2004 NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE
A Life in Science Rewarded
"Odors generate specific behaviors and specific thoughts and how that happens is still an unsolved and fascinating mystery in brain science," says Richard Axel, M.D., University Professor of Biochemistry and Molecular Biophysics and Pathology and recipient of the Nobel Prize in Physiology or Medicine on Oct. 4. "Knowing how our perceptions of the external world, including smell, impact our emotions and our behavior will be extremely important in thinking about diseases like schizophrenia to understand how the brain works."
When Dr. Axel and his former postdoctoral researcher Linda Buck, Ph.D., of the Fred Hutchinson Cancer Research Center and a professor at the University of Washington in Seattle, began their work in the late 1980s, very little was known about the sense of smell.
In 1985, Dr. Buck came across a paper describing the unsolved question of how odors are detected in the nose and was immediately hooked by "the monumental problem and a wonderful puzzle."
The questions would remain unanswered unless the receptors responsible for picking up odorants in the air were identified. In 1988, Dr. Buck, working in Dr. Axel's lab at P&S, started tracking them down.
Several initial attempts failed. "Linda was an extremely creative and tenacious Fellow," Dr. Axel says. "The solution to this problem took quite a long time, but the thoughtfulness of her approach made me think she would eventually succeed."
In 1991 Drs. Axel and Buck broke the field open when they published a paper describing an enormous family of genes in mice that coded for 1,000 different receptors. The study was reported in newspapers and other news media worldwide. Later work revealed about 350 functional receptor genes in humans.
"We were quite surprised that up to 5 percent of the genome was taken up by odor receptors," says Dr. Axel, also a member of Columbia's Center for Neurobiology and Behavior. "That's a sharp distinction to the three genes that the visual system uses to discriminate several hundred different hues. It shows that a system like the visual system would be inadequate to distinguish among the rich variety of odors in the environment."
Gerald Fischbach, M.D., executive vice president and dean, says the finding ranks among the most important discoveries of the past 50 years: "The discovery of the genes opened up a field of sensory biology that didn't exist before."
Once the receptor genes were identified, both researchers independently moved to the more complex question of how the brain knows what the nose smells, with the support of the NIH and the Howard Hughes Medical Institute, where the two are investigators. Their labs and others have revealed that part of the answer is that each odor produces a unique spatial pattern, or map, of neuronal activity in the brain's olfactory center. If the olfactory center was laid out like a map of the United States, it would be as if the aroma from a rose would light up Boston, New York, and San Francisco, while rotting food would light up Los Angeles and Denver.
The question now, Dr. Axel says, is figuring out how an organism uses these odor maps. We can look down at the maps of activity in an organism's brain and see what it's smelling, but how does the process actually work within an organism?
"To know that the world is interested in our work will, I think, intensify our efforts toward reaching an answer," Dr. Axel says.