Americans for Medical Advancement, 2251 Refugio Road, Goleta, CA 93117, USA.
Prog Biophys Mol Biol. 2013 Nov;113(2):231-53. doi: 10.1016/j.pbiomolbio.2013.06.002. Epub 2013 Jun 20.
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.
我们调查了有关肌萎缩侧索硬化症、SOD1 小鼠模型、复杂适应系统、进化、药物开发、动物模型和科学哲学的科学文献,试图在进化的复杂适应系统背景下分析肌萎缩侧索硬化症的 SOD1 小鼠模型。人类和动物是进化的复杂适应系统的例子。由于复杂系统的特征,很难预测对这些系统的干扰会产生什么结果。即使是为了预测干扰的结果而对一个复杂适应系统进行建模,也是困难的。基于第二个系统的结果来预测一个已进化的复杂适应系统的结果,尤其是当干扰发生在更高的组织层次上时,问题更加严重。使用动物模型来预测疾病和药物等干扰对人类的影响,其预测价值应该非常低。我们提供了证实这一点的经验证据,并提出了一种解释这一现象的理论。我们分析了肌萎缩侧索硬化症的 SOD1 小鼠模型,以说明这一立场。