Non-equilibrium thermodynamics and the free energy principle in biology

According to the free energy principle, life is an “inevitable and emergent property of any (ergodic) random dynamical system at non-equilibrium steady state that possesses a Markov blanket” (Friston in J R Soc Interface 10(86):20130475, 2013). Formulating a principle for the life sciences in terms of concepts from statistical physics, such as random dynamical system, non-equilibrium steady state and ergodicity, places substantial constraints on the theoretical and empirical study of biological systems. Thus far, however, the physics foundations of the free energy principle have received hardly any attention. Here, we start to fill this gap and analyse some of the challenges raised by applications of statistical physics for modelling biological targets. Based on our analysis, we conclude that model-building grounded in the free energy principle exacerbates a trade-off between generality and realism, because of a fundamental mismatch between its physics assumptions and the properties of actual biological targets.