388 PHYSIOLOGY 



CHAP. 



adduced to show that uric acid is derived from ammonium com- 

 pounds. On the contrary, an important series of experimental 

 data show that uric acid in mammals and man is derived directly 

 from the group of the purines (traces of some of which exist in 

 the urine), which in their turn are formed from the nucleins ; 

 these nucleins in the cell nucleus of plants and animals correspond 

 with what histologists term chromatin. 



The work of Kossel and his school (1879-96), to which we 

 owe the greater number of determinations of the mother-substance 

 of the purines, has proved the existence in the organs, tissues, and 

 cells of a group of bodies termed nucleins, which are present in the 

 free state in the form of nucleic acids, or in combination with 

 protein in the form of nucleo- protein. Such organs are the 

 thymus, spleen, lyniph glands, spermatozoa (particularly of 

 salmon and sturgeon), erythrocytes (of geese), etc. They further 

 demonstrated that the purines, e.g. xanthine, hypoxanthine, 

 guanine, adenine, sarkine, etc., can be readily obtained from these 

 tissues or cells. Hence nuclein is probably the source of the 

 xanthine bodies. 



On the other hand, Fischer (1884) has clearly demonstrated 

 that there is a close relation in the constitution of purines and of 

 uric acid, that they contain a nucleus which he terms purine, and 

 that uric acid, xanthine, and hypoxanthine might be regarded as 

 oxidation products of this nucleus. 



The most important experimental data on the physiological 

 side which confirm this theory and tend to clear up the ques- 

 tion of the origin of uric acid in the body, are specially due 

 to Horbaczewski (1889-93). Minkowski (1887) had already 

 obtained increase of uric acid in fowls after the injection of 

 .xanthine bodies, and Mares (1888) recognised that uric acid is 

 formed by a process distinct from that which gives rise to urea, 

 because the relative quantity of urea changes at different hours 

 during abstinence and after an abundant meal. 



Starting from the well-known clinical fact that increase of 

 uric acid is constant in Leucaemia splenica, Horbaczewski sought 

 to discover if it were possible to obtain xanthine, hypoxanthine, 

 and uric acid from splenic pulp. The positive results obtained 

 show that the splenic pulp, which contains many leucocytes, also 

 contains the mother substances of the purines and uric acid. On 

 oxidising the splenic pulp with defibrinated blood, hydrogen 

 peroxide, or air, uric acid is obtained : when, on the contrary, 

 it is hydrolysed by boiling, xanthine and hypoxanthine result. 



These experiments of Horbaczewski were confirmed in Italy 

 by Giacosa, who obtained uric acid not only from the spleen but 

 also from the liver when left to oxidise with blood ; by Zagari and 

 Pace, who obtained it from the thymus by the same method ; and 

 by Ludowenj and Formanek in Horbaczewski's laboratory, who 



