Abstract
The structures of protein and DNA were discovered primarily by means of synthesizing component-level information about bond types, lengths, and angles, rather than analyzing X-ray diffraction photographs of these molecules. In this paper, I consider the synthetic and analytic approaches to exemplify alternative heuristics for approaching mid-twentieth-century macromolecular structure determination. I argue that the former was, all else being equal, likeliest to generate the correct structure in the shortest period of time. I begin by characterizing problem solving in these cases as proceeding via the elimination of candidate structures through the successive application of component-level information and interpretations of X-ray diffraction photographs, each of which serves as a kind of constraint on structure. Then, I argue that although each kind of constraint enables the elimination of a considerable proportion of candidate structures, component-level constraints are significantly more likely to do so correctly. Thus, considering them before X-ray diffraction photographs is a better heuristic than one that reverses this order. Because the synthetic approach that resulted in the determination of the protein and DNA structures exemplifies such a heuristic, its use can help account for these discoveries.
Highlights
Within a few years in the mid-twentieth century, Linus Pauling1 determined the structure of protein and Watson and Crick discovered the structure of DNA
Inspired by Pauling’s success, Watson and Crick adopted a similar strategy, constructing threedimensional models from structural features of DNA. Their rivals, Sir Lawrence Bragg, John Kendrew, and Max Perutz in the case of protein and Rosalind Franklin in the case of DNA,4 instead adopted a top-down, decompositional approach: rather than attempting to synthesize information about what was known about the individual components of the molecules, these groups instead analyzed X-ray diffraction photographs of the molecules in question
Which heuristic was best for approaching the problem of determining the structure of a complex macromolecule such as protein or DNA in the mid-twentieth century? In particular, which was likeliest to be the most “cost-effective” in the sense of the second property above? In order to answer these questions, let us begin by characterizing different pieces of empirical evidence and theoretical considerations as constraints on molecular structure: in order to be considered acceptable, a structure must accord with or account for each such piece of evidence and theory
Summary
Within a few years in the mid-twentieth century, Linus Pauling determined the structure of protein and Watson and Crick discovered the structure of DNA In both cases, the eventual discoverers of these structures competed with rival groups in other labs. Inspired by Pauling’s success, Watson and Crick adopted a similar strategy, constructing threedimensional models from structural features of DNA Their rivals, Sir Lawrence Bragg, John Kendrew, and Max Perutz in the case of protein and Rosalind Franklin in the case of DNA, instead adopted a top-down, decompositional approach: rather than attempting to synthesize information about what was known about the individual components of the molecules, these groups instead analyzed X-ray diffraction photographs of the molecules in question. Which heuristic was best for approaching the problem of determining the structure of a complex macromolecule such as protein or DNA in the mid-twentieth century? Bayesians assume that an adequate model of updating beliefs ought to be commutative, i.e. updating on evidence A before evidence B should produce the same degree of confirmation as updating on B before A, and a common criticism of Jeffrey Conditionalization is that it fails to meet this requirement
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