_Philosophy of Molecular Medicine: Foundational Issues in Theory and Practice_ aims at a systematic investigation of a number of foundational issues in the field of molecular medicine. The volume is organized around four broad modules focusing, respectively, on the following key aspects: What are the nature, scope, and limits of molecular medicine? How does it provide explanations? How does it represent and model phenomena of interest? How does it infer new knowledge from data and experiments? The essays collected here, authored (...) by prominent scientists and philosophers of science, focus on a handful of mainstream topics in the philosophical literature, such as _causation_, _explanation_, _modeling_, and _scientific inference_. These previously unpublished contributions shed new light on these traditional topics by integrating them with problems, methods, and results from three prominent areas of contemporary biomedical science: _basic research_, _translational_ and _clinical research_, and _clinical practice_. (shrink)

During his celebrated 1922 debate with Bergson, Einstein famously proclaimed: “the time of the philosopher does not exist, there remains only a psychological time that differs from the physicist’s.” Einstein’s dictum, I maintain, has been metabolized by the natural sciences, which typically presuppose, more or less explicitly, the existence of a single, univocal, temporal substratum, ultimately determined by physics. This reductionistic assumption pervades much biological and biomedical practice. The chronological age allotted to individuals is conceived as an objective quantity, allowing (...) one to straightforwardly assign and compare the biological age of organisms. This essay argues that the standard practice of assessing the age and aging of organisms against the backdrop of a physical conception of time is problematic. This becomes especially evident in light of recent discoveries of various levels of senescence underlying the development of individual organisms—a phenomenon known as ‘age mosaicism.’ The bottom line is that the study of age and aging requires a biological conception of time, as opposed to a physical one. Einstein clearly wasn’t wrong about his operationalization of time in relativity theory. Still time may be less monolithic than he surmised. (shrink)

Causal relations among components and activities are intentionally misrepresented in mechanistic explanations found routinely across the life sciences. Since several mechanists explicitly advocate accurately representing factors that make a difference to the outcome, these idealizations conflict with the stated rationale for mechanistic explanation. We argue that these idealizations signal an overlooked feature of reasoning in molecular and cell biology—mechanistic explanations do not occur in isolation—and suggest that explanatory practices within the mechanistic tradition share commonalities with model-based approaches prevalent in population (...) biology. (shrink)

This article presents and discusses one of the most prominent inferential strategies currently employed in cognitive neuropsychology, namely, reverse inference. Simply put, this is the practice of inferring, in the context of experimental tasks, the engagement of cognitive processes from locations or patterns of neural activation. This technique is notoriously controversial because, critics argue, it presupposes the problematic assumption that neural areas are functionally selective. We proceed as follows. We begin by introducing the basic structure of traditional “location-based” reverse inference (...) and discuss the influential lack of selectivity objection. Next, we rehearse various ways of responding to this challenge and provide some reasons for cautious optimism. The second part of the essay presents a more recent development: “pattern-decoding reverse inference”. This inferential strategy, we maintain, provides an even more convincing response to the lack of selectivity charge. Due to this and other methodological advantages, it is now a prominent component in the toolbox of cognitive neuropsychology. Finally, we conclude by drawing some implications for philosophy of science and philosophy of mind. (shrink)

Philosophers have traditionally addressed the issue of scientific unification in terms of theoretical reduction. Reductive models, however, cannot explain the occurrence of unification in areas of science where successful reductions are hard to find. The goal of this essay is to analyse a concrete example of integration in biology—the developmental synthesis—and to generalize it into a model of scientific unification, according to which two fields are in the process of being unified when they become explanatorily relevant to each other. I (...) conclude by suggesting that this methodological conception of unity, which is independent of the debate on the metaphysical foundations of science, is closely connected to the notion of interdisciplinarity. 1 Introduction2 Some Troubles with Theory Reduction3 Interfield and Mechanistic Unification4 Foundations of the Developmental Synthesis5 Explanatory Relevance6 Concluding Remarks. (shrink)

Bricks and boxes -- Between Scylla and Charybdis -- Lessons from the history of science -- Placeholders -- Black-boxing 101 -- History of science 'black-boxing style' -- Diet mechanistic philosophy -- Emergence reframed -- The fuel of scientific progress -- Sailing through the strait.

The aim of this article is to discuss the conditions under which functional neuroimaging can contribute to the study of higher cognition. We begin by presenting two case studies—on moral and economic decision making—which will help us identify and examine one of the main ways in which neuroimaging can help advance the study of higher cognition. We agree with critics that functional magnetic resonance imaging (fMRI) studies seldom “refine” or “confirm” particular psychological hypotheses, or even provide details of the neural (...) implementation of cognitive functions. However, we suggest that neuroimaging can support psychology in a different way—namely, by selecting among competing hypotheses of the cognitive mechanisms underlying some mental function. One of the main ways in which neuroimaging can be used for hypothesis selection is via reverse inferences, which we here examine in detail. Despite frequent claims to the contrary, we argue that successful reverse inferences do not assume any strong or objectionable form of reductionism or functional locationism. Moreover, our discussion illustrates that reverse inferences can be successful at early stages of psychological theorizing, when models of the cognitive mechanisms are only partially developed. (shrink)

Reductionists in biology claim that all biological events can be explained in terms of genes and macromolecules alone, while antireductionists argue that some biological events must be explained at a higher level. The literature, however, does not distinguish between different kinds of molecular explanation. The goal of this article is to identify and analyze three such kinds. The analysis of molecular explanations herein carries an important philosophical implication; in shunning crude reductionism and extreme versions of holism, we can combine the (...) insights of thoughtful reductionists with sophisticated antireductionism. When this is done, the question of explanatory reductionism becomes less substantial than often supposed. (shrink)

This essay is concerned with concentrations of entities, which play an important—albeit often overlooked—role in scientific explanation. First, I discuss an example from molecular biology to show that concentrations can play an irreducible causal role. Second, I provide a preliminary philosophical analysis of this causal role, suggesting some implications for extant theories of causation. I conclude by introducing the concept of causation by concentration, a form of statistical causation whose widespread presence throughout the sciences has been unduly neglected and which (...) deserves to be studied in more depth. 1 Introduction2 Solving Lillie's Paradox: Lysogenic Induction in Phage λ3 Repressor Concentration and the Tuning of the Switch4 Concentration and Causality5 Preemption in Concentrations: Analysis and Implications6 Causation by Concentration: General Definition, Refinements, and Further Applications. (shrink)

The ‘species problem’ can be characterized, to a first approximation, as the task of providing a viable species concept —that is, a functional analysis that picks out the ‘right’ kind of biological entities. After decades of debate and centuries of taxonomic practice, no overarching consensus has been reached. The individuation and definition of the units of evolution and classification, species included, remains controversial. If anything, there now seems to be more disagreement than ever before.

This essay examines the relation between causation and causal explanation. It distinguishes two prominent roles that causes play within the sciences. On the one hand, causes may work as metaphysical posits. From this standpoint, mainstream in contemporary philosophy, causation provides the ‘raw material’ for explanation. On the other hand, causes may be conceived as explanatory postulates, theoretical hypotheses lacking any substantial ontological commitment. This unduly neglected distinction provides the conceptual resources to revisit longstanding philosophical issues, such as overdetermination and causal (...) pluralism. It also inspires a provocative reframing of Russell’s famous, if notoriously elusive, remarks on the nature of causation. (shrink)

This article explores the complementary strengths and weaknesses of grounded and abstract representations in the domain of early algebra. Abstract representations, such as algebraic symbols, are concise and easy to manipulate but are distanced from any physical referents. Grounded representations, such as verbal descriptions of situations, are more concrete and familiar, and they are more similar to physical objects and everyday experience. The complementary computational characteristics of grounded and abstract representations lead to trade‐offs in problem‐solving performance. In prior research with (...) high school students solving relatively simple problems, Koedinger and Nathan (2004) demonstrated performance benefits of grounded representations over abstract representations—students were better at solving simple story problems than the analogous equations. This article extends this prior work to examine both simple and more complex problems in two samples of college students. On complex problems with two references to the unknown, a “symbolic advantage” emerged, such that students were better at solving equations than analogous story problems. Furthermore, the previously observed “verbal advantage” on simple problems was replicated. We thus provide empirical support for a trade‐off between grounded, verbal representations, which show advantages on simpler problems, and abstract, symbolic representations, which show advantages on more complex problems. (shrink)

While philosophers tend to consider a single type of causal history, biologists distinguish between two kinds of causal history: evolutionary history and developmental history. This essay studies the peculiarity of development as a criterion for the individuation of biological traits and its relation to form, function, and evolution. By focusing on examples involving serial homologies and genetic reprogramming, we argue that morphology (form) and function, even when supplemented with evolutionary history, are sometimes insufficient to individuate traits. Developmental mechanisms bring in (...) a novel aspect to the business of classification—identity of process-type—according to which entities are type-identical across individuals and natural kinds in virtue of the fact that they form and develop through similar processes. These considerations bear important metaphysical implications and have potential applications in several areas of philosophy. (shrink)

Recent advancements in the brain sciences have enabled researchers to determine, with increasing accuracy, patterns and locations of neural activation associated with various psychological functions. These techniques have revived a longstanding debate regarding the relation between the mind and the brain: while many authors claim that neuroscientific data can be employed to advance theories of higher cognition, others defend the so-called ‘autonomy’ of psychology. Settling this significant issue requires understanding the nature of the bridge laws used at the psycho-neural interface. (...) While these laws have been the topic of extensive discussion, such debates have mostly focused on a particular type of link: reductive laws. Reductive laws are problematic: they face notorious philosophical objections and they are too scarce to substantiate current research at the intersection of psychology and neuroscience. The aim of this article is to provide a systematic analysis of a different kind of bridge laws—associative laws—which play a central, albeit overlooked role in scientific practice. (shrink)

The philosophy of mechanisms has developed rapidly during the last 30 years. As mechanisms-based explanations are often seen as an alternative to nomological, law-based explanations, MBEs could be relevant in IS. We begin by offering a short history of mechanistic philosophy and set out to clarify the contemporary landscape. We then suggest that mechanistic models provide an alternative to variance and process models in IS. Finally, we highlight how MBEs typically contain deliberate misrepresentations. Although MBEs have recently been advocated as (...) critical realist accounts in IS, idealizations seem to violate some fundamental tenets of CR and research method principles for CR. Idealizations in MBEs, therefore, may risk being regarded as flawed in IS. If it turns out that CR cannot account for idealizations, naturalism can, and it does so without extra-philosophical baggage. (shrink)

This essay presents a model-theoretic account of dispositional properties, according to which dispositions are not ordinary properties of real entities; dispositions capture the behavior of abstract, idealized models. This account has several payoffs. First, it saves the simple conditional analysis of dispositions. Second, it preserves the general connection between dispositions and regularities, despite the fact that some dispositions are not grounded in actual regularities. Finally, it brings together the analysis and the explanation of dispositions under a unified framework.

Biologists employ a suggestive metaphor to describe the complexities of molecular interactions within cells and embryos: cytological components are said to be part of “ecosystems” that integrate them in a complex network of relations with many other entities. The aim of this essay is to scrutinize the molecular ecosystem, a metaphor that, despite its longstanding history, has seldom be articulated in detail. I begin by analyzing some relevant analogies between the cellular environment and the biosphere. Next, I discuss the applicability (...) of the molecular ecosystem concept in actual scientific practice. (shrink)

Much problem solving and learning research in math and science has focused on formal representations. Recently researchers have documented the use of unschooled strategies for solving daily problems -- informal strategies which can be as effective, and sometimes as sophisticated, as school-taught formalisms. Our research focuses on how formal and informal strategies interact in the process of doing and learning mathematics. We found that combining informal and formal strategies is more effective than single strategies. We provide a theoretical account of (...) this multiple strategy effect and have begun to formulate this theory in an ACT-R computer model. We show why students may reach common impasses in the use of written algebra, and how subsequent or concurrent use of informal strategies leads to better problem-solving performance. Formal strategies facilitate computation because of their abstract and syntactic nature; however, abstraction can lead to nonsensical interpretations and conceptual errors. Reapplying the formal strategy will not repair such errors; switching to an informal one may. We explain the multiple strategy effect as a complementary relationship between the computational efficiency of formal strategies and the sense-making function of informal strategies. (shrink)

This essay enriches causal models capturing the propagation of prejudice, bias, and other aggregative social mechanisms, negative or positive. These explananda include the reinforcement of economic inequality, “mob-like” behavior, peer pressure, and the establishment of social norms. The stage is set by introducing various forms of redundant causation and discussing some difficulties with mainstream preemption. Next the main proposal extends current representations of aggregative social mechanisms in two respects. First, it is more nuanced, as it identifies three distinct kinds of (...) inferences: relevance of causes to effects, degree of redundancy of an effect, and the influence that causes exert on other causes. Second, it offers a quantitative—as opposed to merely qualitative—distinction between the causal contribution of preempting and preempted causes. (shrink)

Recent advancements in the brain sciences have enabled researchers to determine, with increasing accuracy, patterns and locations of neural activation associated with various psychological functions. These techniques have revived a longstanding debate regarding the relation between the mind and the brain: while many authors now claim that neuroscientific data can be used to advance our theories of higher cognition, others defend the so-called `autonomy' of psychology. Settling this significant question requires understanding the nature of the bridge laws used at the (...) psycho-neural interface. While these laws have been the topic of extensive discussion, such debates have mostly focused on a particular type of link: reductive laws. Reductive laws are problematic: they face notorious philosophical objections and they are too scarce to substantiate current research at the interface of psychology and neuroscience. The aim of this article is to provide a systematic analysis of a different kind of bridge laws--associative laws--which play a central, albeit often overlooked, role in scientific practice. (shrink)

These essays engage Jin Y. Park’s recent translation of the work of Kim Iryŏp, a Buddhist nun and public intellectual in early twentieth-century Korea. Park’s translation of Iryŏp’s Reflections of a Zen Buddhist Nun was the subject of two book panels at recent conferences: the first a plenary session at the annual meeting of the Society for Asian and Comparative Philosophy and the second at the Eastern Division of the American Philosophical Association on a group program session sponsored by the (...) International Society for Buddhist Philosophy. This exchange also includes a response from Park. (shrink)

This article develops an analysis of disability according to which disabling conditions are properties of organisms embedded in sets of environments. We begin by presenting the three mainstream accounts of disability—the medical, social, and interactionist models—and rehearsing some known limitations. We argue that, because of their primary focus on etiology, all three models share, more or less implicitly, a problematic assumption. This is the tenet that disabilities are individual properties. The second part of the essay presents an “ecological” interpretation of (...) disability, inspired by classic and contemporary research on biological niches. Our proposal preserves many insights underlying extant approaches, while allowing a more accurate characterization of the nature and experience of disability. We conclude by drawing some general implications of our analysis. (shrink)

The aim of this dissertation is to provide an analysis of central concepts in philosophy of science from the perspective of current molecular and developmental research. Each chapter explores the ways in which particular phenomena or discoveries in molecular biology influences our philosophical understanding of the nature of scientific knowledge. The introductory prologue draws some general connections between the various threads, which revolve around two central themes: causation and explanation. Chapter Two identifies a particular type of causal relation which is (...) widespread across the sciences, but cannot be straightforwardly accommodated by extant accounts of causation and causal explanation. Chapter Three explores how the form of redundant causality identified in the previous chapter plays an important role in causal explanation, by making the effect stable and robust. Chapter Four offers a novel perspective on the debate over biological reductionism by distinguishing between different paradigms of molecular explanation. Chapter Five provides a philosophical analysis of the so-called "Developmental Synthesis" of evolutionary and developmental biology, and suggests a general account of scientific unification grounded in the notion of explanatory relevance. Chapter Six offers an account of dispositional properties inspired by mechanisms of gene regulation, according to which dispositions are not properties of entities, but properties that describe the behavior of abstract idealized models. Finally, Chapter Seven scrutinizes the concept of the molecular ecosystem, a metaphor frequently employed by biologists to describe cellular interactions, but seldom articulated in detail. (shrink)

Science and philosophy have discovered quite a lot about humans. The emergence and development of biology, psychology, anthropology, and cognate fields has substantially increased our knowledge about who we are and where we come from. The first half of this book provides an overview of key cutting-edge topics, from evolutionary psychology to contemporary critiques of essentialism, from genetic determinism to innateness. Nevertheless, these discoveries fall short of a full-blown theory of human nature. Why? Perhaps there is nothing there to discover (...) in the first place. Human nature, from this standpoint, is a myth and it is high time we dispose of it. This conclusion is misguided. The assumption of a shared human nature underlies some of the most pressing socio-political issues of our time. These are the subject matter of the second half of this book. From races to sex and gender, from medical therapy to disability, from biotechnological enhancement to transhumanism, all these hot debates - surveyed here in an accessible, concise, yet detailed fashion - presuppose a robust account of human nature that, however, science and philosophy are unable to provide. How do we get out of this conundrum? This study concludes that human nature is an epistemological indicator, a concept that sets out the agenda for much social, political, and normative discourse. Nevertheless, science cannot adequately capture it without thereby dissolving it. (shrink)

Theories of grounded and embodied cognition offer a range of accounts of how reasoning and body‐based processes are related to each other. To advance theories of grounded and embodied cognition, we explore the cognitive relevance of particular body states to associated math concepts. We test competing models of action‐cognition transduction to investigate the cognitive relevance of directed actions to students’ mathematical reasoning in the area of geometry. The hypotheses we test include (1) that cognitively relevant directed actions have a direct (...) effect on performance (direct cognitive relevance hypothesis), (2) that cognitively relevant directed actions lead to more frequent production of gestures during explanations, which leads to improved performance (mediated cognitive relevance hypothesis), and (3) that performance effects of directed actions are influenced by the presence or absence of gesture production during mathematical explanations (moderated cognitive relevance hypothesis). We explore these hypotheses in an experiment where high school students (N = 85) evaluated the truth of geometry conjectures after performing cognitively relevant or cognitively irrelevant directed actions while playing a movement‐based video game. Contrary to the direct and mediated cognitive relevance hypotheses, we found no overall differences in performance or gesture production between relevant and irrelevant conditions. Consistent with the moderated cognitive relevance hypothesis, cognitive relevance influenced mathematical performance, as measured by the accuracy of students’ intuitions, insights, and the validity of their proofs, provided that students produced certain kinds of gestures during mathematical explanations (i.e., with explanatory gestures as the moderator). Implications for theories of grounded and embodied cognition and the design of embodied forms of educational interventions are discussed. (shrink)