Emergentism as a default: Cancer as a problem of tissue organization |
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Authors: | Ana M Soto Carlos Sonnenschein |
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Institution: | (1) Tufts University School of Medicine, 136 Harrison Ave, 02111 Boston, MA, USA |
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Abstract: | During the last fifty years the dominant stance in experimental biology has been reductionism. For the most part, research
programs were based on the notion that genes were in ’the driver’s seat’ controlling the developmental program and determining
normalcy and disease (genetic reductionism and genetic determinism). Philosophers were the first to realize that the belief
that the Mendelian genes were reduced to DNA molecules was questionable. Soon after these pronouncements, experimental data
confirmed their misgivings. The optimism of molecular biologists, fueled by early success in tackling relatively simple problems,
has now been tempered by the difficulties found when attempting to understand complex biological problems.
Here, we analyse experimental data that illustrate the shortcomings of this sort of reductionism. We also examine the prevailing
paradigm in cancer research, the somatic mutation theory (SMT), the premises of which are: (i) cancer is derived from a single
somatic cell that has accumulated multiple DNA mutations; (ii) the default state of cell proliferation in metazoa is quiescence;
and (iii) cancer is a disease of cell proliferation caused by mutations in genes that control proliferation and the cell cycle.
We challenge the notion that cancer is a cellular problem caused by mutated genes by assessing data gathered both from within
the reductionist paradigm and from an alternative view that regards carcinogenesis as a developmental process gone awry. This
alternative view, explored under the name of the tissue organization field theory (TOFT), is based on premises that place
cancer in a different hierarchical level of complexity from that proposed by the SMT, namely: (i) carcinogenesis represents
a problem of tissue organization comparable to organogenesis, and (ii) proliferation is the default state of all cells.
We propose that the organicist view, in which the TOFT is based, is a good starting point from which to explore emergent phenomena.
However, new theoretical concepts are needed in order to grapple with the apparent circular causality of complex biological
phenomena in development and carcinogenesis. |
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Keywords: | Cell-cell interactions cell communication genetic determinism morphogenesis neoplasms organicism reductionism somatic mutation theory supracellular phenomena tissue organization tissue organization field theory |
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