The Search for Odorant Receptors. Commentary

Linda B. Buck*
Howard Hughes Medical Institute
Basic Sciences Division
Fred Hutchinson Cancer Research Center
1100 Fairview Avenue North
Seattle, Washington 98109

The Question
The first time I thought about olfaction was when I read
a 1985 paper from Sol Snyder's group that discussed
the unsolved question of how odors are detected in the
nose (Pevsner et al., 1985). This paper opened up a
fascinating new world for me. It was estimated that humans
could perceive 10,000 or more chemicals as having
distinct odors. Even more remarkably, subtle
changes in an odorous chemical could dramatically
change its perceived odor. How could the olfactory system
detect such an enormous diversity of chemicals?
And how could the nervous system translate this complexity
of chemical structures into a multitude of different
odor perceptions? To me, this was a monumental
problem and a wonderful puzzle. I was hooked.
As a molecular biologist, the logical first question to
ask was how the recognition of diverse chemical structures
is accomplished in the nose. With this knowledge
in hand, one might then be able to explore how sensory
information is organized in the nose and the brain to
ultimately yield odor perceptions. It seemed obvious
from a molecular standpoint that there must be a family
of odorant receptors that varied in ligand specificity. It
also seemed that olfactory sensory neurons in the nose
that detect odorants must express different receptors
in order for odorants to elicit different signals in the brain
and thereby generate distinct odor perceptions.