Here we discuss the application and articulation of biological principles for mathematical modeling of morphogenesis in the case of mammary ductal morphogenesis, with an emphasis on the default state.
Abstract
Unlike inert objects, organisms and their cells have the ability to initiate activity by themselves, and thus change their properties or states even in the absence of an external cause. This crucial difference led us to search for principles suitable for the study organisms. We propose that cells follow the default state of proliferation with variation and motility, a principle of biological inertia. This means that in the presence of sufficient nutrients, cells will express their default state. We also propose a principle of variation that addresses two central features of organisms, variation and historicity. To address interdependence between parts, we use a third principle, the principle of organization: more specifically, the notion of the closure of constraints. Within this theoretical framework, constraints are specific theoretical entities defined by their relative stability with respect to the processes they constrain. Constraints are mutually dependent in an organized system and act on the default state. Here we discuss the application and articulation of these principles for mathematical modeling of morphogenesis in a specific case, that of mammary ductal morphogenesis, with an emphasis on the default state. Our model has both a biological component, the cells, and a physical component, the matrix that contains collagen fibers. Cells are agents that move and proliferate unless constrained; they exert mechanical forces that i) act on collagen fibers and ii) on other cells. As fibers are organized, they constrain the cells’ ability to move and to proliferate. This model exhibits a circularity that can be interpreted in terms of the closure of constraints. Implementing our mathematical model shows that constraints to the default state are sufficient to explain the formation of mammary epithelial structures. Finally, the success of this modeling effort suggests a step-wise approach whereby additional constraints imposed by the tissue and the organism can be examined in silico and rigorously tested by in vitro and in vivo experiments, in accordance with the organicist perspective we embrace.
The contributive economy is a strategy to disrupt technological disruption by developing knowledge in all its forms. This program has led to several concrete working groups in Plaine Commune.
Abstract
The program Plaine Commune, contributive learning territory, started in late 2016. It emerged from the theoretical work of Bernard Stiegler and the Ars Industrialis group. The contributive economy is a strategy to disrupt technological disruption by developing knowledge in all its forms. This program has led to several concrete working groups in Plaine Commune, while others are still developing. Mainly, work is taking place on the economy, digital urbanism, and young children’s development in the context of the overuse of digital media. Here, we focus on the group on digital media and young children’s development and how academics and inhabitant works integrate.
Quelques remarques sur la pertinence de la philosophie de Canguilhem sur les enjeux contemporains, de la medecine par la preuve à la disruption des organisations biologiques.
In biology, randomness is a critical notion to understand variations; however this notion is typically not conceptualized precisely. Here we provide some elements in that direction.
Abstract
Physics has several concepts of randomness that build on the idea that the possibilities are pre-given. By contrast, an increasing number of theoretical biologists attempt to introduce new possibilities, that is to say, changes of possibility space – an idea already discussed by Bergson and that was not genuinely pursued scientifically until recently (except, in a sense, in systematics, i.e, the method to classify living beings). Then, randomness operates at the level of possibilities themselves and is the basis of the historicity of biological objects. We emphasize that this concept of randomness is not only relevant when aiming to predict the future. Instead, it shapes biological organizations and ecosystems. As an illustration, we argue that a critical issue of the Anthropocene is the disruption of the biological organizations that natural history has shaped, leading to a collapse of biological possibilities.
We question some aspects of medicine from the perspective of theoretical biology, on the one hand, and the technological and social dimension of health and disease on the other hand.
Abstract
Technological developments in genomics and other -omics originated the idea that precise measurements would lead to better therapeutic strategies. However, precision does not entail accuracy. Scientific accuracy requires a theoretical framework to understand the meaning of measurements, the nature of causal relationships, and potential intrinsic limitations of knowledge. For example, a precise measurement of initial positions in classical mechanics is useless without initial velocities; it is not an accurate measurement of the initial condition. Conceptual and theoretical accuracy is required for precision to lead to the progress of knowledge and rationality in action. In the search for accuracy in medicine, we first outline our results on a theory of organisms. Biology is distinct from physics and requires a specific epistemology. In particular, we develop the meaning of biological measurements and emphasize that variability and historicity are fundamental notions. However, medicine is not just biology; we articulate the historicity of biological norms that stems from evolution and the idea that patients and groups of patients generate new norms to overcome pathological situations. Patients then play an active role, in line with the philosophy of Georges Canguilhem. We argue that taking this dimension of medicine into account is critical for theoretical accuracy.
Pour progresser sur la question du rapport entre l’informatique et le calculable, je propose de réinterpréter l’objet de l’informatique théorique.
Abstract
Pour progresser sur la question du rapport entre l’informatique et le calculable, je propose de réinterpréter l’objet de l’informatique théorique puis de faire un détour par la biologie théorique où la question d’un symbole qui empêche de calculer se pose. Enfin, je reviens vers l’informatique en transférant de manière critique certains concepts issus de mes travaux en biologie théorique.
Qu'est qu'une forme en biologie? Au delà des définitions mathématiques, quel est le statut théorique des formes biologiques?
Abstract
Dans l’interface entre biologie et mathématiques, les formes et les processus de morphogenèse sont souvent étudiées pour eux-mêmes. Nous pensons que cette manière de procéder est insuffisante pour capturer le sens biologique de ces formes. La biologie comporte des spécificités qui se manifestent tant sur le plan philosophique que sur celui des principes théoriques : en particulier, tout processus biologique tel qu’un processus de morphogenèse ou une régulation physiologique (i) s’inscrit dans l’évolution et dans une histoire naturelle et (ii) s’intègre dans un organisme dont il dépend et auquel il participe. Nous aborderons alors le sens des formes biologiques à l’aune de ces principes, tant au niveau de la théorie qu’au niveau de la compréhension de l’accès expérimental aux objets biologiques.
Après des précurseurs tels que Georgescu-Roegen, nous soutenons que l'économie politique, dans l'ère Anthropocène est un défi qui nécessite un réexamen fondamental de ses cadres épistémiques et épistémologiques.
Abstract
L’économie industrielle a pris forme entre la fin du XVIIIe siècle et le XIXe siècle – d’abord en Europe occidentale puis en Amérique du Nord. Outre les productions techniques, elle aura conduit à des productions technologiques – mobilisant des sciences pour produire des biens industriels – : comme Marx l’aura montré en 1857, le capitalisme fait du savoir et de sa valorisation économique son élément premier. La physique de Newton et la métaphysique qui l’accompagne sont à l’origine du cadre épistémique (au sens de Michel Foucault) et épistémologique (au sens de Gaston Bachelard) de cette grande transformation – qui est la condition de ce que Karl Polanyi appellera lui-même « la grande transformation ». Dans cette transformation, l’otium (le temps de loisirs productifs) se soumet au negotium (les affaires du monde). Pendant ce temps, les mathématiques sont appliquées à travers des machines à calculer toujours plus puissantes et performatives – appelées computers après la deuxième guerre mondiale. Après des précurseurs tels que Nicholas Georgescu-Roegen, lui-même inspiré par Alfred Lotka, nous soutiendrons dans le présent ouvrage que l’économie politique, dans ce qui est appelé l’ère Anthropocène (thématisée en 2000 par Paul Krutzen, et dont les caractéristiques ont été décrites par Vladimir Vernadsky dès 19263) est un défi qui nécessite un réexamen fondamental de ces cadres épistémiques et épistémologiques. Avec Darwin, les êtres vivants sont devenus partie intégrante d’un processus historique en constant devenir. Chez l’homme, les savoirs sont une partie de ce processus qui est performative, au double sens de ce mot : à la fois au sens de l’efficience et au sens de la prescription. Ce processus devient exosomatique, c’est à dire extra-corporel, comme le montre Lotka, qui façonne et remodèle les modes de vie afin, notamment, de limiter les effets négatifs des nouveautés techniques.
After precursors such as Georgescu-Roegen, we maintain that political economy in the Anthropocene is a challenge that requires a fundamental reconsideration of epistemology.
Abstract
The industrial economy took shape between the late eighteenth century and the nineteenth century, initially in Western Europe and then in North America. Besides technical production, it involves technological production – the integration of sciences in order to produce indus-trial goods –, to the strict extent that, as Marx showed, capitalism makes knowledge and its economic valorization its primary element. Newton’s physics and the metaphysics that goes with it originated the epistemic (in Michel Foucault’s sense) and epistemological (in Gaston Bachelard’s sense) framework of this great transformation. In this transformation, otium (productive leisure time) submits to negotium (worldly affairs, business). All along, mathematics has been applied with ever more powerful and performative calculating machines. After precursors such as Nicholas Georgescu-Roegen, himself inspired by Alfred Lotka, we maintain that political economy in what is now called the Anthropocene (whose features were delineated by Vladimir Vernadsky in 1926) is a challenge that requires a fundamental reconsideration of these epistemic frameworks and epistemological frameworks. With Dar-win, living beings became part of a historical process of becoming. In humans, knowledge is a performative part of this process that shapes and reshapes lifestyles in order to tame the im-pact of technical novelties.
How do mathematical models convey meaning? What is required to build a model? An introduction for biologists and philosophers.
Abstract
Mathematical modeling is a very powerful tool for understanding natural phenomena. Such a tool carries its own assumptions and should always be used critically. In this chapter, we highlight the key ingredients and steps of modeling and focus on their biological interpretation. In particular, we discuss the role of theoretical principles in writing models. We also highlight the meaning and interpretation of equations. The main aim of this chapter is to facilitate the interaction between biologists and mathematical modelers. We focus on the case of cell proliferation and motility in the context of multicellular organisms.
Keywords: Equations, Mathematical modeling, Parameters, Proliferation, Theory
