The history of biochemistry and molecular biology is replete with examples of erroneous theories that persisted for considerable lengths of time before they were rejected. This paper examines patterns of dissolution of three such erroneous hypotheses: The idea that nucleic acids are tetrads of the four nucleobases (‘the tetranucleotide hypothesis’); the notion that proteins are collinear with their encoding genes in all branches of life; and the hypothesis that proteins are synthesized by reverse action of proteolytic enzymes. Analysis of these (...) cases indicates that amassed contradictory empirical findings did not prompt critical experimental testing of the prevailing theories nor did they elicit alternative hypotheses. Rather, the incorrect models collapsed when experiments that were not purposely designed to test their validity exposed new facts. (shrink)

Discovery proceeds in stages of construction, evaluation, and revision. Each of these stages is constrained by what is known or conjectured about what is being discovered. A new characterization of mechanism aids in specifying what is to be discovered when a mechanism is sought. Guidance in discovering mechanisms may be provided by the reasoning strategies of schema instantiation, modular subassembly, and forward/backward chaining. Examples are found in mechanisms in molecular biology, biochemistry, immunology, and evolutionary biology.

An assessment is offered of the recent debate on information in the philosophy of biology, and an analysis is provided of the notion of information as applied in scientific practice in molecular genetics. In particular, this paper deals with the dependence of basic generalizations of molecular biology, above all the ‘central dogma’, on the so-called ‘informational talk’ (Maynard Smith [2000a]). It is argued that talk of information in the ‘central dogma’ can be reduced to causal claims. In that respect, the (...) primary aim of the paper is to consider a solution to the major difficulty of the causal interpretation of genetic information: how to distinguish the privileged causal role assigned to nucleic acids, DNA in particular, in the processes of replication and protein production. A close reading is proposed of Francis H. C. Crick's On Protein Synthesis (1958) and related works, to which we owe the first explicit definition of information within the scientific practice of molecular biology. Introduction 1.1 The basic questions of the information debate 1.2 The causal interpretation (CI) of biological information and Crick's ‘central dogma’ Crick's definitions of genetic information The main requirement for (CI) Types of causation in molecular biology 4.1 Structural causation in molecular biology 4.2 Nucleic acids as correlative causal factors The ‘central dogma’ without the notion of information Concluding remarks This is a new version of this article as there were errors in the abstract and full text in the previous version. (shrink)

According to Kuhn's speciation analogy, scientific specialisation is fundamentally analogous to biological speciation. In this paper, we extend Kuhn's original language-centred formulation of the speciation analogy, to account for episodes of scientific specialisation centred around methodological differences. Building upon recent views in evolutionary biology about the process of speciation by genetic divergence, we will show how these methodology-centred episodes of scientific specialisation can be understood as cases of specialisation driven by value divergence. We will apply our model of specialisation by (...) value divergence to an episode of methodology-centred scientific specialisation: the emergence of molecular biology. (shrink)

A notion of experimental series is developed, in which experiments or experimental sets are connected through experimental suggestions arising from previous experimental outcomes. To that end, the justification of Howard Temin's DNA provirus hypothesis is examined. The hypothesis originated with evidence from two exploratory experimental sets on an oncogenic virus and was substantiated by including evidence from three additional experimental sets. Collectively these sets comprise an experimental series and the accumulative evidence from the series was adequate to justify the hypothesis (...) by persuading the virology community of its veracity. The notion of crucial experiment is also discussed in terms of experimental series. (shrink)

During the 1960s, Howard M. Temin (1934-1994), dared to advocate a "heretical" hypothesis that appeared to be at variance with the central dogma of molecular biology, understood by many to imply that information transfer in nature occurred only from DNA to RNA. Temin's provirus hypothesis offered a simple explanation of both virus replication and viral-induced cancer and stated that Rous sarcoma virus, an RNA virus, is replicated via a DNA intermediate. Popular accounts of this scientific episode, written after the discovery (...) of an RNA-directed DNA polymerase in 1970, tend to describe the reaction to his proposition as ardent opposition. Typically these accounts use a 'molecular biology' standpoint emphasizing the central dogma's part in its rejection. In this article, however, this episode will be examined from a joint perspective of virology and experimental cancer research. From this perspective it is clear that Temin's work was well within the epistemological and methodological boundaries of virology and cancer research. Still, scientists did have reasons to doubt the provirus hypothesis, but these do not seem to be good enough to either justify an account that portrays Temin as a renegade or his ideas as heretical. (shrink)

In the 1950s and 1960s, an interfield interaction between molecular biologists and biochemists integrated important discoveries about the mechanism of protein synthesis. This extended discovery episode reveals two general reasoning strategies for eliminating gaps in descriptions of the productive continuity of mechanisms: schema instantiation and forward chaining/backtracking. Schema instantiation involves filling roles in an overall framework for the mechanism. Forward chaining and backtracking eliminate gaps using knowledge about types of entities and their activities. Attention to mechanisms highlights salient features of (...) this historical episode while providing general reasoning strategies for mechanism discovery. (shrink)

Scientific theories about the origin-of-life theories have historically been characterized by the chicken-and-egg problem of which essential aspect of life was the first to appear, replication or self-sustenance. By the 1950s the question was cast in molecular terms and DNA and proteins had come to represent the carriers of the two functions. Meanwhile, RNA, the other nucleic acid, had played a capricious role in origin theories. Because it contained building blocks very similar to DNA, biologists recognized early that RNA could (...) store information in its linear sequences. With the discovery in the 1980s that RNA molecules were capable of biological catalysis, a function hitherto ascribed to proteins alone, RNA took on the role of the single entity that could act as both chicken and egg. Within a few years of the discovery of these catalytic RNAs scientists had formulated an RNA World hypothesis that posited an early phase in the evolution of life where all key functions were performed by RNA molecules. This paper traces the history the role of RNA in origin-of-life theories with a focus on how the discovery of ribozymes influenced the discourse. (shrink)

Philosophers have proposed various kinds of relations between Mendelian genetics and molecular biology: reduction, replacement, explanatory extension. This paper argues that the two fields are best characterized as investigating different, serially integrated, hereditary mechanisms. The mechanisms operate at different times and contain different working entities. The working entities of the mechanisms of Mendelian heredity are chromosomes, whose movements serve to segregate alleles and independently assort genes in different linkage groups. The working entities of numerous mechanisms of molecular biology are larger (...) and smaller segments of DNA plus related molecules. Discovery of molecular DNA mechanisms filled black boxes that were noted, but unilluminated, by Mendelian genetics. (shrink)

Discovery proceeds in stages of construction, evaluation, and revision. Each of these stages is constrained by what is known or conjectured about what is being discovered. A new characterization of mechanism aids in specifying what is to be discovered when a mechanism is sought. Guidance in discovering mechanisms may be provided by the reasoning strategies of schema instantiation, modular subassembly, and forward/backward chaining. Examples are found in mechanisms in molecular biology, biochemistry, immunology, and evolutionary biology.

In 1958, Francis Crick distinguished the flow of information from the flow of matter and the flow of energy in the mechanism of protein synthesis. Crick’s claims about information flow and coding in molecular biology are viewed from the perspective of a new characterization of mechanisms and from the perspective of information as holding a key to distinguishing work in molecular biology from that of biochemistry in the 1950s–1970s . Flow of matter from beginning to end does not occur in (...) the protein synthesis mechanism; flow of information does. The flow of information and coding in molecular biological mechanisms are distinguished, on the one hand, from formal information theory, and, on the other, from information as used in cognitive neuroscience, where information and representation are often coupled. (shrink)