A Concise History of the Discovery of Mammalian Nitric Oxide (Nitrogen Monoxide) Biogenesis

Abstract In 1986–88 one of the most unexpected and important scientific paradigm shifts of the 20th century occurred, involving several seemingly unrelated phenomena in cardiovascular, immunological, and neurochemical research. It was discovered that mammalian cells produce the molecule nitric oxide (chemical formula NO), which had previously been known in animals as primarily a poison and pollutant. First discovered as a critical signal that is produced by and regulates multiple functions of the vasculature (for which the 1998 Nobel Prize in Physiology or Medicine was awarded to Robert Furchgott, Louis Ignarro, and Ferid Murad), researchers in immunology and neuroscience immediately recognized that many previously puzzling phenomena are explained by NO. Here I present the historical development of this remarkable discovery and the initial establishment of the chemical and physical principles that define its extraordinarily pleiotropic biological actions, emphasizing the importance of the concept.