Many and divers are the theories that have been propounded to account for the genesis of tophi. For some their incidence would appear to predicate something abnormal in the conditions of uric acid solution and circulation. Others have pinned their faith to some affinity on the part of the bodily tissues for uric acid—an enhanced retention capacity on their part for this substance. Some again, impressed by the objective changes that mark the clinical evolution of tophi, have been led to regard them as _concomitants_ or _sequels_ of _gouty inflammation_. But, be the true explanation what it may, we may well preface our discussion of the various theories by the obvious comment, viz., that the origin of tophi must doubtless depend in the ultimate upon _constitutional_ or _systemic_, as well as _local_, factors. SOLUBILITIES OF URIC ACID In the older conceptions of the pathology of gout the hypothesis that found most vogue was that the separation of uric acid from the blood into the tissues was due to _diminished alkalinity_ of the blood and tissue juices; but, as before pointed out, it has been established that the alkalinity of the blood is _not_ reduced, and the theory has consequently been abandoned. But, with the advent of Gudzent’s findings, viz., that uric acid existed in two forms—one soluble and unstable, and the other insoluble and stable, and that the former is constantly changing into the latter—another conception of the origin of tophi arose. It was supposed that, by reason of the disparity in solubility of these _tautomeric_ types of _uric acid_, the blood in gouty subjects must at times be in a state of _super-saturation_ with uric acid; and, moreover, that equilibrium could only be restored through abstraction of the urates by crystallisation. Unfortunately for this theory, it has been shown that the blood of gouty subjects is not _super-saturated_ therewith; indeed, over and above the highest increments hitherto met with in gouty blood, a considerable margin of solubility for uric acid is still available. In truth, the problem is by no means so simple; for the conditions governing the solvency of uric acid in the blood are bewilderingly complex, subject as they are to the manifold variations in solubility exhibited by crystalloids in the presence of the many divers colloids. But, to resume, Minkowski, it will be recalled, noted that from a mixed solution of _uric_ and _nucleinic acids_ the former cannot be precipitated by either acetic acid or alkaline ammonio-silver-magnesia mixture. Accordingly he advanced the view that uric acid “primarily exists in the blood and the tissue juices in combination with nucleinic acid, and that, not only the conversion of the purin bases into uric acid, but also the solubility and transportation, as well as the further changes of the uric acid in the living body, is regulated by this linking with a nucleinic acid rest.”