The successive steps in its production from inorganic materials by this method are: K + C + N → KCN → KCNO → Pb(CNO)2 → CO(NH2)2. Associated with urea as products of metabolism are _uric acid_, _xanthine_, and _sarcine_. Urea was first artificially transformed into uric acid by Horbaczewski, and its synthesis was effected by Behrend and Roosen. Closely related in chemical composition to these substances are _theobromine_ and _caffeine_, the characteristic principles respectively of cocoa (the fruit of _theobroma cacao_); and of coffee, tea, maté (the leaves of _ilex paraguayensis_); “guarana,” obtained from the seeds of the South American plant _paullinia sorbilis_, and the kola-nut of Central Africa. Strecker, in 1860, showed how theobromine may be converted into caffeine; and Emil Fischer, by similar means, transformed xanthine into theobromine. Since that time xanthine itself has been prepared artificially. Caffeine can now be built up from its elements by a series of transformations effected by a succession of chemists, as follows: 1. Carbon and oxygen give carbonic oxide.—_Priestley_, _Cruickshank_. 2. Carbonic oxide and chlorine give carbonyl chloride.—_J. Davy._ 3. Carbonyl chloride and ammonia give urea.—_Natanson._ 4. Urea gives uric acid.—_Horbaczewski_; _Behrend and Roosen_. 5. Uric acid gives xanthine.—_E. Fischer._ 6. Xanthine gives theobromine.—_Strecker._ 7. Theobromine gives caffeine.—_E. Fischer._ Synthetic theobromine is now made on the large scale, and introduced as a soda compound, in combination with sodium acetate, into medicine as a diuretic under the name of agurin. Synthetic caffeine is also prepared on a manufacturing scale from uric acid through the medium of the methylxanthines. The close relationship of xanthine to uric acid is of great physiological significance, since there is little doubt that the xanthine bases are the most important sources of uric acid within the organism. In this connection reference may be made to the large number of synthetic organic products which have been introduced into medicine during the past few years. The investigation of the constitution of the alkaloids has served to show in many cases to what particular molecular grouping the physiological action of the drug is mainly due, and this has led to the production of substances containing these groups, but not necessarily existing as natural products. Among these may be mentioned _antipyrin_, a derivative of the pyrazol group, discovered by Knorr in 1883, and of which upwards of 17,000 kilos, of the approximate value of £35,000, were produced in 1899. This substance is a _phenyl-dimethyl-pyrazolone_. _Acetanilide_ C6H5NH.COCH3, an aniline derivative, was discovered by Gerhardt in 1853. _Phenacetin_ is a derivative of _para_-aminophenol: OC2H5 / C6H4 \ NH.COCH3.