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Pair Probing Mystery of Smell Split Nobel Prize

Posted on: Tuesday, 5 October 2004, 06:00 CDT

Two scientists who discovered how the nose knows one odor from another are savoring the sweet smell of success -- this year's Nobel Prize in medicine.

''The sense of smell long remained the most enigmatic of our senses,'' notes the Nobel Assembly in Sweden. Richard Axel, 58, of the Howard Hughes Medical Institute at Columbia University in New York and Linda Buck, 57, of the Fred Hutchinson Cancer Research Center in Seattle, split the $1.36 million prize for their ''pioneering'' solution to the neurochemical riddle of how people discern individual odors.

''I'm overjoyed, of course, and quite surprised to receive this great honor,'' Buck says. An immune-system expert by training, she was a research fellow in Axel's Columbia University lab when she set out to unravel how the brain perceives smells as part of an effort to learn molecular biology.

Axel said her ''intensity and originality'' convinced him that she would succeed, despite four years of effort.

In a 1991 paper in the journal Cell, the pair revealed that an extensive family of genes produces nasal cells capable of differentiating, with the brain's help, at least 10,000 separate smells. ''It was a landmark in understanding our sense of smell -- a revolutionary paper,'' says cell biologist James Battey of the National Institutes of Health.

Later studies showed that about 350 smell sensors, or ''olfactory receptors,'' embedded in nasal cells are derived from the gene family identified by Buck and Axel, one that comprises about 3% of the human genetic makeup.

Located far back in the nose, highly specialized nasal cells directly signal the brain's smell center, which partly accounts for the power of scent in our awareness of the world, the Nobel citation notes. ''Therefore, we can consciously experience the smell of a lilac flower in the spring and recall this olfactory memory at other times.''

The finding that each nasal cell type is attuned to only one smell-producing chemical was unexpected. In their subsequent, separate research, Buck and Axel showed how the nasal cells are organized and how the brain weaves individual signals from these cells into patterns that we recognize as distinct odors. Buck compared the system to the alphabet, in which 26 letters can combine to form countless words.

Studies in fish and mice of the smell receptor genes underlined their relative importance to different species. Mice possess far more than people, about 1,000 genes, and fish possess far fewer.

''We are interested in our lab in how the brain is capable of representing, in an effective and accessible way, the richness of the external world,'' Axel says.

In more recent work, Buck has found that receptors may underlie the sense of taste, identifying sweetness and bitterness receptors. Axel has pioneered the study of the sense of smell in insects.

On a more practical basis, about 200,000 people nationwide report some loss of their sense of smell every year, usually due to head trauma, sinus ailments or infection, according to the National Institute on Deafness and Other Communication Disorders. They are about twice as likely to have some kinds of accidents, such as eating spoiled food or not smelling leaking gas.

Researchers hope to reverse such losses by using the sense-of-smell research pioneered by Buck and Axel.

''It's the basic scientific underpinning of how the sense of smell works,'' Battey says. Research designed to turn this understanding into pharmaceutical treatments is still underway, ''but this work is the first step on that road,'' Battey says.

The Nobel Prize in Medicine or Physiology has been presented every year since 1901 by the Nobel Assembly at the Karolinska Institute in Stockholm. The last American woman to win the prize was Gertrude Elion of Wellcome Research Laboratories in Research Triangle Park, N.C., in 1988. She shared the prize with two scientists for discoveries that produced new drug treatments for leukemia, malaria and other ailments.

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