Abstract
Over the last two decades, we have challenged the hegemony of the somatic mutation theory of carcinogenesis (SMT) based on the lack of theoretical coherence of the premises adopted by its followers. We offered instead a theoretical alternative, the tissue organization field theory (TOFT), that is based on the premises that cancer is a tissue-based disease and that proliferation and motility is the default state of all cells. We went on to use a theory-neutral experimental protocol that simultaneously tested the TOFT and the SMT. The results of this test favored adopting the TOFT and rejecting the SMT. Recently, an analysis of the differences between the Physics of the inanimate and that of the living matter has led us to propose principles for the construction of a much needed theory of organisms. The three biological principles are (a) a default state, (b) a principle of variation, and (c) one of organization. The TOFT, defined as “development gone awry,” fits well within the principles that we propose for a theory of organisms. This radical conceptual change opened up the possibility of anchoring mathematical modeling on genuine biological principles. By identifying constraints to the default state, multilevel biomechanical explanations become as legitimate as the molecular ones on which other modelers that adopt the SMT rely. Expanding research based on the premises of our theory of organisms will enrich a comprehensive understanding of normal development and of the one that goes awry.
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Acknowledgments
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 (AMS: Pascal Chair 2013). Additional support was provided by Award Number R01ES08314 (P.I. AMS) from the U. S. National Institute of Environmental Health Sciences. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors are grateful to Cheryl Schaeberle for her critical input. The authors have no competing financial interests to declare.
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Sonnenschein, C., Soto, A.M. (2018). An Integrative Approach Toward Biology, Organisms, and Cancer. In: Bizzarri, M. (eds) Systems Biology. Methods in Molecular Biology, vol 1702. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7456-6_2
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