Pharmaceutical applications of biotechnology: promise and reality.

Biotechnology has continued to advance the state of the art in pharmaceutical research and discovery, especially in the generation and screening of molecular diversity [1]. Patents have begun to issue on both chemical [2] and biological [3] strategies for creating and evaluating libraries of compounds. Whether structured or random in design, these combinatorial collections, composed of natural and/or unnatural building blocks, are transforming the face of 'lead' discovery and optimization. Surely, the original 'mimotope' strategies of roughly a decade ago will soon yield to true paradigms of molecular evolution. Of course, discovery is only one stage of pharmaceutical R & D, and few groups have adequately addressed important early development parameters such as absorption (for oral delivery), distribution, metabolism, and elimination. Nevertheless, with more compounds having been made and tested in the 1990s than in the combined history of the pharmaceutical industry before 1990, we are witnessing a literal flood of new compounds and biological data not unlike that presenting itself to the various genome projects. In fact, common bioinformatics solutions may pertain to modern combinatorial drug screening and genome data capture, analysis, and database problems.