The “scientific catastrophe” in nucleic acids research that boosted molecular biology [RNA] (Journal of Biological Chemistry)

The distinctive profile of the double-helix DNA molecule is today, along with Rutherford`s depiction of the atom as a miniature planetary system, a worldwide-recognized symbol of twentieth-century science. The complex story of how DNA`s tertiary structure was determined is also well-known. Surprisingly, however, far less is commonly known about how the structural subunits of the nucleic acids--i.e. nucleotides, nucleosides, and the specific carbohydrates that distinguish DNA and RNA--were first identified and their connectivity ascertained. This comparative oblivion seems due, at least in part, to the conceptual association of those key findings with an erroneous model of nucleic acid structure, which postulated that these macromolecules would consist of repeating sets of four nucleotides. This model came to be known as the `tetranucleotide hypothesis` and prevailed as the dominant paradigm through almost 4 decades of arduous research in the field. When debunked--with researchers referring by then to this hypothesis as an `effort to force nature into a straitjacket of puerile approximations` (1), a `scientific catastrophe` (2), and an `absurd` instance of oversimplification (3)--the whole idea receded into the sidelines of the literature along with its insightful analyses of how the nucleic acids are built in the first place.Early historians have provided more nuanced records (4-6), but later accounts still ignore or greatly deplore the tetranucleotide hypothesis (7, 8) or mention it just as needed without due references (9, 10), and even when giving favorable views they come to the usual conclusion that it became a distraction or an obstacle to further advance...