I present a reconstruction of F.H.C. Crick's two 1957 hypotheses "Sequence Hypothesis" and "Central Dogma" in terms of a contemporary philosophical theory of causation. Analyzing in particular the experimental evidence that Crick cited, I argue that these hypotheses can be understood as claims about the actual difference-making cause in protein synthesis. As these hypotheses are only true if restricted to certain nucleic acids in certain organisms, I then examine the concept of causal specificity and its potential to counter claims about (...) causal parity of DNA and other cellular components. I first show that causal specificity is a special kind of invariance under interventions, namely invariance of generalizations that range over finite sets of discrete variables. Then, I show that this notion allows the articulation of a middle ground in the debate over causal parity. (shrink)

Stem cell biology and systems biology are two prominent new approaches to studying cell development. In stem cell biology, the predominant method is experimental manipulation of concrete cells and tissues. Systems biology, in contrast, emphasizes mathematical modeling of cellular systems. For scientists and philosophers interested in development, an important question arises: how should the two approaches relate? This essay proposes an answer, using the model of Waddington’s landscape to triangulate between stem cell and systems approaches. This simple abstract model represents (...) development as an undulating surface of hills and valleys. Originally constructed by C. H. Waddington to visually explicate an integrated theory of genetics, development and evolution, the landscape model can play an updated unificatory role. I examine this model’s structure, representational assumptions, and uses in all three contexts, and argue that explanations of cell development require both mathematical models and concrete experiments. On this view, the two approaches are interdependent, with mathematical models playing a crucial but circumscribed role in explanations of cell development. (shrink)

The concept of mechanism in biology has three distinct meanings. It may refer to a philosophical thesis about the nature of life and biology (‘mechanicism’), to the internal workings of a machine-like structure (‘machine mechanism’), or to the causal explanation of a particular phenomenon (‘causal mechanism’). In this paper I trace the conceptual evolution of ‘mechanism’ in the history of biology, and I examine how the three meanings of this term have come to be featured in the philosophy of biology, (...) situating the new ‘mechanismic program’ in this context. I argue that the leading advocates of the mechanismic program (i.e., Craver, Darden, Bechtel, etc.) inadvertently conflate the different senses of ‘mechanism’. Specifically, they all inappropriately endow causal mechanisms with the ontic status of machine mechanisms, and this invariably results in problematic accounts of the role played by mechanism-talk in scientific practice. I suggest that for effective analyses of the concept of mechanism, causal mechanisms need to be distinguished from machine mechanisms, and the new mechanismic program in the philosophy of biology needs to be demarcated from the traditional concerns of mechanistic biology. (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)

In this paper I offer an analysis of causation based upon a theory of mechanisms-complex systems whose internal parts interact to produce a system's external behavior. I argue that all but the fundamental laws of physics can be explained by reference to mechanisms. Mechanisms provide an epistemologically unproblematic way to explain the necessity which is often taken to distinguish laws from other generalizations. This account of necessity leads to a theory of causation according to which events are causally related when (...) there is a mechanism that connects them. I present reasons why the lack of an account of fundamental physical causation does not undermine the mechanical account. (shrink)

The official model of explanation proposed by the logical empiricists, the covering law model, is subject to familiar objections. The goal of the present paper is to explore an unofficial view of explanation which logical empiricists have sometimes suggested, the view of explanation as unification. I try to show that this view can be developed so as to provide insight into major episodes in the history of science, and that it can overcome some of the most serious difficulties besetting the (...) covering law model. (shrink)

The concept of mechanism is analyzed in terms of entities and activities, organized such that they are productive of regular changes. Examples show how mechanisms work in neurobiology and molecular biology. Thinking in terms of mechanisms provides a new framework for addressing many traditional philosophical issues: causality, laws, explanation, reduction, and scientific change.

Explanations in the life sciences frequently involve presenting a model of the mechanism taken to be responsible for a given phenomenon. Such explanations depart in numerous ways from nomological explanations commonly presented in philosophy of science. This paper focuses on three sorts of differences. First, scientists who develop mechanistic explanations are not limited to linguistic representations and logical inference; they frequently employ diagrams to characterize mechanisms and simulations to reason about them. Thus, the epistemic resources for presenting mechanistic explanations are (...) considerably richer than those suggested by a nomological framework. Second, the fact that mechanisms involve organized systems of component parts and operations provides direction to both the discovery and testing of mechanistic explanations. Finally, models of mechanisms are developed for specific exemplars and are not represented in terms of universally quantified statements. Generalization involves investigating both the similarity of new exemplars to those already studied and the variations between them. (shrink)

Biologists studying complex causal systems typically identify some factors as causes and treat other factors as background conditions. For example, when geneticists explain biological phenomena, they often foreground genes and relegate the cellular milieu to the background. But factors in the milieu are as causally necessary as genes for the production of phenotypic traits, even traits at the molecular level such as amino acid sequences. Gene-centered biology has been criticized on the grounds that because there is parity among causes, the (...) “privileging” of genes reflects a reductionist bias, not an ontological difference. The idea that there is an ontological parity among causes is related to a philosophical puzzle identified by John Stuart Mill: what, other than our interests or biases, could possibly justify identifying some causes as the actual or operative ones, and other causes as mere background? The aim of this paper is to solve this conceptual puzzle and to explain why there is not an ontological parity among genes and the other factors. It turns out that solving this puzzle helps answer a seemingly unrelated philosophical question: what kind of causal generality matters in biology? (shrink)

This article compares causal and constitutive explanation. While scientific inquiry usually addresses both causal and constitutive questions, making the distinction is crucial for a detailed understanding of scientific questions and their interrelations. These explanations have different kinds of explananda and they track different sorts of dependencies. Constitutive explanations do not address events or behaviors, but causal capacities. While there are some interesting relations between building and causal manipulation, causation and constitution are not to be confused. Constitution is a synchronous and (...) asymmetric relation between relata that cannot be conceived as independent existences. However, despite their metaphysical differences, the same key ideas about explanation largely apply to both. Causal and constitutive explanations face similar challenges (such as the problems of relevance and explanatory regress) and both are in the business of mapping networks of counterfactual dependence—i.e. mechanisms—although the relevant counterfactuals are of a different sort. In the final section the issue of developmental explanation is discussed. It is argued that developmental explanations deserve their own place in taxonomy of explanations, although ultimately developmental dependencies can be analyzed as combinations of causal and constitutive dependencies. Hence, causal and constitutive explanation are distinct, but not always completely separate forms of explanation. (shrink)

This article argues that the basic account of mechanism and mechanistic explanation, involving sequential execution of qualitatively characterized operations, is itself insufficient to explain biological phenomena such as the capacity of living organisms to maintain themselves as systems distinct from their environment. This capacity depends on cyclic organization, including positive and negative feedback loops, which can generate complex dynamics. Understanding cyclically organized mechanisms with complex dynamics requires coordinating research directed at decomposing mechanisms into parts and operations with research using computational (...) models to recompose mechanisms and determine their dynamic behavior. This coordinated endeavor yields dynamic mechanistic explanations. (shrink)

We argue that dynamical and mathematical models in systems and cognitive neuro- science explain (rather than redescribe) a phenomenon only if there is a plausible mapping between elements in the model and elements in the mechanism for the phe- nomenon. We demonstrate how this model-to-mechanism-mapping constraint, when satisfied, endows a model with explanatory force with respect to the phenomenon to be explained. Several paradigmatic models including the Haken-Kelso-Bunz model of bimanual coordination and the difference-of-Gaussians model of visual receptive fields are (...) explored. (shrink)

Many explanations in molecular biology, neuroscience, and other fields of experimental biology describe mechanisms underlying phenomena of interest. These mechanistic explanations account for higher-level phenomena in terms of causally active parts and their spatiotemporal organization. What makes such a mechanistic description explanatory? The best-developed answer, Craver's causal-mechanical account, has several weaknesses. It does not fully explicate the target of explanation, interlevel relation, or interactive nonmodular character of many biological mechanisms as we understand them. An alternative account of MEx, emphasizing interdependence (...) among a mechanism's components, remedies these difficulties. (shrink)

This paper presents a counterfactual account of what a mechanism is. Mechanisms consist of parts, the behavior of which conforms to generalizations that are invariant under interventions, and which are modular in the sense that it is possible in principle to change the behavior of one part independently of the others. Each of these features can be captured by the truth of certain counterfactuals.

Philosophers of science typically associate the causal-mechanical view of scientific explanation with the work of Railton and Salmon. In this paper I shall argue that the defects of this view arise from an inadequate analysis of the concept of mechanism. I contrast Salmon's account of mechanisms in terms of the causal nexus with my own account of mechanisms, in which mechanisms are viewed as complex systems. After describing these two concepts of mechanism, I show how the complex-systems approach avoids certain (...) objections to Salmon's account of causal-mechanical explanation. I conclude by discussing how mechanistic explanations can provide understanding by unification. (shrink)

Stuart Glennan, and the team of Peter Machamer, Lindley Darden, and Carl Craver have recently provided two accounts of the concept of a mechanism. The main difference between these two versions rests on how the behavior of the parts of the mechanism is conceptualized. Glennan considers mechanisms to be an interaction of parts, where the interaction between parts can be characterized by direct, invariant, change-relating generalizations. Machamer, Darden, and Craver criticize traditional conceptualizations of mechanisms which are based solely on parts (...) interacting and introduce a new conceptactivity. This essay is an attempt at carving out a relationship between these two philosophical interpretations of a mechanism. I will claim that, rather than being in conflict, Glennan's concept of interaction and Machamer, Darden, and Craver's notion of activity actually complement one another, each emphasizing a missing element of the other. (shrink)

The stunning possibility of “reprogramming” differentiated somatic cells to express a pluripotent stem cell phenotype (iPS, induced pluripotent stem cell) and the “ground state” character of pluripotency reveal fundamental features of cell fate regulation that lie beyond existing paradigms. The rarity of reprogramming events appears to contradict the robustness with which the unfathomably complex phenotype of stem cells can reliably be generated. This apparent paradox, however, is naturally explained by the rugged “epigenetic landscape” with valleys representing “preprogrammed” attractor states that (...) emerge from the dynamical constraints of the gene regulatory network. This article provides a pedagogical primer to the fundamental principles of gene regulatory networks as integrated dynamic systems and reviews recent insights in gene expression noise and fate determination, thereby offering a formal framework that may help us to understand why cell fate reprogramming events are inherently rare and yet so robust. (shrink)

Machamer, Darden, and Craver argue that causal explanations explain effects by describing the operations of the mechanisms which produce them. One of this paper’s aims is to take advantage of neglected resources of Mechanism to rethink the traditional idea that actual or counterfactual natural regularities are essential to the distinction between causal and non-causal co-occurrences, and that generalizations describing natural regularities are essential components of causal explanations. I think that causal productivity and regularity are by no means the same thing, (...) and that the Regularists are mistaken about the roles generalizations play in causal explanation. Humean, logical empiricist, and other Regularist accounts of causal explanation have had the unfortunate effect of distracting philosophers’ from important non-explanatory scientific uses of laws and lesser generalizations which purport to describe natural regularities. My second aim is to characterize some of these uses, illustrating them with examples from neuroscientific research. (shrink)