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Binding Specificity and Causal Selection in Drug Design

Published online by Cambridge University Press:  01 January 2022

Oliver M. Lean
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Abstract

Binding specificity is a centrally important concept in molecular biology, yet it has received little philosophical attention. Here I aim to remedy this by analyzing binding specificity as a causal property. I focus on the concept’s role in drug design, where it is highly prized and hence directly studied. From a causal perspective, understanding why binding specificity is a valuable property of drugs contributes to an understanding of causal selection—of how and why scientists distinguish between causes, not just causes from noncauses. In particular, the specificity of drugs is precisely what underwrites their value as experimental interventions on biological processes.

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Articles
Information
Philosophy of Science , Volume 87 , Issue 1 , January 2020 , pp. 70 - 90
Copyright
Copyright © The Philosophy of Science Association

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Footnotes

†

This article was vastly improved thanks to feedback from Lindley Darden, Catherine Kendig, Lauren Ross, Ken Waters, James Woodward, two anonymous referees, and audiences at the 2018 SPSP conference in Ghent and the 2018 PSA in Seattle. This work was completed with the support of the John Templeton Foundation, under the research grant From Biological Practice to Scientific Metaphysics.

References

Bourrat, Pierrick. 2019. “Variation of Information as a Measure of One-to-One Causal Specificity.” European Journal for Philosophy of Science 9:11.CrossRefGoogle Scholar
Carothers, James M., Oestreich, Stephanie C., and Szostak, Jack W. 2006. “Aptamers Selected for Higher-Affinity Binding Are Not More Specific for the Target Ligand.” Journal of the American Chemical Society 128 (24): 7929–37.CrossRefGoogle Scholar
Darden, Lindley, Pal, Lipika R., Kundu, Kunal, and Moult, John. 2018. “The Product Guides the Process: Discovering Disease Mechanisms.” In Building Theories: Heuristics and Hypotheses in the Sciences, ed. Danks, David and Ippoliti, Emiliano, 101–17. Cham: Springer.Google Scholar
Dobzhansky, Theodosius. 1973. “Nothing in Biology Makes Sense Except in the Light of Evolution.” American Biology Teacher, 35 (3): 125–29.CrossRefGoogle Scholar
Eaton, Bruce E., Gold, Larry, and Zichi, Dominic A. 1995. “Let’s Get Specific: The Relationship between Specificity and Affinity.” Chemistry and Biology 2 (10): 633–38.CrossRefGoogle ScholarPubMed
Ehrlich, P. 1910. “Die Behandlung der Syphilis mit dem Ehrlichschen Präparat 606.” Deutsche medizinische Wochenschrift: 36(41): 1889–924.Google Scholar
Ehrlich, P. 1911. “Aus Theorie und Praxis der Chemotherapie.” Folia Serologica 7:697–714.Google Scholar
Franklin-Hall, Laura R. 2015. “Explaining Causal Selection with Explanatory Causal Economy: Biology and Beyond.” In Explanation in Biology, ed. Malaterre, Christophe and Braillard, Pierre-Alain, 413–38. New York: Springer.Google Scholar
Franklin-Hall, Laura R. 2016. “High-Level Explanation and the Interventionist’s ‘Variables Problem.’” British Journal for the Philosophy of Science 67:533–77.CrossRefGoogle Scholar
Glennan, Stuart. 2017. The New Mechanical Philosophy. Oxford: Oxford University Press.CrossRefGoogle Scholar
Griffiths, Paul E., Pocheville, Arnaud, Calcott, Brett, Stotz, Karola, Kim, Hyunju, and Knight, Rob. 2015. “Measuring Causal Specificity.” Philosophy of Science 82:529–55.CrossRefGoogle Scholar
Griffiths, Paul E., and Stotz, Karola. 2013. Genetics and Philosophy: An Introduction. New York: Cambridge University Press.CrossRefGoogle Scholar
Hesslow, Germund. 1988. “The Problem of Causal Selection.” In Contemporary Science and Natural Explanation: Commonsense Conceptions of Causality, ed. Hilton, Denis J., 11–32. New York: New York University Press.Google Scholar
Hippel, Peter H. von, and Berg, Otto G. 1986. “On the Specificity of DNA-Protein Interactions.” Proceedings of the National Academy of Sciences of the USA 83:1608–12.Google Scholar
Huggins, David J., Sherman, Woody, and Tidor, Bruce. 2012. “Rational Approaches to Improving Selectivity in Drug Design.” Journal of Medicinal Chemistry 55 (4): 1424–44.CrossRefGoogle ScholarPubMed
Kaiser, Marie I. 2016. “On the Limits of Causal Modeling: Spatially-Structurally Complex Biological Phenomena.” Philosophy of Science 83 (5): 921–33.CrossRefGoogle Scholar
Kangas, Erik, and Tidor, Bruce. 2000. “Electrostatic Specificity in Molecular Ligand Design.” Journal of Chemical Physics 112 (20): 9120–31.CrossRefGoogle Scholar
Liu, Yi, and Gray, Nathanael S. 2006. “Rational Design of Inhibitors That Bind to Inactive Kinase Conformations.” Nature Chemical Biology 2:358–64.CrossRefGoogle ScholarPubMed
Machamer, Peter, Darden, Lindley, and Craver, Carl F. 2000. “Thinking about Mechanisms.” Philosophy of Science 67 (1): 1–25.CrossRefGoogle Scholar
Mill, John S. 1843/1981. A System of Logic. Toronto: University of Toronto Press.Google Scholar
Sarkar, Sahotra. 2005. “How Genes Encode Information for Phenotypic Traits.” In Molecular Models of Life: Philosophical Papers on Molecular Biology, 261–83. Cambridge, MA: MIT Press.Google Scholar
Schasfoort, Richard B. M., Lau, Wim de, van der Kooi, Alex, Clevers, Hans, and Engbers, Gerard H. M. 2012. “Method for Estimating the Single Molecular Affinity.” Analytical Biochemistry 421 (2): 794–96.CrossRefGoogle ScholarPubMed
Stegmann, Ulrich E. 2004. “The Arbitrariness of the Genetic Code.” Biology and Philosophy 19 (2): 205–22.CrossRefGoogle Scholar
Stotz, Karola, and Griffiths, Paul E. 2017. “Biological Information, Causality and Specificity: An Intimate Relationship.” In From Matter to Life: Information and Causality, ed. Walker, Sara I., Davies, Paul C. W., and Ellis, George F. R., 366–90. Cambridge: Cambridge University Press.Google Scholar
Strebhardt, Klaus, and Ullrich, Axel. 2008. “Ehrlich’s Magic Bullet Concept: 100 Years of Progress.” Nature Reviews Cancer 8:473–80.CrossRefGoogle ScholarPubMed
Tabery, James, Piotrowska, Monika, and Darden, Lindley. 2015. “Molecular Biology.” In Stanford Encyclopedia of Philosophy, ed. Zalta, Edward N. Stanford, CA: Stanford University. https://plato.stanford.edu/archives/sum2018/entries/molecular-biology/.Google Scholar
Waters, C. Kenneth. 2007. “Causes That Make a Difference.” Journal of Philosophy 104 (11): 551–79.CrossRefGoogle Scholar
Weber, Marcel. 2006. “The Central Dogma as a Thesis of Causal Specificity.” History and Philosophy of the Life Sciences 28 (4): 595–609.Google ScholarPubMed
Weber, Marcel. 2017. “Which Kind of Causal Specificity Matters Biologically?” Philosophy of Science 84 (3): 574–85.CrossRefGoogle Scholar
Woodward, James. 2003. Making Things Happen: A Theory of Causal Explanation. Oxford: Oxford University Press.Google Scholar
Woodward, James. 2010. “Causation in Biology: Stability, Specificity, and the Choice of Levels of Explanation.” Biology and Philosophy 25 (3): 287–318.CrossRefGoogle Scholar
Woodward, James. 2017. “Response to Franklin-Hall and Weslake on Stability and Proportionality.” Unpublished manuscript, PhilSci Archive. http://philsci-archive.pitt.edu/14117/1/Response%20to%20Franklin-Hall%20and%20Weslake.docx.Google Scholar