Emily Liman and David Corey found a gene for a sixth sense in humans, but it is muted and cannot detect chemical messages. Photo by Rose Lincoln.

The ancestors of humans may have communicated by a sixth sense, by detecting chemical signals given off by each other. They received these signals through a specialized organ in the nose, vestiges of which still exist. Some researchers think the organ still functions and influences our behavior; others believe it is extinct.

The controversy is producing a lot of interesting research and some questionable products labeled as sexual attractants.

Located just behind the nostrils in the nose's dividing septum are two tiny pits referred to as the vomeronasal organ (VNO), the seat of the sixth sense. Named for the vomer bone, where the septum meets the top of the mouth, the VNO contains nerve cells that sense chemicals called pheromones, secreted by many animals, including, perhaps, humans.

In creatures from insects to monkeys, pheromones trigger a variety of hormonal changes and instinctive behaviors, such as mating and aggression. Catherine Dulac, an assistant professor of molecular and cellular biology at Harvard, tries to pin down how pheromones are detected and how the brain translates their signals into behavioral changes. She collaborates with Emily Liman, an instructor in neurobiology, and David Corey, a professor of neurobiology, at Harvard Medical School. Last week, the trio reported that they have isolated a gene in rats and mice that appears to play a major role in the detection of pheromones. The gene is also present in humans, but it contains mutations that apparently make it useless for sniffing out pheromones.

Catherine Dulac notes that genes not yet discovered may reveal that a sixth sense exists now, or did in the past. Photo by Jon Chase.

"This is consistent with the idea that the human VNO is no longer functional," says Liman.

"But humans may rely on different genes from rodents," Dulac counters. "No one has made a careful search for such genes."

Rats and mice boast well-developed VNOs crammed with millions of nerve cells. Humans possess similar structures during early development in the womb, but by birth these structures become tiny cigar-shaped pits. No evidence has been found that these pits contain nerve cells, or that they don't.

That leaves a door open for various entrepreneurs to sell products with names like Realm, Desire 22, and Pheromone 10X, which they claim contain pheromones that promote sexual attraction and enhance self-confidence. Some of these products are suggestively known as "copulins."

Menstrual Synchrony

A variety of pheromones from insects and rodents are known, but none from humans has been identified. The best evidence for their existence comes from experiments in which women sniffed pads containing the underarm secretions of female classmates. The pads, worn during distinct phases of menstrual cycles, were wiped under the noses of other women every day for a month. By this means, Martha McClintock of the University of Chicago showed that the menstrual cycles of the sniffers can be advanced or retarded so that they achieved synchrony with the sniffees.

A sixth sense is not needed to explain such results, however. Ordinary odors from things like coffee and flowers, which travel through the air, are picked up by a separate system of nerve cells, higher up in the nose. Called the main olfactory system (MOS), these sensors may be capable of picking up both scents and pheromones. Pigs, for example, use nerve cells in the MOS to detect a pheromone called androstenone. One whiff of it, and a sow will immediately assume a mating position.

If humans are sensitive to pheromones, by whatever route, the pheromones don't trigger immediate, instinctive changes in behavior like they do in pigs and rats. "Pheromones might make a contribution to the unconscious part of the brain, but the conscious part, through other senses, education, and culture, exerts a higher level of control," Dulac says.

Making Scents Of It

Why would humans, pigs, or other animals need separate systems to detect odors and pheromones?

"Access is one possible explanation," Liman answers. Many animals that rely on pheromones for information and communication physically contact them with their noses. Sensory organs at the front part of the nose or snout can most easily contact blood, sweat, or other bodily surfaces or secretions.

Odors, on the other hand, consist of molecules vaporized from things such as baking bread, cologne, or gasoline. Air currents carry them up nostrils to a second set of sensors located at about the level of the eyes. There lies the MOS, an area containing millions of nerve cells that convert smells to nerve impulses that are sent to the brain.

Nerves from pheromone detectors go to a central collecting region, known as the accessory olfactory bulb, then to a part of the brain dealing with emotions and instinct. Nerve impulses from odor sensors collect in a separate region, called simply the olfactory bulb, then go to both emotional and cognitive levels of the brain. The latter make humans aware of the identity of what they smell and associate the odor with past experiences. The smell of tea brewing, for example, may remind you of pleasant days at grandma's house.

In other words, pheromone reception is unconscious and unchangeable, while odor reception is conscious and modified by experience.

Getting into the Brain

Liman, Corey, and Dulac, working at Harvard and Massachusetts General Hospital in Boston, added to the understanding of pheromones by clarifying how a chemical message received by the nose is transformed into a nerve signal to the brain.

A molecule, known as TRP2 sits on the surface of long thin extensions from VNO nerve cells. When a pheromone binds to these hairs, the researchers believe it opens a tiny channel through the TRP2 molecule. That allows ions from outside the nerve cells to pour into the cells. These ions change voltages inside the cells in a way that sends impulses along projections of the cells and into the accessory olfactory bulb.

That research was reported in the May 11 issue of the Proceedings of the National Academy of Sciences. In addition to their Harvard affiliation, the three researchers are investigators at the Howard Hughes Medical Institute.

Dulac has also identified as many as 200 pheromone receptors in a rodent's snout. Georgy Koentges, a postdoctoral fellow in Dulac's lab, painstakingly traced the threadlike projections from two different kinds of detectors from the snout into the brain. In a report published in April's issue of the journal Cell, Dulac, Koentges, and collaborators from Columbia University show how each projection connects to as many as 30 different structures in the accessory olfactory bulb.

That was surprising. Two hundred different types of projections each going to 30 sites in the accessory bulb multiples to thousands of connections. It was hard to believe that a simple rat needs all those connections; rats have only a few instinctive behaviors.

"Additional work leads us to conclude that the connections are organized into clusters, possibly one cluster for each type of behavior," Dulac notes. "That makes sense. Each behavior must be governed by more than one pheromone signal. A rat looking for a mate needs to find another rat of a specific species, sex, and age, sometimes in the dark. No one pheromone can supply all that information, but a blend of pheromones can do the job."

Having all the right elements woven together in a cluster prevents the confusion of fighting with a potential mate or trying to mate with a potential competitor.

Humans don't possess an accessory olfactory bulb, so could they do the same kind of signal processing in the olfactory bulb, which receives signals from odor sensors in the nose? That's not known. There are other questions as well. Do humans have a working sixth sense? Do invisible chemicals still affect our behavior on an unconscious level?

Dulac says she's keeping an open mind, but she's critical of the two extreme opinions: that a human sixth sense is nonsense, and that pheromones can be used to enhance mood and sexual attractiveness. "I believe further research will tell us what we want to know," she says. "In particular, I think we'll find exciting things about the role of pheromones in the evolution of higher animals, including humans, as well as how animals sense the world around them and adapt their behavior to it."