In the Beginning

In the early 1800's, the composition of the human body was thought to be the result of a “vital force” or “internal flame.” Scientists were discouraged from thinking about the processes of everyday digestion and nutrition. Yet, these problems came to dominate the mind of a young scientist, Friedrich Wöhler.

Wöhler’s early investigations into the passage of waste into urine were often performed on himself and his dog. In 1828, Wöhler was able to synthesize urea “without requiring a kidney of an animal, either man or dog.” Wöhler had speculated on the conversion of benzoic acid to hippuric acid in the body, but his initial experiments in dogs led him to conclude that only benzoic acid was excreted in the urine. (Not surprising considering that hippuric acid was not fully characterized by Liebig until 1829!)

In the first human metabolism study, A. Ure observed the conversion of benzoic acid to hippuric acid and proposed the use of benzoic acid for the treatment of gout. In Wöhler’s laboratory, W. Keller confirmed Ure’s experiments:

“In the evening, shortly before going to bed, I ingested 2 grams of benzoic acid in a sugar syrup. During the night I started sweating, which could be an effect of this acid, since I otherwise very rarely sweat profusely. I experienced no other obvious effect, even over the course of the following days when I took the same dose, and neither did the sweating reoccur. The urine eliminated the next morning was found to be unusually acidic, even after being allowed to stand 12 hours after evaporation . . . After the residue was mixed with hydrochloric acid and allowed to stand, a large amount of long prismatic brown crystals was formed, which did look like benzoic acid. Another portion, which had been concentrated to a syrupy thickness, formed a magma of crystalline plates after being mixed with hydrochloric acid . . . Long, colorless prismatic crystals were then isolated. These crystals consisted of pure hippuric acid.

“As long as I continued to ingest benzoic acid, I could very easily continue to produce quantities of hippuric acid, without any apparent unhealthy effects, so it would be quite easy to produce in such a way great quantities of hippuric acid. One could keep a subject on hand for weeks, in order to continue this method of production.”

Not only had Keller and Wöhler undertaken the first biochemical study, they unveiled a ready source for new compounds. Metabolism investigators would continue to serve as their own subjects for the next century.