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European Biopharmaceutical Review

A Complex System

The concept of complex adaptive systems has a long history of use in describing and analysing the behaviour of biological systems across multiple different scales from collective animal behaviour to the emergence of cellular function from the interaction of large collections of molecules. The key characteristics of any complex adaptive system are that the behaviour of the system emerges due to the interactions between multiple typically much simpler entities, and that the behaviour of the system cannot be predicted by linear combinations of the isolated behaviour of the individual elements.

In addition, these systems adapt to changes in both the environment and underlying elements. Complex system theory aims to provide a framework in which non-linear behaviour can be understood and predicted. When applied to biological systems, and considered in the context of natural selection, these properties are thought to give rise to system resilience, robustness and evolvability (1,2).

Consideration of the cell as a complex system has consequences for drug discovery. Cellular function, including disease, arises due to interactions between proteins, secondmessengers and intrinsic small molecules within the cell (3). Cellular mechanisms of disease can be considered as a collection of pathological interactions that only occur in that disease state (4). This view of disease mechanism has found multiple recent applications including the hallmarks of cancer, immuno-oncology, cardiovascular disease and more.

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Jonny Wray is currently Head of Discovery Informatics at e-Therapeutics and has led the conceptual development of the networkdriven discovery approach and the design of the software platform embodying that method. He was a Fellow in Theoretical Neuroscience at The Neurosciences Institute, US, where his research was aimed at understanding how system function arises from network structure.
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