Greek Ray, Rice Mark J
Americans For Medical Advancement (www,AFMA-curedisease,org), 2251 Refugio Rd, Goleta, CA 93117, USA.
Theor Biol Med Model. 2012 Sep 10;9:40. doi: 10.1186/1742-4682-9-40.
The concept of conserved processes presents unique opportunities for using nonhuman animal models in biomedical research. However, the concept must be examined in the context that humans and nonhuman animals are evolved, complex, adaptive systems. Given that nonhuman animals are examples of living systems that are differently complex from humans, what does the existence of a conserved gene or process imply for inter-species extrapolation?
We surveyed the literature including philosophy of science, biological complexity, conserved processes, evolutionary biology, comparative medicine, anti-neoplastic agents, inhalational anesthetics, and drug development journals in order to determine the value of nonhuman animal models when studying conserved processes.
Evolution through natural selection has employed components and processes both to produce the same outcomes among species but also to generate different functions and traits. Many genes and processes are conserved, but new combinations of these processes or different regulation of the genes involved in these processes have resulted in unique organisms. Further, there is a hierarchy of organization in complex living systems. At some levels, the components are simple systems that can be analyzed by mathematics or the physical sciences, while at other levels the system cannot be fully analyzed by reducing it to a physical system. The study of complex living systems must alternate between focusing on the parts and examining the intact whole organism while taking into account the connections between the two. Systems biology aims for this holism. We examined the actions of inhalational anesthetic agents and anti-neoplastic agents in order to address what the characteristics of complex living systems imply for inter-species extrapolation of traits and responses related to conserved processes.
We conclude that even the presence of conserved processes is insufficient for inter-species extrapolation when the trait or response being studied is located at higher levels of organization, is in a different module, or is influenced by other modules. However, when the examination of the conserved process occurs at the same level of organization or in the same module, and hence is subject to study solely by reductionism, then extrapolation is possible.
保守过程的概念为在生物医学研究中使用非人类动物模型提供了独特的机会。然而，必须在人类和非人类动物是进化的、复杂的、适应性系统的背景下审视这一概念。鉴于非人类动物是与人类复杂性不同的生命系统的例子，保守基因或过程的存在对于种间推断意味着什么？
我们查阅了包括科学哲学、生物复杂性、保守过程、进化生物学、比较医学、抗肿瘤药物、吸入麻醉剂和药物开发期刊在内的文献，以确定在研究保守过程时非人类动物模型的价值。
通过自然选择的进化既利用了组成部分和过程在物种间产生相同的结果，也产生了不同的功能和特征。许多基因和过程是保守的，但这些过程的新组合或参与这些过程的基因的不同调控导致了独特的生物体。此外，复杂生命系统存在组织层次结构。在某些层面，组成部分是可以用数学或物理科学分析的简单系统，而在其他层面，该系统不能通过将其简化为物理系统来完全分析。对复杂生命系统的研究必须在关注部分和检查完整的整个生物体之间交替进行，同时考虑两者之间的联系。系统生物学旨在实现这种整体观。我们研究了吸入麻醉剂和抗肿瘤药物的作用，以探讨复杂生命系统的特征对于与保守过程相关的性状和反应的种间推断意味着什么。
我们得出结论，当所研究的性状或反应位于更高的组织层次、处于不同的模块或受到其他模块的影响时，即使存在保守过程也不足以进行种间推断。然而，当对保守过程进行检查是在相同的组织层次或相同的模块中进行，因此仅通过还原论即可进行研究时，那么推断是可能的。
