Editor's suggested further reading in BioEssays: Fields and field cancerization: The preneoplastic origins of cancer Abstract.

Evolution exploits the physics of non‐neural bioelectricity to implement anatomical homeostasis: a process in which embryonic patterning, remodeling, and regeneration achieve invariant anatomical outcomes despite external interventions. Linear “developmental pathways” are often inadequate explanations for dynamic large‐scale pattern regulation, even when they accurately capture relationships between molecular components. Biophysical and computational aspects of collective cell activity toward a target morphology reveal interesting aspects of causation in biology. This is critical not only for unraveling evolutionary and developmental events, but also for (...) the design of effective strategies for biomedical intervention. Bioelectrical controls of growth and form, including stochastic behavior in such circuits, highlight the need for the formulation of nuanced views of pathways, drivers of system‐level outcomes, and modularity, borrowing from concepts in related disciplines such as cybernetics, control theory, computational neuroscience, and information theory. This approach has numerous practical implications for basic research and for applications in regenerative medicine and synthetic bioengineering. (shrink)

It has long been recognized that cancer onset and progression represent a type of reversion to an ancestral quasi‐unicellular phenotype. This general concept has been refined into the atavistic model of cancer that attempts to provide a quantitative analysis and testable predictions based on genomic data. Over the past decade, support for the multicellular‐to‐unicellular reversion predicted by the atavism model has come from phylostratigraphy. Here, we propose that cancer onset and progression involve more than a one‐off multicellular‐to‐unicellular reversion, and are (...) better described as a series of reversionary transitions. We make new predictions based on the chronology of the unicellular‐eukaryote‐to‐multicellular‐eukaryote transition. We also make new predictions based on three other evolutionary transitions that occurred in our lineage: eukaryogenesis, oxidative phosphorylation and the transition to adaptive immunity. We propose several modifications to current phylostratigraphy to improve age resolution to test these predictions. Also see the video abstract here: https://youtu.be/3unEu5JYJrQ. (shrink)

The building of a global model of carcinogenesis is one of modern biology’s greatest challenges. The traditional somatic mutation theory is now supplemented by a new approach, called the Tissue Organization Field Theory. According to TOFT, the original source of cancer is loss of tissue organization rather than genetic mutations. In this paper, we study the argumentative strategy used by the advocates of TOFT to impose their view. In particular, we criticize their claim of incompatibility used to justify the necessity (...) to definitively reject SMT. First, we note that since it is difficult to build a non-ambiguous experimental demonstration of the superiority of TOFT, its partisans add epistemological and metaphysical arguments to the debate. This argumentative strategy allows them to defend the necessity of a paradigm shift, with TOFT superseding SMT. To do so, they introduce a notion of incompatibility, which they actually use as the Kuhnian notion of incommensurability. To justify this so-called incompatibility between the two theories of cancer, they move the debate to a metaphysical ground by assimilating the controversy to a fundamental opposition between reductionism and organicism. We show here that this argumentative strategy is specious, because it does not demonstrate clearly that TOFT is an organicist theory. Since it shares with SMT its vocabulary, its ontology and its methodology, it appears that a claim of incompatibility based on this metaphysical plan is not fully justified in the present state of the debate. We conclude that it is more cogent to argue that the two theories are compatible, both biologically and metaphysically. We propose to consider that TOFT and SMT describe two distinct and compatible causal pathways to carcinogenesis. This view is coherent with the existence of integrative approaches, and suggests that they have a higher epistemic value than the two theories taken separately. (shrink)