Again, taking a typical instance of acute gout in the big toe, how difficult to conceive that the same owes its origin to uric acid circulating in the blood especially when we realise that the blood content of uric acid in gout exceeds but by a few milligrammes that in _normal_ blood. Moreover, if it does so, then why does it fail to ensue in leukæmia and in other states associated with uricæmia. Also, we like to think that the penchant of acute gout for the toe is that the circulation is inefficient at this peripheral site. But how often is the circulation all too vigorous in gout, and for that matter frequently feeble in leukæmia and in ill-nourished children. But, notwithstanding that in the two latter conditions, _uricæmia_ exists yet, despite favouring circulatory conditions, they develop no gout. Garrod contended that the violent pain, intense inflammation, and profound constitutional disturbance of acute gout were due to _mechanical_ irritation occasioned by the sudden deposition of biurate crystals in the delicate interior of the implicated joint. Also, that the absence of constitutional disturbance in the inter-paroxysmal periods was because the deposition of urates, being gradual, the tissues acquired tolerance, and yet, forsooth, this same substance is held responsible for the fulminant outbreak that ensues anon. But it is, as Ringrose Gore shrewdly observed, “against the usual laws of nature that, if an irritant foreign body remains in any organ the symptoms should quickly subside, while the irritant actually increases, for after each attack, and during the intervals between the attacks, the deposits of such biurate enlarge.” In conclusion, is it not infinitely more probable, as Gore states, that the inflammatory reaction _precedes_ the deposition of urates and that these latter, in short, are the _consequence_ and not the cause of the gouty arthritis? Reverting to tophi, their experimental production, it is claimed, has been achieved by His.[24] Administering alcohol to dogs and simultaneously injecting them locally with sodium mono-urate, he produced deposits which seemed identical with tophi produced spontaneously in gout. But, unfortunately, up to the present, it has been found impossible to induce their formation by flooding the circulation with urates. The utmost, indeed, that His and other workers in this sphere feel able to postulate is that uric acid is a “weak tissue poison.”[25] Scarcely the words in which to describe the poison responsible for gout! for, as we have before stated, the agent that is responsible for _tophi_ must also be capable of inducing the arthritic phenomena and other features of the disorder.