One of the challenges in studying abiogenesis is that the system of reproduction and metabolism utilized by all extant life involves three distinct types of interdependent macromolecules (DNA, RNA, and proteins). This suggests that life could not have arisen in its current form, which has led researchers to hypothesize mechanisms whereby the current system might have arisen from a simpler precursor system. American molecular biologist Alexander Rich was the first to posit a coherent hypothesis on the origin of nucleotides as precursors of life. In an article he contributed to a volume issued in honor of Nobel-laureate physiologist Albert Szent-Györgyi, he explained that the primitive Earth's environment could have produced RNA molecules (polynucleotide monomers) that eventually acquired enzymatic and self-replicating functions.
Further concept of RNA as a primordial molecule can be found in papers by Francis Crick and Leslie Orgel, as well as in Carl Woeses 1967 book The Genetic Code'. Hans Kuhn in 1972 laid out a possible process by which the modern genetic system might have arisen from a nucleotide-based precursor, and this led Harold White in 1976 to observe that many of the cofactors essential for enzymatic function are either nucleotides or could have been derived from nucleotides. He proposed a scenario whereby the critical electrochemistry of enzymatic reactions would have necessitated retention of the specific nucleotide moieties of the original RNA-based enzymes carrying out the reactions, while the remaining structural elements of the enzymes were gradually replaced by protein, until all that remained of the original RNAs were these nucleotide cofactors, "fossils of nucleic acid enzymes". The phrase "RNA World" was first used by Nobel laureate Walter Gilbert in 1986, in a commentary on how recent observations of the catalytic properties of various forms of RNA fit with this hypothesis.