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Woehler: The Birth of Metabolism Research

The earliest history of drug metabolism is interwoven with the birth of Organic Chemistry. In the early 1800's, the belief prevailed that the composition of the human body and indeed, of all living things, was a result of a "vital force" or "internal flame" and that mere mortals were incapable of understanding these workings and would be particularly unable to synthesize constituent compounds of the human body. Faced with this daunting concept, scientists were discouraged from thinking about the processes that dominated everyday digestion and nutrition. It was this problem that came to dominate the mind of a young scientist, Friedrich Woehler.

Woehler was born in the early nineteenth century near Frankfort-on -the-Main the son of Auguste Woehler , a man educated in Science and Philosophy. Woehler was interested in minerals in his youth and developed a keen interest in chemistry. He proceeded to Marburg University and started to study medicine. As a harbinger of his lifelong interest in metabolism he won a prize for his investigations on the passage of waste materials into urine. Many of these early investigations were performed upon his dog and upon himself. It is a continuing theme of early metabolism studies that the major subjects studied were also the authors of the studies. After working in the labs of Gmelin in Heidelburg and Berzelius in Stockholm, Woehler was convinced that Chemistry , not Medicine , was his future. In 1828, Woehler was able to synthesize urea, one of the compounds he had examined in his studies on urinary waste products and sent a note to Berzelius "I must tell you that I can prepare urea without requiring a kidney of an animal, either man or dog".1

In modern day terminology this was a true "paradigm shift" and led to revised thinking on what chemists could accomplish with regards to "organic" compounds. Woehler became interested in potential chemical transformations occurring in the body and began experiments in dogs toward this end.2 He had speculated on the conversion of benzoic acid to hippuric acid but his initial experiments in dogs3led to the conclusion that only benzoic acid was excreted in the urine. Part of the problem with these studies was the fact that hippuric was not fully characterized until 1829 by Liebig.

The first human metabolism study was performed in 1841 by Alexander Ure, who observed the conversion of benzoic acid to hippuric acid and proposed the use of benzoic acid for the treatment of gout.4

W.Keller, in Woehler's laboratory provided the confirmation of Ure's experiments Thus, not only had Keller and Woehler delineated the first biochemical study they unveiled a ready source for new compounds. The theme of metabolism investigators being their own subjects would continue for the next century.

1 "Crucibles-The strories of great chemists" by Bernard Jaffe, The World Publishing Company, Cleveland and New York 1942:pp.175-198. 2 Quoted by J. Berzelius in Lehrbuch der Chemie, 4:376(1831) Dresden. 3F. Woehler, Tiedemann's Z. physiol. 1:142(1824). 4A. Ure, Pharm. J. Transact, 1:24(1841). 5Keller, W. Ann. der Chemie 43:108(1842)

Photographs of Friedrich Woehler, Woehler's Laboratory in Goettingen courtesy of Photo Deutsches Museum Munchen

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