Given that the human nose lacks a functional VNO, is there any reason to think that people can communicate through pheromones? Many scientists have been skeptical, yet in the popular imagination a belief in some sort of sexual "chemistry" between human beings continues to thrive. Whether this is true remains unknown, but several recent experiments have revealed a previously unsuspected capacity of the main olfactory system to detect pheromone signals—at least in some mammals—possibly representing an evolutionary backup to the VNO for receiving these crucial communications.

In 2002, Dulac reported that mice whose VNO function had been knocked out were nevertheless able to respond to pheromonal mating signals. Even without a working VNO, they sensed fertility pheromones in the environment and went into mating mode. But, to the researchers' surprise, males could no longer distinguish between a male and female mouse—nor did they show stereotypical aggression against other males. The experiment "told us the VNO function is not required for mating behavior," says Dulac. "What people were saying was the detector of the 'love potion'—the VNO—was not true. So there is something else, in the olfactory system, that is detecting cues and getting animals to mate."

In another intriguing finding, Buck and postdoctoral fellow Stephen Liberles reported in the August 10, 2006, issue of Nature that they had identified a second family of chemosensory receptors in the olfactory epithelium of the mouse that is unrelated to the odorant receptor family and that may detect pheromones. These receptors, called "trace amine-associated receptors," or TAARs, were previously proposed to function in the brain as receptors for chemical messengers called trace amines. However, the researchers could not detect any of the 15 mouse TAARs in the brain, whereas they found that 14 of the 15 are expressed by olfactory neurons in the nose. Each TAAR gene is expressed by a unique set of neurons, just like each odorant receptor gene.

Zebrafish have 57 of these receptors—many or all found in the olfactory epithelium—and humans, interestingly, have six TAARs. By testing TAARs with more than 200 compounds, Liberles and Buck found that several mouse TAARs recognize stress or gender-linked signals in mouse urine, and one TAAR recognizes a male pheromone that stimulates puberty in female mice. "The evolutionary conservation of TAARs, their expression patterns in mouse and fish, and the TAAR ligands we have identified so far together suggest that TAARs serve a different function from that of odorant receptors, and that they may be involved in recognizing social cues such as pheromones," Buck says. Since humans have TAARs, might they be capable of detecting pheromonal signals among people? That's a question Buck is pursuing.

The discovery of TAARs as olfactory receptors is not the only recent finding that suggests pheromones can be detected in the nose as well as in the VNO. Dulac and Buck have also found evidence in mice of connections between the olfactory epithelium and brain neurons that control reproductive hormones and perhaps sexual behavior. "So now, if you ask the question 'Where are the neurons that detect pheromones? '" Dulac says, "we can say that both the VNO and the main olfactory system are involved." Why have animals developed two sensory systems to detect pheromones? Dulac has shown that the brain coding of VNO information is very different from the main olfactory system and favors the processing of complex blends of pheromone compounds as contrasted with single pheromone compounds.

If these discoveries carry over to humans, they could help explain intriguing observations of what appear to be pheromone-like communications between people—even in the absence of a functioning VNO. Among them: the well-studied phenomenon that women working or living in close proximity tend to have synchronized menstrual cycles and reports that members of opposite sexes have more "chemistry" with individuals whose immune systems are genetically different. (The evolutionary explanation is that such couples would theoretically produce offspring with a broader range of disease-fighting immune cells.)

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