The discovery of the ability of living organisms to oxidize compounds grew out of the conjugation experiments of Ure1 and subsequently Erdmann and Marchand2,3 . The observation that other acids besides benzoic could lead to the excretion of hippuric acid in the urine necessitated the postulation of the intermediate step of oxidation. Erdmann and Marchand administered 5 to 6 g of cinnamic acid to volunteers and isolated what appeared to be hippuric acid from the urine, however, the glycine conjugate of cinnamic acid could not be excluded. The postulated oxidation of cinnamic acid to benzoic acid was confirmed by Woehler and Frerichs4 in dogs where they isolated hippuric acid in the urine after administration of cinnamic acid. When these authors administered benzaldehyde to dogs and rabbits they also were able to isolate hippuric acid in the urine.
It was in the clinical labs of Friedrich Frerichs (pictured above right) where the next major discovery regarding chemical oxidation occurred. Bernhard Naunyn (pictured left) was predominantly interested in various aspects of disease pathology but also had a keen interest in the use of the experimental laboratory to investigate interesting questions that arose in the course of his work. In his studies on stomach fermentation he found that benzene had the ability to "counteract" fermentation. He began to wonder about the effect of benzene on the patients and in studying this found that phenol was eliminated after the administration of benzene. Schultzen, who also worked in Frerichs' clinic and who had greater chemical experience, joined with Naunyn to study what happened in the body to hydrocarbons associated with benzene, namely, toluene, xylene etc. Their paper on "The behavior of benzene-derived hydrocarbons in the animal organism"5 unveiled entirely new capabilities of the body to perform chemistry that , to that time, had been impossible for chemists to accomplish in the lab.
Another student in Frerichs' clinic was Marcell Nencki (pictured right) who had come to Berlin to study medicine but was enthused by the work of Naunyn and Schultzen and changed to chemistry. Nencki went on to perform many pioneering studies in the field of metabolism In his 1870 thesis devoted to studies on the oxidation of aromatic compounds in animals Nencki also defined the guiding principle of drug metabolism research performed so that "...one will on the one hand be able to establish laws allowing predictions on the fate of new compounds, and on the other hand gain increasing insight into the organism as a "chemical agent."6
Naunyn and his Medical Colleagues
L to R: B.Naunyn; H.Quincke; Trendelenburg; L.Riess; D.Schultzen;
Fritsch (the anatomist) Berlin; E.Hitzig; Doenatz; Generalarzt Rath; Schoenhorn
Ref: 1A.Ure, quoted by J.Liebig, Ann.Chem. Pharm.,44:345 (1842),2 O.L.Erdmann and R.F.Marchand, Ibid.,44:344 (1842),3 O.L.ELrdmann and R.F.Marchand, J.Prakt.Chem.,26:491 (1842),4 F.Wohler and F.T.Frerichs,Ann.Chem.Pharm. 63:335 (1848),5 O.Schultzen and B.Naunyn,duBois-Reymond's Arch.Anat.Physiol.349 (1867),6 M.Nencki, du Bois-Reymond's Arch.Anat.Physiol. 1870,399
Pictures: Naunyn- "Bernhard Naunyn, Memories, Thoughts, and Convictions". Ed. David L. Cowen , Science History Publications USA 1994 Naunyn and medical colleagues (including Schultzen)-ibid.p.95 Frerichs-courtesy of M.Bickel,Nencki-Conti and Bickel-Drug Metabolism Reviews 6:14 (1977)