Brief chloride ion channel activator drug exposure converts normal melanocytes to melanoma-like phenotype in an all-or-none population-level fashion (Blackiston et al. 2011, Lobikin et al. 2015)

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• Model-predicted intervention (two drugs and a dominant negative construct) broke concordance among melanocytes, producing first partially-pigmented animals (Lobo et al. 2017)finding0.767
  Demonstrates that breaking collective decision-making can be achieved, separating the decision from its coordination across cells.
• A computational model of melanocyte regulatory pathway revealed state-space decision points explaining all-or-none conversion (Lobikin et al. 2015)finding0.765
  Mathematical modeling showed how cells navigate biochemical state space and face collective decision points.
• Most of Crump et al.'s other criteria are met by non-neural morphogenetic agents via a simple pivot of terms to 'electrically active cell'.claim0.762
  Generalization of the criteria beyond neurons.
• The cancer phenotype can be reverted by artificially managing the bioelectric connections between a cell and its neighbors.hypothesis0.749
  Predicts that restoring gap junctional coupling or appropriate Vmem can normalize oncogene-expressing cells.
• Bioelectric depolarization induces melanoma transformationfinding0.747
  Experimentally validated prediction: depolarizing specific cell populations in normal tadpoles induces metastatic melanoma transformation, demonstrating causal role of bioelectric communication.
• Bioelectric Control of Melanocyte Behaviorfinding0.746
  Serotonergic signaling from instructor cells controls melanocyte proliferation and invasiveness in frog embryos; bioelectric perturbations produce stochastic organism-level outcomes (70% conversion) while maintaining cell-level concordance.
• Bioelectric state manipulation induces metastatic melanoma or suppresses tumorigenesis in wild-type genetic backgroundfinding0.738
  Depolarization of melanocytes converts them to a metastatic state; conversely, hyperpolarization prevents tumor formation even with oncogene expression.
• Co-expression of a hyperpolarizing ion channel prevents tumorigenesis by oncogene p53 in Xenopus tadpolesfinding0.738
  Bioelectric state modulation can override strong oncogenic mutations, preventing cancer and restoring normal development.