Introduction: RNA Polymerase—A Personal History

Abstract

When asked to write an account of the events that led to the discovery of RNA polymerase, I felt that having been intimately involved with the early history of this enzyme I was up to the task. Yet I was aware that personal accounts of a particular period in scientific history are inevitably biased, and that retrospective vision tends to portray a clear and orderly process in scientific thought and method that usually did not occur. Even though there was little likelihood that I could avoid these pitfalls, I decided to accept this assignment, believing that the early days of RNA polymerase might be of some general interest.

The Phosphodiester Linkage

I believe it is fair to say that the basic chemical structure of nucleic acid molecules was reasonably well understood by the middle 1950’s, at least to the extent that it stimulated questions as to how the repeating mononucleotide units were assembled in vivo. Once it had been established that the chemical bridge between the nucleosides was a diester of monophosphate, it seemed that the key for elucidating the assembly mechanism of nucleic acid chains resided in understanding how this type of phosphate linkage was formed.

As a student of biochemistry in the early 1950’s in Dr. Harry J. Deuel’s department at the University of Southern California, the subject of nucleic acid metabolism held only peripheral interest, largely because so little was known about it. Greater emphasis was placed on enzyme kinetics, the Embden-Myerhoff pathway for sugar metabolism, the...