The genotype-phenotype distinction: from Mendelian genetics to 21st century biology.

The Genotype-Phenotype (G-P) distinction was proposed in the context of Mendelian genetics, in the wake of late nineteenth 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 its observable and non-transmissible effect, the phenotype. 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 non-genetic 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 relation 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.

The Identity of Organisms in Scientific Practice: Integrating Historical and Relational Conceptions.

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.

Glycemia Regulation: From Feedback Loops to Organizational Closure.

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.

Toward a theory of organisms: Three founding principles in search of a useful integration.

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, 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.

Theoretical principles for biology: 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.

Theoretical principles for biology: 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.

Functions, Organization and Etiology: A Reply to Artiga and Martinez.

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.

Biological organisation as closure of constraints.

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.

Organisational closure in biological organisms.

The central aim of this paper consists in arguing that biological organisms realize a specific kind of causal regime that we call "organisational closure"; i.e., a distinct level of causation, operating in addition to physical laws, generated by the action of material structures acting as constraints. We argue that organisational closure constitutes a fundamental property of biological systems since even its minimal instances are likely to possess at least some of the typical features of biological organisation as exhibited by more complex organisms. Yet, while being a necessary condition for biological organization, organisational closure underdetermines, as such, the whole set of requirements that a system has to satisfy in order to be taken as a paradigmatic example of organism. As we suggest, additional properties, as modular templates and control mechanisms via dynamical decoupling between constraints, are required to get the complexity typical of full-fledged biological organisms.

A computable expression of closure to efficient causation.

In this paper, we propose a mathematical expression of closure to efficient causation in terms of lambda-calculus; we argue that this opens up the perspective of developing principled computer simulations of systems closed to efficient causation in an appropriate programming language. An important implication of our formulation is that, by exhibiting an expression in lambda-calculus, which is a paradigmatic formalism for computability and programming, we show that there are no conceptual or principled problems in realizing a computer simulation or model of closure to efficient causation. We conclude with a brief discussion of the question whether closure to efficient causation captures all relevant properties of living systems. We suggest that it might not be the case, and that more complex definitions could indeed create crucial some obstacles to computability.

Traveled distances: new insights into the role of optic flow.

In this study, we addressed four related issues concerning the estimation of traveled distances in a distance-matching visual task, using a virtual reality (VR) setup. Firstly, we found that when explicit counting strategies were blocked by an interfering dual task, the performance of 35% of subjects was strongly impaired. Secondly, we found that, when encoding and test phases took place in similar perceptual contexts, subjects' performance could be extremely accurate, which suggests that the inaccuracy and variability reported in previous studies could stem from the use of inefficient mechanisms to building context-independent representations. Thirdly, by systematically manipulating the visual cues available, we ascertained that depth cues and texture regularity were not necessary to estimate traveled distances accurately. Fourthly, we evidenced two distinct groups of subjects according to their dependence on the invariance of speed. While performance remained accurate in some subjects when we manipulated the speed of the test phase it was severely impaired in other subjects, whose strategy seemed to rely on an implicit, time-based estimation. We suggest that the existence of these different groups could account for the inaccuracy and variability observed in previous studies.

Action-dependent perceptual invariants: from ecological to sensorimotor approaches.

Ecological and sensorimotor theories of perception build on the notion of action-dependent invariants as the basic structures underlying perceptual capacities. In this paper we contrast the assumptions these theories make on the nature of perceptual information modulated by action. By focusing on the question, how movement specifies perceptual information, we show that ecological and sensorimotor theories endorse substantially different views about the role of action in perception. In particular we argue that ecological invariants are characterized with reference to transformations produced in the sensory array by movement: such invariants are transformation-specific but do not imply motor-specificity. In contrast, sensorimotor theories assume that perceptual invariants are intrinsically tied to specific movements. We show that this difference leads to different empirical predictions and we submit that the distinction between motor equivalence and motor-specificity needs further clarification in order to provide a more constrained account of action/perception relations.