The Role of Methods in the Discovery of the Cytochromes P450

The progress of science is frequently the result of the mtroductlon of new types of instruments, and new instruments bring with them new techmques that must be mastered if one is to optimize new methods when seeking answers to specific questlons. The hlstory of cytochrome P450 (P450) research is intimately woven with seminal discoveries resulting from the development and application of new methodologies and new instruments. It is the purpose of this article to reflect back on research in the premolecular biology era by describing the impact of a few specific methodologic advances that played a crucial role in the discovery of the P450s. In this article, I have chosen to intro duce personal reflections, in the form of anecdotes, of experiences I recall. Most of these occurred nearly 40 years ago when the group at the University of Pennsylvania set out on the journey that led to the discovery of the functions of P450s. For some readers, this article may provide some answers to the ques tions often posed to a grandfather who enjoys describing what life was like before television and computers.