In search of the best explanation about the nature of the gene: Avery on pneumococcal transformation

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Abstract

In this paper I present a model of rational belief change, and I show how to use it to obtain a better insight into the debate about the nature of pneumococcal transformation, genes and DNA that took place in the forties, as a result of Oswald T. Avery’s work. The model offers a particular elaboration of the concept of inference to the best explanation, along decision theoretic lines. Within this framework, I distinguish different senses in which Avery’s team can be said to have proceeded with caution, thus throwing some light upon a persistent source of disagreement among researchers in the history of genetics. In addition, I explain why we are entitled to say that rival parties such as physicist Maclyn McCarty and biochemist Alfred Mirsky were epistemically rational, in spite of the fact that they reached different conclusions on the basis of the same evidence.

Introduction

In this paper I present a model of rational belief change, and I show how to use it to obtain a better insight into the debate about the nature of pneumococcal transformation, genes and DNA that took place in the forties, as a result of Oswald T. Avery’s work. In very few words, the model offers a particular elaboration of the concept of inference to the best explanation, along decision theoretic lines. I have worked through the details of this approach elsewhere, so here I shall only sketch the main features of the proposal, and focus on its ability to carry out a successful analysis of Avery’s case. In particular, I hope to explain why we are entitled to say that rival parties such as Oswald T. Avery and biochemist Alfred Mirsky were both, for the most part, epistemically rational, in spite of the fact that they reached different conclusions on the basis of the same evidence. In addition, I hope to show that the proposed framework provides the necessary tools to distinguish different senses in which Avery’s team can be said to have proceeded with caution, which has been a persistent source of disagreement among researchers in the history of genetics.

The paper is organized as follows. In Section 2 I state the main controversies and problems that appear in the literature on Avery’s research; I describe the basic structure of the model in Section 3, and I apply it to Avery’s case in Sections 4 Avery et al. on bacterial transformation, 5 Avery’s question set, 6 Competing hypotheses, 7 Accepting that DNA is the ‘transforming substance’, 8 In search of a suitable explanation (I): McCarty and Avery, 9 In search of a suitable explanation (II): Mirsky’s case, with the aim of solving some of the problems mentioned in Section 2. In Section 4 I present a brief historical introduction to bacterial transformation; Sections 5 Avery’s question set, 6 Competing hypotheses address Avery’s attitude, while Sections 7 Accepting that DNA is the ‘transforming substance’, 8 In search of a suitable explanation (I): McCarty and Avery, 9 In search of a suitable explanation (II): Mirsky’s case provide rational reconstructions of competing inferences to the best explanation that might have been carried out by different members of the scientific community in the forties and early fifties. Finally, in Section 10 I offer some conclusions.

Section snippets

Avery’s case: overview and main problems

Avery and his team are remembered for having stated that the substance capable of transforming pneumococcal types in controlled experiments was DNA, which in turn paved the way for the conjecture that genes were made of DNA.

A model of inference to the best explanation

Let me suggest the following model of rational inquiry, within a decision theoretic framework. I shall describe a research process as a series of steps aimed at the acceptance of the best explanation available for the set of perplexities of a given agent at a given time. I shall call it a process of inference to the best explanation, or, for short, an IBE process.

Very roughly, an IBE process goes as follows. At a given time t, an agent X is assumed to have a set of full beliefs KX,t. Then, for

Avery et al. on bacterial transformation

Let me go back to Avery’s case. What did people have in mind, in the thirties and forties, when they talked about ‘bacterial transformation’, or, more specifically, ‘pneumococcal transformation’? Let me begin by recalling that pneumococci had been found to come in different specific types; in addition, virulent organisms of any type were known to be surrounded by a capsule—the reason for the virulence being precisely that white cells of infected hosts were not able to digest the capsule.

Avery’s question set

Let QA be Avery’s question set in the thirties, which prompted the research that led to the 1944 paper and its sequels. We can say that the content of Griffith’s (1928) report acted as the surprising fact that called for an explanation, in Peircean terms.9 But what was it exactly that Avery sought to explain? We read, for instance:

[Our] major interest has centered in attempts to isolate the active principle from crude bacterial extracts and to

Competing hypotheses

How shall we reconstruct the set of basic explanations EA built as responses to question (i)? As time went by, different hypotheses were suggested, prompted by the need to purify the transforming substance by discarding from the killed type III cells what the transforming principle was probably not. As a result of the process of proposing specific conjectures and putting them to a test, Avery and his co-workers ended up with a definite set of options, with specific probabilities attached.

Accepting that DNA is the ‘transforming substance’

In this section I want to discuss the timing of acceptance of H6 by various members of the scientific community; I shall provide suitable explanations for their epistemic behavior in Sections 8 In search of a suitable explanation (I): McCarty and Avery, 9 In search of a suitable explanation (II): Mirsky’s case.

We have already seen that Avery might have accepted H6 by 1946 (although, as a matter of fact, there is no unequivocal first-person account stating so). The situation is less

In search of a suitable explanation (I): McCarty and Avery

How shall we explain the epistemic behavior of members of Avery’s team by 1943? Consider first the probabilities that might have been at stake. It is plausible to say that Avery, MacLeod and McCarty’s personal probability functions did not differ too much from one another, insofar as the cumulative effect of the tests reported in the 1944 paper tended to wash priors away. (This would occur even more so as new experiments were conducted in the late forties and early fifties, but the phenomenon

In search of a suitable explanation (II): Mirsky’s case

As we have seen, it is safe to assume that Mirsky was, at the very least, still skeptic about H6 by 1952. In addition, we can also assume that Mirsky had already rejected H1H4 by the late forties; recall that, as early as in 1946 he stated explicitly that the two serious options were H5 and H6.19 So let Mirsky’s set of basic explanations by 1952 be EM = {H5, H6}.

Consider

Conclusions

I hope to have shown that the model sketched in Section 3 can be successfully used to clarify a number of misunderstandings about Avery’s attitude towards his own research, as well as about the early reaction of the scientific community to the 1944 article. By being sensitive to the structure of questions and explanatory answers presupposed in Avery’s case, the model helped us identify in what sense (if any) we can say that Avery was overly cautious, and why. In addition, by being sensitive to

Acknowledgements

I would like to thank John Collins, Philip Kitcher, Isaac Levi, Achille Varzi, and an anonymous referee for Studies in History and Philosophy of Biological and Biomedical Sciences for very helpful comments and suggestions.

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