Smell, the conversion of volatile molecules in the environment to information or behaviors by a creature, is foundational to life on Earth. Its inner workings in animals, however, long eluded a detailed description. Particularly mysterious has been the initial step: how odorant molecules are detected by the neurons that transmit their signals to the brain. At the close of the twentieth century, Buck and Axel discovered the family of G protein-coupled receptors expressed in the membranes of olfactory neurons that detect odorants. These olfactory receptors (ORs) are one of the largest multigene families in vertebrates. Humans have about 400 ORs, although mice have closer to 1000 ; they account for almost half of the known G protein-coupled receptors, themselves among the largest families of protein-coding genes . Axel and Buck shared the 2004 Nobel Prize in Physiology or Medicine for their discovery .