An enormous amount of research work has in recent years been accomplished in connection with purin metabolism, and from its results we are quite clear that uric acid is the end-product of nuclear decomposition.

So far as one can judge by the results of extensive experimentation on man and animals, the sequence of events is somehow as follows: - The nucleic acid formed from the disintegration of nucleo-protein is acted upon by the ferment nuclease, thus liberating the purin bases. Guanin and adenin are deaminised by the ferments guanase and adenase when present - and the xanthin oxidases complete the process by converting hypoxanthin and xanthin into uric acid. Finally a uricolytic ferment, varying in potency according to the tissue or animal in which it is formed, may attack the uric acid and destroy it. The liver appears to possess this uricolytic power in the highest degree, and although it may be present in the kidney, this organ is less liable to exercise this function than that of simple elimination. Uric acid in dogs is mostly excreted as urea and allantoin, although when the liver is cut out of the circulation by an Eck fistula, uric acid appears in the urine in considerable quantities, proving that it is normally oxidised in the dog's liver. Croftan declares, in opposition to Burian and Schur, that the human kidney apparently destroys more uric acid than the liver, and the muscles more than either - a striking commentary in favour of exercise, and a corroboration of the belief that the man who lives and works with his muscles in the open air can within reason eat any food he thinks fit. Even here, however, the excessive consumption of tea and meat soups and beer may occasion much of the rheumatism which is such a common feature of the working man's life; and Mendel has shown that alcohol taken at a meal delays the excretion of the purins, because it interferes with the destruction of nuclein. Purins are bodies of a highly complex chemical composition, and in excess form unusual combinations in the body which may act as irritants. Too little account is taken of the endogenous purins or those which are due to the daily wear and tear or metabolic activity of the cell constituents. They are the expression of that amount of protoplasmic activity necessary for the maintenance of cell function. Metabolism, as is pointed out by Dr. Hutchison, is not a hard-and-fast process proceeding along rigid lines to a definite conclusion, but a process as varied as temperaments, and marching in different individuals by different ways to diverse results.

It is clearly proven that exogenous purins - that is, those which exist in the food, both in a free and a bound condition - are excreted, the former very rapidly, and 50 per cent, of the latter in forty-eight hours. The other 50 per cent, is excreted as urea or bodies intermediate between uric acid and urea. Endogenous purins are said to be excreted in the same manner and the same time, but manifestly there can be no definite information derivable on such a point. May they not be the cause of most of the trouble associated with uric acid? It is an interesting fact that most uric acid appears in the urine when the body is freshest - namely, in the morning hours and after a holiday. If, as we are informed by Haig, all the retained uric acid stored up in the tissues from the digestion of exogenous purins is expelled in - at the outside - twenty-four months when the patient is on a purin-free diet, then it is obvious that the trouble in many of the cases just detailed, if it were due to uric acid at all - must have been caused by endogenous uric acid.

This would prove that uric acid was not the cause of deficient metabolism, but the result. In most of the cases there was an undoubted diminution of tissue combustion, becoming increasingly evident the longer the purin-free diet was persisted in; and it is a notable fact that without exception they became much more susceptible to the influence of external cold. Dr. Haig naively asserts that those who practise his dietetic scheme can clothe themselves much more warmly without suffering from lethargic depression and debility - that, in fact, they are always active and lightsome. The truth appears to be that they are compelled to clothe more warmly because they cannot bear exposure to cold. I am not forgetting that many of his supporters contend that by eschewing purins in their food they are practically immune from nasal and other catarrhs. But, in common with the cases I have just detailed, there is no clear evidence that it was the diminution of purins per se that was the cause of any improvement in their condition, and I am inclined to think that, in addition, the following factors contributed to any good result obtained: (1) diminished amount of food; (2) diminished amount of protein; (3) greater attention to mastication and other laws of health previously ignored, such as expunging common salt from the diet.

Doubtless personal idiosyncrasy has much to do with the matter, as in other things, and it is a fact that exogenous purins are badly metabolised by gouty patients. But this is not the whole truth, for it has been proved that white meats like chicken and fish contain more purins than red meats, and yet the gouty man appears to suffer no worse results from the former than from the latter: the reason, I believe, is that he can digest them much better than the larger-fibred red meats.

The pathology of gout is not nearly so simple as the purin-free advocate maintains, and it is quite certain that it originates in different ways in different subjects. It may have a renal origin or a metabolic origin, although in all cases there is a deficient purin metabolism, the purin bases being in excess in the gouty man's blood, even when he is living on a purin-free diet, so that while the endogenous uric-acid-content of the blood is raised, the total result is a diminished uric acid output. But perverted function of one or more organs of the body has much to do with the origin of gout, and it is conceivable that a blood charged with highly complex chemical substances like purins, or with toxic products of mal-assimi-lation, may, on physico-chemical grounds alone, render it difficult for the cells to get rid of their own waste products. The gouty man may inherit a perverted function of one or more of his organs, or the uricolytic enzyme may be inhibited or inactive, and thus his intolerance for purins may be explained. But there is no doubt that in cases not frankly gouty we can find the same intolerance as is instanced in most of these I have mentioned, and one can hardly escape the conclusion that in them cell-metabolism is at fault, and is rendered worse by the cells being bathed in blood already full of the very products which are endeavouring to escape from them - the outcome being a low endogenous uric acid output.