Limitaciones de la complejidad en las Ciencias Ómicas: simplificación epistemológica en el abordaje de enfermedades

Ailin Delvitto; Nicolás Lavagnino

doi:10.5007/1808-1711.2023.e85523

Authors

Ailin Delvitto Grupo de filosofia de la Biologia- FCEN/FFyL
Nicolás Lavagnino

DOI:

https://doi.org/10.5007/1808-1711.2023.e85523

Keywords:

Omic Sciences, Genomics, Biological Basis of Disease, Epistemological Simplification

Abstract

Omic Sciences are presented as having the potential to carry out complex approaches to the phenomena they study, as well as the capacity to intervene on human health through the development of technologies for diagnosis and treatment of disease. In this regard, we show an epistemological analysis of the use and scope of complex conceptualizations of gene action in the genotype-phenotype relationship in Omic Sciences. In particular, we focus on whether or not epistemological simplifications occur when human diseases are studied Our comparative analysis shows that, in general, in Omic Sciences there are both simple and complex conceptualizations of gene action in the genotype-phenotype relationship, while in omics investigations that address human diseases an exacerbation of simplifying conceptualizations is found. It is discussed whether this epistemological simplification is favored in scenarios of intervention in human health, such as the generation of knowledge for the development of Omics technologies for improved diagnosis and treatment of disease. Overall, as in other fields of Natural Sciences, in omics studies of disease a necessary link between epistemological simplifications and the promise of intervention is found.

References

Aebersold, R.; Bader, G. D.; Edwards, A. M.; Van Eyk, J. E.; Kussmann, M.; Qin, J. & Omenn, G. S. 2013. The biology/disease-driven human proteome project (B/D-HPP): enabling protein research for the life sciences community. Journal of proteome research 12(1): 23–27.

Beck, U. 1992. Risk society: towards a new modernity. London: SAGE Publications Ltd.

Bunge, M. 1966. Technology as applied science. Technology and Culture 7(3): 329-347.

Burguete, A.; Bermúdez-Morales, V.H.; Madrid-Marina, V. 2009. Medicina genómica aplicada a la salud pública. Salud Pública de México 51(3): S379-S385.

Cheifet, B. 2019. Where is genomics going next?. Genome Biology 20(1): 17.

Childs, B. & Valle, D. 2000. Genetics, biology and disease. Annual Review of Genomics and Human Genetics 1: 1-19.

Collins, F.S. & McKusick, V.A. 2001. Implications of the Human Genome Project for Medical Science. Journal of the American Medical Association 285(5): 540–544.

Cummings, B.B.; Marshall J.L.; Tukiainen T.; Lek M.; Donkervoort S.; Foley A.R.; Bolduc V.; Waddell L.B.; Sandaradura S.A.; O'Grady G.L.; Estrella E.; Reddy H.M.; Zhao F.; Weisburd B.; Karczewski K.J.; O'Donnell-Luria A.H.; Birnbaum D.; Sarkozy A.; Hu Y.; Gonorazky H.; Claeys K.; Joshi H.; Bournazos A.; Oates E.C.; Ghaoui R.; Davis M.R.; Laing N.G.; Topf A.; Genotype-Tissue Expression Consortium; Kang P.B.; Beggs A.H.; North K.N.; Straub V.; Dowling J.J.; Muntoni F.; Clarke N.F.; Cooper S.T.; Bönnemann C.G.; MacArthur D.G. 2017. Improving genetic diagnosis in Mendelian disease with transcriptome sequencing. Science translational medicine 9(386): eaal5209.

Delahaye-Duriez, A.; Srivastava, P.; Shkura, K.; Langley, S. R.; Laaniste, L.; Moreno-Moral, A.; Danis, B.; Mazzuferi, M.; Foerch, P.; Gazina, E. V.; Richards, K.; Petrou, S.; Kaminski, R. M.; Petretto, E.; Johnson, M. R. 2016. Rare and common epilepsies converge on a shared gene regulatory network providing opportunities for novel antiepileptic drug discovery. Genome biology 17(1): 245.

de Ortúzar, M. G. 2006. Análisis crítico del concepto de enfermedad como criterio de acceso a la atención de la salud: "naturalismo" vs. "normativismo". Revista Latinoamericana de Filosofía 32(1): 73-101.

Dekeuwer, C. 2017. Conceptualization of Genetic Disease. In: T Schramme & S. Edwards (eds), Handbook of the Philosophy of Medicine, p. 325-345. Dordrecht: Springer.

Dickmann, L. J. & Ware, J. A. 2016. Pharmacogenomics in the age of personalized medicine. Drug Discovery Today Technologies 21: 11–16.

Dudley, J. T. & Karczewski, K. J. 2013. Exploring personal genomics. Londres: Oxford University Press.

Echeverría, J. 2003. La revolución tecnocientífica. Madrid: Fondo de Cultura Económica.

ENCODE Project Consortium. 2004. The ENCODE (ENCyclopedia Of DNA Elements) Project. Science 306(5696): 636-640.

ENCODE Project Consortium. 2012. An integrated encyclopedia of DNA elements in the human genome. Nature 489(7414): 57-74.

Fenech, M.; El-Sohemy, A.; Cahill, L.; Ferguson, L. R.; French, T. A.; Tai, E. S.; Milner, J.; Koh, W. P.; Xie, L.; Zucker, M.; Buckley, M.; Cosgrove, L.; Lockett, T.; Fung, K. Y.; Head, R. 2011. Nutrigenetics and nutrigenomics: viewpoints on the current status and applications in nutrition research and practice. Journal of nutrigenetics and nutrigenomics 4(2): 69–89.

Fox Keller, E. 2002. The century of the gene. New York: Harvard University Press.

Francese, C. & Folguera, G. 2018. Saberes simplificados, tecnociencia y omisión de riesgos. El caso de los organismos genéticamente modificados. RUNA 39(2): 5-27.

García, R. 2006. Sistemas complejos. Conceptos, método y fundamentación epistemológica de la investigación interdisciplinaria. Barcelona: Gedisa.

Hill-Burns, E. M.; Wissemann, W. T.; Hamza, T. H.; Factor, S. A.; Zabetian, C. P.; Payami, H. 2014. Identification of a novel Parkinson's disease locus via stratified genome-wide association study. BMC genomics, 15(118): 1-9.

Huang, S. 2015. Limits to deterministic-linear causality in biomedicine: efects of stochasticity and non-linearity in molecular networks. In: M. Bertolaso (ed.), The future of scientific practice: ‘bio-techno-logos’, p. 41-64. Londres: Pickering y Chatto.

International Human Genome Sequencing Consortium (IHGSC). 2001. Initial sequencing and analysis of the human genome. Nature 409(6822): 860-921.

International Human Genome Sequencing Consortium (IHGSC). 2004. Finishing the euchromatic sequence of the human genome. Nature 431(7011): 931-945.

Karczewski, K. J. & Snyder, M. P. 2018. Integrative omics for health and disease. Nature Reviews Genetics 19(5): 299–310.

Kauwe, J. S.; Bailey, M. H.; Ridge, P. G.; Perry, R.; Wadsworth, M. E.; Hoyt, K. L.; Staley, L. A.; Karch, C. M.; Harari, O.; Cruchaga, C.; Ainscough, B. J.; Bales, K.; Pickering, E. H.; Bertelsen, S.; Alzheimer's Disease Neuroimaging Initiative, Fagan, A. M.; Holtzman, D. M.; Morris, J. C.; Goate, A. M. 2014. Genome-wide association study of CSF levels of 59 alzheimer's disease candidate proteins: significant associations with proteins involved in amyloid processing and inflammation. PLoS Genetics 10(10): e1004758.

Kussmann, M. 2014. Omics: technologies and translations. In: B. Weinheim Bressan (ed.), From physics to daily life: applications in biology, medicine, and healthcare, p. 121-152. Weinheim: Willey Blackwell.

Lacey, H. 2012. Reflections on science and technoscience. Scientiae studia 10: 103-128.

Lavagnino, N. J.; Barbero S.; Folguera, G. 2018. Caracterización, alcances y dificultades de las “bases biológicas” del Trastorno de Déficit de Atención e Hiperactividad (TDAH). Un abordaje desde la Filosofía de la Biología. PHYSIS 28(1): e280110.

Lee, S. H.; Weerasinghe, W.; Van der Werf, J. 2017. Genotype-environment interaction on human cognitive function conditioned on the status of breastfeeding and maternal smoking around birth. Scientific reports 7(1): 6087.

Lewontin, R. C. 2001. The dream of the Human genome. In: R. C. Lewontin, It ain't necessarily so: the dream of the human genome and other illusions, p. 133-187. New York: New York Review of Books.

Linares, J. E. 2008. Ética y mundo tecnológico. México: Fondo de Cultura Económica / UNAM.

Lippman, A. 1991. Prenatal genetic testing and screening: constructing needs and reinforcing inequities. American Journal of Law and Medicine 17:15–50.

Lippman, A. 1992. Led (astray) by genetic maps: the cartography of the human genome and health care. Social Science and Medicine,35 (12): 1469–76.

Lippman, A. 1998. The politics of health: geneticization versus health promotion. In: S. Sherwin (ed), The Politics of Women’s Health: Exploring Agency and Autonomy, p. 64-82. Philadelphia: Temple University Press.

Manolio, T. A. 2013. Bringing genome-wide association findings into clinical use. Nature Reviews Genetics 14(8): 549–558.

Martinhago, F.; Lavagnino, N. J.; Folguera, G. & Caponi S. 2019. Factores de riesgo y bases genéticas: el caso del TDAH. Salud Colectiva 15 (1): e1952.

Morin, E. 1998. Introducción al pensamiento complejo. Barcelona: Gedisa Editorial.

Nebert, D.W.; Zhang, G.; Vesell, E.S. 2008. From human genetics and genomics to pharmacogenetics and pharmacogenomics: past lessons, future directions. Drug Metabolism Reviews 40(2): 187-224.

Pearson, H. 2008. Biologists initiate plan to map human proteome. Nature 452(7190): 920–921.

Penchaszadeh, V.B. 1995. Genética, individuo y sociedad: desafíos para la medicina social. Boletín de la Oficina Sanitaria Panamericana 118(3): 254-263.

Peltonen, L. & McKusick, V. A. 2001. Dissecting human disease in the postgenomic era. Science 291(5507): 1224–1229.

Pigliucci, M. 2010. Genotype-phenotype mapping and the end of the 'genes as blueprint' metaphor. Philosophical Transactions of The Royal Society B: Biological Sciences 365(1540): 557–566.

Ramos, R.G. & Olden, K. 2008. Gene-environment interactions in the development of complex disease phenotypes. International journal of environmental research and public health 5(1): 4–11.

Quintanilla, M. A. 1999. Tecnología: un enfoque filosófico. Buenos Aires: EUDEBA.

Ristova, D.; Carré, C.; Pervent, M.; Medici, A.; Kim, G. J.; Scalia, D.; Ruffel, S.; Birnbaum, K. D.; Lacombe, B.; Busch, W.; Coruzzi, G. M.; Krouk, G. 2016. Combinatorial interaction network of transcriptomic and phenotypic responses to nitrogen and hormones in the Arabidopsis thaliana root. Science signaling 9(451): rs13.

Somel, M.; Guo, S.; Fu, N.; Yan, Z.; Hu, H. Y.; Xu, Y.; Yuan, Y.; Ning, Z.; Hu, Y.; Menzel, C.; Hu, H.; Lachmann, M.; Zeng, R.; Chen, W.; Khaitovich, P. 2010. MicroRNA, mRNA, and protein expression link development and aging in human and macaque brain. Genome research 20(9): 1207–1218.

Suárez-Díaz, E. 2010. Making room for new faces: evolution, genomics and the growth of bioinformatics. History & Philosophy of the Life Science 32(1): 65-90.

Thomer, A.; Gottschalk, M.; Christmann, A.; Naccache, F.; Jung, K.; Hewicker-Trautwein, M.; Distl, O.; Metzger, J. 2018. An epistatic effect of KRT25 on SP6 is involved in curly coat in horses. Scientific reports 8(1): 6374.

Torres, J.M. 2014. El concepto de salud y el proceso de genetización. Revista de Humanidades de Valparaíso 3: 13-21.

Venter, J. C.; Adams, M. D.; Myers, E. W.; Li, P. W.; Mural, R. J.; Sutton, G. G.; Smith, H. O.; Yandell, M.; Evans, C. A.; Holt, R. A.; Gocayne, J. D.; Amanatides, P.; Ballew, R. M.; Huson, D. H.; Wortman, J. R.; Zhang, Q.; Kodira, C. D.; Zheng, X. H.; Chen, L.; Skupski, M.; … Zhu, X. (2001). The sequence of the human genome. Science (New York, N.Y.), 291(5507), 1304–1351.

Wishart D.S.; Knox C.; Guo A. C.; Eisner R.; Young N.; Gautam B.; Hau D. D.; Psychogios N.; Dong E.; Bouatra S.; Mandal R.; Sinelnikov I.; Xia J.; Jia L.; Cruz J.A.; Lim E.; Sobsey C.A.; Shrivastava S.; Huang P.; Liu P.; Fang L.; Peng J.; Fradette R.; Cheng D.; Tzur D.; Clements M.; Lewis A.; De Souza A.; Zuniga A.; Dawe M.; Xiong Y.; Clive D.; Greiner R.; Nazyrova A.; Shaykhutdinov R.; Li L.; Vogel H.J.; Forsythe I. 2009. HMDB: a knowledgebase for the human metabolome. Nucleic acids research 37(Database issue): 603-610.

Wishart, D. S.; Feunang, Y. D.; Marcu, A.; Guo, A. C.; Liang, K.; Vázquez-Fresno, R.; Sajed, T.; Johnson, D.; Li, C.; Karu, N.; Sayeeda, Z.; Lo, E.; Assempour, N.; Berjanskii, M.; Singhal, S.; Arndt, D.; Liang, Y.; Badran, H.; Grant, J.; Serra-Cayuela, A.; Scalbert, A. 2018. HMDB 4.0: the human metabolome database for 2018. Nucleic acids research 46(1): 608-617.

Worthey E. A.; Mayer A. N.; Syverson G. D.; Helbling D.; Bonacci B. B.; Decker B.; Serpe J. M.; Dasu T.; Tschannen M. R.; Veith R. L.; Basehore M. J.; Broeckel U.; Tomita-Mitchell A.; Arca M. J.; Casper J. T.; Margolis D.A.; Bick D. P.; Hessner M. J., Routes J. M.; Verbsky J. W.; Jacob H. J.; Dimmock D.P. 2011. Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease. Genetics in Medicine. 13(3): 255-62.