4 GENERAL PART 



1. That the substance in question be found in the efferent blood-path or 

 lymph-path* 



2. That after experimental extirpation of the ductless gland in question 

 the' symptoms due to the removal are combated by peroral or sub- 

 cutaneous administration. 



3. That through the long-continued administration of this substance 

 manifestations are elicited that are similar to those which clinical 

 evidence leads us to regard as the symptoms following upon increased 

 function, a conception that, as the results of the surgical therapy of 

 these conditions, has in recent years been -made certain. 



All these postulates are not fulfilled in the case of adrenalin. Adrenalin 

 has been demonstrated in the blood of the suprarenal vein, but the relation- 

 ship to clinical medicine is still lacking in clearness. In the case of iodthy- 

 roglo^ulin, the demonstration in the blood or the lymph is as yet lacking. 

 Hypophysis extract has as yet not been studied enough, so that we can- 

 not say that it fulfills any of these postulates. As far as the other ductless 

 glands are concerned (for example, the insular apparatus of the pancreas, or 

 the parathyroid glands), the significance of which in experimental or clinical 

 pathology is extraordinarily imperfect, we have not as yet succeeded in 

 obtaining active extracts, or we are not at all certain that the observed 

 actions of the extracts are specific. The physiological chemistry of the 

 internal secretions is still in its childhood. From it alone, however, is a 

 sharp definition of the disease picture to be expected; the chemical demon- 

 stration of the specific substances in the blood even in combined form, the 

 possibility of the demonstration that these substances in lessened, normal, or 

 increased quantities circulate in the blood, would be of great importance for 

 clinical medicine. The biological method in this direction has up to the pres- 

 ent failed. The chemical definition and isolation in pure form of these spe- 

 cific substances will also furnish an important advance in the therapy of the 

 diseases due to lack of these glandular substances in the organism. The 

 domain of the internal secretions constitutes for physiological chemistry an 

 inexhaustible field for labor that theoretically and practically represents a 

 rich reward. 



The backwardness of the physiologico-chemical knowledge in this 

 territory explains why it has not been possible up to the present to obtain a 

 clear definition of the idea of internal secretion. According to the original 

 assumption, we understand by internal secretion the giving off of physio- 

 logically active substances into the circulation, of substances that through 

 their action on distantly-lying organs act in a regulatory manner on the 

 complex processes sustaining life. According to this general definition, how- 

 ever, every tissue in the animal body really yields an internal secretion, as 

 von Krehl has already pointed out. The point of emphasis in this defini- 

 tion lies in the assumption of a chemical correlation of the individual organs 



