Below is a podcast and transcript of the interview concerning the 1st chapter of the book Bifurquer
Abstract
Endocrine disruptors alter mammary gland development, impair the ability to nourish offspring, and increase the cancer risk in animal models. Epidemiological studies reveal trends towards early mammary development, nursing problems, and breast cancer in younger women. Morphological changes in mouse postnatal mammary gland development are considered sensitive markers of endocrine disruption. While the mouse mammary gland is easily amenable to morphometric measurements from the fetal stage to full maturity, the rat mammary gland grows more conspicuously into the third dimension, hindering conventional morphometric analysis. However, since rats are more commonly used in international toxicological reproductive studies, it would be beneficial to include mammary gland whole-mount analysis in these studies. Using our quantitative software to perform computer-driven analysis of the rat mammary epithelium we examined the effects of gestational and postnatal exposure to ketoconazole, an antifungal medication that affects steroidogenesis, and to the estrogen diethylstilbestrol in the mammary glands of 6- and 22-day-old females. Both treatments produced effects at both ages; the epithelium was smaller and less complex in exposed animals compared to controls. Global analysis with the permutation test showed that morphological evaluation of the PND22 mammary gland is sensitive to endocrine disruption and possibly non-monotonic. In addition to revealing that ketoconazole altered the mammary gland structure, these results suggest that for future toxicology studies, day 22 (at weaning) is more suitable than day 6 because it showed significant measurements and trends. If the collection of mammary glands is added to existing international test methods, PND22 could be a relevant time point.
Biologists are increasingly documenting anthropogenic disruptions, both at the organism and ecosystem levels, indicating that these disruptions are a fundamental, qualitative component of the Anthropocene.
Abstract
Biologists increasingly report anthropogenic disruptions of both organisms and ecosystems, suggesting that these processes are a fundamental, qualitative component of the Anthropocene crisis, seemingly generating disorder. Nonetheless, the notion of disruption has not yet been theorized as such in biology. To progress on this matter, we build on a specific case. Relatively minor temperature changes disrupt plant-pollinator synchrony, tearing apart the web of life. Understanding this phenomenon requires a specific rationale since models describing them use both historical and systemic reasoning. Specifically, history justifies that the system is initially in a narrow part of the possibility space where it is viable, and the disruption randomizes this configuration. Building on this rationale, we develop a formal framework inspired by Boltzmann’s entropy. This framework defines the randomization of the system and leads to analyze its consequences systematically. Notably, maximum randomization does not lead to the complete collapse of the ecosystem. Moreover, pollinators’ robustness mostly increases viability for low randomizations, while resilience enhances viability after high randomizations. Applying this framework to empirical networks, we show historical trends depending on latitude, providing further evidence of climate change’s impact on ecosystems via phenology changes. These results lead to an initial definition of disruption in ecology. When a specific historical outcome contributes to a system’s viability, disruption is the randomization of this outcome, decreasing this viability.
Below is a podcast and transcript of the interview concerning the 1st chapter of the book Bifurquer
Abstract
This is a transcribed and translated a podcast of the interview concerning the 1st chapter of the book Biurquer: Il n’y a pas d’alternative (Bifurcate: There Is No Alternative) on the scientific, technological and political stakes of the notion of entropy. The discussion took place between Bernard Stiegler, Maël Montévil, Marie Chollat-Namy and Victor Chaix, on the 1st of July 2020.
Entropy is a transversal notion to understand the Anthropocene, from physics to biology and social organizations. For the living, it requires a counterpart: anti-entropy.
Abstract
The Anthropocene crisis is frequently described as the rarefaction of resources or resources per capita. However, both energy and minerals correspond to fundamentally conserved quantities from the perspective of physics. A specific concept is required to understand the rarefaction of available resources. This concept, entropy, pertains to energy and matter configurations and not just to their sheer amount. However, the physics concept of entropy is insufficient to understand biological and social organizations. Biological phenomena display both historicity and systemic properties. A biological organization, the ability of a specific living being to last over time, results from history, expresses itself by systemic properties, and may require generating novelties The concept of anti-entropy stems from the combination of these features. We propose that Anthropocene changes disrupt biological organizations by randomizing them, that is, decreasing anti-entropy. Moreover, second-order disruptions correspond to the decline of the ability to produce functional novelties, that is, to produce anti-entropy.
Si la philosophie est entrée en stasis et se porte vers un nécessaire Autre Commencement de la Philosophie, alors les sciences aussi sont à un autre commencement.
Abstract
Ce texte est le séminaire public donné le 31 mai à l’École Normale Supérieure de Paris. Les sciences se sont écartées de la philosophie. Si la philosophie est entrée en stasis et se porte vers un nécessaire Autre Commencement de la Philosophie, alors les sciences aussi sont à un autre commencement. L’Anastasis des sciences exige une enquête sur la persistance des concepts théologiques en leur sein et en même temps la découverte de nouveaux principes par lesquels les sciences peuvent recommencer de telle manière qu’elles soient libérées des fardeaux métaphysiques. Les homologies d’un autre commencement des sciences sont déjà visibles dans les crises conceptuelles, y compris dans les concepts de singularité en physique et d’immunité en biologie. Pour commencer à nouveau, une épistémologie bâtarde est proposée comme nouveau rapport entre les sciences et la famille bâtarde de la déconstruction.
A new look at theoretical computer sciences by changing perspective with a biological approach.
Abstract
The analogy between living beings and computers was introduced with circumspection by Schrödinger and has been widely propagated since, rarely with a precise technical meaning. Critics of this perspective are numerous. We emphasize that this perspective is mobilized to justify what may be called a regressive reductionism by comparison with physics or the Cartesian method. <br> Other views on the living are possible, and we focus on an epistemological and theoretical framework where historicity is central, and the regularities susceptible to mathematization are constraints whose existence is fundamentally precarious and historically contingent. <br> We then propose to reinterpret the computer, no longer as a Turing machine but as constituted by constraints. This move allows us to understand that computation in the sense of Church-Turing is only a part of the theoretical determination of what actually happens in a computer when considering them in their larger theoretical context where historicity is also central.
What do mainstream scientists acknowledge as original scientific contributions, that is, what is the current épistémè in natural sciences?
Abstract
What do mainstream scientists acknowledge as original scientific contributions? In other words, what is the current épistémè in natural sciences? This essay attempts to characterize this épistémè as computational empiricism. Scientific works are primarily empirical, generating data and computational, to analyze them and reproduce them with models. This épistémè values primarily the investigation of specific phenomena and thus leads to the fragmentation of sciences. It also promotes attention-catching results showing limits of earlier theories. However, it consumes these theories since it does not renew them, leading more and more fields to be in a state of theory disruption.
To provide a rational assessment of COVID-19 vaccines, we take a step back on both the history of this practice and the current theories in immunology.
Abstract
Vaccines for COVID-19 have led to questions, debates, and polemics on both their safety and the political and geopolitical dimension of their use. We propose to take a step back on both the history of this practice and how current theories in immunology understand it. Both can contribute to providing a rational assessment of COVID-19 vaccines. This assessment cannot consider vaccine as an isolated procedure, and we discuss its intergradation with the broader question of knowledge and politics in the COVID-19 pandemic.
We show that symmetries play a radically different role in biology by comparison with physics. This article is an updated version of the 2011 paper.
Abstract
Symmetries play a major role in physics, in particular since the work by E. Noether and H. Weyl in the first half of last century. Herein, we briefly review their role by recalling how symmetry changes allow to conceptually move from classical to relativistic and quantum physics. We then introduce our ongoing theoretical analysis in biology and show that symmetries play a radically different role in this discipline, when compared to those in current physics. By this comparison, we stress that symmetries must be understood in relation to conservation and stability properties, as represented in the theories. We posit that the dynamics of biological organisms, in their various levels of organization, are not “just” processes, but permanent (extended, in our terminology) critical transitions and, thus, symmetry changes. Within the limits of a relative structural stability (or interval of viability), qualitative variability is at the core of these transitions.
Keywords: Coherent structures, Critical transitions, downward causation, Hidden variables, Levels of organization, Symmetries, Systems biology
Most mathematical modeling in biology rely on the epistemology of physics. By contrast, we argue that historicity comes first in biology.
Abstract
Most mathematical modeling in biology relies either implicitly or explicitly on the epistemology of physics. The underlying conception is that the historicity of biological objects would not matter to understand a situation here and now, or, at least, historicity would not impact the method of modeling. We analyze that it is not the case with concrete examples. Historicity forces a conceptual reconfiguration where equations no longer play a central role. We argue that all observations depend on objects defined by their historical origin instead of their relations as in physics. Therefore, we propose that biological variations and historicity come first, and regularities are constraints with limited validity in biology. Their proper theoretical and empirical use requires specific rationales.
We address the identity of biological organisms in scientific practices by combining relational and historical conceptions, and introduce a new symbol for that.
Abstract
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.
We can and should take advantage of nonmonotonic properties to perform statistical analysis rigorously by new statistical and morphometric methods.
Abstract
We aimed to a) determine whether BPA showed effects on the developing rat mammary gland using new quantitative and established semiquantitative methods in two laboratories, b) develop a software tool for automatic evaluation of quantifiable aspects of the mammary ductal tree, and c) compare those methods. Conclusions: Both the semiquantitative and the quantitative methods revealed nonmonotonic effects of BPA. The quantitative unsupervised analysis used 91 measurements and produced the most striking nonmonotonic dose–response curves. At all time points, lower doses resulted in larger effects, consistent with the core study, which revealed a significant increase of mammary adenocarcinoma incidence in the stop-dose animals at the lowest BPA dose tested.
We characterize measurement in biology from a theoretical perspective with a focus on historicity. We analyze experimental strategies and reproducibility.
Abstract
We characterize access to empirical objects in biology from a theoretical perspective. Unlike objects in current physical theories, biological objects are the result of a history and their variations continue to generate a history. This property is the starting point of our concept of measurement. We argue that biological measurement is relative to a natural history which is shared by the different objects subjected to the measurement and is more or less constrained by biologists. We call symmetrization the theoretical and often concrete operation which leads to considering biological objects as equivalent in a measurement. Last, we use our notion of measurement to analyze research strategies. Some strategies aim to bring biology closer to the epistemology of physical theories, by studying objects as similar as possible, while others build on biological diversity.
Like theoretical physics, theoretical biology is not just mathematical modeling. Instead, it should strive to find principles to frame experiments and models.
Abstract
Like theoretical physics, theoretical biology is not just mathematical modeling. Instead, theoretical biology should strive to find suitable first principles to ground the understanding of biological phenomena and ultimately frame biological experiments and mathematical models. First principles in physics are expressed in terms of symmetries and the associated conservations, on the one side, and optimization on the other side. In biology, we argue instead that a strong notion of variation is fundamental. This notion encompasses new possibilities and the historicity of biological phenomena. By contrast, the relative regularity of some aspects of biological organisms, which we call constraints, should be regarded as the consequence of a mutual stabilization of the parts of organisms. We exemplify several aspects of this framework with the modeling of allometric relationships. Our change of perspective leads to reconsider the meaning of measurements and the structure of the space of description.
Keywords: Allometry, first principles, Historicity, invariants, theoretical biology, Variability
What is a biological novelty? Is it possible to coin a sound concept of new possibility? What articulation between the concepts of novelty and function?
Abstract
We provide a new perspective on the relation between the space of description of an object and the appearance of novelties. One of the aims of this perspective is to facilitate the interaction between mathematics and historical sciences. The definition of novelties is paradoxical: if one can define in advance the possibles, then they are not genuinely new. By analyzing the situation in set theory, we show that defining generic (i.e., shared) and specific (i.e., individual) properties of elements of a set are radically different notions. As a result, generic and specific definitions of possibilities cannot be conflated. We argue that genuinely stating possibilities requires that their meaning has to be made explicit. For example, in physics, properties playing theoretical roles are generic; then, generic reasoning is sufficient to define possibilities. By contrast, in music, we argue that specific properties matter, and generic definitions become insufficient. Then, the notion of new possibilities becomes relevant and irreducible. In biology, among other examples, the generic definition of the space of DNA sequences is insufficient to state phenotypic possibilities even if we assume complete genetic determinism. The generic properties of this space are relevant for sequencing or DNA duplication, but they are inadequate to understand phenotypes. We develop a strong concept of biological novelties which justifies the notion of new possibilities and is more robust than the notion of changing description spaces. These biological novelties are not generic outcomes from an initial situation. They are specific and this specificity is associated with biological functions, that is to say, with a specific causal structure. Thus, we think that in contrast with physics, the concept of new possibilities is necessary for biology.
Two theories aim to understand cancer: the reductionist Somatic Mutation Theory (SMT) and the organicist Tissue Organization Field Theory (TOFT).
Abstract
Two main theories aim at understanding carcinogenesis: the reductionist smt locates cancer in cancer cells, while the organicist toft locates cancer at the tissue level. For toft, the ‘cancer cell’ is a phlogiston, smt is an old paradigm which ought to be replaced. Recently two critics have argued that toft and smt, despite their apparent strong incompatibilities, are actually compatible. Here we review their arguments. We show that these arguments are based on interpretation mistakes that become understandable once one grants that criticizing a paradigm from the point of view of another, in which words do not have the same signification, bears the risk of strong misunderstandings. These misunderstandings, in our experience, are common. We hope that this discussion will help clarifying the differences between toft and smt.
Keywords: TOFT, reductionism, organicism, levels of organization, SMT
We summarize the theoretical ideas of our book, Perspectives on Organisms, where we discuss biological time, anti-entropy, randomness, incompleteness, symmetries.
Abstract
This short text summarizes the work in biology proposed in our book, Perspectives on Organisms, where we analyse the unity proper to organisms by looking at it from different viewpoints. We discuss the theoretical roles of biological time, complexity, theoretical symmetries, singularities and critical transitions. We explicitly borrow from the conclusions in some key chapters and introduce them by a reflection on "incompleteness", also proposed in the book. We consider that incompleteness is a fundamental notion to understand the way in which we construct knowledge. Then we will introduce an approach to biological dynamics where randomness is central to the theoretical determination: randomness does not oppose biological stability but contributes to it by variability, adaptation, and diversity. Then, evolutionary and ontogenetic trajectories are continual changes of coherence structures involving symmetry changes within an ever-changing global stability.
Keywords: Incompleteness, symmetries, randomness, critical transitions, biological evolution and ontogenesis
We propose a theoretical framework to model the behavior of cells in tissues and develop an application in the case of duct morphogenesis in mammary glands.
Abstract
We developed 3D culture methods that reproduce in vitro mammary gland ductal morphogenesis. We are proposing a conceptual framework to understand morphogenetic events based on epistemologically sound biological principles instead of the common practice of using only physical principles. More specifically, our theoretical framework is based on the principle that the default state of cells is proliferation with variation and motility. We emphasize the role played by the agency of cells embedded in a gel and the circularity that is relevant for the intended process, whereby cells act upon other cells and on matrix elements, and are subject to the agentivity of neighboring cells. This circularity strongly differs from classical linear causality. Finally, our approach opens up the study of causal determination to multilevel explanations rather than to reductive ones involving only molecules in general and genes in particular.
Keywords: Morphogenesis, extracellular matrix, theoretical principles, default state of cells, modelization.
We developed a mathematical model of mammary gland based on proper biological principles: the default state of cells and the principle of organization.
Abstract
Abstract In multicellular organisms, relations among parts and between parts and the whole are contextual and interdependent. These organisms and their cells are ontogenetically linked: an organism starts as a cell that divides producing non-identical cells, which organize in tri-dimensional patterns. These association patterns and cells types change as tissues and organs are formed. This contextuality and circularity makes it difficult to establish detailed cause and effect relationships. Here we propose an approach to overcome these intrinsic difficulties by combining the use of two models; 1) an experimental one that employs 3D culture technology to obtain the structures of the mammary gland, namely, ducts and acini, and 2) a mathematical model based on biological principles. The typical approach for mathematical modeling in biology is to apply mathematical tools and concepts developed originally in physics or computer sciences. Instead, we propose to construct a mathematical model based on proper biological principles. Specifically, we use principles identified as fundamental for the elaboration of a theory of organisms, namely i) the default state of cell proliferation with variation and motility and ii) the principle of organization by closure of constraints. This model has a biological component, the cells, and a physical component, a matrix which contains collagen fibers. Cells display agency and move and proliferate unless constrained; they exert mechanical forces that i) act on collagen fibers and ii) on other cells. As fibers organize, they constrain the cells on their ability to move and to proliferate. The model exhibits a circularity that can be interpreted in terms of closure of constraints. Implementing the mathematical model shows that constraints to the default state are sufficient to explain ductal and acinar formation, and points to a target of future research, namely, to inhibitors of cell proliferation and motility generated by the epithelial cells. The success of this model suggests a step-wise approach whereby additional constraints imposed by the tissue and the organism could be examined in silico and rigorously tested by in vitro and in vivo experiments, in accordance with the organicist perspective we embrace.
Biological variation should be given the status of a fundamental theoretical principle in biology. Variation goes with randomness, historicity and contextuality.
Abstract
Abstract 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.
Keywords: Variability, Historicity, Genericity, Biological randomness, Organization, Theory of organisms
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