The epidemiologist Bradford Hill famously argued that in epidemiology, specificity of association (roughly, the fact that an environmental or behavioral risk factor is associated with just one or at most a few medical outcomes) is strong evidence of causation. Prominent epidemiologists have dismissed Hill’s claim on the ground that it relies on a dubious `one-cause one effect’ model of disease causation. The paper examines this methodological controversy, and argues that specificity considerations do have a useful role to play in causal (...) inference in epidemiology. More precisely, I argue that specificity considerations help solve a pervasive inferential problem in contemporary epidemiology: the problem of determining whether an exposure-outcome correlation might be due to confounding by a social factor. This examination of specificity has interesting consequences for our understanding of the methodology of epidemiology. It highlights how the methodology of epidemiology relies on local tools designed to address specific inference problems peculiar to the discipline, and shows that observational causal inference in epidemiology can proceed with little prior knowledge of the causal structure of the phenomenon investigated. I also argue that specificity of association cannot (despite claims to the contrary) be entirely explained in terms of Woodward’s well-known concept of “one-to-one” causal specificity. This is because specificity as understood by epidemiologists depends on whether an exposure (or outcome) is associated with a `heterogeneous’ set of variables. This dimension of heterogeneity is not captured in Woodward’s notion, but is crucial for understanding the evidential import of specificity of association. (shrink)

Binding specificity is a centrally important concept in molecular biology, yet it has received little philosophical attention. Here I aim to remedy this by analyzing binding specificity as a causal property. I focus on the concept’s role in drug design, where it is highly prized and hence directly studied. From a causal perspective, understanding why binding specificity is a valuable property of drugs contributes to an understanding of causal selection—of how and why scientists distinguish between causes, not just causes from (...) noncauses. In particular, the specificity of drugs is precisely what underwrites their value as experimental interventions on biological processes. (shrink)

This PhD dissertation examines the conceptual and theoretical foundations of the most general and most widely used framework for understanding social evolution, W. D. Hamilton's theory of kin selection. While the core idea is intuitive enough (when organisms share genes, they sometimes have an evolutionary incentive to help one another), its apparent simplicity masks a host of conceptual subtleties, and the theory has proved a perennial source of controversy in evolutionary biology. To move towards a resolution of these controversies, we (...) need a careful and rigorous analysis of the philosophical foundations of the theory. My aim in this work is to provide such an analysis. I begin with an examination of the concepts behavioural ecologists employ to describe and classify types of social behaviour. I stress the need to distinguish concepts that are often conflated: for example, we need to distinguish simple cooperation from collaboration in collective tasks, behaviours from strategies, and control from manipulation and coercion. I proceed from here to the formal representation of kin selection via George R. Price’s covariance selection mathematics. I address a number of interpretative issues the Price formalism raises, including the vexed question of whether kin selection theory is ‘formally equivalent’ to multi-level selection theory. In the second half of the dissertation, I assess the uses and limits of Hamilton’s rule for the evolution of social behaviour; I provide a precise statement of the conditions under which the rival neighbour-modulated fitness and inclusive fitness approaches in contemporary kin selection theory are equivalent (and describe cases in which they are not); and I criticize recent formal attempts to establish the controversial claim that kin selection leads to organisms behaving as if maximizing their inclusive fitness. (shrink)

Griffiths and Russell D. Gray (1994, 1997, 2001) have argued that the fundamental unit of analysis in developmental systems theory should be a process – the life cycle – and not a set of developmental resources and interactions between those resources. The key concepts of developmental systems theory, epigenesis and developmental dynamics, both also suggest a process view of the units of development. This chapter explores in more depth the features of developmental systems theory that favour treating processes as fundamental (...) in biology and examines the continuity between developmental systems theory and ideas about process in the work of several major figures in early 20th century biology, most notable C.H Waddington. (shrink)

The biological sciences have always proven a fertile ground for philosophical analysis, one from which has grown a rich tradition stemming from Aristotle and flowering with Darwin. And although contemporary philosophy is increasingly becoming conceptually entwined with the study of the empirical sciences with the data of the latter now being regularly utilised in the establishment and defence of the frameworks of the former, a practice especially prominent in the philosophy of physics, the development of that tradition hasn’t received the (...) wider attention it so thoroughly deserves. This review will briefly introduce some recent significant topics of debate within the philosophy of biology, focusing on those whose metaphysical themes (in everything from composition to causation) are likely to be of wide-reaching, cross-disciplinary interest. (shrink)

Developmental systems theory (DST) is a wholeheartedly epigenetic approach to development, inheritance and evolution. The developmental system of an organism is the entire matrix of resources that are needed to reproduce the life cycle. The range of developmental resources that are properly described as being inherited, and which are subject to natural selection, is far wider than has traditionally been allowed. Evolution acts on this extended set of developmental resources. From a developmental systems perspective, development does not proceed according to (...) a preformed plan; what is inherited is much more than DNA; and evolution is change not only in gene frequencies, but in entire developmental systems. (shrink)

This paper examines causal theories of reference with respect to how plausible an account they give of non-physical natural kind terms such as ‘gene’ as well as of the truth of the associated theoretical claims. I first show that reference fixism for ‘gene’ fails. By this, I mean the claim that the reference of ‘gene’ was stable over longer historical periods, for example, since the classical period of transmission genetics. Second, I show that the theory of partial reference does not (...) do justice to some widely held realist intuitions about classical genetics. This result is at loggerheads with the explicit goals usually associated with partial theories of reference, which is to defend a realist semantics for scientific terms. Thirdly, I show that, contrary to received wisdom and perhaps contrary to physics and chemistry, neither reference fixism nor partial reference are necessary in order to hold on to scientific realism about biology. I pinpoint the reasons for this in the nature of biological kinds, which do not even remotely resemble natural kinds (i.e., Lockean real essences) as traditionally conceived. (shrink)

This paper attempts to elucidate three characteristics of causal relationships that are important in biological contexts. Stability has to do with whether a causal relationship continues to hold under changes in background conditions. Proportionality has to do with whether changes in the state of the cause “line up” in the right way with changes in the state of the effect and with whether the cause and effect are characterized in a way that contains irrelevant detail. Specificity is connected both to (...) David Lewis’ notion of “influence” and also with the extent to which a causal relation approximates to the ideal of one cause–one effect. Interrelations among these notions and their possible biological significance are also discussed. (shrink)

The history of developmental biology is interwoven with debates as to whether mechanistic explanations of development are possible or whether alternative explanatory principles or even vital forces need to be assumed. In particular, the demonstrated ability of embryonic cells to tune their developmental fate precisely to their relative position and the overall size of the embryo was once thought to be inexplicable in mechanistic terms. Taking a causal perspective, this Element examines to what extent and how developmental biology, having turned (...) molecular about four decades ago, has been able to meet the vitalist challenge. It focuses not only on the nature of explanations but also on the usefulness of causal knowledge – including the knowledge of classical experimental embryology – for further scientific discovery. It also shows how this causal perspective allows us to understand the nature and significance of some key concepts, including organizer, signal and morphogen. This title is also available as Open Access on Cambridge Core. (shrink)

According to Denis Noble, one of the greatest illusions of the Modern Synthesis is embodied in the Central Dogma, a principle first formulated by Francis Crick in 1958. The principle holds that DNA makes protein, not the other way around. For Noble, the Dogma has contributed to the illusion that genes alone are responsible for the development and evolution of an organism’s phenotype. Though I am largely sympathetic to Noble’s critique, I argue that there may be alternative grounds for accepting (...) the plausibility of the Central Dogma and also the illusion it perpetuates. (shrink)

Biologists and philosophers often use the language of determination in order to describe the nature of developmental phenomena. Accounts in terms of determination have often been reductionist. One common idea is that DNA is supposed to play a special explanatory role in developmental explanations, namely, that DNA is a developmental determinant. In this article we try to make sense of determination claims in developmental biology. Adopting a manipulationist approach, we shall first argue that the notion of developmental determinant is causal. (...) We suggest that two different theses concerning developmental determination can be articulated: determination of occurrence and structural determination. We shall argue that, while the first thesis is problematic, the second, opportunely qualified, is feasible. Finally, we shall argue that an analysis of biological causation in terms of determination cannot account for entangled dynamics. Characterising causal entanglement as a particular kind of interactive causation whereby difference-making causes ascribable to different levels of biological organisation influence a particular ontogenetic outcome, we shall, via two illustrative examples, diagnose some potential limits of a reductionist, molecular and intra-level understanding of biological causation. (shrink)

Griffiths et al. (2015) have proposed a quantitative measure of causal specificity and used it to assess various attempts to single out genetic causes as being causally more specific than other cellular mechanisms, for example, alternative splicing. Focusing in particular on developmental processes, they have identified a number of important challenges for this project. In this discussion note, I would like to show how these challenges can be met.

John Cook Wilson (1849–1915) was Wykeham Professor of Logic at New College, Oxford and the founder of ‘Oxford Realism’, a philosophical movement that flourished at Oxford during the first decades of the 20th century. Although trained as a classicist and a mathematician, his most important contribution was to the theory of knowledge, where he argued that knowledge is factive and not definable in terms of belief, and he criticized ‘hybrid’ and ‘externalist’ accounts. He also argued for direct realism in perception, (...) criticizing both empiricism and idealism, and argued for a moderate nominalist view of universals as being in rebus and only ‘apprehended’ by their particulars. His influence helped swaying Oxford away from idealism and, through figures such as H. A. Prichard, Gilbert Ryle, or J. L. Austin, his ideas were also to some extent at the origin of ‘moral intuitionism’ and ‘ordinary language philosophy’ which defined much of Oxford philosophy until the second half of the twentieth-century. Nevertheless, his name and legacy were all but forgotten for generations after World War II. Still, his views on knowledge are with us today, being in part at work in the writings of philosophers as diverse as John McDowell, Charles Travis, and Timothy Williamson. (shrink)

Several authors have argued that causes differ in the degree to which they are ‘specific’ to their effects. Woodward has used this idea to enrich his influential interventionist theory of causal explanation. Here we propose a way to measure causal specificity using tools from information theory. We show that the specificity of a causal variable is not well-defined without a probability distribution over the states of that variable. We demonstrate the tractability and interest of our proposed measure by measuring the (...) specificity of coding DNA and other factors in a simple model of the production of mRNA. (shrink)

Philosophical discussions on causal inference in medicine are stuck in dyadic camps, each defending one kind of evidence or method rather than another as best support for causal hypotheses. Whereas Evidence Based Medicine advocates the use of Randomised Controlled Trials and systematic reviews of RCTs as gold standard, philosophers of science emphasise the importance of mechanisms and their distinctive informational contribution to causal inference and assessment. Some have suggested the adoption of a pluralistic approach to causal inference, and an inductive (...) rather than hypothetico-deductive inferential paradigm. However, these proposals deliver no clear guidelines about how such plurality of evidence sources should jointly justify hypotheses of causal associations. We here develop such guidelines by first giving a philosophical analysis of the underpinnings of Hill’s viewpoints on causality. We then put forward an evidence-amalgamation framework adopting a Bayesian net approach to model causal inference in pharmacology for the assessment of harms. Our framework accommodates a number of intuitions already expressed in the literature concerning the EBM vs. pluralist debate on causal inference, evidence hierarchies, causal holism, relevance, and reliability. (shrink)

This paper develops axiomatic foundations for a probabilistic-interventionist theory of causal strength. Transferring methods from Bayesian confirmation theory, I proceed in three steps: I develop a framework for defining and comparing measures of causal strength; I argue that no single measure can satisfy all natural constraints; I prove two representation theorems for popular measures of causal strength: Pearl's causal effect measure and Eells' difference measure. In other words, I demonstrate these two measures can be derived from a set of plausible (...) adequacy conditions. The paper concludes by sketching future research avenues. (shrink)

The Central Dogma of molecular biology, which holds that DNA makes protein and not the other way around, is as influential as it is controversial. Some believe the Dogma has outlived its usefulness, either because it fails to fully capture the ins-and-outs of protein synthesis (Griffiths and Stotz, 2013; Stotz, 2006), because it turns on a confused notion of information (Sarkar, 2004), or because it problematically assumes the unidirectional flow of information from DNA to protein (Gottlieb, 2001). This paper evaluates (...) an underexplored defense of the Dogma, which relies on the assumption that the Dogma and the Inheritance of Acquired Traits, a principle which dates as far back as Jean Baptiste-Lamarck, are incompatible principles (Smith, 1993; Judson, 1979; Dawkins, 1970; Cobb, 2017; Wilkins, 2002; Graur, 2018). By appealing to empirical evidence in molecular science, I argue that this apparent incompatibility is indeed merely apparent. I conclude by briefly demonstrating how these considerations bear on the topic of conceptual pluralism in the philosophy of science (Stencel and Proszewska, 2018; Lu and Bourrat, 2018). (shrink)

The interventionist account provides us with several notions permitting the qualification of causal relationships. In recent years, there has been a push toward formalizing these notions using information theory. In this paper, I discuss one of them, namely causal specificity. The notion of causal specificity is ambiguous as it can refer to at least two different concepts. After having presented these, I show that current attempts to formalize causal specificity in information theoretic terms have mostly focused on one of these (...) two concepts. I then propose and apply a new information-theoretic measure which captures the other concept. (shrink)

Heritability is routinely interpreted causally. Yet, what such an interpretation amounts to is often unclear. Here, I provide a causal interpretation of this concept in terms of range of causal influence, one of several causal dimensions proposed within the interventionist account of causation. An information-theoretic measure of range of causal influence has recently been put forward in the literature. Starting from this formalization and relying upon Woodward’s analysis, I show that an important problem associated with interpreting heritability causally, namely the (...) locality problem, amounts, at least partly, to a low invariance and low stability between the genotype/environment and the phenotype of individuals. In light of this, I plead for a causal interpretation of heritability that takes the notions of Woodward’s invariance and stability into consideration. In doing so, I defuse naive causal interpretations of heritability. (shrink)

This article reconsiders the theoretical role of the genetic code. By drawing on published and unpublished sources from the 1950s, I analyse how the code metaphor was actually employed by the scientists who first promoted its use. The analysis shows that the term ‘code’ picked out mechanism sketches, consisting of more or less detailed descriptions of ordinary molecular components, processes, and structural properties of the mechanism of protein synthesis. The sketches provided how-possibly explanations for the ordering of amino acids by (...) nucleic acids. I argue that employing the code metaphor was justified in virtue of its descriptive-denotational and explanatory roles, and because it highlighted a similarity with conventional codes that was particularly salient at the time. 1 Introduction2 Coding Schemes in the 1950s2.1 The research problem: Determining amino acid sequences2.2 The solution: Mapping schemes or ‘codes’3 The Code Metaphor Played Descriptive and Explanatory Roles4 Theness of Codes and the Expendability of the Code Metaphor5 The Role of Arbitrariness6 Conclusions. (shrink)

The interventionist account of causation offers a criterion to distinguish causes from non-causes. It also aims at defining various desirable properties of causal relationships, such as specificity, proportionality and stability. Here we apply an information-theoretic approach to these properties. We show that the interventionist criterion of causation is formally equivalent to non-zero specificity, and that there are natural, information-theoretic ways to explicate the distinction between potential and actual causal influence. We explicate the idea that the description of causes should be (...) proportional to that of their effects. Then we draw a distinction between two ideas in the existing literature, the range of invariance of a causal relationship and its stability. The range of invariance is related to specificity and range of causal values. Stability concerns the effect of additional variables on the relationship between some focal pair of cause and effect variables. We show how to distinguish and measure the direct influence of background variables on the effect variable, and their influence on the relationship between the focal cause and the effect variable. Finally, we discuss the limitations of the information-theoretic approach, and offer prospects for complementary approaches. (shrink)

A crucial question for a process view of life is how to identify a process and how to follow it through time. The genidentity view can contribute decisively to this project. It says that the identity through time of an entity X is given by a well-identified series of continuous states of affairs. Genidentity helps address the problem of diachronic identity in the living world. This chapter describes the centrality of the concept of genidentity for David Hull and proposes an (...) extension of Hull’s view to the ubiquitous phenomenon of symbiosis. Finally, using immunology as a key example, it shows that the genidentity view suggests that the main interest of a process approach is epistemological rather than ontological and that its principal claim is one of priority, namely that processes precede and define things, and not vice versa. (shrink)

There is no denying the Central Dogma’s impact on the biological sciences. Since the Dogma’s formulation by Francis Crick in 1958, however, many have debated the Dogma’s empirical adequacy. My aim is to move beyond these discussions, and instead consider the Central Dogma’s significance to contemporary biological practice. To do this, I consider four distinct approaches for determining the non-descriptive methodological significance of a scientific principle. I argue that these approaches fail to vindicate the Central Dogma, and that, under many (...) of these approaches, the Dogma amounts to a triviality. (shrink)

Griffiths et al. have proposed a quantitative measure of causal specificity and used it to assess various attempts to single out genetic causes as being causally more specific than other cellular mechanisms, for example, alternative splicing. Focusing in particular on developmental processes, they have identified a number of important challenges for this project. In this discussion note, I would like to show how these challenges can be met.

This paper aims to clarify the consequences of new scientific and philosophical approaches for the practical-theoretical framework of modern developmental biology. I highlight normal development, and the instructive-permissive distinction, as key parts of this framework which shape how variation is conceptualised and managed. Furthermore, I establish the different dimensions of biological variation: the units, temporality and mode of variation. Using the analytical frame established by this, I interpret a selection of examples as challenges to the instructive-permissive distinction. These examples include (...) the phenomena of developmental plasticity and transdifferentiation, the role of the microbiome in development, and new methodological approaches to standardisation and the assessment of causes. Furthermore, I argue that investigations into organismal development should investigate the effects of a wider range of kinds of variation including variation in the units, modes and temporalities of development. I close by examining various possible opportunities for producing and using normal development free of the assumptions of the instructive-permissive distinction. These opportunities are afforded by recent developments, which include new ways of producing standards incorporating more natural variation and being based on function rather than structure, and the ability to produce, store, and process large quantities of data. (shrink)

The discovery of RNA interference in 1998 has made a lasting impact on biological research. Identifying the regulatory role of small RNAs changed the modes of molecular biological inquiry as well as biologists' understanding of genetic regulation. This article examines the early years of small RNA biology's success story. I query which factors had to come together so that small RNA research came into life in the blink of an eye. I primarily look at scientific repertoires as facilitators of rapid (...) scientific change. I show that for a short period of time, between the years 1998 and 2002, different model organism communities, investigative strategies, technological innovations, and research interests could be successfully aligned to take small RNA research off the ground. I discuss how the keystone discoveries were situated in specific experimental traditions and what strategies were employed to establish these discoveries as more general phenomena. Providing thus a practice-based approach of rapid scientific change, I ask how to relate the change in propositional bits of scientific knowledge with changes in scientific practice. (shrink)

I argue that Calcott :481–505, Calcott 2017) mischaracterizes in an important way the notion of causal specificity proposed by Woodward :287–318, Woodward 2010). This leads him to rely too heavily on one single aspect of Woodward’s analysis on causal specificity; propose an information-theoretic measure he calls ‘precision’ which is partly redundant with, but less general than one of the dimensions in Woodward’s analysis of specificity, without acknowledging Woodward’s analysis; and claim that comparing the specificities of two or more causes under (...) what he calls a competitive analysis of causes, does not permit to capture the distinction between permissive and instructive causes. After having restated Woodward’s analysis of causal specificity, I present an information-theoretic measure which, although related to Calcott’s measure, is more general than his and corresponds to the notion of specificity he missed in Woodward's analysis. I then show how this measure can be used, together with mutual causal information, to distinguish permissive from instructive causes in a competitive analysis of causes. (shrink)

The philosophy of biology literature offers several arguments aimed at showing that information theory is conceptually unsuited to capture the informational talk in molecular biology. Such arguments led to the consensus that, if the informational talk in biology can be defended and explained at all, we need a different strategy. The debate, in fact, developed mostly along this line. However, recent contributions seem to (and even claim to) challenge the consensus and thus to vindicate the role and relevance of information (...) theory to this particular debate. In this paper, I examine the main arguments leading to such a consensus and I analyze the extent to which those recent accounts actually succeed in vindicating the invocation of information theory. I argue that these attempts fail to vindicate the information-theoretic strategy and, therefore, the consensus remains unaffected by them. (shrink)

Invariance is one of several dimensions of causal relationships within the interventionist account. The more invariant a relationship between two variables, the more the relationship should be considered paradigmatically causal. In this paper, I propose two formal measures to estimate invariance, illustrated by a simple example. I then discuss the notion of invariance for causal relationships between non-nominal (i.e., ordinal and quantitative) variables, for which Information theory, and hence the formalism proposed here, is not well suited. Finally, I propose how (...) invariance could be qualified for such variables. (shrink)