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Rising atmospheric oxygen (O<sub>2</sub> ) levels provided a selective pressure for the evolution of O<sub>2</sub> -dependent micro-organisms that began with the autotrophic eukaryotes. Since these primordial times, the respiring mammalian cell has become entirely dependent on the constancy of electron flow, with molecular O<sub>2</sub> serving as the terminal electron acceptor in mitochondrial oxidative phosphorylation. Indeed, the ability to 'sense' O<sub>2</sub> and maintain homeostasis is considered one of the most important roles of the central nervous system (CNS) and probably represented a major driving force in the evolution of the human brain. Today, modern humans have evolved with an oversized brain committed to a continually active state and, as a consequence, paradoxically vulnerable to failure if the O<sub>2</sub> supply is interrupted. However, our pre-occupation with O<sub>2</sub> , the elixir of life, obscures the fact that it is a gas with a Janus face, capable of sustaining life in physiologically controlled amounts yet paradoxically deadly to the CNS when in excess. A closer look at its quantum structure reveals precisely why; the triplet ground state diatomic O<sub>2</sub> molecule is paramagnetic and exists in air as a free radical, constrained from reacting aggressively with the brain's organic molecules due to its 'spin restriction', a thermodynamic quirk of evolutionary fate. By further exploring O<sub>2</sub> 's free radical 'quantum quirkiness', including emergent (quantum) physiological phenomena, our understanding of precisely how the human brain senses O<sub>2</sub> deprivation (hypoxia) and the elaborate redox-signalling defence mechanisms that defend O<sub>2</sub> homeostasis has the potential to offer unique insights into the pathophysiology and treatment of human brain disease.