A Look to the Future

A s we review the history of xenobiotic metabolism, the rapidly accelerating pace of discovery becomes quite clear. From the beginning of the 19th century, reactions were enumerated at a slow, deliberate pace. As the 20th century began, the basics of transformation-oxidation, reduction, hydrolysis, and synthesis were understood but the coherence of applications was unclear. It took another 50 years for the field to coalesce in the writings of R.T. Williams. From the early 1950’s through the 60’s the actual enzymes involved in metabolism, as well as their intracellular locations, came under scrutiny. By the 1980’s, x-ray structures of key enzymes were unveiled and molecular biology began to explore the expression and synthesis of individual proteins.

As the new millennium approaches we find xenobiotic disposition playing a major role in understanding why individuals vary in their response to drugs and the chemical environment. It takes little imagination to see the day when a patient’s knowledge of his or her genetic make-up and degree of expression is as important as the knowledge of the disease in shaping appropriate therapy. An understanding of how minor genetic changes can alter an individual’s response to the environment will build our database for controlling responses to new agents.

The combination of genomics and proteomics with potent analytical techniques will allow us to probe human responses at the molecular level. The use of high-powered computer programs should allow us to assemble the molecular data into predictive models relating an organism’s response to its surroundings. The dawn of the next century holds great promise and challenge for the field of xenobiotic metabolism.