The aim of this paper is to present some system-theoretical notions ─ such as constraint, closure, integration, coordination, etc. ─ which have recently raised a renovated interest and have undergone a deep development, especially in those branches of philosophy of biology characterized by a systemic approach. The im- plications of these notions for the analysis and characterization of self-maintaining organizations will be discussed with the aid of examples taken from models of minimal living systems, and some conceptual distinctions will be (...) provided. In the last part of the paper the epistemic implications of these ideas will be presented. (shrink)

Living systems employ several mechanisms and behaviors to achieve robustness and maintain themselves under changing internal and external conditions. Regulation stands out from them as a specific form of higher-order control, exerted over the basic regime responsible for the production and maintenance of the organism, and provides the system with the capacity to act on its own constitutive dynamics. It consists in the capability to selectively shift between different available regimes of self-production and self-maintenance in response to specific signals and (...) perturbations, due to the action of a dedicated subsystem which is operationally distinct from the regulated ones. The role of regulation, however, is not exhausted by its contribution to maintain a living system’s viability. While enhancing robustness, regulatory mechanisms play a fundamental role in the realization of an autonomous biological organization. Specifically, they are at the basis of the remarkable integration of biological systems, insofar as they coordinate and modulate the activity of distinct functional subsystems. Moreover, by implementing complex and hierarchically organized control architectures, they allow for an increase in structural and organizational complexity while minimizing fragility. Finally, they endow living systems, from their most basic unicellular instances, with the capability to control their own internal dynamics to adaptively respond to specific features of their interaction with the environment, thus providing the basis for the emergence of minimal forms of cognition. (shrink)

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

The aim of this paper is to present the ontic approach to the normativity of cognitive functions and mechanisms, which is directly related to the understanding of biological normativity in terms of normative mechanisms. This approach assumes the hypothesis that cognitive processes contain a certain normative component independent of external attributions and researchers’ beliefs. This component consists of specific cognitive mechanisms, which I call normative. I argue that a mechanism is normative when it constitutes given actions or behaviors of a (...) system. More precisely, it means that, on the one hand, it is their constitutive cause, and on the other hand, it determines a certain field of possibilities from which the system, guided by its own goals, preferences, environmental constraints, etc., chooses the appropriate action or behavior according to a given situation. The background for the analyses presented here is the predictive processing framework, in which it can be shown that at least some of the predictive mechanisms are in fact normative mechanisms. I refer here to the existence of a motivational relation which determines the normative dependence of the agent’s actions due to specific predictions and environmental constraints. (shrink)

In this paper, we advocate the idea that an adequate explanation of biological systems requires appealing to organizational closure as an emergent causal regime. We first develop a theoretical justification of emergence in terms of relatedness, by arguing that configurations, because of the relatedness among their constituents, possess ontologically irreducible properties, providing them with distinctive causal powers. We then focus on those emergent causal powers exerted as constraints, and we claim that biological systems crucially differ from other natural systems in (...) that they realize a closure of constraints, i.e. a second-order emergent regime of causation such that the constituents, each of them acting as a constraint, realize a mutual dependence among them, and are collectively able to self-maintain. Lastly, we claim that closure can be justifiably taken as an emergent regime of causation, without admitting that it inherently involves whole-parts causation, which would require to commit to stronger ontological and epistemological assumptions. (shrink)

Much of the current research in regenerative medicine concentrates on stem-cell therapy that exploits the regenerative capacities of stem cells when injected into different types of human tissues. Although new therapeutic paths have been opened up by induced pluripotent cells and human mesenchymal cells, the rate of success is still low and mainly due to the difficulties of managing cell proliferation and differentiation, giving rise to non-controlled stem cell differentiation that ultimately leads to cancer. Despite being still far from becoming (...) a reality, these studies highlight the role of physical and biological constraints (e.g., cues and morphogenetic fields) placed by tissue microenvironment on stem cell fate. This asks for a clarification of the coupling of stem cells and microenvironmental factors in regenerative medicine. We argue that extracellular matrix and stem cells have a causal reciprocal and asymmetric relationship in that the 3D organization and composition of the extracellular matrix establish a spatial, temporal, and mechanical control over the fate of stem cells, which enable them to interact and control (as well as be controlled by) the cellular components and soluble factors of microenvironment. Such an account clarifies the notions of stemness and stem cell regeneration consistently with that of microenvironment. (shrink)

Moral rationalism has long been an attractive position within moral philosophy. However, among empirical-minded philosophers, it is widely dismissed as scientifically untenable. In this essay, I argue that moral rationalism’s lack of uptake in the empirical domain is due to the widespread supposition that moral rationalists must hold that moral judgments and actions are produced by rational capacities. But this construal is mistaken: moral rationalism’s primary concern is not with the relationship between moral judgments and rational capacities per se, but (...) rather with developing a conception objectivity normativity that avoids Platonism. In light of this, I develop an alternative approach to translating moral rationalism into the empirical domain that builds on the common rationalist view that normative requirements are explained by the relationship between agents and the social structures and practices in which they are embedded. I propose that this social conception of normativity can be translated into a scientific framework by interpreting it as a claim about the importance of constraint-based explanation when accounting for norm-governed behavior. In order to develop this point more concretely and show that it is empirically tractable, I turn to research on macaque social organization that highlights the ways in which normative standards are generated by empirically observable social structures. The insights garnered from the macaque case allow me to then locate moral rationalism’s core claims about the relationship between morality and the standards of practical rationality within an empirically plausible framework. (shrink)

The concept of levels of organization, despite its widespread scientific currency, has recently been criticized by a number of philosophers of science. This paper diagnoses the main source of problems facing theories of levels. On this basis, the problems with the usual criteria for distinguishing levels are evaluated: compositional relations, organizational types, and spatial scales. Drawing on some work on hierarchies in ecology, I argue in favor of an alternative conception of levels defined by the criterion of rates or time (...) scales of processes. (shrink)

The logic of genetic discovery has changed little over time, but the focus of biology is shifting from simple genotype–phenotype relationships to complex metabolic, physiological, developmental, and behavioral traits. In light of this, the traditional reductionist view of individual genes as privileged difference‐making causes of phenotypes is re‐examined. The scope and nature of genetic effects in complex regulatory systems, in which dynamics are driven by regulatory feedback and hierarchical interactions across levels of organization are considered. This review argues that it (...) is appropriate to treat genes as specific actual difference‐makers for the molecular regulation of gene expression. However, they are often neither stable, proportional, nor specific as causes of the overall dynamic behavior of regulatory networks. Dynamical models, properly formulated and validated, provide the tools to probe cause‐and‐effect relationships in complex biological systems, allowing to go beyond the limitations of genetic reductionism to gain an integrative understanding of the causal processes underlying complex phenotypes. (shrink)

The Linda paradox is a key topic in current debates on the rationality of human reasoning and its limitations. We present a novel analysis of this paradox, based on the notion of verisimilitude as studied in the philosophy of science. The comparison with an alternative analysis based on probabilistic confirmation suggests how to overcome some problems of our account by introducing an adequately defined notion of verisimilitudinarian confirmation.

The aim of this paper is to provide a theoretical framework to understand how multicellular systems realize functionally integrated physiological entities by organizing their intercellular space. From a perspective centered on physiology and integration, biological systems are often characterized as organized in such a way that they realize metabolic self-production and self-maintenance. The existence and activity of their components rely on the network they realize and on the continuous management of the exchange of matter and energy with their environment. One (...) of the virtues of the organismic approach focused on organization is that it can provide an understanding of how biological systems are functionally integrated into coherent wholes. Organismic frameworks have been primarily developed by focusing on unicellular life. Multicellularity, however, presents additional challenges to our understanding of biological systems, related to how cells are capable to live together in higher-order entities, in such a way that some of their features and behaviors are constrained and controlled by the system they realize. Whereas most accounts of multicellularity focus on cell differentiation and increase in size as the main elements to understand biological systems at this level of organization, we argue that these factors are insufficient to provide an understanding of how cells are physically and functionally integrated in a coherent system. In this paper, we provide a new theoretical framework to understand multicellularity, capable to overcome these issues. Our thesis is that one of the fundamental theoretical principles to understand multicellularity, which is missing or underdeveloped in current accounts, is the functional organization of the intercellular space. In our view, the capability to be organized in space plays a central role in this context, as it enables (and allows to exploit all the implications of) cell differentiation and increase in size, and even specialized functions such as immunity. We argue that the extracellular matrix plays a crucial active role in this respect, as an evolutionary ancient and specific (non-cellular) control subsystem that contributes as a key actor to the functional specification of the multicellular space and to modulate cell fate and behavior. We also analyze how multicellular systems exert control upon internal movement and communication. Finally, we show how the organization of space is involved in some of the failures of multicellular organization, such as aging and cancer. (shrink)