But Walker Hall, discussing the good results obtained by Schmoll and Fenner from the administration of thyminic acid, states that his experiments do not indicate that the improvement is at all associated with any change in the _uric acid_ excretion. To sum up, it is obvious, from the mere variety of the hypotheses advanced, that we are still much in the dark as to the actual form in which uric acid circulates in the blood. While on the one hand the quadriurate theory appears no longer tenable,[9] on the other the nature of the suggested uric acid organic complex is still unknown. Nay, more, Walker Hall, writing in 1913-14, states “there are many who consider that the _sodium mono-urate_ is the only possible compound;” while Wells, in his “Chemical Pathology” (1918), claims that the best evidence points to uric acid existing in the blood “in a _free_ state and not combined, as was at one time urged by several students of gout.” COMPLEXITY OF THE PROBLEM How complex, indeed, the task of the bio-chemist may be gathered from some reflections of Walker Hall. He reminds us that the oxidation and deaminisation of the nuclein derivatives, nucleins, nucleotides and nucleosides, is never complete. For _purin bases_ and _pyrimidin_ bases run side by side in the blood-stream together with uric acid. Also, that the unstable but soluble biurate is constantly changing into a less soluble type, viz., from one isomer to another. Moreover, since the red blood corpuscles abound in potassium, urates of _potassium_ must also occur, and to these may be added, too, ammonium and calcium compounds in small quantities. But more striking is his inference that the occurrence of _isomeric forms_ of _uric acid_ suggests that _isomers_ of _purins_ and _pyrimidins_ also may occur. For the purin ring or pyrimidin nucleus, with their numerous receptors for the linking up of other substances, offer wide potentialities in the direction of isomerism.[10] Some of these, he hazards, may be born of one type of cell nucleus, some of another, while it is not inherently improbable that, “In response to abnormal stimuli or excessive demand, other isomers may be formed.” Now, though uric acid and the urates can be extracted from the blood, it does not, as he remarks, necessarily follow that they circulate as such _in vivo_; for, despite modern achievements, “the best of the existing methods for the determination of uric acid in the blood are nearly barbarous in their crudity and intensity.” The various procedures available for such estimates fall short of distinction between the several tautomeric forms of uric acid, much less do they furnish any information as to the associations or combinations of purins or pyrimidins with other substances. For himself, recognising the generally more complex nature of biological processes, he considers that “the circulation of the purins as sodium mono-urate and its simple extraction by kidney cells, seems almost too simple to be true.”