The Laws of Complexity and Self-organization: A Framework for Understanding Neoplasia

Abstract

Background: Current biologic research is based on reductionism, through which organisms and cells are merely combinations of simpler systems. However this approach has failed to substantially reduce cancer-related deaths. Complexity theory suggests that emergent properties, based on unpredictable, nonlinear interactions between the parts, are important in understanding fundamental features of systems with large numbers of independent agents, such as living systems. Methods and Findings: The laws of complexity and self-organization are summarized and applied to neoplasia: 1.In life, as in other complex systems, the whole is greater than the sum of the parts.2.There is an inherent inability to predict the future of complex systems.3.Life emerges from non-life when the diversity of a closed system of biomolecules exceeds a threshold of complexity.4.Much of the order in organisms is due to generic network properties.5.Numerous biologic pressures push cellular pathways towards disorder.6.Organisms resist common pressures towards disorder through multiple layers of redundant controls, many related to cell division.7.Neoplasia arises due to failure in these controls, with histologic and molecular characteristics related to the cell of origin, the nature of the biologic pressures and the individual’s germline configuration. Conclusions: Cells maintain order by redundant control features that resist inherent biologic pressures towards disorder. Neoplasia is due to the accumulation of changes that undermine these controls. Studying neoplasia within this context may generate new therapeutic approaches by focusing on the underlying pressures on cellular networks. An expanded version of this paper is available at http://natpernick.com/TheLawsJune2017.pdf.