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Crick's Adaptor Hypothesis and the Discovery of Transfer RNA: Experiment Surpassing Theoretical Prediction

Historically, hypotheses failed in most cases to correctly forecast the workings of complex biological systems. Francis Crick’s adaptor hypothesis, however, stands out as an exceptional case of a confirmed abstract prediction. This hypothesis presciently anticipated the existence of RNA adaptors that function as bridges between amino acids and the chemically different nucleic acid template for proteins. Crick conjectured that the adaptors are enzymatically charged with cognate amino acids, they bind to complementary protein-coding nucleic acid, and their liberated amino acids are incorporated into growing protein chains. Independently from and concomitantly with Crick’s hypothesis, Mahlon Hoagland and Paul Zamecnik conducted experiments with no guiding theory that culminated in discoveries of the actual adaptors, transfer RNA (tRNA) molecules, and their amino acids charging enzymes. This paper traces the parallel histories of Crick’s adaptor hypothesis and of the experimental discovery of tRNA and compares their relative impacts on the scientific community. Remarkably, despite the brilliance of Crick’s confirmed prognostication, it had marginal impact on practicing scientists. Conversely, Hoagland and Zamecnik’s experimental discoveries and their evidence-based model of protein synthesis had immediate and enduring impact. I discuss possible explanations for the different impacts of the theoretical prediction and experimental identifications of the same entities.