190 R. G. HOSKINS 



augmentation both of rate and force was then seen. In one case fibrilla- 

 tion of the ventricle ensued when the blood-pressure reached a maximum 

 height. 



The British observers investigated the distribution of the active prin- 

 ciple as between the cortex and the medulla of the suprarenals. Glands 

 were frozen and the cortex carefully peeled off from the medulla. Extracts 

 were then made from each portion. Those from the cortex when in- 

 jected gave little or no reaction, whereas those from the medulla were 

 very active. Opportunity was offered to investigate the activity of 

 extracts from the glands of a patient who had died of Addison's disease. 

 The extracts proved to be inert. 



This epoch-making paper of Oliver and Schafer's is reported some- 

 what at length because it embodies a large proportion of all of the more 

 significant data that have been recorded as regards suprarenal pharma- 

 cology. A few months after the publication of this paper there appeared 

 the reports of the Polish physiologists Cybulski and Szymonowicz, who 

 had independently been studying the same problem in much the same 

 way. In general, Oliver and Schafer's observations were confirmed, but 

 the Polish investigators were led to one erroneous conclusion, namely, that 

 the action of suprarenal extracts is exerted primarily upon the central 

 nervous system. Cybulski contributed an additional observation of major 

 importance, that is, that the blood of the suprarenal vein could be shown 

 to contain an active substance presumably the same as that in the supra- 

 renal extracts. 



All of these new data seemed to fit in most satisfactorily with those 

 previously secured by Addison, Brown-Sequard and others, and to permit a 

 conclusive answer to the much debated problem as to the functional sig- 

 nificance of the suprarenal glands. The obvious deduction Oliver and 

 Schafer did not fail to draw. It had previously been shown that de- 

 ficiency of the suprarenals leads to circulatory failure. It was now seen 

 that the glands are capable of elaborating a substance that is astonish- 

 ingly potent in stimulating the heart and augmenting vasomotor tonus. 

 This substance or at least one having similar properties can be found 

 in the efferent blood from the glands. The conclusion seemed unavoid- 

 able that the function of the suprarenals is to secrete an active substance 

 which exerts a constant stimulating influence on the cardiovascular mech- 

 anism, and thus maintains blood-pressure. Thus the "tonus theory" 

 was formulated. It immediately received unquestioned acceptance and 

 stood almost unchallenged for two decades. Indeed, it still serves as a 

 cardinal doctrine in the minds of one class of endocrin theorists, despite 

 the fact that numerous data are now on record with which the tonus 

 theory can scarcely be reconciled. 



During the next few years after the publication of this epochal paper 

 on suprarenal pharmacology, the observations were extended in various 



