title: Questions regarding the predictive value of one evolved complex adaptive system for a second: exemplified by the SOD1 mouse.
abstract: We surveyed the scientific literature regarding amyotrophic lateral sclerosis, the SOD1 mouse model, complex adaptive systems, evolution, drug development, animal models, and philosophy of science in an attempt to analyze the SOD1 mouse model of amyotrophic lateral sclerosis in the context of evolved complex adaptive systems. Humans and animals are examples of evolved complex adaptive systems. It is difficult to predict the outcome from perturbations to such systems because of the characteristics of complex systems. Modeling even one complex adaptive system in order to predict outcomes from perturbations is difficult. Predicting outcomes to one evolved complex adaptive system based on outcomes from a second, especially when the perturbation occurs at higher levels of organization, is even more problematic. Using animal models to predict human outcomes to perturbations such as disease and drugs should have a very low predictive value. We present empirical evidence confirming this and suggest a theory to explain this phenomenon. We analyze the SOD1 mouse model of amyotrophic lateral sclerosis in order to illustrate this position.
authors.affiliation: Americans for Medical Advancement, 2251 Refugio Road, Goleta, CA 93117, USA. Electronic address: DrRayGreek@gmail.com.
authors.forename: Ray
authors.initials: R
authors.lastname: Greek
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Hansen
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000503:physiopathology*; D003198:Computer Simulation; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D009473:Neuronal Plasticity / Q000235:genetics*; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: ALS; Animal models; Complex systems; Evolution; Predictive value; SOD1 mouse