Problems of an RNA Genome Operating in a DNA-Dominated Biological Universe

The existence of viruses which use RNA rather than DNA to store genetic information poses an interesting challenge to those concerned with the nature and function of genetic material. Questions are raised concerning replication, transcription, and translation involving a gene which cannot be distinguished from its message. These, and related problems posed by RNA genomes, must be resolved before our understanding of gene action and replication can be either satisfying or complete. We began our study of RNA replication soon after the announcement some years ago by Loeb and Zinder (1) that they had found an RNA bacteriophage. This discovery ultimately made possible the use of the whole armamentarium of techniques that had accumulated as a result of the pioneering efforts of Luria, Delbrfick, Hershey, and others with the E. coli-T-phage system. We will trace here our own efforts at understanding the functioning of RNA genomes. In the process an attempt will be made to provide a background of the thinking that went into the experiments to be described. Because of the dominance of serendipity in biological and biochemical research, it is not often either informative or useful to record the reasons for a particular set of experiments; noting the outcome is usually sufficient. It is possible that the present instance may represent an exception.