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Study of How We Identify Smells Wins U.S. Scientists Nobel Prize

By Lawrence K. Altman

The New York Times -- Two American scientists who solved the enigma of how people can smell 10,000 different odors and recall them later were awarded the 2004 Nobel Prize in physiology or medicine on Monday.

The winners, who will share the $1.3 million award, were Dr. Richard Axel, 58, a university professor at Columbia, and Dr. Linda B. Buck, 57, of the Fred Hutchinson Cancer Research Center and a professor at the University of Washington in Seattle.

Until publication of their fundamental paper in 1991, the sense of smell had been “the most enigmatic of our senses,” the Nobel Assembly of the Karolinska Institute in Stockholm, Sweden, said in recognizing the discovery that Axel and Buck made while working together at Columbia University in New York.

As the two scientists went on to work independently, the assembly said, “they have in several elegant, often parallel, studies clarified the olfactory system, from the molecular level to the organization of the cells.”

Their work provides a molecular understanding of how people who smell a lilac in childhood can recognize the fragrance later in life and also recall associated memories.

The molecules start a process by which olfactory cells send messages to the olfactory bulb, a structure in the front of the brain that is a clearinghouse for the sense of smell. Information from the olfactory bulb is then relayed to other parts of the brain where it is combined to form a pattern in a system of smell that allows humans and animals to distinguish good from bad.

“A good wine or a sun-ripe wild strawberry activates a whole array of odorant receptors, helping us to perceive the different odorant molecules,” the assembly said.

Buck, who was born in Seattle, received degrees in psychology and microbiology from the University of Washington, and a doctorate in immunology from the University of Texas Southwestern Medical Center in Dallas. Yearning to learn the techniques of molecular biology, she said, she joined Axel’s laboratory, working on the side to understand “how the nervous system deals with the tremendous problem of diversity.”

After “trying a number of crazy ideas,” she said, she became so fascinated with the olfactory system that “I was totally hooked and obsessed in finding the receptors, and Axel provided the funding so I could keep working on it.”

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Axel credited Buck for coming up with “an extremely clever twist” by making three assumptions that allowed her to zero in on a group of genes that appeared to code for the odorant receptor proteins.

The scientists discovered a large gene family, comprising 1,000 different genes representing about 3 percent of all genes in the body. The olfactory genes give rise to an equivalent number of olfactory receptors located on 5 million cells in a small area in the upper part of the nostrils. The cells are highly specialized to detect molecules of a few inhaled odors.

The ability to detect and identify chemical substances in the environment offers an obvious survival benefit. But the number of odorant receptors varies among species.

For their studies, Axel and Buck used mice, which have about 1,000 odorant receptors. That is about 10 times the number in fish. Humans have about 350 such receptors.

“Smell is absolutely essential for a newborn mammalian pup to find the teats of its mother and obtain milk -- without the olfaction the pup does not survive,” said the Nobel Assembly.