Pezzulo Giovanni, Levin Michael
Institute of Cognitive Sciences and Technologies, National Research Council, Rome, Italy.
Biology Department, Allen Discovery Center at Tufts, Tufts University, Medford, MA 02155, USA
J R Soc Interface. 2016 Nov;13(124). doi: 10.1098/rsif.2016.0555.
It is widely assumed in developmental biology and bioengineering that optimal understanding and control of complex living systems follows from models of molecular events. The success of reductionism has overshadowed attempts at top-down models and control policies in biological systems. However, other fields, including physics, engineering and neuroscience, have successfully used the explanations and models at higher levels of organization, including least-action principles in physics and control-theoretic models in computational neuroscience. Exploiting the dynamic regulation of pattern formation in embryogenesis and regeneration requires new approaches to understand how cells cooperate towards large-scale anatomical goal states. Here, we argue that top-down models of pattern homeostasis serve as proof of principle for extending the current paradigm beyond emergence and molecule-level rules. We define top-down control in a biological context, discuss the examples of how cognitive neuroscience and physics exploit these strategies, and illustrate areas in which they may offer significant advantages as complements to the mainstream paradigm. By targeting system controls at multiple levels of organization and demystifying goal-directed (cybernetic) processes, top-down strategies represent a roadmap for using the deep insights of other fields for transformative advances in regenerative medicine and systems bioengineering.
发育生物学和生物工程领域普遍认为，对复杂生命系统的最佳理解和控制源于分子事件模型。还原论的成功使生物系统中自上而下的模型和控制策略的尝试黯然失色。然而，包括物理学、工程学和神经科学在内的其他领域，已经成功地运用了更高层次组织的解释和模型，包括物理学中的最小作用原理和计算神经科学中的控制理论模型。利用胚胎发生和再生过程中模式形成的动态调节，需要新的方法来理解细胞如何朝着大规模解剖学目标状态进行协作。在此，我们认为模式稳态的自上而下模型可作为将当前范式扩展到涌现和分子水平规则之外的原理证明。我们在生物学背景下定义自上而下的控制，讨论认知神经科学和物理学如何利用这些策略的例子，并说明它们作为主流范式补充可能具有显著优势的领域。通过在多个组织层次上针对系统控制并揭开目标导向（控制论）过程的神秘面纱，自上而下的策略代表了一条路线图，用于利用其他领域的深刻见解推动再生医学和系统生物工程的变革性进展。
