Physiology of nitrogen: A life or death matter

With each breath, four out of every five molecules we inspire are nitrogen (N₂), since this gas constitutes ∼80% of the atmospheric air that surrounds us. Despite its abundance and unlike molecular oxygen, N₂ has traditionally held less appeal among physiologists given its lack of reactivity and corresponding inability to support combustion or life, rendering it metabolically nugatory. The controversial application of N₂ asphyxiation for the inhumane purposes of human execution of convicted criminals and assisted suicide of a terminally ill patient has thrust this important gas into the scientific and public spotlight, sparking widespread condemnation. In the current review, we take an opportunity to explore the molecular bases and clinical consequences linked to the Janus-faced physiology of N₂ to better explain its life-and-death qualities. We highlight the complex history that led to its discovery and the physio-geochemical evolution of Earth's uniquely N₂-rich atmosphere, including intimate links with oxygen (O₂), another life-and-death homonuclear diatomic gas that preceded aerobic respiration and the emergence of complex multicellular life. Diving deep into N₂'s quantum state, we expose its unique physiochemical properties to better understand why this gas is metabolically inert and physiologically deadly when in excess and especially to the exclusion of O₂. We apply this integrated physiological knowledge to further inform the controversial public debate and directly challenge the misconceived notion that N₂ gas asphyxiation offers a quick, indolent and dignified death for the inhumane purposes of human execution and assisted suicide.