Synthetic versus analytic approaches to protein and DNA structure determination

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.

Scientific Thinking About Legal Truth

“…The DNA molecules encode the biological information of each individual. This specificity follows from the laws of inheritance, proven by many observations and experiments (Bolinska, 2018 ).…”

Epistemic expression in the determination of biomolecular structure

“…1 For instance, if one had evidence that DNA contains two rather than three strands, one could eliminate all three-stranded structures from further consideration. If one then learned that these strands were connected by the bases, one could eliminate all structures that had the bases radiating outwards (Bolinska, 2018).…”

“…It reduces the likelihood of becoming misled by some piece of information, eliminating the correct structure from the possibility space (as Bragg, Kendrew, and Perutz did) and necessitating starting the process all over again to determine where one went wrong. Such a strategy minimizes how many iterations are required, on average, to get the right solution by reducing the likelihood of having to backtrack on any given occasion (Bolinska, 2018). Further, an efficient strategy directs one's attention toward parts of the possibility 1 'Information' here is understood broadly, as any bit of theory or empirical evidence that might be relevant to what the structure looks like.…”

“…X-ray diffraction photographs were amenable to several interpretations, which could be based on mistaken assumptions. On the other hand, precise values for bond lengths and angles had been determined and refined over years using a variety of experimental methods, and stereochemical principles held the status of highly confirmed theory (Bolinska, 2018). Thus, it was unlikely that the correct structure would be incompatible with these pieces of information; they were "constraints that the final answer had in any case to satisfy" (Crick, 1988, p. 60;emphasis added).…”

Negotiating history: Contingency, canonicity, and case studies

“…Asking such questions is relevant not only to the apportioning of credit, which might be regarded as a historical question, but also to answering philosophical questions. For example, one of us (Bolinska 2018) has considered the question of which research strategy for determining the structure of DNA-that of building the model up from component parts (Watson and Crick's) or that of deriving it from X-ray diffraction photographs (Franklin's)-was most promising. The contention is that, given certain features of available evidence in the context of mid-twentieth century biochemistry-how well-confirmed it was and how many structural candidates it enabled one to rule out-Watson and Crick's bottom-up strategy was, all else being equal, most likely to lead to the correct structure in the shortest period of time.…”