Vast though the increase in our knowledge of the chemical structure of uric acid and its allies, uncertainty still dogs our steps. Doubtful of the pathway to solution of the pathological mystery of gout, we must perforce approach the problem in a more strictly catholic attitude. _Uric acid_ has apparently failed us as the _causa causans_. We can, therefore, no longer restrict our enquiry to _purin_, but must take cognisance of _protein_ metabolism as a whole, for some, perhaps not unnaturally despairing of the _uric acid_ hypothesis, are turning therefrom to other end-products of metabolism, _e.g._, _creatinine_. In keeping with this altered outlook, it will not be out of place if we, at this juncture, allude, though in brief, to the later revelations as to protein metabolism, before we pass on to more detailed consideration of those relating to the _purin_ bodies. PROTEIN METABOLISM No longer can we, like the older physiologists, envisage _protein_ as being absorbed as such from the alimentary canal and forthwith incorporated with the body tissue, for the researches of Fischer have revealed that the complex _protein_ molecule must previously undergo complete disruption into the _a-amino-acids_, its ultimate “building stones,” this through the hydrolytic action of the digestive enzymes of the alimentary tract. The fact that Fischer[6] was able to maintain nitrogen equilibrium in animals fed with completely digested protein mixtures is, of course, direct evidence in favour of his contention, viz., that proteins undergo disruption into amino-acids. THE FORMATION OF UREA The question as to whether urea, the end-product of general nitrogenous catabolism, was derived from the _amino-acids_, brought in the portal blood to the liver, was for long a vexed one. This because the earlier attempts to detect amino-acids in the _portal blood_, during the digestion of copious amounts of protein, proved futile. On the other hand, the same workers found that free _ammonia_ was present in greater amounts in the portal vein than in the systemic circulation. This, to their mind, seemed to indicate that the amino-acids, during their passage through the intestinal mucous membrane, underwent _deaminisation_. According to this view the _ammonia_, thus split off from the amino-acids, was the precursor of _urea_. But the claim that more free ammonia was present in the portal vein than in the systemic circulation was disproved by Folin and Denis. Invoking more delicate methods of hæmo-analysis, they found that the amount of ammonia and urea in the portal blood was not increased during the absorption of amino-acids from the lumen of the intestine. Moreover, they found that the ammonia present was of minimal amount, produced in the main by putrefactive bacteria. Lastly, they discovered that _amino-acids_ were actually present in the _portal blood_. FATE OF THE AMINO-ACIDS