Theoretical principles for biology: Organization
Introduction
For the past five decades, most of biological research has been framed on the hypothesis that biological organisms are essentially determined by genetic information,1 and the molecular mechanisms through which such information is expressed. This hypothesis – which we refer to here as genocentrism – acknowledges of course that a variety of causal factors (e.g. physical, environmental …) concur in enabling the development and functioning of biological organisms. Yet, among these factors, genetic ones would have a special status, insofar as they determine the distinctive features of biological phenomena. In particular, protein synthesis, (and thereby biological functions) results from the expression of genetic information. According to a genocentric perspective, therefore, what makes biological systems specific with respect to other natural systems is ultimately the fact that they would be the result of the expression of genetic information.
Understood in this way, genocentrism carries on a form of explanatory reductionism insofar as biological phenomena are assumed to be adequately explained2 by appealing to genetic information. In particular, the concept of organism loses centrality in biological sciences (Laubichler, 2000) because of its supposed derivability from genes: organisms would be, under adequate conditions, the result of the expression of genetic information through development.
The research program framed on genocentrism has undergone a spectacular development, remarkably represented by the Human Genome Project, which was declared complete in 2003. Recently, however, experimental evidence is increasingly challenging the idea that genetic information determines biological functions: in particular, gene expression is subject to massive variability, which suggests that DNA underdetermines functional proteins and, in the end, the very organization of the organism. Far from being mere “noise”, variation is increasingly conceived as an inherent dimension of gene expression (Lestas et al., 2010, Dueck et al., 2016). Moreover, experimental biology shows not only that gene expression is variable, but even inherently stochastic (Raj and van Oudenaarden, 2008, Kupiec and Sonigo, 2000).3
As a matter of fact, the accumulation of experimental evidence at odds with genocentrism has induced a progressive renewal of interest in more integrative accounts, which aim at complementing genes with other determinants of biological phenomena. A main example of this trend is Systems Biology (Kitano, 2002) that elaborates mathematical and computational models on large, multi-scale molecular networks, whose dynamics cannot be determined by genetic information and which, in turn, control the activity of genetic templates.
In the search for integrative accounts, a specific theoretical option consists in claiming that the relevant level of description at which Biology should be framed is that of the organism: the alternative to genocentrism would therefore be organicism (Gilbert and Sarkar, 2000, Ruiz-Mirazo et al., 2000, Soto and Sonnenschein, 2005). From an organicist perspective, organisms are the main object of biological science because they are the systems that underlie biological phenomena and – crucially – they cannot be reduced to more fundamental biological entities (such as the genes or other inert components of the organism).
The elaboration of a theory of biological organisms requires dealing with their distinctive complexity, which in turn requires taking into account a number of dimensions, including individuation (see Clarke, 2011; Miquel and Hwang, 2016), agency (Barandiaran et al., 2009, Arnellos and Moreno, 2015, Soto et al., 2008, 2016), regulation (Bich et al., 2015), adaptivity (Di Paolo, 2005), historicity (Ruiz-Mirazo and Moreno, 2012, Longo and Montévil, 2011, Longo and Montevil, 2014), … and cognition (Thompson, 2007). In this paper and in Montévil et al. (2016a), we take a theoretical step toward a Biology of Organisms by arguing that organisms are governed by two theoretical principles: organization and variation. All biological organisms, in all their diversity and richness of forms and kinds, meet two general principles without exceptions: they are organized, and their organization undergoes variation.
As theoretical principles, organization and variation constitute overarching hypotheses that frame the intelligibility of the objects within the biological domain. Taken together, they characterize the relevant aspects of biological objects, that are measurable observables, relations and changes. To better grasp their nature, a relevant comparison can be made with the role of space and time in Physics, ever since Newton and Kant. One may consider space and time as “conditions of possibility” for constructing physical knowledge; in more modern terms, positing a priori the phase space (i.e. the list of pertinent observables and parameters) allows us to spell out a complete determination of the intended processes in physical theories, by equations or evolution functions. Analogously, the ambitious aim of this work is to single-out the principles to be posited as a priori conceptual tools for the intelligibility of ontogenesis.
In the general discussion of Montévil et al. (2016a), we further elaborate on the status of organization and variation as theoretical principles. One important implication of this strategy is that, although the two principles are supposed to lay the foundations of a biology of organisms, their domain of application is not necessarily restricted to the latter. Indeed, the set of systems that comply with the two principles – and can therefore be taken, by definition, as biological systems – is presumably larger than that of organisms. For instance, it has been recently argued (Nunes-Neto et al., 2014) that ecosystems might be described as organized systems by appealing to the same organization principle we are presenting herein. Accordingly, if they were shown to comply with both the organization and variation principles, ecosystems might be conceived of as biological systems, although not necessarily as organisms (Moreno and Mossio, 2015). In other words, we submit that biology is the science of systems meeting the principles of organization and variation, organisms being a specific, particularly relevant, class of biological systems. In the general discussion of Montévil et al. (2016a), we further elaborate on the status of organization and variation as theoretical principles.
To characterize each principle, as well as their mutual relations, we elaborated in two distinct papers: the present one deals with organization, while Montévil et al. (2016a) explores variation. Within our framework, the two principles are closely related, and each one is involved in the biological realization of the other. On the one hand, organization is a condition for variation, in the sense that the variation we focus on is that of the organization: relevant biological variation is that affecting organized systems and their parts. In addition, organization favors the propagation of variation because the mutual dependence between the parts enables the maintenance of changes. On the other hand, variation is a condition for the maintenance and adaptation of organisms over time, as well as the appearance of functional innovations. Biological organization would neither display its current complexity, nor would it last, unless it varied, both during phylogenesis and ontogenesis.
Section snippets
A primer on the relationship between organization and variation
The principle of organization focuses on the specific complexity of biological systems. Organization refers to the differentiation of functional roles (i.e. division of labor) among the parts of a system and, at the same time, to their integration and coordination as a whole. Furthermore, organization involves a generative dimension in the form of a mutual dependence, such that the very activity and existence of each organized part depends on its mutual relationship with the others. As we
Biological organization: a historical perspective
In the history of biology and philosophy of biology, the organicist tradition has advocated an understanding of biological systems as organized systems (Wolfe, 2010). As Gilbert and Sarkar (2000) explain, organicism constitutes a middle ground between reductionist perspectives and non-naturalist ones. The former assume that the whole can be reduced to its parts (for instance the genes), while the latter appeal to non-natural entities.5
Biological organization as closure of constraints
By relying and elaborating on the biological and philosophical tradition outlined in the previous section, we submit that biological organization is to be understood as a closure of constraints. In other words, claiming that biological systems are “organized” means, in a theoretical precise sense, that some of its constituents acting as constraints realize a regime of mutual dependence between them, which we label ‘closure’.
As mentioned above, the concept of closure relates to that of openness.
Bringing variation into the picture
One central implication of adopting organization as a theoretical principle for biology concerns the understanding of the interplay between the stability and variation of biological phenomena.
On the one hand, we submit that the closure of constraints underlies the stability of biological systems (both at the individual and evolutionary scale), and determines the maintenance of their constitutive dynamics over time. On the other hand, organizational closure undergoes variation, as we argue at
Conclusions
We have claimed that the elaboration of a sound theory of biological organisms should adopt organization as a theoretical principle.
By elaborating on the long organicist tradition, we have put forward a specific understanding of the notion of organization, expressed in terms of closure of constraints. By relying on Montévil and Mossio (2015), we have proposed a diagrammatic description of closure, which provides a structured understanding of the principle. In this framework, biological
Acknowledgements
We would like to warmly thank Ana Soto, Carlos Sonnenschein, Cheryl Schaeberle, Paul-Antoine Miquel, Charles Wolfe and Leonardo Bich for their careful reading and useful remarks on previous versions of this paper. This work was conducted as part of the research project “Addressing biological organization in the post-genomic era” which is supported by the International Blaise Pascal Chairs, Region Ile de France. Maël Montévil was supported by Labex “Who am I?”, Laboratory of Excellence No.
References (89)
Autophagy: a cell repair mechanism that retards ageing and age-associated diseases and can be intensified pharmacologically
Mol. Asp. Med.
(2006)- et al.
From L'Homme machine to metabolic closure: steps towards understanding life
J. Theor. Biol.
(2011) - et al.
Is information a proper observable for biological organization?
Prog. Biophys. Mol. Biol.
(2012) - et al.
“From physics to biology by extending criticality and symmetry breakings.” Systems biology and cancer
Prog. Biophys. Mol. Biol.
(2011) - et al.
Why do we need theories?
Prog. Biophys. Mol. Biol.
(2016) - et al.
From physical to biological individuation
Prog. Biophys. Mol. Biol.
(2016) - et al.
Biological organisation as closure of constraints
J. Theor. Biol.
(2015) - et al.
Theoretical principles for biology: Variation. Prog. Biophys. Mol. Biol.
(2016) - et al.
Modeling mammary organogenesis from biological first principles: cells and their physical constraints
Prog. Biophys. Mol. Biol.
(2016) - et al.
Reductionist perspectives and the notion of information
Prog. Biophys. Mol. Biol.
(2016)
Nature, nurture, or chance: stochastic gene expression and its consequences
Cell
Identification and characterization of the enzymatic activity of zeta-crystallin from Guinea pig lens. A novel NADPH: quinone oxidoreductase
J. Biol. Chem.
Organisms and their place in biology
Theory Biosci.
The biological default state of cell proliferation with variation and motility, a fundamental principle for a theory of organisms. Prog
Biophys. Mol. Biol.
Autopoiesis: the organisation of living systems, its characterization and a model
BioSystems
Multicellular agency: an organizational view
Biol. Philos.
On the Parts of Animals I-IV (Clarendon Aristotle Series). Translated by James Lennox
The Second Law
Über Entwickelungsgeschichte der Thiere: Beobachtung und Reflexion
Defining agency. Individuality, normativity, asymmetry and spatio-temporality in action
J. Adapt. Behav.
Introduction á l’étude de la médecine expérimentale
Problems of Life: an Evaluation of Modern Biological Thought
Biological regulation: controlling the system from within
Biol. Philos.
Autopoiesis, autonomy and organizational biology: critical remarks on “life after ashby”
Cybern. Hum. Knowing
Autonomy, function, and representation
Commun. Cognit. Artif. Intell.
How microgravity affects the biology of living systems
BioMed Res. Int.
Rethinking heredity, again
Trans. Ecol.
Organisation for physiological homeostasis
Physiol. Rev.
An interactivist-constructivist approach to intelligence: self-directed anticipative learning
Philos. Psychol.
The problem of biological individuality
Biol. Theory
Leçons d’anatomie Comparée
Le règne animal distribué d’après son organisation, pour servir de base à l’histoire naturelle des animaux et d’introduction à l’anatomie comparée
The Origin of Species. Chapter V: the Laws of Variation
Autopoiesis, adaptivity, teleology, agency
Phenomenol. Cogn. Sci.
Leibniz et Stahl: divergences sur le concept d'organisme
Stud. Leibnit.
Variation is function: are single cell differences functionally important?
BioEssays
Organización y organismo en la Biología Teórica ¿Vuelta al organicismo?
Ludus Vitalis
Leibniz et les machines de la nature
Stud. Leibnit.
DNA Repair and Mutagenesis
Embracing complexity: organicism for the 21st century
Dev. Dyn.
Naturalizing purpose: from comparative anatomy to the “adventures of reason”
Stud. Hist. Philos. Life Sci.
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