Archivi del mese: aprile 2014

Riduzionismo vs complessità nella biologia molecolare: il caso dei topi knockout

[Van Regenmortel MH. Reductionism and complexity in molecular biology. Scientists now have the tools to unravel biological and overcome the limitations of reductionism. EMBO Rep. 2004 Nov;5(11):1016-20.]

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“Scientists now have the tools to unravel biological complexity and overcome the limitations of reductionism”

Nel testo:

“However, there is probably a more fundamental reason for these failures: namely, that most of these approaches have been guided by unmitigated reductionism. As a result, the complexity of biological systems, whole organisms and patients tends to be underrated (Horrobin, 2001). Most human diseases result from the interaction of many gene products, and we rarely know all of the genes and gene products that are involved in a particular biological function. Nevertheless, to achieve an understanding of complex genetic networks, biologists tend to rely on experiments that involve single gene deletions. Knockout experiments in mice, in which a gene that is considered to be essential is inactivated or removed, are widely used to infer the role of individual genes. In many such experiments, the knockout is found to have no effect whatsoever, despite the fact that the gene encodes a protein that is believed to be essential. In other cases, the knockout has a completely unexpected effect (Morange, 2001a). Furthermore, disruption of the same gene can have diverse effects in different strains of mice (Pearson, 2002). Such findings question the wisdom of extrapolating data that are obtained in mice to other species. In fact, there is little reason to assume that experiments with genetically modified mice will necessarily provide insights into the complex gene interactions that occur in humans (Horrobin, 2003). […]
The disappointing results of knockout experiments are partly caused by gene redundancy and pleiotropy, and the fact that gene products are components of pathways and networks in which genes acting in parallel systems can compensate for missing ones (Morange, 2001b). As many factors simultaneously influence the behaviour of a system, one part might function only in the presence of other components. The essential contribution of other genes in achieving a particular function will therefore be missed, which will further encourage the reductionist view that a single gene has adequate explanatory power (Van Regenmortel, 2004).”