Shape Theory of Olfaction - History

History

In 1949, R.W. Moncrieff published an article in American Perfumer called "What is odor: a new theory," which used Linus Pauling's notion of shape-based molecular interactions to propose a shape-based theory of odor. This superseded the older vibration theory of olfaction and remains the mainstream theory, in both commercial fragrance chemistry and academic molecular biology. Three years after Moncrieff proposed the theory, John Amoore speculated further that the over ten thousand smells distinguishable by the human olfaction system resulted from the combination of seven basic primary odors correlating to odor receptors for each, much as the spectrum of perceived colors in visible light is generated by the activation of three primary color receptors. Amoore's seven primary odors included sweaty, spermous, fishy, malty, urinous and musky. His most convincing work was done on the camphoraceous odor, for which he posited a hemispherical socket in which spherical molecules, such as camphor, cyclooctane, and naphthalene could bind.

When Linda Buck and Richard Axel published their Nobel Prize winning research on the olfactory receptors in 1991, they identified in mice 1,000 G-protein-coupled receptors used for olfaction. Since all types of G-protein receptors currently known are activated through binding of molecules with highly specific conformations, or shape, it is assumed that olfactory receptors operate in a similar fashion. Further research on human olfaction systems identified 347 olfactory receptors.

The most recent shape theory, also known as odotope theory or Weak Shape Theory, holds that a combination of activated receptors is responsible for any one smell, as opposed to the older model of one receptor, one shape, one smell. Receptors in the odotope model recognize only small structural features on each molecule, and the brain is responsible for processing the combined signal into an interpreted smell. Much current work on shape theory focuses on neural processing, rather than the specific interaction between odorant and receptor that generates the original signal .