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Strategies of Explanatory Abstraction in Molecular Systems Biology

Published online by Cambridge University Press:  01 January 2022

Abstract

I consider three explanatory strategies from recent systems biology that are driven by mathematics as much as mechanistic detail. Analysis of differential equations drives the first strategy; topological analysis of network motifs drives the second; mathematical theorems from control engineering drive the third. I also distinguish three abstraction types: aggregations, which simplify by condensing details; generalizations, which simplify by generalizing details; and structurations, which simplify by contextualizing details. Using a common explanandum as a reference point—namely, the robust perfect adaptation of chemotaxis in Escherichia coli—I argue that each strategy targets various abstraction types to different mechanistic details.

Type
Research Article
Copyright
Copyright © The Philosophy of Science Association

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Footnotes

I thank Philippe Huneman for organizing the symposium on explanatory strategies across the life sciences and our cosymposiast Anya Plutynski. For helpful comments, I also thank Lindley Darden, Maureen O’Malley, anonymous reviewers for this journal, and audiences from the symposium, the Alabama Philosophical Society, Mississippi State University, and the Society for Philosophy of Science in Practice.

References

Alon, Uri, Surette, Mike G., Barkai, Naama, and Leibler, Stan. 2009. “Robustness in Bacterial Chemotaxis.” Nature 397:168–71.Google Scholar
Andersen, Holly. 2018. “Complements, Not Competitors: Causal and Mathematical Explanations.” British Journal for the Philosophy of Science 69:485508.CrossRefGoogle Scholar
Barkai, Naama, and Leibler, Stan. 1997. “Robustness in Simple Biochemical Networks.” Nature 387:913–17.CrossRefGoogle ScholarPubMed
Bechtel, William, and Abrahamsen, Adele. 2005. “Explanation: A Mechanistic Alternative.” Studies in History and Philosophy of Biological and Biomedical Science 36:421–41.CrossRefGoogle Scholar
Bechtel, William, and Abrahamsen, Adele 2010. “Dynamic Mechanistic Explanation: Computational Modeling of Circadian Rhythms as an Exemplar for Cognitive Science.” Studies in History and Philosophy of Science 41:321–33.CrossRefGoogle ScholarPubMed
Berg, Howard C. 2004. E. coli in Motion. New York: Springer.CrossRefGoogle Scholar
Braillard, Philippe A. 2010. “Systems Biology and the Mechanistic Framework.” History and Philosophy of the Life Sciences 32:4362.Google ScholarPubMed
Briat, Corentin, Gupta, Ankit, and Khammash, Mustafa. 2016. “Antithetical Integral Feedback Ensures Robust Perfect Adaptation in Noisy Biomolecular Networks.” Cell Systems 2:1526.CrossRefGoogle Scholar
Brigandt, Ingo. 2013. “Systems Biology and the Integration of Mechanistic Explanation and Mathematical Explanation.” Studies in History and Philosophy of Biological and Biomedical Sciences 44:477–92.CrossRefGoogle ScholarPubMed
Brigandt, Ingo, Green, Sara, and O’Malley, Maureen A.. 2017. “Systems Biology and Mechanistic Explanation.” In The Routledge Handbook of Mechanisms and Mechanical Philosophy, ed. Glennan, S. and Illari, P., 362–73. New York: Routledge.Google Scholar
Craver, Carl F. 2006. “When Mechanistic Models Explain.” Synthese 153:355–76.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 Cook, Michael. 1994. “Reasoning Strategies in Molecular Biology: Abstractions, Scans and Anomalies.” In PSA 1994: Proceedings of the 1994 Biennial Meeting of the Philosophy of Science Association, Vol. 2, ed. David Hull, Micky Forbes, and Richard M. Burian, 179–91. East Lansing, MI: Philosophy of Science Association.Google Scholar
French, Steven. 2010. “Keeping Quiet on the Ontology of Models.” Synthese 172:231–49.CrossRefGoogle Scholar
Godfrey-Smith, Peter. 2009. “Abstractions, Idealizations, and Evolutionary Biology.” In Mapping the Future of Biology: Evolving Concepts and Theories, ed. Barberousse, A., Morange, M., and Pradeu, T., 4756. Dordrecht: Springer.CrossRefGoogle Scholar
Green, Sara, and Jones, Nicholaos. 2016. “Constraint-Based Reasoning for Search and Explanation: Strategies for Understanding Variation and Patterns in Biology.” Dialectica 70:343–74.CrossRefGoogle Scholar
Green, Sara, and Wolkenhauer, Olaf. 2013. “Tracing Organizing Principles: Learning from the History of Systems Biology.” History and Philosophy of the Life Sciences 35:553–76.Google ScholarPubMed
Haslanger, Sally. 2016. “What Is a (Social) Structural Explanation?Philosophical Studies 173:113–30.CrossRefGoogle Scholar
Huneman, Philippe. 2010. “Topological Explanation and Robustness in Biological Sciences.” Synthese 177:213–45.CrossRefGoogle Scholar
Jones, Nicholaos. 2014. “Bowtie Structures, Pathway Diagrams, and Topological Explanation.” Erkenntnis 79:1135–55.CrossRefGoogle Scholar
Jones, Nicholaos, and Wolkenhauer, Olaf. 2012. “Diagrams as Locality Aids for Search and Explanation in Molecular Cell Biology.” Biology and Philosophy 27 (5): 705–21..CrossRefGoogle Scholar
Levy, Arnon. 2013. “Three New Kinds of Mechanism.” Biology and Philosophy 28:99114.CrossRefGoogle Scholar
Levy, Arnon, and Bechtel, William. 2013. “Abstraction and the Organization of Mechanisms.” Philosophy of Science 80:241–61.CrossRefGoogle Scholar
Ma, Wenzhe, Trusina, Ala, El-Samad, Hana, Lim, Wendell A., and Tang, Chao. 2009. “Defining Network Topologies That Can Achieve Biochemical Adaptation.” Cell 138:760–73.CrossRefGoogle ScholarPubMed
Machamer, Peter, Darden, Lindley, and Craver, Carl F.. 2000. “Thinking about Mechanisms.” Philosophy of Science 67:125.CrossRefGoogle Scholar
Matthiessen, Dana. 2017. “Mechanistic Explanation in Systems Biology: Cellular Networks.” British Journal for Philosophy of Science 68:125.CrossRefGoogle Scholar
Ordorica, Ordorica Sergio Armando. 2015. “The Explanatory Role of Abstraction Processes in Models: The Case of Aggregations.” Studies in History and Philosophy of Science 56:161–67.Google Scholar
Pincock, Christopher. 2015. “Abstract Explanations in Science.” British Journal for the Philosophy of Science 66:857–78.CrossRefGoogle Scholar
Rao, Christopher V., and Ordal, George W.. 2009. “The Molecular Basis of Excitation and Adaptation during Chemotaxic Sensory Transduction in Bacteria.” In Bacterial Sensing and Signaling, ed. Collin, M. and Schuch, R., 3364. Basil: Karger.CrossRefGoogle Scholar
Rice, Collin. 2015. “Moving beyond Causes: Optimality Models and Scientific Explanation.” Nous 49:589615.CrossRefGoogle Scholar
Spudich, John L., and Koshland, D. E. Jr. 1976. “Non-genetic Individuality: Chance in the Single Cell.” Nature 262:467–71.CrossRefGoogle ScholarPubMed
Ukai-Tadenuma, Maki, Yamada, Rikuhiro G., Xu, Haiyan, Ripperger, Jurgen A., Liu, Andrew C., and Ueda, Hiroki R.. 2011. “Delay in Feedback Repression by Cryptochrome 1 Is Required for Circadian Clock Function.” Cell 144:268–81.CrossRefGoogle ScholarPubMed
Wadhams, George H., and Armitage, Judith P.. 2004. “Making Sense of It All: Bacterial Chemotaxis.” Nature Reviews: Molecular Cell Biology 5:1024–37.CrossRefGoogle ScholarPubMed
Wouters, Arno G. 2007. “Design Explanation: Determining the Constraints on What Can Be Alive.” Erkenntnis 67:6580.CrossRefGoogle Scholar
Yi, Tau-Mu, Huang, Yun, Simon, Melvin I., and Doyle, John. 2000. “Robust Perfect Adaptation in Bacterial Chemotaxis through Integral Feedback Control.” Proceedings of the National Academy of Sciences of the USA 97:4649–53.CrossRefGoogle ScholarPubMed