Starting with the achievements of microscopists in the 1880s, attention was directed at the cell's nucleus and its chromosomes as the carriers of the genetic material, to the exclusion of the role of the cytoplasm and all its components (the cell membrane was considered inherently irrelevant). Nuclei were composed of nucleo-proteins. Based on the repetitive tetranucleotide structure hypothesis, first proposed by Hermann Steudel in 1906 and developed by Phoebus Levene in 1931 (Deichmann, 2004), the prevailing conception was that nucleic acids comprised stoichiometric aggregates of nucleotide tetrads. Proteins, being the material of enzymes, were celebrated at the first half of the twentieth century as the essence of life. They seemed to be able to provide the diversity that would be expected of the material of heredity thanks to the large number of known amino acids involved in their composition. Toward the end of the 1940s Fred Singer directly demonstrated the diversity of polypeptide chains, and Wendell Stanley's initial erroneous claim in 1935 that crystallized tobacco mosaic virus was a pure self-replicating protein (a study for which Stanley was awarded the 1946 Nobel Prize) further upheld the centrality of proteins in the deliberations on the nature of the hereditary material (see Deichmann, 2004; Lederberg, 1994). These studies were foreign to genetic analysis and its methodology (see Chapter 1).

Two kinds of nucleic acids were conceived, named after their main source at the time, alkali-stable “thymus” nucleic acid, and alkali-labile “yeast” nucleic acid; corresponding to today's DNA and RNA, respectively.