60 per cent, of iodine, which was 

 very active therapeutically and proved to be a derivative of Indol, 

 being therefore related to tryptophane. Kendall believes that this 

 compound which he designates Thyroxin is a tri-iodo-oxy-indol-pro- 

 pionic acid, and has tentatively suggested the following constitutional 

 formula: 



HI 



IHC C = =C.CH 2 .CH 2 .COOH 



IHC C C=O 



H 



1 The alleged presence of iodine in the pituitary gland has not proved possible to 

 confirm. 



