Apart from this general distinction, before gout could with justice be relegated to the same category of disorders, it would be necessary to prove that uric acid was an _intermediary_ and not a terminal product of metabolism. All modern research, however, tends to indicate that uric acid is an _end-product_, and, moreover, that there are no _uricolytic_ ferments within the body whereby its destruction can be accomplished. The term “chemical malformation,” therefore, though strictly applicable to alkaptonuria, cystinuria, etc., is inapplicable to gout. In other words, though, for example, the _homogentisic acid_ met with in alkaptonuria is a “chemical malformation,” _uric acid_ cannot be regarded as such. We see, therefore, that though gout may, superficially regarded, appear to have kinship with alkaptonuria and its congeners, yet in reality there is a profound and essential difference between it and this fascinating group of disorders. CHAPTER VI NUCLEIN METABOLISM No hard and fast line can be drawn between the metabolism of protein and that of nuclein. For though, morphologically speaking, the _nuclei_ of cells are sharply differentiated from the circumambient _cytoplasm_, and exhibit equally distinct staining reactions, yet, _chemically_, the differences between them are _quantitative_ rather than qualitative. But while, as far as chemical changes are concerned, nuclein metabolism is comparable with that of protein, nevertheless the former in respect of its “energy” and its bearing upon growth and production, is infinitely more vital, incomparably more active; for it is in _nuclear_ changes that we may best discern evidence of the initiation of _oxidation_ processes and other varieties of enzymatic activity. Moreover, as Walker Hall points out, “the presence of masked iron phosphorus and certain forms of fat in the cell nucleus strengthens this view, and thus we are led to recognise the important part played by the nucleus in the life of the cell, and to appreciate the influence of nuclein heredity in cellular exchanges.” So much by way of prelude, but the story of the growth of our knowledge of _nuclein_ as opposed to protein is so fascinating as to be worthy of a slight digression. THE ISOLATION OF NUCLEIC ACID