In search of the best explanation about the nature of the gene: Avery on pneumococcal transformation
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 H1–H4 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.
References (87)
The quiet revolution
Current Biology
(2004)The dawning of molecular genetics
Trends in microbiology
(2000)Van Fraassen’s critique of inference to the best explanation
Studies in History and Philosophy of Science
(2000)The transformation in vitro of R pneumococci into S forms of different specific types by the use of filtered pneumococcus extracts
Journal of Expermiental Medicine
(1932)Further observations on the use of pneumococcus extracts in effecting transformation of type in vitro
Journal of Experimental Medicine
(1933)From pneumonia to DNA: The research career of Oswald T. Avery
Historical Studies in the Physical and Biological Sciences
(1993)- Avery, O. T. (1947). Report of Dr. Avery (assisted by Drs. Hotchkiss, McCarty and Taylor). In Report of the Director of...
- et al.
Immunological relationships of cell constituents of pneumococcus
Journal of Experimental Medicine
(1923) - Avery, O. T., & Horsfall, F. L. (1943). Report of Drs. Avery and Horsfall: Study on the chemical nature of the...
- Avery, O. T., MacLeod, C. M., & McCarty, M. (1959). Studies on the chemical nature of the substance inducing...
Is truth a goal of inquiry? Rorty and Davidson on truth
Skepticism and pragmatism
Directed mutation in colon bacilli, by an inducing principle of deoxyribonucleic nature: Its meaning for the general biochemistry of heredity
Cold Spring Harbor Symposium on Quantitative Biology
L’acide desoxyribonucleique du noyau cellulaire, depositaire des caractéres hereditaires; arguments d’ordre analytique
Comptes Rendus Hebdomadaires des Séances de l’Académie des Sciences
On conceptual change in biology: The case of the gene
Changing patterns: An atypical autobiography
Possible existence of a neutron
Nature
Chemical specificity of nucleic acids and mechanism of their enzymatic degradation
Experientia
Heraclitean fire: Sketches from a life before nature
How genetics got a chemical education
Annals of the New York Academy of Sciences
An essay on belief and acceptance
Alfred Ezra Mirsky
Biographical memoirs. National Academy of Sciences
Science and partial truth: A unitary approach to models and scientific reasoning
In vitro transformation of pneumococcal types, I. A technique for inducing transformation of pneumococcal types in vitro
Journal of Experimental Medicine
Putting inference to the best explanation in its place
Synthèse
Early responses to Avery et al.’s paper on DNA as hereditary material
Historical Studies in the Physical and Biological Sciences
Avery’s ‘neurotic reluctance’
Perspectives in Biology and Medicine
The professor, the institute and DNA
Emigré physicists and the biological revolution
Perspectives in American History
An essay on contraction
The significance of pneumococcal types
Journal of Hygiene
The soluble specific substance of pneumococcus
Journal of Experimental Medicine
Independent functions of viral protein and nucleic acid in growth of bacteriophage
Journal of General Physiology
The role of desoxyribonucleates in bacterial transformation
Oswald T. Avery
Genetics
Gene, transforming principle and DNA
The identification of nucleic acid as genetic determinants
Annals of the New York Academy of Sciences
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2016, Journal of the History of Biology