Matteo Mossio

The Genotype-Phenotype (G-P) distinction was proposed in the context of Mendelian genetics, in the wake of late 19th century studies about heredity. In this paper, we provide a conceptual analysis that highlights that the G-P distinction was grounded on three pillars: observability, transmissibility, and causality. Originally, the genotype is the non-observable and transmissible cause of the phenotype, which is its observable and non-transmissible effect. We argue that the current developments of biology have called the validity of such pillars into question. First, molecular biology has unveiled the putative material substrate of the genotype (qua DNA), making it an observable object. Second, numerous findings on nongenetic heredity suggest that some phenotypic traits can be directly transmitted. Third, recent organicist approaches to biological phenomena have emphasized the reciprocal causality between parts of a biological system, which notably applies to the relations between genotypes and phenotypes. As a consequence, we submit that the G-P distinction has lost its general validity, although it can still apply to specific situations. This calls for forging new frameworks and concepts to better describe heredity and development.

We characterize Hegel's stance on biological purposiveness as consisting in a twofold move, which conceives organisms as intrinsically purposive natural systems and focuses on their behavioral and cognitive abilities. We submit that a Hegelian stance is at play in enactivism, the branch of the contemporary theory of biological autonomy devoted to the study of cognition and the mind. What is at stake in the Hegelian stance is the elaboration of a naturalized, although non-reductive, understanding of natural purposiveness.

Abstract : Through the comparison between two major, long-lasting theoretical frameworks-geocentrism and genocentrism-we discuss the different epistemological role played by metaphors in physics and biology. Throughout its history, physics developed theories and mathematical formalisms, which either do not seem to rely on metaphors at all (as geocentrism) or have absorbed initial thrusting metaphors into original theoretical frameworks. When considering genocentrism, in turn, the situation looks different. For some authors, genocentric theories are not metaphorical, but for opposite reasons with respect to geocentrism: pivotal concepts of information theories are straightforwardly imported as theoretical ones into biology. For others, the reference to information in genocentrism is indeed metaphorical, although the similarities and dissimilarities are not spelt out. Some problematic consequences of the application of genocentrism to biology are discussed.

We address the identity of biological organisms at play in experimental and modeling practices. We first examine the central tenets of two general conceptions, and we assess their respective strengths and weaknesses. The historical conception, on the one hand, characterizes organisms' identity by looking at their past, and specifically at their genealogical connection with a common ancestor. The relational conception, on the other hand, interprets organisms' identity by referring to a set of distinctive relations between their parts, and between the organism and its environment. While the historical and relational conceptions are understood as opposed and conflicting, we submit that they are also fundamentally complementary. Accordingly, we put forward a hybrid conception, in which historical and relational (and more specifically, organizational) aspects of organisms' identity sustain and justify each other. Moreover, we argue that organisms' identity is not only hybrid but also bounded, insofar as the compliance with specific identity criteria tends to vanish as time passes, especially across generations. We spell out the core conceptual framework of this conception, and we outline an original formal representation. We contend that the hybrid and bounded conception of organisms' identity suits the epistemological needs of biological practices, particularly with regards to the generalization and reproducibility of experimental results, and the integration of mathematical models with experiments.

Endocrinologists apply the idea of feedback loops to explain how hormones regulate certain bodily functions such as glucose metabolism. In particular, feedback loops focus on the maintenance of the plasma concentrations of glucose within a narrow range. Here, we put forward a different, organicist perspective on the endocrine regulation of glycaemia, by relying on the pivotal concept of closure of constraints. From this perspective, biological systems are understood as organized ones, which means that they are constituted of a set of mutually dependent functional structures acting as constraints, whose maintenance depends on their reciprocal interactions. Closure refers specifically to the mutual dependence among functional constraints in an organism. We show that, when compared to feedback loops, organizational closure can generate much richer descriptions of the processes and constraints at play in the metabolism and regulation of glycaemia, by making explicit the different hierarchical orders involved. We expect that the proposed theoretical framework will open the way to the construction of original mathematical models, which would provide a better understanding of endocrine regulation from an organicist perspective.

What does it mean to be the same organism over time? This chapter develops an understanding of diachronic identity of organisms from an organizational perspective. We argue that a necessary condition for diachronic identity is organizational continuity, i.e., the presence of a continuous causal process linking successive organizational regimes, irrespective of material and functional changes. Organizational continuity is not a sufficient condition, however, because it cannot discriminate between the development of the same individual and the reproduction of a new individual. We therefore suggest that there are temporal boundaries of identity when there are changes in the number of continuous organized systems, which occurs through fission, fusion, or a combination of the two. We discuss the utility of the resulting organizational view, as well as its relations with other approaches to biological individuality.

We develop a conceptual framework that connects biological heredity and organization. Heredity designates the cross-generation conservation of functional elements, defined as constraints subject to organizational closure. While hereditary objects are functional constituents of biological systems, any other entity that is stable across generations—and possibly involved in the recurrence of phenotypes—belongs to their environment. The central outcome of the organizational perspective consists in extending the scope of heredity beyond the genetic domain without merging it with the broad category of cross-generation stability. After discussing some implications, we conclude with a reflection on the relationship between stability and variation.

Darwin introduced the concept that random variation generates new living forms.  In this paper, we elaborate on Darwin's notion of random variation to propose that biological variation should be given the status of a fundamental theoretical principle in biology. We state that biological objects such as organisms are specific objects. Specific objects are special in that they are qualitatively different from each other. They can undergo unpredictable qualitative changes, some of which are not defined before they happen. We express the principle of variation in terms of symmetry changes, where symmetries underlie the theoretical determination of the object. We contrast the biological situation with the physical situation, where objects are generic (that is, different objects can be assumed to be identical) and evolve in well-defined state spaces. We derive several implications of the principle of variation, in particular, biological objects show randomness, historicity and contextuality. We elaborate on the articulation between this principle and the two other principles proposed in this special issue: the principle of default state and the principle of organization.

In the search of a theory of biological organisms, we propose to adopt organization as a theoretical principle. Organization constitutes an overarching hypothesis that frames the intelligibility of biological objects, by characterizing their relevant aspects. After a succinct historical survey on the understanding of organization in the organicist tradition, we offer a specific characterization in terms of closure of constraints. We then discuss some implications of the adoption of organization as a principle and, in particular, we focus on how it fosters an original approach to biological stability, as well as and its interplay with variation.

We reply to Artiga and Martinez’s claim according to which the organizational account of cross-generation functions implies a backward looking interpretation of etiology, just as standard etiological theories of function do. We argue that Artiga and Martinez’s claim stems from a fundamental misunderstanding about the notion of ‘‘closure’’, on which the organizational account relies. In particular, they incorrectly assume that the system, which is relevant for ascribing cross-generation organizational function, is the lineage. In contrast, we recall that organizational closure refers to a relational description of a network of mutual dependencies, abstracted from time, in which production relations are irrelevant. From an organizational perspective, ascribing a function to an entity means locating it in the abstract system that realizes closure. In particular, the position of each entity within the relational system conveys an etiological explanation of its existence, because of its dependence on the effects exerted by other entities subject to closure. Because of the abstract relational nature of closure, we maintain that the organizational account of functions does not endorse a backward looking interpretation of etiology. As a consequence, it does not fall prey of epiphenomenalism.

Organisms, be they uni- or multi-cellular, are agents capable of creating their own norms; they are continuously harmonizing their ability to create novelty and stability, that is, they combine plasticity with robustness. Here we articulate the three principles for a theory of organisms proposed in this issue, namely: the default state of proliferation with variation and motility, the principle of variation and the principle of organization. These principles profoundly change both biological observables and their determination with respect to the theoretical framework of physical theories. This radical change opens up the possibility of anchoring mathematical modeling in biologically proper principles.

Biological regulation is what allows an organism to handle the effects of a perturbation, modulating its own constitutive dynamics in response to particular changes in internal and external conditions. With the central focus of analysis on the case of minimal living systems, we argue that regulation consists in a specific form of second-order control, exerted over the core (constitutive) regime of production and maintenance of the components that actually put together the organism. The main argument is that regulation requires a distinctive architecture of functional relationships, and specifically the action of a dedicated subsystem whose activity is dynamically decoupled from that of the constitutive regime. We distinguish between two major ways in which control mechanisms contribute to the maintenance of a biological organisation in response to internal and external perturbations: dynamic stability and regulation. Based on this distinction an explicit definition and a set of organisational requirements for regulation are provided, and thoroughly illustrated through the examples of bacterial chemotaxis and the lac-operon. The analysis enables us to mark out the differences between regulation and closely related concepts such as feedback, robustness and homeostasis.

Since Darwin, Biology has been framed on the idea of evolution by natural selection, which has profoundly influenced the scientific and philosophical comprehension of biological phenomena and of our place in Nature. This book argues that contemporary biology should progress towards and revolve around an even more fundamental idea, that of autonomy. Biological autonomy describes living organisms as organised systems, which are able to self-produce and self-maintain as integrated entities, to establish their own goals and norms, and to promote the conditions of their existence through their interactions with the environment. Topics covered in this book include organisation and biological emergence, organisms, agency, levels of autonomy, cognition, and a look at the historical dimension of autonomy. The current development of scientific investigations on autonomous organisation calls for a theoretical and philosophical analysis. This can contribute to the elaboration of an original understanding of life - including human life - on Earth, opening new perspectives and enabling fecund interactions with other existing theories and approaches. This book takes up the challenge.

We propose a conceptual and formal characterisation of biological organisation as a closure of constraints. We first establish a distinction between two causal regimes at work in biological systems: processes, which refer to the whole set of changes occurring in non-equilibrium open thermodynamic conditions; and constraints, those entities which, while acting upon the processes, exhibit some form of conservation (symmetry) at the relevant time scales. We then argue that, in biological systems, constraints realise closure, i.e. mutual dependence such that they both depend on and contribute to maintaining each other. With this characterisation in hand, we discuss how organisational closure can provide an operational tool for marking the boundaries between interacting biological systems. We conclude by focusing on the original conception of the relationship between stability and variation which emerges from this framework.

This paper argues that biological organisation can be legitimately conceived of as an intrinsically teleological causal regime. The core of the argument consists in establishing a connection between organisation and teleology through the concept of self-determination: biological organisation determines itself in the sense that the effects of its activity contribute to determine its own conditions of existence. We suggest that not any kind of circular regime realises self-determination, which should be specifically understood as self-constraint: in biological systems, in particular, self-constraint takes the form of closure, i.e. a network of mutually dependent constitutive constraints. We then explore the occurrence of intrinsic teleology in the biological domain and beyond. On the one hand, the organisational account might possibly concede that supra-organismal biological systems (as symbioses or ecosystems) could realise closure, and hence be teleological. On the other hand, the realisation of closure beyond the biological realm appears to be highly unlikely. In turn, the occurrence of simpler forms of self-determination remains a controversial issue, in particular with respect to the case of self-organising dissipative systems.

L’objectif principal de ce chapitre est de distinguer entre deux formes de réductionnisme possibles en Biologie, de sorte à mieux comprendre les enjeux du débat contemporain à ce sujet. En effet, une attitude réductionniste au sein de la biologie moléculaire peut, en effet, prendre deux formes distinctes, que l’on nommera respectivement « réductionnisme moléculaire » à proprement parler et « réductionnisme génétique». Alors que la première forme soutient une thèse sur la réduction entre les niveaux de description d’un système, et s’oppose à une posture émergentiste, la deuxième forme soutient une thèse sur la réduction entre les systèmes considérés pour expliquer un phénomène, et s’oppose plutôt à une posture holiste. Nous suggérerons que l’évolution de la biologie vers des approches « moins réductionnistes » au cours des dernières décennies se comprend plutôt comme une critique du réductionnisme génétique que comme une critique du réductionnisme moléculaire. Par conséquent, il existe une tendance allant davantage vers des postures holistes sans qu’elles ne soient pour autant plus émergentistes.

Ce chapitre propose un aperçu de la tradition théorique et philosophique qui, au cours des deux derniers siècles, a mis la circularité au centre de l’analyse des phénomènes biologiques.
Selon cette tradition, les organismes réalisent un régime causal circulaire dans la mesure où leur existence dépend des effets de leur propre activité : les organismes biologiques
s’autodéterminent. A son tour, l’autodétermination est le fondement d’un certain nombre de propriétés et dimensions biologiques, telles que l’individuation, la téléologie, la normativité ou encore la fonctionnalité. Nous montrons comment cette idée générale a fait l’objet d’une
théorisation qui a pris, selon les cas, la forme d’une conceptualisation, d’une modélisation ou les deux à fois. Nous analysons les différences principales entre les différentes contributions, en soulignant leurs qualités et faiblesses. Enfin, nous concluons en évoquant certains développements contemporains de cette tradition, ainsi que quelques pistes de recherche futures.

In this paper, we advocate the idea that an adequate explanation of biological systems requires appealing to organisational 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 realise a closure of constraints, i.e. a higher-level emergent regime of causation such that the constituents, each of them acting as a constraint, realise 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 committing to stronger ontological and epistemological assumptions.