The presence of this salt protamine nucleate led to the conclusion that nuclein was merely a salt of protein and nucleic acid. THE DISCOVERY OF PURINS Miescher, who had already isolated nuclein and nucleic acid, came nigh to one other equally important discovery. Heating a specimen of protamine with nitric acid, he noted that a yellow spot formed which turned to bright red when moistened with alkali. Alive to the import of the reaction, Miescher requested Piccard to examine salmon sperm for _purin_ bases. Extracting the same with hydrochloric acid, Piccard found _guanine_, and what he thought was _hypoxanthine_, but which was in truth _adenine_. Another distinguished worker in this sphere, Kossel, noted that, subjected to the action of hydrolytic agents, nucleins always yield _purin derivatives_; also that the same were derived, not from the _protein_ of the nuclein, but from the _nucleic acid_. Thus it was to Kossel that we are indebted for the discovery of the purin bases, hypoxanthine, xanthine, guanine, and lastly adenine. It was, indeed, through his brilliant achievements that _nucleic acid_ became recognisable as a definite entity, distinguishable from proteins and other body elements, this latter differentiation by token of the _purin bases_ which are contained in nucleic acid. Moreover, it led to the dissipation of the old belief that _uric acid_ was an intermediate product of _protein_ metabolism, for the revelation of purin bases as decomposition products of _nucleic acid_ carried with it the inference that uric acid also had chemical affinities therewith. The chemical structure of the purin bases and that of uric acid betrayed a common likeness, and, therefore, a presumptive physiological connection; in other words, that a chemical _nexus_ obtained between the cell nucleus or _nucleic acid_ and uric acid. The physiological derivation of uric acid from nucleic acid did not long lack experimental proof. In 1886 Minkowski found that, given extirpation of their livers, the urine of birds contained ammonium lactate, evidently a substitute for the uric acid normally present, notwithstanding the uric acid never entirely disappeared from the urine. This indicated the derivation of uric acid from two sources:— (1) Conversion in the liver of ammonium lactate into uric acid. (2) Some other, though unknown, process of formation. To clear up the obscurity regarding the latter, V. Mach, after extirpating the livers of geese, injected them subcutaneously with hypoxanthine, finding that the same was converted into uric acid, which was excreted in the urine. In this way the capacity of the organism to elaborate uric acid from a purin precursor was demonstrated. URIC ACID A DERIVATIVE OF NUCLEIC ACID