Xenobiotic Metabolism

R.T. Williams

R.T. Williams: The Founding of the Field

The modern field of xenobiotic metabolism grew from the convictions of a Welshman named R. Tecwyn Williams. His early experiences studying the ring structure of glucuronic acid—then a chemical curiosity—inspired Williams’ life-long interest in the biological importance of this carbohydrate acid and in detoxication mechanisms in general.

As a chemist studying conjugation, Williams became convinced that foreign compounds had a biochemistry, just as the natural components of the body did. It wasn’t until the 1940’s that scientists began to accept the idea that metabolism of a foreign compound was related to its toxicity and possible therapeutic activity—an idea propelled in part by Domagk’s finding that antibacterial properties of Prontosil were related to a metabolic conversion in the body. The importance and potential of xenobiotic metabolism were made evident with Williams’ publication of Detoxication Mechanisms in 1947.

In the 1950’s, metabolic studies on compounds of basic interest added considerably to the systematization of the metabolic routes of xenobiotics, culminating in publication of an expanded Detoxication Mechanisms in 1959. In this edition, Williams proposed systematized concepts of the principal biochemical reactions whereby drugs and other foreign compounds are metabolized in the body. Most importantly, he proposed that foreign compounds were metabolized in two phases: one including oxidations, reductions, and hydrolyses and the other comprised of conjugation reactions. This scheme recognized the significance of the biphasic metabolic process in relation to the biological properties of the compound.

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