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The Importance of Constraints and Control in Biological Mechanisms: Insights from Cancer Research

Published online by Cambridge University Press:  01 January 2022

William Bechtel
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Abstract

Research on diseases such as cancer reveals that primary mechanisms, which have been the focus of study by the new mechanists in philosophy of science, are often subject to control by other mechanisms. Cancer cells employ the same primary mechanisms as healthy cells but control them differently. I use cancer research to highlight just how widespread control is in individual cells. To provide a framework for understanding control, I reconceptualize mechanisms as imposing constraints on flows of free energy, with control mechanisms operating on flexible constraints in primary mechanisms. I argue that control mechanisms themselves often form complex, integrated networks.

Type
Research Article
Information
Philosophy of Science , Volume 85 , Issue 4 , October 2018 , pp. 573 - 593
Copyright
Copyright © The Philosophy of Science Association

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Footnotes

†

I thank Sara Green and Jason Winning for extremely helpful comments on previous drafts of this article and discussion of topics mentioned in it. I also thank anonymous reviewers for this journal for valuable suggestions.

References

Adams, Jerry M., and Cory, Suzanne. 2007. “The Bcl-2 Apoptotic Switch in Cancer Development and Therapy.” Oncogene 26:1324–37.CrossRefGoogle ScholarPubMed
Ashburner, Michael, Ball, Catherine A., Blake, Judith A., Botstein, David, Butler, Heather, Cherry, J. Michael, Davis, Allan P., Dolinski, Kara, Dwight, Selina S., Eppig, Janan T., Harris, Midori A., Hill, David P., Issel-Tarver, Laurie, Kasarskis, Andrew, Lewis, Suzanna, Matese, John C., Richardson, Joel E., Ringwald, Martin, Rubin, Gerald M., and Sherlock, Gavin. 2000. “Gene Ontology: Tool for the Unification of Biology.” Nature Genetics 25:25–29.CrossRefGoogle ScholarPubMed
Bechtel, William. 2006. Discovering Cell Mechanisms: The Creation of Modern Cell Biology. Cambridge: Cambridge University Press.Google Scholar
Bechtel, William 2008. Mental Mechanisms: Philosophical Perspectives on Cognitive Neuroscience. London: Routledge.Google Scholar
Bechtel, William 2017a. “Analyzing Network Models to Make Discoveries about Biological Mechanisms.” British Journal for the Philosophy of Science, forthcoming.Google Scholar
Bechtel, William 2017b. “Using the Hierarchy of Biological Ontologies to Identify Mechanisms in Flat Networks.” Biology and Philosophy 32:627–49.CrossRefGoogle Scholar
Bechtel, William, and Abrahamsen, Adele. 2005. “Explanation: A Mechanist Alternative.” Studies in History and Philosophy of Biological and Biomedical Sciences 36:421–41.CrossRefGoogle ScholarPubMed
Bechtel, William, and Abrahamsen, Adele 2009. “Decomposing, Recomposing, and Situating Circadian Mechanisms: Three Tasks in Developing Mechanistic Explanations.” In Reduction and Elimination in Philosophy of Mind and Philosophy of Neuroscience, ed. Leitgeb, H. and Hieke, A., 173–86. Frankfurt: Ontos.Google Scholar
Hieke, A. 2010. “Dynamic Mechanistic Explanation: Computational Modeling of Circadian Rhythms as an Exemplar for Cognitive Science.” Studies in History and Philosophy of Science A 41:321–33.Google Scholar
Hieke, A. 2013. “Thinking Dynamically about Biological Mechanisms: Networks of Coupled Oscillators.” Foundations of Science 18:707–23.Google Scholar
Bechtel, William, and Richardson, Robert C. 2010. Discovering Complexity: Decomposition and Localization as Strategies in Scientific Research. Repr. Cambridge, MA: MIT Press.CrossRefGoogle Scholar
Braillard, Pierre-Alain. 2010. “Systems Biology and the Mechanistic Framework.” History and Philosophy of the Life Sciences 32:43–62.Google ScholarPubMed
Bryja, Vítězslav, Červenka, Igor, and Čajánek, Lukáš. 2017. “The Connections of Wnt Pathway Components with Cell Cycle and Centrosome: Side Effects or a Hidden Logic?” Critical Reviews in Biochemistry and Molecular Biology 52 (6): 614–37..CrossRefGoogle ScholarPubMed
Burkhart, Deborah L., and Sage, Julien. 2008. “Cellular Mechanisms of Tumour Suppression by the Retinoblastoma Gene.” Nature Reviews Cancer 8:671–82.CrossRefGoogle ScholarPubMed
Cancer Genome Atlas Research Network. 2008. “Comprehensive Genomic Characterization Defines Human Glioblastoma Genes and Core Pathways.” Nature 455:1061–68.Google Scholar
Courtnay, R., Ngo, D. C., Malik, N., Ververis, K., Tortorella, S. M., and Karagiannis, T. C. 2015. “Cancer Metabolism and the Warburg Effect: The Role of HIF-1 and Pi3k.” Molecular Biology Reports 42 (4): 841–51..CrossRefGoogle ScholarPubMed
Craver, Carl F. 2007. Explaining the Brain: Mechanisms and the Mosaic Unity of Neuroscience. New York: Oxford University Press.CrossRefGoogle Scholar
Craver, Carl F., and Darden, Lindley. 2013. In Search of Mechanisms: Discoveries across the Life Sciences. Chicago: University of Chicago Press.CrossRefGoogle Scholar
Darden, Lindley, and Craver, Carl. 2002. “Strategies in the Interfield Discovery of the Mechanism of Protein Synthesis.” Studies in History and Philosophy of Biological and Biomedical Sciences 33:1–28.CrossRefGoogle Scholar
Ellis, Ronald W., Defeo, Deborah, Shih, Thomas Y., Gonda, Matthew A., Young, Howard A., Tsuchida, Nubuo, Lowy, Douglas R., and Scolnick, Edward M. 1981. “The P21 Src Genes of Harvey and Kirsten Sarcoma Viruses Originate from Divergent Members of a Family of Normal Vertebrate Genes.” Nature 292:506–11.CrossRefGoogle ScholarPubMed
Feng, Yuchen, He, Ding, Yao, Zhiyuan, and Klionsky, Daniel J. 2014. “The Machinery of Macroautophagy.” Cell Research 24:24–41.CrossRefGoogle ScholarPubMed
Ferrara, Napoleone. 2009. “Vascular Endothelial Growth Factor.” Arteriosclerosis, Thrombosis, and Vascular Biology 29:789.CrossRefGoogle ScholarPubMed
Fruton, Joseph S. 1972. Molecules and Life: Historical Essays on the Interplay of Chemistry and Biology. New York: Wiley Interscience.Google Scholar
Ghosh, Amal K., and Chance, Britton. 1964. “Oscillations of Glycolytic Intermediates in Yeast Cells.” Biochemical and Biophysical Research Communications 16:174–81.CrossRefGoogle ScholarPubMed
Green, Sara, Şerban, Maria, Scholl, Raphael, Jones, Nicholaos, Brigandt, Ingo, and Bechtel, William. 2018. “Network Analyses in Systems Biology: New Strategies for Dealing with Biological Complexity.” Synthese 195:1751–77.CrossRefGoogle Scholar
Hanahan, Douglas, and Weinberg, Robert A. 2000. “The Hallmarks of Cancer.” Cell 100:57–70.CrossRefGoogle ScholarPubMed
Hanahan, Douglas, and Weinberg, Robert A. 2011. “Hallmarks of Cancer: The Next Generation.” Cell 144:646–74.CrossRefGoogle ScholarPubMed
Hayflick, Leonard, and Moorhead, Paul S. 1961. “The Serial Cultivation of Human Diploid Cell Strains.” Experimental Cell Research 25:585–621.CrossRefGoogle ScholarPubMed
Hooker, Clifford A. 2013. “On the Import of Constraints in Complex Dynamical Systems.” Foundations of Science 18:757–80.CrossRefGoogle Scholar
Kang, Hyo Jung, Choi, Yoon Sik, Hong, Seung-Beom, Kim, Kee-Won, Woo, Ran-Sook, Won, Seok Joon, Kim, Eun Ju, Jeon, Hee Kyung, Jo, So-Young, Kim, Tae Kook, Bachoo, Robert, Reynolds, Ian J., Gwag, Byoung Joo, and Lee, Han-Woong. 2004. “Ectopic Expression of the Catalytic Subunit of Telomerase Protects against Brain Injury Resulting from Ischemia and Nmda-Induced Neurotoxicity.” Journal of Neuroscience 24:1280–87.CrossRefGoogle ScholarPubMed
Keijzer, Fred, van Duijn, Marc, and Lyon, Pamela. 2013. “What Nervous Systems Do: Early Evolution, Input-Output, and the Skin Brain Thesis.” Adaptive Behavior 21:67–85.CrossRefGoogle Scholar
Leonelli, Sabina. 2010. “Documenting the Emergence of Bio-Ontologies; or, Why Researching Bioinformatics Requires Hpssb.” History and Philosophy of the Life Sciences 32:105–25.Google ScholarPubMed
Lowe, Scott W., Cepero, Enrique, and Evan, Gerard. 2004. “Intrinsic Tumour Suppression.” Nature 432:307–15.CrossRefGoogle ScholarPubMed
Machamer, Peter, Darden, Lindley, and Craver, Carl F. 2000. “Thinking about Mechanisms.” Philosophy of Science 67:1–25.CrossRefGoogle Scholar
Masutomi, Kenkichi, Possemato, Richard, Wong, Judy M. Y., Currier, Jennifer L., Tothova, Zuzana, Manola, Judith B., Ganesan, Shridar, Lansdorp, Peter M., Collins, Kathleen, and Hahn, William C. 2005. “The Telomerase Reverse Transcriptase Regulates Chromatin State and DNA Damage Responses.” Proceedings of the National Academy of Sciences of the USA 102:8222–27.CrossRefGoogle ScholarPubMed
Matthiessen, Dana. 2017. “Mechanistic Explanation in Systems Biology: Cellular Networks.” British Journal for the Philosophy of Science 68:25.CrossRefGoogle Scholar
Mizushima, Noboru. 2007. “Autophagy: Process and Function.” Genes and Development 21:2861–73.CrossRefGoogle ScholarPubMed
Moreno, Alvaro, and Mossio, Matteo. 2015. Biological Autonomy: A Philosophical and Theoretical Inquiry. Dordrecht: Springer.CrossRefGoogle Scholar
Murakami, Takashi, Nishiyama, Toshihiko, Shirotani, Tetsuya, Shinohara, Yasuo, Kan, Masshara, Ishii, Kazuo, Kanai, Fumihiko, Nakazuru, Shiochi, and Ebina, Yousuke. 1992. “Identification of Two Enhancer Elements in the Gene Encoding the Type 1 Glucose Transporter from the Mouse Which Are Responsive to Serum, Growth Factor, and Oncogenes.” Journal of Biological Chemistry 267:9300–9306.CrossRefGoogle ScholarPubMed
Murphree, A. Linn, and Benedict, William F. 1984. “Retinoblastoma: Clues to Human Oncogenesis.” Science 223:1028–33.CrossRefGoogle ScholarPubMed
Needham, Dorothy M. 1971. Machina Carnis: The Biochemistry of Muscular Contraction in Its Historical Development. Cambridge: Cambridge University Press.CrossRefGoogle Scholar
Park, Jae-Il, Venteicher, Andrew S., Hong, Ji Yeon, Choi, Jinkuk, Jun, Sohee, Shkreli, Marina, Chang, Woody, Meng, Zhaojing, Cheung, Peggie, Ji, Hong, McLaughlin, Margaret, Veenstra, Timothy D., Nusse, Roel, McCrea, Pierre D., and Artandi, Steven E. 2009. “Telomerase Modulates Wnt Signalling by Association with Target Gene Chromatin.” Nature 460:66–77.CrossRefGoogle ScholarPubMed
Pattee, Howard Hunt, and Rączaszek-Leonardi, Joanna. 2012. Laws, Language and Life: Howard Pattee’s Classic Papers on the Physics of Symbols with Contemporary Commentary by Howard Pattee and Joanna Rączaszek-Leonardi. Dordrecht: Springer.CrossRefGoogle Scholar
Pavlova, Natalya N., and Thompson, Craig B. 2016. “The Emerging Hallmarks of Cancer Metabolism.” Cell Metabolism 23:27–47.CrossRefGoogle ScholarPubMed
Potter, Van Rensselaer. 1958. “The Biochemical Approach to the Cancer Problem.” Federation Proceedings 17:691–97.Google Scholar
Semenza, Gregg L. 2010. “HIF-1: Upstream and Downstream of Cancer Metabolism.” Current Opinion in Genetics and Development 20:51–56.CrossRefGoogle ScholarPubMed
Shannon, Paul, Markiel, Andrew, Ozier, Owen, Baliga, Nitin S., Wang, Jonathan T., Ramage, Daniel, Amin, Nada, Schwikowski, Benno, and Ideker, Trey. 2003. “Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks.” Genome Research 13:2498–2504.CrossRefGoogle ScholarPubMed
Vander Heiden, M. G., Cantley, L. C., and Thompson, C. B. 2009. “Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation.” Science 324:1029–33.CrossRefGoogle ScholarPubMed
Végran, Frédérique, Boidot, Romain, Michiels, Carine, Sonveaux, Pierre, and Feron, Olivier. 2011. “Lactate Influx through the Endothelial Cell Monocarboxylate Transporter Mct1 Supports an Nf-Κb/Il-8 Pathway That Drives Tumor Angiogenesis.” Cancer Research 71:2550.CrossRefGoogle ScholarPubMed
Vetter, Ingrid R., and Wittinghofer, Alfred. 2001. “The Guanine Nucleotide-Binding Switch in Three Dimensions.” Science 294:1299–1304.CrossRefGoogle ScholarPubMed
Warburg, Otto Heinrich. 1930. The Metabolism of Tumours. London: Constable.Google Scholar
Warburg, Otto Heinrich 1956. “On Respiratory Impairment in Cancer Cells.” Science 124:269–70.CrossRefGoogle ScholarPubMed
White, Eileen, and DiPaola, Robert S. 2009. “The Double-Edged Sword of Autophagy Modulation in Cancer.” Clinical Cancer Research 15:5308–16.CrossRefGoogle ScholarPubMed
White, Eileen, Karp, Cristina, Strohecker, Anne M., Guo, Yanxiang X., and Mathew, Robin. 2010. “Role of Autophagy in Suppression of Inflammation and Cancer.” Current Opinion in Cell Biology 22:212–17.CrossRefGoogle ScholarPubMed
Willis, Simon N., and Adams, Jerry M. 2005. “Life in the Balance: How Bh3-Only Proteins Induce Apoptosis.” Current Opinion in Cell Biology 17:617–25.CrossRefGoogle ScholarPubMed
Wu, Guanming, Feng, Xin, and Stein, Lincoln. 2010. “A Human Functional Protein Interaction Network and Its Application to Cancer Data Analysis.” Genome Biology 11:R53.CrossRefGoogle ScholarPubMed