When methods for in vitro hybridization of polynucleotide molecules were developed by Doty and Marmur and their colleagues (Marmur and Lane, 1960), it opened new vistas for genetic research. These new methods soon transformed and extended much of genetic research to genetic analysis of hybridization at the polynucleotide level. Such notions had been anticipated by Crick regarding the genetics and taxonomy of proteins (1958, 142): “Biologists should realize that before long we shall have a subject which might be called ‘protein taxonomy’ – the study of the amino acid sequences of the proteins of an organism and the comparison of them between species.” The beginnings of these analyses, developmental (pathological) on the one hand and taxonomic on the other, were already evident from the studies of changes of single amino acids in hemoglobin molecules (Ingram, 1957, 1963).

Hoyer, Bolton, and McCarthy isolated RNA complementary to DNA, based on the demonstration that specific cellular RNA could be hybridized with heat-denatured DNA from the same cells. The hybrids were isolated by cesium chloride density gradient centrifugation (Bolton and McCarthy, 1962). These researchers examined primarily bacterial species relationships, “where there exists only the faintest paleontological record and the simplest of all ontogenetic processes.”