As we review the history of xenobiotic metabolism, the rapid acceleration of the 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 (pictured on the left). From the early 1950s through the 60s the actual enzymes involved in metabolism as well as their intracellular locations came under study. In the 80s the x-ray structure of key enzymes was unveiled and molecular biology began to explore the expression and synthesis of the individual proteins. The role of genetic polymorphisms in pharmacotherapy became apparent. In the new millenium, we find xenobiotic disposition playing a major role in understanding individual response to drugs and to the chemical environment. It takes little imagination to see the day when a patient's knowledge of their 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 response to the environment will build our database for controlling our response to new agents. The combination of genomics and proteomics and powerful 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 paradigms relating to the individual organism's response to its surroundings. The dawn of the new millennium holds great promise and challenge for the field of xenobiotic metabolism.
This page completes our series on the History of Xenobiotic Metabolism. Two historical review articles that provided much of the information included in this series were written by M.Bickel and his coworkers1. The publishers and authors have kindly given us permission to reproduce those articles on the web site. The articles are below and are available for downloading in PDF format.
History of Drug Metabolism: Discoveries of the Major Pathways in the 19th Century by A.Conti and M.H. Bickel was published in 1977 in Drug Metabolism R eviews.
History of Drug Metabolism:The First Half of the Twentieth Century by C. Bachmann and M.H.Bickel was published in 1985-86 in Drug Metabolism Reviews.
Ref: 1Conti, A. and Bickel, M.H.Drug Metabolism Reviews,6:1-50 (1977); Bachmann and Bickel, M.H.Drug Metabolism Reviews, 16:185-253(1985-86)