Physiology or medicine.

In recognition of more than a decade of pioneering exploration of the sense of smell, two Americans received the 2004 Nobel Prize in Physiology or Medicine on Oct. 4. The researchers, Richard Axel of Columbia University and Linda Buck of the Fred Hutchinson Cancer Center in Seattle, will share the nearly $1.4 million prize.

The award largely honors the pair's close collaboration on a paper published in Cell in 1991 and their continuing independent efforts. Before the paper appeared, scientists knew little about the cellular and molecular mechanisms underlying the olfactory system, which transmits information on odorant molecules from the nose to the brain. Anatomical studies had shown that olfactory neurons project hairlike cilia into the nasal cavity. However, researchers were unable to pinpoint olfactory receptors on these cilia or explain how such receptors might work.

According to Kerry Resster, an associate professor of psychiatry at Emory University in Atlanta and Buck's first graduate research assistant in the mid-1990s, the olfactory system had been largely ignored by sensory scientists who were more apt to explore the mechanisms behind other senses such as sight and hearing. The reasons were twofold: The sense of smell is the most expendable of human senses. In addition, says Ressler, "there was a lack of good tools for how to dissect this system in the right way."

At the time of the Cell paper, Buck was a postdoctoral fellow in Axel's lab at Columbia. Taking advantage Of a then-novel DNA-copying technique known as polymerase chain reaction, the colleagues searched for genes that encode olfactory receptors in rats. After several false starts, the two researchers achieved success.

Since publishing preliminary information about 18 rat olfactory genes in the 1991 paper, the researchers have discovered almost 1,000 others. The number discovered so far in people is only about 350. Scientists estimate that these genes allow a healthy person to distinguish and remember upwards of 10,000 different scents.

The seminal 1991 discovery of this specific family of genes enabled researchers to probe the sense of smell using modern molecular- and cellular-biology techniques. Subsequent studies by Axel, Buck, and others have shown that each olfactory neuron expresses only one type of receptor on its surface. Scents composed of several different odorant molecules bend to these receptors in a particular pattern. For example, the odorant molecules wafting from sizzling bacon might stimulate only receptors 2, 45, and 54.

These odorant-receptor interactions trigger neurons to send signals to the olfactory bulb, a structure located in the front of the brain. The bulb then relays information about the scent to the brain's thought and emotion centers.

Andrew Chess, a former postdoctoral fellow in Buck's lab and a current olfactory researcher at the Whitehead Institute in Cambridge, Mass., says that Axel and Buck were an "excellent choice" to receive this year's Nobel prize. "Their work basically started this field of applying modern molecular biology approaches to this sensory system," he says.