Predictive hypotheses are ineffectual in resolving complex biochemical systems

Fry, Michael

doi:10.1007/s40656-018-0192-3

“…Francis Crick's so-called 'adaptor hypothesis' presents a rare case of a confirmed abstract conjecture in biology. This astute hypothesis stands in stark contrast to previously reviewed theories whose conceptions of the constitution and mode of operation of diverse complex bio-molecular systems were incorrect (Fry 2016(Fry , 365-370, 2018(Fry , 2020). Crick's hypothesis warrants the special analysis of this paper because it is singled out by its exceptional success from the habitual failures of other theoretical predictions about the working of other systems.…”

Section: The Exceptional Case Of Crick's Prescient Adaptor Hypothesiscontrasting

confidence: 64%

“…Thus, for instance, because messenger RNA was not envisaged and searched for in the 1950s, the dominant theory of the time erroneously maintained that  OPEN ACCESS -PTPBIO.ORG it was ribosomal RNA which mediated transmission of genetic information from DNA to the protein synthesis machinery (Fry 2016, 365-370). Similarly, theories made wrong predictions on the mode of non-lysosomal degradation of proteins (Fry 2018), the mechanism of translation of nucleic acid into protein, or the manner of antibody formation (Fry 2020). Ultimately, these and other complex bio-molecular systems were elucidated by experiment and organization of the gathered data into accommodation theories.…”

Section: Complexity Of Biological Systems Thwarted Predictions Of The...mentioning

confidence: 99%

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

Fry

¹

2021

Philosophy, Theory, and Practice in Biology

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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.

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Question-driven stepwise experimental discoveries in biochemistry: two case studies

Fry

¹

2022

HPLS

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

Fry

¹

2022

Philosophy, Theory, and Practice in Biology

0

View full text Add to dashboard Cite

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.

show abstract

Predictive hypotheses are ineffectual in resolving complex biochemical systems

Cited by 3 publications

References 145 publications

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

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

Question-driven stepwise experimental discoveries in biochemistry: two case studies

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

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