International Society for History, Philosophy, and Social Studies of Biology

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MONDAY, JULY 6  /  11:00 - 12:30  /  DS-1545
Organized session / standard talks
From the tissue organization field theory of carcinogenesis to a theory of organisms and back

Mael Montévil (Université Paris Diderot - Paris 7, France); Matteo Mossio (IHPST/ Université Paris 1 Panthéon-Sorbonne, France); Ana Soto (Centre Cavaillès, École Normale Supérieure, France); Carlos Sonnenschein (Tufts University, United States)

In 1999, C Sonnenschein and AM Soto proposed the tissue organization field theory (TOFT) that views cancer as a tissue-based disease akin to morphogenesis gone awry. Understanding cancer requires paradigmatic changes which are incompatible with the reductionist genocentric perspective of the molecular biology revolution. While the theory of evolution provides increasingly adequate explanations of phylogeny, biology still lacks a theory of organisms that would encompass ontogeny and life cycles. To achieve this goal we propose that theoretical extensions of physics are required in order to grasp the living state of matter. Such extensions will help to describe the proper biological observables, i.e. the phenotypes. Biological entities must also follow the underlying principles used to understand inert matter. However, these physical laws and principles do not make biological dynamics intelligible at the phenotypic level. We will propose a default state and a framing principle as basis for a theory of organisms

The biological default state

Ana Soto (Centre Cavaillès, École Normale Supérieure, France); Mael Montévil (Université Paris Diderot - Paris 7, France); Carlos Sonnenschein (Tufts University, United States)

A theoretical transition from physics to biology requires defining a default states that is a limit case. By describing inertia as the default state in mechanics, Galileo could focus on the analysis of the forces constraining it. Organisms are far-from-equilibrium systems that require a flow of energy and matter. More specifically, the “unconstrained” condition proper to the biological default state requires adequate physical conditions (temperature, pressure and pH). Sufficient nutrients provide a flow of energy and matter canalized through metabolic processes that keep cells alive regardless of whether cells are proliferating or quiescent, moving or immobile. In contrast, “a default state happens when nothing happens to prevent it”. The default state should not be conflated with conditions necessary for life. The biological default state is cell proliferation with variation and motility and represent the constitutive properties of the living. Variation is generated in particular by the mere fact that cell division generates two overall similar, but not identical cells. Darwin explicitly stated “…There is no exception to the rule that every organic being naturally increases at so high a rate, that, if not destroyed, the earth would soon be covered by the progeny of a single pair”. Reproduction comes with “modification” (descent with modification, in Darwin’s words). Reproduction with variation is intrinsic to organisms regardless of whether they are unicellular or multicellular. Darwin's narrative implies that reproduction with variation is a default state. Motility, which encompasses cell and organismic movements as well as movement within cells is the most obvious manifestation of the agentivity of the living. The analysis of constraints to proliferation with variation and to motility are fundamental to organismal biology like the constraints to inertia (forces) are fundamental to mechanics. Finally, the default state provides a theoretical link between the theory of evolution and the theory of organisms.

A novel framing principle for biology

Mael Montévil (Université Paris Diderot - Paris 7, France); Carlos Sonnenschein (Tufts University, United States); Ana Soto (Centre Cavaillès, École Normale Supérieure, France)

Biophysical approaches to biological phenomena have provided fruitful insights, yet they generally suffer from the direct transposition of physical paradigms and methods into biology, without the appropriate analysis of the deep theoretical implications of the transposed concept (for example, about the conservation of energy, or the symmetries involved). In this context, we are now proposing theoretical principles that are genuinely biological in order to discuss the mathematical analysis of biological processes. Namely, biological processes can be interpreted as the never-identical iteration of morphogenetic processes. This iteration takes place both a) at the level of tissues and organs, where for example, it can lead to fractal-like structures, and b) at the level of organisms (including cells), where it leads to the flow of generations, which phylogeny aims to reconstruct. The non-identical character of these iterations correspond to a specific form of variation, not just of a quantitative nature but of changes in the mathematical regularities that enable to study the corresponding processes. We will discuss how the concept of never-identical iteration of a morphogenetic process facilitates an understanding of both ontogenetic and phylogenetic processes, and we will give examples of its usefulness when applied to the process of branching morphogenesis of the mammary gland epithelium. It is noteworthy that phylogenetic analyses are based on the notion that individuals that are afar in the genealogy have different relevant characters. Finally, we will briefly discuss the epistemological consequences of this proposal as for the nature of the articulation between mathematics and biological phenomena.

From a theory of organisms to carcinogenesis

Carlos Sonnenschein (Tufts University, United States); Ana Soto (Centre Cavaillès, École Normale Supérieure, France); Mael Montévil (Université Paris Diderot - Paris 7, France)

The tissue organization field theory (TOFT) posits that cancer is a tissue-based disease akin to development and morphogenesis gone awry. Carcinogens (directly) and mutations in the germ-line (indirectly) may alter normal interactions between the different cellular components of the morphogenetic field, including the reciprocal interactions between stroma and adjacent epithelium. The principles we postulated for the construction of a theory of organisms provide novel insight into normal and neoplastic development. Regarding the latter, carcinogens alter and relax the constraints that operate from tissues to the cells inside them. This, in turn, allows the cells within tissues to regain their constitutive properties, which are proliferation with variation and motility. Because proliferation with variation and motility represents the fundamental postulate (i.e., the equivalent of inertia), they do not require an explanation. What requires an explanation are the constraints that limit the default state. This novel perspective makes useless the search stimulators of proliferation (i.e., the so-called growth factors) and cellular movement and migration. We will analyze experimental data obtained from this theoretical framework, including the normalization of “cancer cells” achieved when those cells are transplanted in the midst of normal tissues.