174 INTERNAL SECRETION 



subcutaneous and intravenous injections of the watery extract 

 of suprarenal. He did not believe that this action was specific, 

 for he found that similar results were produced by means of 

 other organic extracts. But very soon after, Ziino and di Mattei 

 denied the toxicity of suprarenal extract and they referred the 

 results which followed its exhibition to infective processes, more 

 particularly the influence of products of the decomposition of the 

 albuminoids introduced into the system with it. On the other 

 hand, Pellacani and Foa (1883) proved that the toxic substance 

 in the suprarenal cannot be identical with the fibrin ferment, 

 which is present even in the alcoholic extracts of these organs 

 and is specific to the suprarenal. Guarnieri and Marino Zucco 

 (1888) confirmed the extreme toxicity of the watery extracts and 

 they considered that the active agents were neurin and the organic 

 phosphorus compounds. The brothers Marino Zucco even went 

 so far as to believe that the symptom-complex of Addison's 

 disease could be produced by means of neurin injection. These 

 authors, together with Dutto, proved that neurin was present 

 in the urine of persons with Addison's disease, and, 

 towards the end of the 'eighties, a hypothesis arose that 

 the physiological function of the suprarenals consisted in 

 the neutralization of neurin, which was a product of the decom- 

 position of the nervous tissue. This doctrine seemed to find a 

 support in Albanese's experiments with frogs. But both Boinet 

 and Langlois were unable to confirm the experiments upon which 

 the theory was founded; while Supino further showed that the 

 toxic conditions which follow the injection of neurin are entirely 

 different from the clinical complex produced by suprarenal extir- 

 pation. Alezais and Arnaud, and later Tizzoni, denied the exist- 

 ence of a toxic agent in the suprarenal, confirming the view of 

 an earlier observer, namely, Alexander. They attributed the 

 effects of suprarenal extract to post-mortem changes in the tissues. 



The discovery by Oliver and Schafer (1894) f the specific 

 physiological action of suprarenal extract, drove all previous con- 

 clusions as to the general toxic activity of these organs into the 

 background. The experiments which followed were, naturally 

 enough, chiefly concerned with the more minute analysis of in- 

 dividual pharmacodynamic effects. But since the discovery that 

 these effects are principally due to an active substance present 

 in the medulla and, more particularly since the isolation of this 

 active principle in the form known as adrenalin, inquiry into the 

 general effects of suprarenal extract has somewhat languished. 

 The lack of any method of exact dosage is a serious drawback to 

 experiment. 



A consideration of the material furnished by the subject shows 

 that there is no sufficient justification for identifying the general 

 effects of suprarenal extract with those of adrenalin. For, in 

 .addition to adrenalin, suprarenal extract contains other substances 



