The celebrated Miller experiments reported on the spontaneous formation of amino acids from a mixture of simple molecules reacting under an electric discharge, giving birth to the research field of prebiotic chemistry. However, the chemical reactions involved in those experiments have never been studied at the atomic level. Here we report on, to our knowledge, the first ab initio computer simulations of Miller-like experiments in the condensed phase. Our study, based on the recent method of treatment of aqueous systems under electric fields and on metadynamics analysis of chemical reactions, shows that glycine spontaneously forms from mixtures of simple molecules once an electric field is switched on and identifies formic acid and formamide as key intermediate products of the early steps of the Miller reactions, and the crucible of formation of complex biological molecules.I n 1953, Miller reported (1) the surprising results he had achieved by the application of an electric discharge on a mixture of the gases CH 4 , NH 3 , H 2 O, and H 2 that simulated what was considered at the time as a model atmosphere for the primordial Earth. The result of this experiment was a substantial yield of a mixture of amino acids (2-4). Similarly, Orò demonstrated the spontaneous formation of nucleic acid bases from aqueous hydrogen cyanide subject to heating and/or spark discharges (5). Since then, a number of different hypotheses have been formulated to explain the synthesis, from simple molecules (water, ammonia, methane, carbon oxides), of simple organic molecules (formaldehyde, hydrogen cyanide, formic acid), and from the latter ones to biological monomers (amino acids, purines, pyrimidines) up the ladder of the complexity of life (6, 7). However, a "standard model" explaining the emergence of larger and larger molecular assemblies is lacking. Various sources of energy that might have initiated this synthesis have been suggested in the last 60 y, including UV irradiation both in extraterrestrial and terrestrial environments (8-11), hydrothermal energy from deep sea vents (12, 13), shock waves from meteorite impact (14-20), redox energy in the "iron−sulphur world" hypothesis (21), radioactive emission from uranium accumulation (22), and, of course, electric discharges originated by lightning, which motivated the Miller experiment, and are the inspiration of the present work. Despite the historical importance of Miller's experiments, no attempts have been made to explore the role of the electric field, traditionally considered merely in terms of just another thermal activation.A key aspect of that experiment was the formation of hydrogen cyanide, aldehydes, ketones, and amino acids, suggesting that the compounds were produced by the Strecker cyanohydrin reaction (23). Subsequent Miller-like experiments, run with other types and combinations of gases (24, 25) representing plausible geochemical conditions, produced other classes of basic building block molecules, namely sugars and nucleotides. To date, all of the major classes of...