Russo and Williamson claim that establishing causal claims requires mechanistic and difference-making evidence. In this article, I will argue that Russo and Williamson's formulation of their thesis is multiply ambiguous. I will make three distinctions: mechanistic evidence as type vs object of evidence; what mechanism or mechanisms we want evidence of; and how much evidence of a mechanism we require. I will feed these more precise meanings back into the Russo–Williamson thesis and argue that it is both true and false: (...) two weaker versions of the thesis are worth supporting, while the stronger versions are not. Further, my distinctions are of wider concern because they allow us to make more precise claims about what kinds of evidence are required in particular cases. (shrink)

Craver claims that mechanistic explanation is ontic, while Bechtel claims that it is epistemic. While this distinction between ontic and epistemic explanation originates with Salmon, the ideas have changed in the modern debate on mechanistic explanation, where the frame of the debate is changing. I will explore what Bechtel and Craver’s claims mean, and argue that good mechanistic explanations must satisfy both ontic and epistemic normative constraints on what is a good explanation. I will argue for ontic constraints by drawing (...) on Craver’s work in Sect. 2.1, and argue for epistemic constraints by drawing on Bechtel’s work in Sect. 2.2. Along the way, I will argue that Bechtel and Craver actually agree with this claim. I argue that we should not take either kind of constraints to be fundamental, in Sect. 3, and close in Sect. 4 by considering what remains at stake in making a distinction between ontic and epistemic constraints on mechanistic explanation. I suggest that we should not concentrate on either kind of constraint, to the neglect of the other, arguing for the importance of seeing the relationship as one of integration. (shrink)

In this paper, we compare the mechanisms of protein synthesis and natural selection. We identify three core elements of mechanistic explanation: functional individuation, hierarchical nestedness or decomposition, and organization. These are now well understood elements of mechanistic explanation in fields such as protein synthesis, and widely accepted in the mechanisms literature. But Skipper and Millstein have argued that natural selection is neither decomposable nor organized. This would mean that much of the current mechanisms literature does not apply to the mechanism (...) of natural selection.We take each element of mechanistic explanation in turn. Having appreciated the importance of functional individuation, we show how decomposition and organization should be better understood in these terms. We thereby show that mechanistic explanation by protein synthesis and natural selection are more closely analogous than they appear—both possess all three of these core elements of a mechanism widely recognized in the mechanisms literature. (shrink)

In an Isis 2008 review of research in History and Philosophy of Science (HPS), Galison opened discussion on ten on-going HPS problems. It is however unclear to what extent these problems, and constraints on their solutions, are of HPS’s own making. Recent research provides a basic resolution of these issues. In a recent paper Hooker (Perspect Sci 26(2): 266–291, 2018b) proposed that the discipline(s) of HPS should themselves also be understood to employ paradigms in HPS to understand science, analogously to (...) those employed in science to understand scientific domains. The paper argued for recognising at least two paradigms, one based on logic, and analytic forms more generally, the other based on deliberative judgement making. The present paper aims to use paradigmatic responses to Galison’s problems to explore the differing natures, merits and limitations of these two paradigms. This exploration also reveals the basic inadequacy of the analytic paradigm to illuminate the conduct of science, thereby permitting many of his problems to be dissolved rather than solved. (shrink)

Pseudo‐mechanistic explanations in psychology and cognitive neuroscienceThis paper focuses on the level of systems/cognitive neuroscience. It argues that the great majority of explanations in psychology and cognitive neuroscience is “pseudo‐mechanistic.” On the basis of various case studies, Hommel argues that cognitive neuroscience should move beyond what he calls an “Aristotelian phase” to become a mature “Galilean” science seeking to discover actual mechanisms of cognitive phenomena.

It is often claimed that the greatest value of the Bayesian framework in cognitive science consists in its unifying power. Several Bayesian cognitive scientists assume that unification is obviously linked to explanatory power. But this link is not obvious, as unification in science is a heterogeneous notion, which may have little to do with explanation. While a crucial feature of most adequate explanations in cognitive science is that they reveal aspects of the causal mechanism that produces the phenomenon to be (...) explained, the kind of unification afforded by the Bayesian framework to cognitive science does not necessarily reveal aspects of a mechanism. Bayesian unification, nonetheless, can place fruitful constraints on causal–mechanical explanation. 1 Introduction2 What a Great Many Phenomena Bayesian Decision Theory Can Model3 The Case of Information Integration4 How Do Bayesian Models Unify?5 Bayesian Unification: What Constraints Are There on Mechanistic Explanation?5.1 Unification constrains mechanism discovery5.2 Unification constrains the identification of relevant mechanistic factors5.3 Unification constrains confirmation of competitive mechanistic models6 ConclusionAppendix. (shrink)

The term ‘cell’, in addition to designating fundamental units of life, has also been applied since the nineteenth century to technical apparatuses such as fuel and galvanic cells. This paper shows that such technologies, based on the electrical effects of chemical reactions taking place in containers, had a far-reaching impact on the concept of the biological cell. My argument revolves around the controversy over oxidative phosphorylation in bioenergetics between 1961 and 1977. In this scientific conflict, a two-level mingling of technological (...) culture, physical chemistry and biological research can be observed. First, Peter Mitchell explained the chemiosmotic hypothesis of energy generation by representing cellular membrane processes via an analogy to fuel cells. Second, in the associated experimental scrutiny of membranes, material cell models were devised that reassembled spatialized molecular processes in vitro. Cells were thus modelled both on paper and in the test tube not as morphological structures but as compartments able to perform physicochemical work. The story of cells and membranes in bioenergetics points out the role that theories and practices in physical chemistry had in the molecularization of life. These approaches model the cell as a ‘topology of molecular action’, as I will call it, and it involves concepts of spaces, surfaces and movements. They epitomize an engineer’s vision of the organism that has influenced diverse fields in today’s life sciences. (shrink)

In the context of 1960s research on biological membranes, scientists stumbled upon a curiously coloured material substance, which became called the “purple membrane.” Interactions with the material as well as chemical analyses led to the conclusion that the microbial membrane contained a photoactive molecule similar to rhodopsin, the light receptor of animals’ retinae. Until 1975, the find led to the formation of novel objects in science, and subsequently to the development of a field in the molecular life sciences that comprised (...) biophysics, bioenergetics as well as membrane and structural biology. Furthermore, the purple membrane and bacteriorhodopsin, as the photoactive membrane transport protein was baptized, inspired attempts at hybrid bio-optical engineering throughout the 1980s. A central motif of the research field was the identification of a functional biological structure, such as a membrane, with a reactive material substance that could be easily prepared and manipulated. Building on this premise, early purple membrane research will be taken as a case in point to understand the appearance and transformation of objects in science through work with material substances. Here, the role played by a perceptible material and its spontaneous change of colour, or reactivity, casts a different light on objects and experimental practices in the late twentieth century molecular life sciences. With respect to the impact of chemical working and thinking, the purple membrane and rhodopsins represent an influential domain straddling the life and chemical sciences as well as bio- and material technologies, which has received only little historical and philosophical attention. Re-drawing the boundary between the living and the non-enlivened, these researches explain and model organismic activity through the reactivity of macromolecular structures, and thus palpable material substances. (shrink)

Inspired by the success of synthesising organic substances by Friedrich Wöhler in 1828, the vision of creating life in the laboratory synthetically has become increasingly accessible for today’s synthetic biology and synthetic genomics, respectively. The engineering of biology – a contemporary version of the liaison of technology and organic form – creates cellular machines, biobricks, biomolecular ‘borgs’, and entire synthetic genomes of artificial organisms. Besides major ethical concerns, the shift in scientific epistemology is of interest. Unlike classical analytical science, synthetic (...) science understands by a process of generation, through which myriads of new things are created, dramatically changing the living environment. (shrink)

The concept of scaffolding has wide resonance in several scientific fields. Here we attempt to adopt it for the study of development. In this perspective, the embryo is conceived as an integral whole, comprised of several hierarchical modules as in a recurrent circularity of emerging patterns. Within the developmental hierarchy, each module yields an inter-level relationship that makes it possible for the scaffolding to mediate the production of selectable variations. A wide range of genetic, cellular and morphological mechanisms allows the (...) scaffolding to integrate these modular variations into a functionally coordinate unit. A genetic scaffolding accounts for the inherited invariance of pattern formation during the embryo’s growth. At higher level, cells behave as agents endowed with the capacity to interpret any scaffolding variation as signs. The full hierarchy of a multi-level scaffolding is eventually attained when the embryo acquires the capacity to impose a number of developmental constraints on its constituting parts in a top-down direction. The acquisition of this capacity allows a semiotic threshold to emerge between the living cellular world and the underlying non-living molecular world. As this boundary is gradually defined during development, cells enter into new functional relationships, while, at the same time, are relieved from their physical determinism. The resulting constraints can thus become the driving forces that upgrade embryonic scaffolding from the simple molecular signalling to the complexity of sign recognition proper of a cellular community. In this semiotic perspective, the apparent goal directness of any developmental strategy should no longer be accounted for by a predetermined genetic program, but by the gradual definition of the relationships selected amongst the ones historically explored. (shrink)

Philosophers have traditionally conceived of discovery in terms of internal cognitive acts. Close consideration of Rosalind Franklin's role in the discovery of the DNA double helix, however, reveals some problems with this traditional conception. This article argues that defining discovery in terms of mental operations entails problematic conclusions and excludes acts that should fall within the domain of discovery. It proposes that discovery be expanded to include external acts of making visible. Doing so allows for a reevaluation of Franklin's role (...) in the discovery of the structure of DNA. (shrink)

In this paper, I argue that explaining cognitive behavior can be achieved through what I call hybrid explanatory inferences: inferences that posit mechanisms, but also draw on observed regularities. Moreover, these inferences can be used to achieve unification, in the sense developed by Allen Newel in his work on cognitive architectures. Thus, it seems that explanatory pluralism and unification do not rule out each other in cognitive science, but rather that the former represents a way to achieve the latter.

In this paper we argue that in recent literature on mechanistic explanations, authors tend to conflate two distinct features that mechanistic models can have or fail to have: plausibility and richness. By plausibility, we mean the probability that a model is correct in the assertions it makes regarding the parts and operations of the mechanism, i.e., that the model is correct as a description of the actual mechanism. By richness, we mean the amount of detail the model gives about the (...) actual mechanism. First, we argue that there is at least a conceptual reason to keep these two features distinct, since they can vary independently from each other: models can be highly plausible while providing almost no details, while they can also be highly detailed but plainly wrong. Next, focusing on Craver's continuum of ?how-possibly,? to ?how-plausibly,? to ?how-actually? models, we argue that the conflation of plausibility and richness is harmful to the discussion because it leads to the view that both are necessary for a model to have explanatory power, while in fact, richness is only so with respect to a mechanism's activities, not its entities. This point is illustrated with two examples of functional models. (shrink)

In this paper, I explicate and discuss performance-similarity reasoning as a strategy for mechanism schema evaluation, understood in Lindley Darden’s sense. This strategy involves inferring hypotheses about the mechanism responsible for cognitive capacities from premises describing the performance of those capacities; performance-similarity reasoning is a type of Inference to the Best Explanation, or IBE. Two types of such inferences are distinguished: one in which the performance of two systems is compared, and another when the performance of two systems under intervention (...) is compared. Both types of inferences are illustrated with examples taken from cognitive science. I conclude that performance-similarity reasoning is an important strategy for evaluating mechanistic hypotheses. (shrink)

This paper tracks the commitments of mechanistic explanations focusing on the relation between activities at different levels. It is pointed out that the mechanistic approach is inherently committed to identifying causal connections at higher levels with causal connections at lower levels. For the mechanistic approach to succeed a mechanism as a whole must do the very same thing what its parts organised in a particular way do. The mechanistic approach must also utilise bridge principles connecting different causal terms of different (...) theoretical vocabularies in order to make the identities of causal connections transparent. These general commitments get confronted with two claims made by certain proponents of the mechanistic approach: William Bechtel often argues that within the mechanistic framework it is possible to balance between reducing higher levels and maintaining their autonomy at the same time, whereas, in a recent paper, Craver and Bechtel argue that the mechanistic approach is able to make downward causation intelligible. The paper concludes that the mechanistic approach imbued with identity statements is no better candidate for anchoring higher levels to lower ones while maintaining their autonomy at the same time than standard reductive accounts are, and that what mechanistic explanations are able to do at best is showing that downward causation does not exist. (shrink)

I propose a dynamic causal approach to characterizing the notion of a mechanism. Levy and Bechtel, among others, have pointed out several critical limitations of the new mechanical philosophy, and pointed in a new direction to extend this philosophy. Nevertheless, they have not fully fleshed out what that extended philosophy would look like. Based on a closer look at neuroscientific practice, I propose that a mechanism is a dynamic causal system that involves various components interacting, typically nonlinearly, with one another (...) to produce a phenomenon of interest. (shrink)

Stem cell biology is driven by experiment. Its major achievements are striking experimental productions: "immortal" human cell lines from spare embryos (Thomson et al. 1998); embryo-like cells from "reprogrammed" adult skin cells (Takahashi and Yamanaka 2006); muscle, blood and nerve tissue generated from stem cells in culture (Lanza et al. 2009, and references therein). Well-confirmed theories are not so prominent, though stem cell biologists do propose and test hypotheses at a profligate rate. 1 This paper aims to characterize the role (...) of experiment in stem cell biology, so as to answer the following question: how do experiments contribute to our knowledge of stem cells and related phenomena? The .. (shrink)

We argue that artificial networks are explainable and offer a novel theory of interpretability. Two sets of conceptual questions are prominent in theoretical engagements with artificial neural networks, especially in the context of medical artificial intelligence: Are networks explainable, and if so, what does it mean to explain the output of a network? And what does it mean for a network to be interpretable? We argue that accounts of “explanation” tailored specifically to neural networks have ineffectively reinvented the wheel. In (...) response to, we show how four familiar accounts of explanation apply to neural networks as they would to any scientific phenomenon. We diagnose the confusion about explaining neural networks within the machine learning literature as an equivocation on “explainability,” “understandability” and “interpretability.” To remedy this, we distinguish between these notions, and answer by offering a theory and typology of interpretation in machine learning. Interpretation is something one does to an explanation with the aim of producing another, more understandable, explanation. As with explanation, there are various concepts and methods involved in interpretation: Total or Partial, Global or Local, and Approximative or Isomorphic. Our account of “interpretability” is consistent with uses in the machine learning literature, in keeping with the philosophy of explanation and understanding, and pays special attention to medical artificial intelligence systems. (shrink)

Mechanism realists assert the existence of mechanisms as objective structures in the world, but their exact metaphysical commitments are unclear. We introduce Local Hierarchy Realism (LHR) as a substantive and plausible form of mechanism realism. The limits of LHR reveal a deep tension between two aspects of mechanists’ explanatory strategy. Functional decomposition identifies locally relevant entities and activities, while these same entities and activities are also embedded in a nested hierarchy of levels. In principle, a functional decomposition may identify entities (...) engaging in causal interactions that crosscut the hierarchical structure of composition relations, violating the mechanist’s injunction against interlevel causation. We argue that this possibility is realized in the example of ephaptic coupling, a subsidiary process of neural computation that crosscuts the hierarchy derived from synaptic transmission. These considerations undermine the plausibility of LHR as a general view, yet LHR has the advantages that (i) its metaphysical implications are precisely stateable; (ii) the structure it identifies is not reducible to mere aggregate causation; and (iii) it clearly satisfies intuitive and informal definitions of mechanism. We conclude by assessing the prospects for a form of mechanism realism weaker than LHR that nevertheless satisfies all three of these requirements. (shrink)

Mechanism realists assert the existence of mechanisms as objective structures in the world, but their exact metaphysical commitments are unclear. We introduce Local Hierarchy Realism (LHR) as a substantive and plausible form of mechanism realism. The limits of LHR reveal a deep tension between two aspects of mechanists’ explanatory strategy. Functional decomposition identifies locally relevant entities and activities, while these same entities and activities are also embedded in a nested hierarchy of levels. In principle, a functional decomposition may identify entities (...) engaging in causal interactions that crosscut the hierarchical structure of composition relations, violating the mechanist’s injunction against interlevel causation. We argue that this possibility is realized in the example of ephaptic coupling, a subsidiary process of neural computation that crosscuts the hierarchy derived from synaptic transmission. These considerations undermine the plausibility of LHR as a general view, yet LHR has the advantages that (i) its metaphysical implications are precisely stateable; (ii) the structure it identifies is not reducible to mere aggregate causation; and (iii) it clearly satisfies intuitive and informal definitions of mechanism. We conclude by assessing the prospects for a form of mechanism realism weaker than LHR that nevertheless satisfies all three of these requirements. (shrink)

The new research program to understand mechanisms in biology has developed rapidly in the last 10 years. Reconsideration of the characterization of mechanisms in biology in the light of this recent work is now in order. This article discusses the perspectival aspect of the characterization of mechanisms, refinements in claims about working entities and kinds of activities, challenges and responses to claims about regularity, productive continuity, and the organizational aspects of a mechanism, and issues about representations of mechanisms in schemas (...) and sketches. †To contact the author, please write to: Committee for Philosophy and the Sciences, Department of Philosophy, 1125A Skinner Building, University of Maryland, College Park, MD 20742 USA; e‐mail: [email protected]. (shrink)

The technique of nuclear transplantation – popularly known as cloning – has been integrated into several different histories of twentieth century biology. Historians and science scholars have situated nuclear transplantation within narratives of scientific practice, biotechnology, bioethics, biomedicine, and changing views of life. However, nuclear transplantation has never been the focus of analysis. In this article, I examine the development of nuclear transplantation techniques, focusing on the people, motivations, and institutions associated with the first successful nuclear transfer in metazoans in (...) 1952. The conflict between embryologists and geneticists over the mechanisms of differentiation motivated Robert Briggs to pursue nuclear transplantation experiments as a way to resolve the debate. Briggs worked at the Lankenau Hospital Research Institute, a research facility devoted to the study of cancer. The goal of understanding cancer would play a role in the development of the technique, and the story of nuclear transplantation sheds light on the role that biomedical contexts play in biological research in the second half of the twentieth century. (shrink)

We argue that intelligible appeals to interlevel causes (top-down and bottom-up) can be understood, without remainder, as appeals to mechanistically mediated effects. Mechanistically mediated effects are hybrids of causal and constitutive relations, where the causal relations are exclusively intralevel. The idea of causation would have to stretch to the breaking point to accommodate interlevel causes. The notion of a mechanistically mediated effect is preferable because it can do all of the required work without appealing to mysterious interlevel causes. When interlevel (...) causes can be translated into mechanistically mediated effects, the posited relationship is intelligible and should raise no special philosophical objections. When they cannot, they are suspect. (shrink)

In what sense are the activities and properties of components in a mechanism explanatorily relevant to the behavior of a mechanism as a whole? I articulate this problem, the problem of constitutive relevance, and I show that it must be solved if we are to understand mechanisms and mechanistic explanation. I argue against some putative solutions to the problem of constitutive relevance, and I sketch a positive account according to which relevance is analyzed in terms ofrelationships of mutual manipulability between (...) the behavior of a mechanism as a whole and the properties and activities of its components. My account is a causal-mechanical account in the sense that it is a particular expression of the idea that constitutive explanation is a matter of showing how an explanandum phenomenon is situated within the causal structure of the world. It is thus offered as a rival to epistemic (argument-centered) and psychological accounts of interlevel explanation. (shrink)

Although “theory” has been the prevalent unit of analysis in the meta-study of science throughout most of the twentieth century, the concept remains elusive. I further explore the leitmotiv of several authors in this issue: that we should deal with theorizing (rather than theory) in biology as a cognitive activity that is to be investigated naturalistically. I first contrast how philosophers and biologists have tended to think about theory in the last century or so, and consider recent calls to upgrade (...) the role of theory in the life sciences against the background of the recent “data deluge” in molecular biology, systems biology, etc. I then review thinking about theory in biology in relation to physical theory as a positive or negative exemplar. I conclude by discussing various aspects of a positive program for “naturalizing theorizing.”. (shrink)

I propose we abandon the unit concept of "the evolutionary synthesis". There was much more to evolutionary studies in the 1920s and 1930s than is suggested in our commonplace narratives of this object in history. Instead, four organising threads capture much of evolutionary studies at this time. First, the nature of species and the process of speciation were dominating, unifying subjects. Second, research into these subjects developed along four main lines, or problem complexes: variation, divergence, isolation, and selection. Some calls (...) for 'synthesis' focused on these problem complexes (sometimes on one of these; other times, all). In these calls, comprehensive and pluralist compendia of plausibly relevant elements were preferred over reaching consensus about the value of particular formulae. Third, increasing confidence in the study of common problems coincided with methodological and epistemic changes associated with experimental taxonomy. Finally, the surge of interest in species problems and speciation in the 1930s is intimately tied to larger trends, especially a shifting balance in the life sciences towards process-based biologies and away from object-based naturalist disciplines. Advocates of synthesis in evolution supported, and were adapting to, these larger trends. (shrink)

The terms “perspectivism” and “perspectivalism” have been the focus of an intense philosophical discussion with important repercussions for the debate about the role of mechanisms in scientific explanations. However, leading exponents of the new mechanistic philosophy have conceded more than was necessary to the radically subjectivistic perspectivalism, and fell into the opposite error, by retaining not negligible residues of objectivistic views about mechanisms. In order to remove this vacillation between the subjective-cultural and the objective-natural sides of mechanisms, we shall raise (...) the question about theory-ladenness over again and interpret it in its connection with the technical–experimental nature of scientific knowledge, as affirming the perspectival character of scientific knowledge: It is because of the character at once theory-laden and practice-laden, i.e. technique-laden, of our putting questions to nature that empirical reality must be investigated from particular perspectives: nature can be known scientifically only from a potentially infinite number of perspectives or theoretical points of view, concretely exemplified by mechanisms or experimental ‘machines’ that allow specific access to specific aspects of sensible reality. (shrink)

In this introductory article to the special issue on Multi-level semiosis we attempt to stage the background for qualifying the notion of “multi-levelness” when considering communication processes and semiosis in all life forms, i.e. from the cellular to the organismic level. While structures are organized hierarchically, communication processes require a kind of processual organization that may be better described as being heterarchical. Theoretically, the challenge arises in the temporal domain, that is, in the developmental and evolutionary dimension of dynamic semiotic (...) processes. We discuss the importance of this fundamental difference in order to explain how levels, domains and orders of magnitude, on the one hand, and synchronic and diachronic processes, on the other, contribute to the overall organization of every living being. To account for such multi-level organization, semiotic freedom is assumed to be a scalar property that endows living systems at different levels and domains with the capacity to ponder selectively the overall structural coherence and functional compatibility of their heterarchical processing, which is increasingly less conditioned by the underlying molecular determinism. (shrink)

The paper discusses how systems biology is working toward complex accounts that integrate explanation in terms of mechanisms and explanation by mathematical models—which some philosophers have viewed as rival models of explanation. Systems biology is an integrative approach, and it strongly relies on mathematical modeling. Philosophical accounts of mechanisms capture integrative in the sense of multilevel and multifield explanations, yet accounts of mechanistic explanation have failed to address how a mathematical model could contribute to such explanations. I discuss how mathematical (...) equations can be explanatorily relevant. Several cases from systems biology are discussed to illustrate the interplay between mechanistic research and mathematical modeling, and I point to questions about qualitative phenomena, where quantitative models are still indispensable to the explanation. Systems biology shows that a broader philosophical conception of mechanisms is needed, which takes into account functional-dynamical aspects, interaction in complex networks with feedback loops, system-wide functional properties such as distributed functionality and robustness, and a mechanism’s ability to respond to perturbations. I offer general conclusions for philosophical accounts of explanation. (shrink)

This essay analyzes and develops recent views about explanation in biology. Philosophers of biology have parted with the received deductive-nomological model of scientific explanation primarily by attempting to capture actual biological theorizing and practice. This includes an endorsement of different kinds of explanation (e.g., mathematical and causal-mechanistic), a joint study of discovery and explanation, and an abandonment of models of theory reduction in favor of accounts of explanatory reduction. Of particular current interest are philosophical accounts of complex explanations that appeal (...) to different levels of organismal organization and use contributions from different biological disciplines. The essay lays out one model that views explanatory integration across different disciplines as being structured by scientific problems. I emphasize the philosophical need to take the explanatory aims pursued by different groups of scientists into account, as explanatory aims determine whether different explanations are competing or complementary and govern the dynamics of scientific practice, including interdisciplinary research. I distinguish different kinds of pluralism that philosophers have endorsed in the context of explanation in biology, and draw several implications for science education, especially the need to teach science as an interdisciplinary and dynamic practice guided by scientific problems and explanatory aims. (shrink)

The paper works towards an account of explanatory integration in biology, using as a case study explanations of the evolutionary origin of novelties-a problem requiring the integration of several biological fields and approaches. In contrast to the idea that fields studying lower level phenomena are always more fundamental in explanations, I argue that the particular combination of disciplines and theoretical approaches needed to address a complex biological problem and which among them is explanatorily more fundamental varies with the problem pursued. (...) Solving a complex problem need not require theoretical unification or the stable synthesis of different biological fields, as items of knowledge from traditional disciplines can be related solely for the purposes of a specific problem. Apart from the development of genuine interfield theories, successful integration can be effected by smaller epistemic units (concepts, methods, explanations) being linked. Unification or integration is not an aim in itself, but needed for the aim of solving a particular scientific problem, where the problem's nature determines the kind of intellectual integration required. (shrink)

Mechanistic models in molecular systems biology are generally mathematical models of the action of networks of biochemical reactions, involving metabolism, signal transduction, and/or gene expression. They can be either simulated numerically or analyzed analytically. Systems biology integrates quantitative molecular data acquisition with mathematical models to design new experiments, discriminate between alternative mechanisms and explain the molecular basis of cellular properties. At the heart of this approach are mechanistic models of molecular networks. We focus on the articulation and development of mechanistic (...) models, identifying five constraints which guide the articulation of models in molecular systems biology. These constraints are not independent of one another, with the result that modeling becomes an iterative process. We illustrate the use of these constraints in the modeling of the mechanism for bistability in the lac operon. (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)

New sciences born or developed in the 20th century (information, materials, life science) are based on forms of complementarity that differ from the past. The paper discusses cognitive, or disciplinary, institutional, and technical complementarity. It argues that new sciences apply a reductionist explanatory strategy to complex multi-layered systems. In doing so the reductionist promise is falsified, generating the need for multi-level kinds of explanation (e.g. in post-genomic molecular biology), new forms of complementarity between scientific and non-scientific organizations, and new forms (...) of experimental and informational facilities. The paper develops the argument in theoretical terms, comparing it with the STS literature, and offers preliminary evidence based on the experience of Networks of Excellence. (shrink)

Not only has the philosophical debate on causation been gaining ground in the last few decades, but it has also increasingly addressed the sciences. The biomedical sciences are among the most prominent fields that have been considered, with a number of works tackling the understanding of the notion of cause, the assessment of genuinely causal relations and the use of causal knowledge in applied contexts. Far from denying the merits of the debate on causation and the major theories it comprises, (...) this paper is meant as a stimulus for theorists of causation in the philosophy of biomedicine, with a focus on clinical matters. Without aiming at putting forward an original theory of causation and starting from the narration of two actual but paradigmatic cases at the joints between biomedical research and clinical practice, we want to point out that some pathological situations addressed by molecular medicine actually prove resistant to some of our major epistemological accounts of causal explanation. Given this scenario, which is very frequent in our hospitals, our analysis aims to provide a stimulus for the debate among theorists of causation in biomedicine interested in real cases in science in practice. We believe that this might in turn encourage some more general rethinking of the complex intertwinement of science, philosophy of science and ethics, as well as of the role of philosophy of science for clinical medicine itself. (shrink)

Research on diseases such as cancer reveals that primary mechanisms, which have been the focus of study by the new mechanists in philosophy of science, are often subject to control by other mechanisms. Cancer cells employ the same primary mechanisms as healthy cells but control them differently. I use cancer research to highlight just how widespread control is in individual cells. To provide a framework for understanding control, I reconceptualize mechanisms as imposing constraints on flows of free energy, with control (...) mechanisms operating on flexible constraints in primary mechanisms. I argue that control mechanisms themselves often form complex, integrated networks. (shrink)

Research in many fields of biology has been extremely successful in decomposing biological mechanisms to discover their parts and operations. It often remains a significant challenge for scientists to recompose these mechanisms to understand how they function as wholes and interact with the environments around them. This is true of the eukaryotic cell. Although initially identified in nineteenth-century cell theory as the fundamental unit of organisms, researchers soon learned how to decompose it into its organelles and chemical constituents and have (...) been highly successful in understanding how these carry out many operations important to life. The emphasis on decomposition is particularly evident in modern cell biology, which for the most part has viewed the cell as merely a locus of the mechanisms responsible for vital phenomena. The cell, however, is also an integrated system and for some explanatory purposes it is essential to recompose it and understand it as an organized whole. I illustrate both the virtues of decomposition (treating the cell as a locus) and recomposition (treating the cell as an object) with recent work on circadian rhythms. Circadian researchers have both identified critical intracellular operations that maintain endogenous oscillations and have also addressed the integration of cells into multicellular systems in which cells constitute units. Ó 2010 Elsevier Ltd. All rights reserved. (shrink)

Cognitive science is an interdisciplinary research endeavor focusing on human cognitive phenomena such as memory, language use, and reasoning. It emerged in the second half of the 20th century and is charting new directions at the beginning of the 21st century. This chapter begins by identifying the disciplines that contribute to cognitive science and reviewing the history of the interdisciplinary engagements that characterize it. The second section examines the role that mechanistic explanation plays in cognitive science, while the third focuses (...) on the importance of mental representations in specifically cognitive explanations. The fourth section considers the interdisciplinary nature of cognitive science and explores how multiple disciplines can contribute to explanations that exceed what any single discipline might accomplish. The conclusion sketches some recent developments in cognitive science and their implications for philosophers. (shrink)

The neuron doctrine, according to which nerves consist of discontinuous neurons, presented investigators with the challenge of determining what activities occurred between them or between them and muscles. One group of researchers, dubbed the sparks, viewed the electrical current in one neuron as inducing a current in the next neuron or in muscles. For them there was no gap between the activities of neurons or neurons and muscles that required filling with a new type of activity. A competing group, the (...) soups, came to argue for chemicals, subsequently referred to neurotransmitters, as carrying out the activities between neurons or between neurons and muscles. But even for them the conclusion that chemicals performed this activity was only arrived over time. I examine the prolonged period in which proponents of chemical transmission developed their account and challenged the sparks. My goal is to illuminate the epistemic processes that led to the discovery of a new scientific phenomenon—chemical transmission between neurons. (shrink)

The pursuit of mechanistic explanations in biology has produced a great deal of knowledge about the parts, operations, and organization of mechanisms taken to be responsible for biological phenomena. Holist critics have often raised important criticisms of proposed mechanistic explanations, but until recently holists have not had alternative research strategies through which to advance explanations. This paper argues both that the results of mechanistic strategies has forced mechanists to confront ways in which whole systems affect their components and that new (...) representational and modeling strategies are providing tools for understanding these effects of whole systems upon components. Drawing from research on the mechanism responsible for circadian rhythms in mammals, I develop two examples in which mechanistic analysis is being integrated into a more holist perspective: research revealing intercellular integration of circadian mechanisms with those involved in cell metabolism and research revealing that stable␣rhythms are dependent on how individual cells in the suprachiasmatic nucleus synchronize with each other to generate regular rhythms. Tools such as network diagramming and computational modeling are providing means to integrate mechanistic models into accounts of whole systems. (shrink)

Cognitive psychologists, like biologists, frequently describe mechanisms when explaining phenomena. Unlike biologists, who can often trace material transformations to identify operations, psychologists face a more daunting task in identifying operations that transform information. Behavior provides little guidance as to the nature of the operations involved. While not itself revealing the operations, identification of brain areas involved in psychological mechanisms can help constrain attempts to characterize the operations. In current memory research, evidence that the same brain areas are involved in what (...) are often taken to be different memory phenomena or in other cognitive phenomena is playing such a heuristic function. †To contact the author, please write to: Department of Philosophy, 0119, University of California, San Diego, La Jolla, CA 92093‐0119; e‐mail: [email protected]. (shrink)

Accounts of mechanistic explanation have emphasized the importance of looking down—decomposing a mechanism into its parts and operations. Using research on visual processing as an exemplar, I illustrate how productive such research has been. But once multiple components of a mechanism have been identified, researchers also need to figure out how it is organized—they must look around and determine how to recompose the mechanism. Although researchers often begin by trying to recompose the mechanism in terms of sequential operations, they frequently (...) find that the components of a mechanism interact in complex ways involving positive and negative feedback and that the organization often exhibits highly interactive local networks linked by a few long-range connections (small-worlds organization) and power law distributions of connections. The mechanisms are themselves active systems that are perturbed by inputs but not set in motion by them. Researchers also need to look up —situate a mechanism in its context, which may be a larger mechanism that modulates its behavior. When looking down is combined with looking around and up, mechanistic research results in an integrated, multi-level perspective. (shrink)

Developing models of biological mechanisms, such as those involved in respiration in cells, often requires collaborative effort drawing upon techniques developed and information generated in different disciplines. Biochemists in the early decades of the 20th century uncovered all but the most elusive chemical operations involved in cellular respiration, but were unable to align the reaction pathways with particular structures in the cell. During the period 1940-1965 cell biology was emerging as a new discipline and made distinctive contributions to understanding the (...) role of the mitochondrion and its component parts in cellular respiration. In particular, by developing techniques for localizing enzymes or enzyme systems in specific cellular components, cell biologists provided crucial information about the organized structures in which the biochemical reactions occurred. Although the idea that biochemical operations are intimately related to and depend on cell structures was at odds with the then-dominant emphasis on systems of soluble enzymes in biochemistry, a reconceptualization of energetic processes in the 1960s and 1970s made it clear why cell structure was critical to the biochemical account. This paper examines how numerous excursions between biochemistry and cell biology contributed a new understanding of the mechanism of cellular respiration. (shrink)

In many domains of biology, explanation takes the form of characterizing the mechanism responsible for a particular phenomenon in a specific biological system. How are such explanations generalized? One important strategy assumes conservation of mechanisms through evolutionary descent. But conservation is seldom complete. In the case discussed, the central mechanism for circadian rhythms in animals was first identified in Drosophila and then extended to mammals. Scientists' working assumption that the clock mechanisms would be conserved both yielded important generalizations and served (...) as a heuristic for discovery, especially when significant differences between the insect and mammalian mechanism were identified. †To contact the author, please write to: Department of Philosophy and Interdisciplinary Programs in Science Studies and Cognitive Science, 0119, University of California, San Diego, La Jolla, CA 92093‐0119; e‐mail: [email protected]. (shrink)

In many fields in the life sciences investigators refer to downward or top-down causal effects. Craver and Bechtel defended the view that such cases should be understood in terms of a constitution relation between levels in a mechanism and causation as solely an intra-level relation. Craver and Bechtel, however, provided insufficient specification as to when entities constitute a higher-level mechanism. In this paper I appeal to graph-theoretic representations of networks that are now widely employed in systems biology and neuroscience to (...) identify mechanisms with the modules that exhibit high clustering. As a result of the interconnections of nodes in these modules/mechanisms, they often exhibit complex dynamic behaviors that constrain how the individual components respond to external inputs, an important feature of cases viewed as involving top-down causation. (shrink)

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)

Two widely accepted assumptions within cognitive science are that (1) the goal is to understand the mechanisms responsible for cognitive performances and (2) computational modeling is a major tool for understanding these mechanisms. The particular approaches to computational modeling adopted in cognitive science, moreover, have significantly affected the way in which cognitive mechanisms are understood. Unable to employ some of the more common methods for conducting research on mechanisms, cognitive scientists’ guiding ideas about mechanism have developed in conjunction with their (...) styles of modeling. In particular, mental operations often are conceptualized as comparable to the processes employed in classical symbolic AI or neural network models. These models, in turn, have been interpreted by some as themselves intelligent systems since they employ the same type of operations as does the mind. For this paper, what is significant about these approaches to modeling is that they are constructed specifically to account for behavior and are evaluated by how well they do so—not by independent evidence that they describe actual operations in mental mechanisms. (shrink)