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:
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1.
In life, as in other complex systems, the whole is greater than the sum of the parts.
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There is an inherent inability to predict the future of complex systems.
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3.
Life emerges from non-life when the diversity of a closed system of biomolecules exceeds a threshold of complexity.
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4.
Much of the order in organisms is due to generic network properties.
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5.
Numerous biologic pressures push cellular pathways towards disorder.
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6.
Organisms resist common pressures towards disorder through multiple layers of redundant controls, many related to cell division.
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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.
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References
Institute NC: National Cancer Act of 1971. National Cancer Institute (2016). https://www.cancer.gov/about-nci/legislative/history/national-cancer-act-1971. Accessed 27 May 2018
Bailar 3rd, J.C., Smith, E.M.: Progress against cancer? N. Engl. J. Med. 314(19), 1226–1232 (1986)
Society AC: Cancer Facts & Figures 2016. American Cancer Society, Atlanta (2016)
Kolata, G.: Grant system leads cancer researchers to play it safe. N. Y. Times (2009). http://www.nytimes.com/2009/06/28/health/research/28cancer.html. Accessed 21 Nov 2016
Kauffman, S.A.: Reinventing the Sacred: A New View of Science, Reason and Religion. Basic Books, New York (2008)
Mazzocchi, F.: Complexity in biology: exceeding the limits of reductionism and determinism using complexity theory. EMBO Rep. 9(1), 10–14 (2008)
Van Regenmortel, M.H.: Reductionism and complexity in molecular biology: scientists now have the tools to unravel biological and overcome the limitations of reductionism. EMBO Rep. 5(11), 1016–1020 (2004)
Ott, G., Rosenwald, A.: Molecular pathogenesis of follicular lymphoma. Haematologica 93(12), 1773–1776 (2008)
Waldrop, M.M.: Complexity: the emerging science at the edge of order and chaos. Simon & Schuster, New York (1992)
Rickles, D., Hawe, P., Shiell, A.: A simple guide to chaos and complexity. J. Epidemiol. Community Health 61(11), 933–937 (2007)
Bak, P.: How Nature Works: The Science of Self-organized Criticality. Copernicus, New York (1996)
Huang, S., Ernberg, I., Kauffman, S.: Cancer attractors: a systems view of tumors from a gene network dynamics and developmental perspective. Semin. Cell Dev. Biol. 20(7), 869–876 (2009)
Camazine, S.: Self-organization in Biological Systems (Princeton Studies in Complexity). Princeton University Press, Princeton (2001)
Colussi, D., Brandi, G., Bazzoli, F., Ricciardiello, L.: Molecular pathways involved in colorectal cancer: implications for disease behavior and prevention. Int. J. Mol. Sci. 14(8), 16365–16385 (2013)
Corning, P.A.: The re-emergence of “emergence”: a venerable concept in search of a theory. Complexity 7(6), 18–30 (2002)
Hawking, S.: Does God play dice? (1999). http://www.hawking.org.uk/does-god-play-dice.html. Accessed 23 Nov 2016
Dizikes, P.: When the Butterfly Effect Took Flight. MIT (2011). https://www.technologyreview.com/s/422809/when-the-butterfly-effect-took-flight/. Accessed 23 Nov 2016
Allison, A.C.: Polymorphism and natural selection in human populations. Cold Spring Harb. Symp. Quant. Biol. 29, 137–149 (1964)
Sabeti, P.: Natural selection: uncovering mechanisms of evolutionary adaptation to infectious disease. Nat. Educ. 1(1), 13 (2008)
Kauffman, S.A.: The Origins of Order: Self-organization and Selection in Evolution. Oxford University Press, New York (1993)
Smith, J.I., Steel, M., Hordijk, W.: Autocatalytic sets in a partitioned biochemical network. J. Syst. Chem. 5, 2 (2014)
Sousa, F.L., Hordijk, W., Steel, M., Martin, W.F.: Autocatalytic sets in E. coli metabolism. J. Syst. Chem. 6(1), 4 (2015)
Hutchison 3rd, C.A., et al.: Design and synthesis of a minimal bacterial genome. Science 351(aad6280), 6253 (2016)
Fraser, C.M., et al.: The minimal gene complement of Mycoplasma genitalium. Science 270(5235), 397–403 (1995)
International Human Genome Sequencing C: Finishing the euchromatic sequence of the human genome. Nature 431(7011), 931–945 (2004)
Kauffman, S.: Metabolic stability and epigenesis in randomly constructed genetic nets. J. Theor. Biol. 22(3), 437–467 (1969)
Murrugarra, D., Laubenbacher, R.: Regulatory patterns in molecular interaction networks. J. Theor. Biol. 288, 66–72 (2011)
Murrugarra, D., Dimitrova, E.S.: Molecular network control through boolean canalization. EURASIP J. Bioinform. Syst. Biol. 2015(1), 9 (2015)
Kauffman, S.: Homeostasis and differentiation in random genetic control networks. Nature 224(5215), 177–178 (1969)
Torres-Sosa, C., Huang, S., Aldana, M.: Criticality is an emergent property of genetic networks that exhibit evolvability. PLoS Comput. Biol. 8(9), e1002669 (2012)
Mukherjee, S.: The Emperor of All Maladies: A Biography of Cancer. Scribner, New York (2011). 1st Scribner trade paperback edn
Sole, R.V., Newman, M.: Extinctions and biodiversity in the fossil record. In: Mooney, H.A., Canadell, J.G. (ed) Encyclopedia of Global Environmental Change. The Earth System: Biological and Ecological Dimensions of Global Environmental Change, vol. 2, pp. 297–301. Wiley, Chichester (2002)
Kauffman, S.A.: At Home in The Universe: The Search for Laws of Self-organization and Complexity. Oxford University Press, New York (1995)
Shmulevich, I., Kauffman, S.A., Aldana, M.: Eukaryotic cells are dynamically ordered or critical but not chaotic. Proc. Natl. Acad. Sci. USA 102(38), 13439–13444 (2005)
Kauffman, S.A.: Requirements for evolvability in complex systems: orderly dynamics and frozen components. Phys. D: Nonlinear Phenom. 42(1), 135–152 (1990)
Wood, R.D.: Human DNA Repair Genes (2014). http://sciencepark.mdanderson.org/labs/wood/dna_repair_genes.html. Accessed 28 Dec 2016
Pray, L.: DNA replication and causes of mutation. Nat. Educ. 1(1), 214 (2008)
Rosenfeldt, M.T., Ryan, K.M.: The multiple roles of autophagy in cancer. Carcinogenesis 32(7), 955–963 (2011)
Chin, C.F., Yeong, F.M.: Safeguarding entry into mitosis: the antephase checkpoint. Mol. Cell. Biol. 30(1), 22–32 (2010)
Stracker, T.H., Usui, T., Petrini, J.H.: Taking the time to make important decisions: the checkpoint effector kinases Chk1 and Chk2 and the DNA damage response. DNA Repair (Amst) 8(9), 1047–1054 (2009)
Grivennikov, S.I., Greten, F.R., Karin, M.: Immunity, inflammation, and cancer. Cell 140(6), 883–899 (2010)
Rama, I., Grinyo, J.M.: Malignancy after renal transplantation: the role of immunosuppression. Nat. Rev. Nephrol. 6(9), 511–519 (2010)
Nordling, C.O.: A new theory on cancer-inducing mechanism. Br. J. Cancer 7(1), 68–72 (1953)
Knudson Jr., A.G.: Mutation and cancer: statistical study of retinoblastoma. Proc. Natl. Acad. Sci. USA 68(4), 820–823 (1971)
Limpens, J., et al.: Lymphoma-associated translocation t(14;18) in blood B cells of normal individuals. Blood 85(9), 2528–2536 (1995)
Marculescu, R., Le, T., Simon, P., Jaeger, U., Nadel, B.: V(D)J-mediated translocations in lymphoid neoplasms: a functional assessment of genomic instability by cryptic sites. J. Exp. Med. 195(1), 85–98 (2002)
Pernick, N.L.: How Cancer Arises Based on Complexity Theory (2017). http://www.natpernick.com/HowCancerArises.pdf. Accessed 27 May 2018
Lindor, N.M., McMaster, M.L., Lindor, C.J., Greene, M.H., National Cancer Institute DoCPCO, Prevention Trials Research Group: Concise Handbook of Familial Cancer Susceptibility Syndromes, 2nd edn. (2008). J. Natl. Cancer Inst. Monogr. (38), 1–93
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The author thanks Christine Billecke, PhD, for her excellent editorial assistance in preparing this manuscript.
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Pernick, N. (2018). The Laws of Complexity and Self-organization: A Framework for Understanding Neoplasia. In: Morales, A., Gershenson, C., Braha, D., Minai, A., Bar-Yam, Y. (eds) Unifying Themes in Complex Systems IX. ICCS 2018. Springer Proceedings in Complexity. Springer, Cham. https://doi.org/10.1007/978-3-319-96661-8_6
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