Problemas contemporáneos en la filosofía de la bioquímica

lecciones desde el plegamiento de proteínas y el problema in-vitro/in-vivo



Palabras clave:

Bioquímica, Plegamiento de proteínas, In-vitro/in-vivo, Pluralismo, Reduccionismo


Si bien en la filosofía de las ciencias ya se han explorado algunos ejemplos provenientes de la bioquímica como casos de estudio, la filosofía de la bioquímica (i.e. el estudio filosófico sistemático de los problemas metacientíficos de esta ciencia) es una subdisciplina naciente. En este artículo estudiaremos dos problemas filosóficos de relevancia contemporánea en esta ciencia. Por un lado, examinaremos las bases epistemológicas del problema del plegamiento de proteínas. En particular lo relacionado con la predicción de la estructura tridimensional de las proteínas a partir de su secuencia, asunto que ha dado mucho que hablar debido a los nuevos avances utilizando deep learning. Por otro lado, exploraremos el problema in-vitro/in-vivo y, más generalmente, el problema de la extrapolación en las ciencias biológicas. Finalmente, a partir de las consecuencias de ambos temas consideraremos algunas reflexiones filosóficas generales acerca del reduccionismo, el pluralismo y el lugar de la bioquímica en las ciencias biológicas.


Los datos de descarga aún no están disponibles.


Abeln, S., Feenstra, K. A. y Heringa, J. (2019). “Protein Three-Dimensional Structure Prediction”. Encyclopedia of Bioinformatics and Computational Biology, 2: 497-511.

Alassia, F. (2022). “¿Es posible una ontología procesual de las entidades bioquímicas? Consideraciones a partir del caso de los receptores celulares y la señalización celular”. Estudios De Filosofía, (65): 153–175.

Alleva, K., Díez, J. y Federico, L. (2017). “Models, theory structure and mechanisms in biochemistry: The case of allosterism”. Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences, 63: 1-14.

AlQuraishi, M. (2019). “AlphaFold at CASP13”. Bioinformatics, 35(22): 4862–4865,

AlQuraishi, M. (2020). AlphaFold2 at CASP14: “It feels like one’s child has left home”.

Anfinsen C. B., Haber, E., Sela, M. y White F. H. Jr. (1961). “The kinetics of formation of native ribonuclease during oxidation of the reduced polypeptide chain”. PNAS, 47(9): 1309–1314.

Anfinsen, C. B. (1973). “Principles that govern the folding of protein chains”. Science, 181(4096): 223–230.

Ankeny, R. (2001). “Model Organisms as Models: Understanding the ‘Lingua Franca’ of the Human Genome Project”. Philosophy of Science, 68(S3): S251-S261.

Ankeny, R. y Leonelli, S. (2021). Model Organisms. Cambridge University Press.

Ankeny, R., y Leonelli, S. (2011). “What’s so special about model organisms?”. Studies in History and Philosophy of Science Part A, 42: 313–323.

Baetu, T. (2019). Mechanisms in molecular biology. Cambridge University Press.

Baetu, T. 2016. "The ‘Big Picture’: The Problem of Extrapolation in Basic Research". British Journal for the Philosophy of Science, 67(4): 941-964.

Bartol, J. (2016). “Biochemical Kinds”. The British Journal for the Philosophy of Science, 67(2): 531–551.

Beatty, J. (1997) "Why do biologists argue like they do?". Philosophy of Science 64 (S4): s432-s443.

Bechtel, W. y Richardson, R. C. (1993). Discovering Complexity: Decomposition and Localization as Strategies in Scientific Research. Cambridge: MIT Press.

Berman H. M. (2008). “The Protein Data Bank: a historical perspective”. Acta Crystallogr A., 64(Pt 1): 88-95.

Berman H. M. y Gierasch L. M. (2021). “How the Protein Data Bank changed biology: An introduction to the JBC Reviews thematic series, part 1”. Journal of Biological Chemistry. 296: 100608.

Bolker, J. (1995). “Model systems in developmental biology”. BioEssays, 17: 451–455.

Bolker, J. (2009). “Exemplary and surrogate models: Two modes of representation in biology”. Perspectives in Biology and Medicine, 52; 485–499.

Brigandt, I. y Love, A. (2017). "Reductionism in Biology". En E. N. Zalta (ed.) The Stanford Encyclopedia of Philosophy.

Briggs, H. (2020). One of biology's biggest mysteries 'largely solved' by AI. BBC News.

Burian, R. (1993). “How the Choice of Experimental Organism Matters: Epistemological Reflections on an Aspect of Biological Practice”. Journal of the History of Biology, 26: 351–367.

Burian, R. (1995). “Comments on Rheinberger”. En G. Wolters, J. G. Lennox y P. McLaughlin (eds.). Concepts, Theories, and Rationality in the Biological Sciences. Pittsburgh: University of Pittsburgh Press.

Clarke, A. E. y Fujimura J. H. (1992). The Right Tools for the Job. At Work in Twentieth-century Life Sciences. Princeton: Princeton University Press.

Collins, H. M. (1987). Changing order: Replication and induction in scientific practice. Chicago: Chicago University Press.

Culp, S. (1995). “Objectivity in Experimental Inquiry: Breaking Data-Technique Circles”, Philosophy of Science, 62: 430–450.

Culp, S. (1997). “Establishing genotype/phenotype relationships: Gene targeting as an experimental approach”. Philosophy of Science, 64(4): S268–S278.

Dahlin, J., Inglese, J. y Walters, M. (2015) “Mitigating risk in academic preclinical drug discovery”. Nature Reviews Drug Discovery, 14: 279–294.

de Chadarevian, S. (2011). Designs for Life: Molecular Biology after World War II. Cambridge University Press.

Douglas, H. (2000). “Inductive risk and values in science”. Philosophy of Science, 67: 559–579.

Douglas, H. (2009). Science, Policy, and the Value-Free Ideal. University of Pittsburgh Press.

Eronen, M. (2015). “Robustness and reality”. Synthese”. 192: 3961–3977.

Esposito, M. y Vallejos, G. (2020). “Performative Epistemology and the Philosophy of Experimental Biology: A Synoptic Overview”. En Baravalle, L. y Zaterka, L. (eds.). Life and Evolution. Latin American Essays on the History and Philosophy of Biology. Springer.

Evans P, McCoy A. (2008). “An introduction to molecular replacement”. Acta Crystallographica Section D, 64(Pt 1): 1-10.

Fasman, G. D. (1989). “The Development of the Prediction of Protein Structure”. En G.D Fasman (ed.). Prediction of Protein Structure and the Principles of Protein Conformation. Boston: Springer.

Fersht, A. (2017). Structure and Mechanism in Protein Science: A Guide to Enzyme Catalysis and Protein Folding. Singapore: World Scientific.

Figueroa, M., Sleutel, M., Vandevenne, M., Parvizi, G., Attout, S., Jacquin, O., Vandenameele, J., Fischer, A. W., Damblon, C., Goormaghtigh, E., Valerio-Lepiniec, M., Urvoas, A., Durand, D., Pardon, E., Steyaert, J., Minard, P., Maes, D., Meiler, J., Matagne, A., Martial, J. A. y Van de Weerdt, C. (2016). “The unexpected structure of the designed protein Octarellin V.1 forms a challenge for protein structure prediction tools”. Journal of Structural Biology, 195(1): 19-30.

Gannett, L. (1999). “What’s in a cause? The pragmatic dimensions of genetic explanations”. Biol. Philos, 14(3): 349–373.

García P. (2015). "Computer simulations and experiments: in vivo–in vitro conditions in biochemistry". Foundations of Chemistry, 17(1): 49-65.

Gelfert, A. (2011). "Scientific models, simulation, and the experimenter's regress". En P. Humphreys y C. Imbert (eds.). Models, Simulations, and Representations. Routledge.

Gomes, C. y Faísca, P. (2019). Protein Folding: An Introduction. Springer.

Goodwin, W. (2011). “Structure, function, and protein taxonomy”. Biology & Philosophy, 26: 533–545.

Guttinger, S. (2018). “A Process Ontology for Macromolecular Biology”. En D. J. Nicholson y J. Dupré (eds.). Everything Flows: Towards a Processual Philosophy of Biology. Oxford: Oxford University Press.

Havstad, J. C. (2018). “Messy chemical kinds”. The British Journal for the Philosophy of Science, 69(3): 719–743.

Hossenfelder, S. (2021). Has Protein Folding Been Solved? [Archivo de video]. Youtube.

Hüttemann, A., y Love, A. C. (2011). “Aspects of reductive explanation in biological science: intrinsicality, fundamentality, and temporality”, British Journal for the Philosophy of Science, 62(3): 519–549.

Ibarra, A. y Mormann, T. (2006). "Scientific Theories as Intervening Representations" Theoria, 21(55): 21-38.

Jacob, C. (2002). “Philosophy and biochemistry: Research at the interface between chemistry and biology”. Foundations of Chemistry, 4(2): 97-125.

Jha, S. K., Ramanathan, A., Ewetz, R., Velasquez, A., Jha, A. (2021). "Protein Folding Neural Networks Are Not Robust". arXiv.

Jumper, J., Evans, R., Pritzel, A. et al. (2021). “Highly accurate protein structure prediction with AlphaFold”. Nature, 596: 583–589.

Kaczanowski, S., Zielenkiewicz, P. (2010). “Why similar protein sequences encode similar three-dimensional structures?”. Theoretical Chemistry Accounts, 125: 643–650.

Kaiser, M. I. (2011). “The limits of reductionism in the life sciences”. History and Philosophy of the Life Sciences, 33: 453–476.

Kaiser, M. I. (2018). "Individuating Part-whole Relations in the Biological World". En O. Bueno, R. L. Chen y M. B. Fagan (eds.). Individuation Across Experimental and Theoretical Sciences. Oxford University Press.

Kelley, L. A. (2017). “Fold Recognition”. En D. J. Rigden (ed.) From Protein Structure to Function with Bioinformatics. Dordrecht: Springer.

Kohler, R. (1994). Lords of the Fly: Drosophila genetics and the experimental life. Chicago: Chicago University Press.

Krebs, J., Goldstein, E., Kilpatrick, S. (2017). Lewin's GENES XII. Jones & Bartlett Learning

Kryshtafovych, A., Schwede, T., Topf, M., Fidelis, K., Moult, J. (2019). "Critical assessment of methods of protein structure prediction (CASP)—Round XIII". Proteins, 87(12): 1011-1020.

LaFollette, H., y Shanks, N. (1993). “Animal models in biomedical research: Some epistemological worries”. Public Affairs Quarterly, 7: 113–130.

LaFollette, H., y Shanks, N. (1995). “Two models of models in biomedical research”. The Philosophical Quarterly, 45: 141–160.

Laskowski, R. A. (2011). “Protein Structure Databases”. Molecular Biotechnology, 48: 183–198.

Lee, J., Freddolino, P. L., Zhang, Y. (2017). “Ab Initio Protein Structure Prediction”. En D, J. Rigden (ed.). From Protein Structure to Function with Bioinformatics. Dordrecht: Springer.

Levinthal, C. (1968). “Are there pathways for protein folding?” J. Chim. Phys., 65: 44–45.

Levinthal, C. (1969). “How to fold graciously”. En J. T. P Debrunnder, E. Munck (eds.). Mossbauer spectroscopy in biological systems: proceedings of a meeting held at Allerton House. Monticello: University of Illinois Press.

Lowe, D. (2022). “Fooling the Protein Folding Software”. En Science (Commentary).

Lupas, A., Pereira, J., Alva, V., Merino, F., Coles, M. y Hartmann, M. D. (2021). “The breakthrough in protein structure prediction”. Biochemical Journal, 478(10): 1885–1890.

Masrati, G., Landau, M., Ben-Tal, N., Lupas, A., Kosloff, M. y Kosinski, J. (2021). “Integrative Structural Biology in the Era of Accurate Structure Prediction”. Journal of Molecular Biology, 433(20): 167127.

McCoy A. J., Sammito M. D., Read R. J. (2022). “Implications of AlphaFold2 for crystallographic phasing by molecular replacement”. Acta Crystallographica Section D, 78(Pt.1): 1-13.

Mertens, R. (2019). The Construction of Analogy-Based Research Programs: The Lock-and-Key Analogy in 20th Century Biochemistry. Transcript publishing.

Mitchell, S. (2003). Biological Complexity and Integrative Pluralism. Cambridge: Cambridge University Press.

Mitchell, S. D., Gronenborn, A. G. (2017). “After fifty years, why are protein X-ray crystallographers still in business?”. The British Journal for the Philosophy of Science, 68(3): 703–723.

Mithcell, S. (2019) “Perspectives, Representation, and Integration”. En M. Massimi y MCoy, C. Understanding Perspectivism: Scientific Challenges and Methodological Prospects. New York: Routledge.

Morange, M. (2006). “The protein side of the central dogma: permanence and change”. History and philosophy of the life sciences, 28(4): 513-24.

Moult, J., Pedersen J. T., Judson, R. y Fidelis, K. (1995). “A large-scale experiment to assess protein structure prediction methods”. Proteins, 23(3): ii-v.

Mullard, A. (2021). “What does AlphaFold mean for drug discovery?”. Nature reviews drug discovery, 20(10): 725-727.

Nagel, E. (1961). The structure of science: Problems in the logic of scientific explanation. Brace and World: Harcourt.

Neal, J. (2021). Protein Structure, Dynamics, and Function: A Philosophical Account of Representation and Explanation in Structural Biology. Doctoral dissertation Dietrich School of Arts and Sciences.

Nederbragt, H. (2003). “Strategies to improve the reliability of a theory: The experiment of bacterial invasion into cultured epithelial cells”. Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences, 34: 593–614.

Obermayer, A. y Uversky V. (2021). “Solving Protein Structure with AI: Viva AlphaFold and Co.!”. Current Protein y Peptide Science 2021, 22(12): 826 – 826.

Pearce, R. y Zhang, Y. (2021). “Toward the solution of the protein structure prediction problem”. Journal of Biological Chemistry, 297(1): 100870.

Perdigão, N. y Agostinho, R. (2019). "Dark Proteome Database: Studies on Dark Proteins". High-Throughput, 8(2): 8.

Perrakis, A. y Sixma, T. K. (2021). “AI revolutions in biology: The joys and perils of AlphaFold”. EMBO Reports, 22: e54046.

Ramsey, J. L. (2007). “Calibrating and constructing models of protein folding”. Synthese, 155: 307–320.

Rheinberger, H. J. (1997). Toward a History of Epistemic Things: Synthesizing Proteins in the Test Tube. Stanford University Press.

Rincon, P. (2021). AI breakthrough could spark medical revolution. BBC News.

Rohl, C. A., Strauss, C. E, Misura, K. M. y Baker, D. (2004). “Protein structure prediction using Rosetta”. Methods in Enzymology, 383: 66-93.

Ross, J. L. (2016). “The Dark Matter of Biology”. Biophysical perspective, 111(5): 909-916.

Ross, L. N. (2017). “Causal selection and the pathway concept”. PhilSci Archive.

Sample, I. (2020). DeepMind AI cracks 50-year-old problem of protein folding. The Guardian.

Santos, G., Vallejos, G. y Vecchi, D. (2020). “A relational-constructionist account of protein macrostructure and function”. Foundations of Chemistry, 22: 363–382.

Sarkar, S. (1992). “Models of reduction and categories of reductionism”. Synthese, 91: 167–194.

Schaarschmidt, J., Monastyrskyy, B., Kryshtafovych, A. y Bonvin, A. M. J. J. (2018). “Assessment of contact predictions in CASP12: Co-evolution and deep learning coming of age”. Proteins, 86(S1): 51-66.

Senior, A.W., Evans, R., Jumper, J. et al. (2020) “Improved protein structure prediction using potentials from deep learning”. Nature, 577: 706–710.

Shi, Y. (2014). “A glimpse of structural biology through X-ray crystallography”. Cell, 159(5): 995-1014.

Sills, G. J. (2006). “The mechanisms of action of gabapentin and pregabalin”. Current Opinion in Pharmacology, 6(1): 108-13.

Slater, M. (2009). “Macromolecular pluralism”. Philosophy of Science, 76(5): 851–863.

Soler, L., Trizio, E., Nickles, T. y Wimsatt, W. (2012). Characterizing the Robustness of Science: After the Practice Turn in Philosophy of Science. Springer

Steel, D. (2008). Across the boundaries. Extrapolation in biology and social science. Oxford: Oxford University Press.

Strand, R. (1999). "Towards a useful philosophy of biochemistry: Sketches and examples". Foundations of Chemistry, 1(3): 269-292.

Strand, R., Fjelland, R. y Flatmark, T. (1996). "In vivo interpretation of in vitro effect studies with a detailed analysis of the method of in vitro transcription in isolated cell nuclei". Acta Biotheoretica, 44: 1–21.

Strasser, B.J. (2010) “Collecting, Comparing, and Computing Sequences: The Making of Margaret O. Dayhoff’s Atlas of Protein Sequence and Structure, 1954–1965”. Journal of the History of Biology, 43: 623–660.

Suárez, E. y Martínez S. (1998). “El problema del reduccionismo en biología: tendencias y debates actuales”. En S. Martínez y A. Barahona. Historia y explicación en Biología. Fondo de Cultura Económica.

Tahko, T. E. (2020). “Where Do You Get Your Protein? Or: Biochemical Realization”. The British Journal for the Philosophy of Science, 71 (3): 799-825.

Tanford, C. y Reynolds, J. A. (2003). Nature’s Robots: A History of Proteins. New York; Oxford: Oxford University Press.

Tee, S-H. (2019). "Model Organisms as Simulators: The Context of Cross-Species Research and Emergence". Axiomathes, 29(4): 363-382.

Tobin, E. (2010). “Microstructuralism and macromolecules: the case of moonlighting proteins”. Foundations of Chemistry, 12: 41–54.

Tunyasuvunakool, K., Adler, J., Wu, Z. et al. (2021). “Highly accurate protein structure prediction for the human proteome”. Nature, 596: 590–596.

Ureta, T. (2003). En el filo de la navaja de Occam: reflexiones reduccionistas sobre algunos problemas del ser humano. Editorial Universitaria.

Vecchi, D. (2020). "DNA is not an ontologically distinctive developmental cause". Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences, 81: 101245.

Voet, D. y Voet, J. (2010). Biochemistry (4th Edition). Wiley

Wang, J., Lutrell IV, J., Zhang, N., Khan, S., Shi, N., Wang, M., Kang, J-Q., Wang, Z. y Xu, D. (2016). “Exploring Human Diseases and Biological Mechanisms by Protein Structure Prediction and Modeling”. En: Shen, B., Tang, H., Jiang, X. (eds). Advances in Experimental Medicine and Biology (vol. 939). Singapore: Springer.

Waters, C. K. (2007). "Causes that Make a Difference". The Journal of Philosophy, 104(11): 551-579.

Waters, C. K. (2008). "How Practical Know‐How Contextualizes Theoretical Knowledge: Exporting Causal Knowledge from Laboratory to Nature". Philosophy of Science, 75(5): 707-719.

Waters, C. K. (2019). “An epistemology of scientific practices”. Philos. Sci. 86(4): 585–611.

Weber, M. (2005). Philosophy of Experimental Biology. Cambridge: Cambridge University Press.

Weber, M. (2006). "The Central Dogma as a Thesis of Causal Specificity". History and Philosophy of the Life Sciences, 28(4): 595-610.

Wimsatt, W. (1981). “Robustness. Reliability and Overdetermination”, En M. Brewer y B. Collins. (eds.), Scientific Inquiry and the Social Sciences (p. 124-163). San Francisco: Jossey-Bass.

Wimsatt, W. C. (1974). “Complexity and organization”. En K.F. Schaffner y R. S. Cohen (eds.). Proceedings of the 1972 meeting of the Philosophy of Science Association (p. 67–86.). Dordrecht: D. Reidel.

Winther, R.G. (2011), “Part-whole science”. Synthese, 178: 397–427.

Wlodawer, A., Minor, W., Dauter, Z. y Jaskolski, M. (2013). “Protein crystallography for aspiring crystallographers or how to avoid pitfalls and traps in macromolecular structure determination”. The FEBS Journal, 280(22): 5705-36.

Woodward, J. (2010). “Causation in biology: stability, specificity, and the choice of levels of explanation”. Biology & Philosophy, 25: 287–318.

Wooley, J. C. y Ye, Y. (2007). “A Historical Perspective and Overview of Protein Structure Prediction”. En Xu, Y., Xu, D. y Liang, J. (eds.), Computational Methods for Protein Structure Prediction and Modeling. BIOLOGICAL AND MEDICAL PHYSICS BIOMEDICAL ENGINEERING. New York: Springer.

Xu, D. y Xu, Y. (2004). “Protein databases on the internet”. Current Protocols in Molecular Biology. 68: 19.4.1-19.4.15.

Xu, D. y Zhang, Y. (2012) “Ab initio protein structure assembly using continuous structure fragments and optimized knowledge-based force field”. Proteins, 80: 1715-1735.

Zuppone, R. (2010). "El argumento del regreso del experimentador y la replicación de experimentos". Scientiae Studia, 8(2): 243-271.






Dossier Problemas de la Filosofía Contemporánea de la Biología

Cómo citar

Problemas contemporáneos en la filosofía de la bioquímica: lecciones desde el plegamiento de proteínas y el problema in-vitro/in-vivo. (2022). Culturas Científicas, 3(1), 45-77.