Mind & Brain / Senses

A word of advice, should you ever find yourself in George Preti's lab: Don't inhale. From the doorway, his windowless lair at the Monell Chemical Senses Center in Philadelphia looks harmless, with its wonky assemblage of test tubes, beakers, reagents, rubber gloves, and laminar-flow hoods. Then Preti guides you to a bench under one of the hoods. He unscrews a cap from a bottle of clear liquid and waves the vessel under your nose. When your reaction falls short of nausea, he tries another bottle, the fumes from which will ruin your appetite for hours.

The human armpit is packed
with two kinds of sweat glands.
Eccrine glands help regulate
temperature through fluid evaporation;
the average human body
possesses up to 3 million of them.
Apocrine glands number approximately
2,000; most are concentrated
in the armpit and genital regions.
Men and women may communicate
chemically through secretions
from the apocrine glands, which lie
beneath hair follicles. Skin bacteria
break down the secretions,
creating a distinctive bouquet.

Preti grins and turns the bottle so that its label faces you.

The label says PSEUDO ARM PIT.

Preti tells you the bottle contains a synthetic version of that sweet elixir brewed in nature just south of the shoulder and north of the ribs. "Better living through chemistry!" he exclaims.
Preti is hot on the scent of the human armpit because he believes that secretions from the so-called axillary region harbor pheromones, airborne chemical signals that influence mating, dominance, family ties, and maturation in other species of the animal kingdom. Scientists already know that in humans pheromones convey information about identity, kinship, age, health, happiness, fertility, and arousal. And studies have shown that exposure to some human emanations can boost mood, tweak hormones, and inspire aggression or attraction in others. Nonetheless, scientists haven't figured out how human pheromones work. They can't even agree on a single chemical worthy of the title.

"We have no clue what the active ingredients are," Preti laments.

So he is determined to find them. An organic chemist who specializes in body odor, Preti is well versed on the glands in the human armpit—not to mention those in the mouth, breasts, crotch, and feet—that secrete chemicals that vaporize readily. He catalogs dozens of volatile secretions and studies the skin-borne microbes that process them before they're released to the air. And he looks for physiological benchmarks that give hard proof of pheromonal effects in recipients. "It's very arduous, time-consuming, and expensive," says his partner at Monell, neuroscientist Charles J. Wysocki. But in their latest work, the two have documented a specific effect of men's underarm chemistry on the hormones underlying women's menstrual cycles, and they say it's only a matter of time before they isolate the culpable constituents. "It might be the whole bouquet," Wysocki notes.

Much of the evidence that people exchange and respond to airborne chemical messages is inferential. Men who have no idea what they're smelling inexplicably prefer the aroma of T-shirts worn by ovulating women to those worn by women in another part of their cycle. A woman will unknowingly rate male body odor as more pleasant if the source of the odor shares fewer of her immune-system genes (which means he's less likely to be close kin). People exposed to cotton underarm pads worn by moviegoers can tell whether a viewer was scared or amused.

The effects of chemical messages among creatures other than humans are far more dramatic. Coined in 1959 from the Greek words meaning "carrier of excitement," the term pheromone first referred to substances produced by insects to communicate with members of their own species. The first pheromone to be identified, called bombykol, is a substance made by female silk moths that attracts males. Attracts is perhaps too coy a word; bombykol pretty much strips a male moth of free will. Candidate pheromones have also been proposed for mice, elephants, pigs, hamsters, and deer. Compounds released in the urine or body odor of male mice, for example, can signal dominance and spark aggression between males and prompt reproductively dormant females to start cycling. The scent of a strange male mouse will cause pregnant females to abort their fetuses. A substance called androstenone induces a female pig to round her haunches and flex the muscles of her pelvic floor in anticipation of mating. In nature, androstenone resides in the saliva of male pigs; in commerce it resides in a product called Boar Mate, which makes sows more receptive to artificial insemination.

No chemical elixir has been found to have effects analogous to bombykol or androstenone in humans. But researchers have known for decades that human pheromonal effects extend beyond vibes and preferences to basic physiology. One of the earliest hints came from the work of a young psychology student named Martha McClintock. In the late 1960s, McClintock, still a student, showed that the menstrual cycles of her classmates at Wellesley College became synchronized among women who spent a lot of time together: best friends, roommates, and dorm mates. In the 30 years since then, McClintock, now at the University of Chicago, and many other investigators have shown that exposure to female underarm secretions alone is sufficient to effect changes in the timing and length of menstruation. Male axillary secretions also can shift menstrual schedules. Somehow, an airborne message penetrates the endocrine system: from the breeze, to the brain, to the blood.

Vials in the freezer at the Monell Chemical Senses Center in
Philadelphia contain odoriferous substances that may be involved
in chemosensory communication. The study of chemical ecology
and communication is one of the center's six areas of research.

Preti hopes that he can map this route by identifying specific physiological responses to pheromonal stimulation. Experiments with female goats, for example, suggest that the timing of sexual receptivity can be modulated by pulses of luteinizing hormone, or LH, a compound that rhythmically surges in the bloodstream of women as well as goats many times a day. The frequency of LH pulses increases as women approach ovulation. In a study published earlier this year, Preti and Wysocki found that a single smear of male underarm extracts around the noses of female subjects would shorten the interval to the next LH pulse by an average of 20 percent. The extract odor was disguised with a fragrance, and subjects never guessed the nature of the test substance. According to Preti, "something in the application is influencing the timing mechanism in the hypothalamus," the reproductive command center in the brain.

The extract also seemed to put women at ease: Recipients reported feeling more relaxed and less tense than they did without the extracts, even though the procedure required a hospital stay and repeated bloodlettings. Granted, it's no Boar Mate. But chemosensory experts say the role of pheromones in human life is bound to be less than deterministic. For one thing, our sense of smell is embarrassingly inept compared with that of other mammals. And human beings probably aren't endowed with a functional vomeronasal organ—an anatomic sensor of pheromone signals that is found in many amphibians, reptiles, and mammals. The vomeronasal organ got its reputation as a kind of sixth sense because in rodents, nerve fibers from the organ's receptors bypass the cerebral cortex—the seat of consciousness—in favor of the amygdala and the limbic system, brain structures that coordinate emotional and autonomic responses. If you disable the gene for a single vomeronasal protein in mice, a male mouse loses his ability to distinguish other males from females and will try to mate with both.

A functional vomeronasal organ is present in new-world monkeys but not in chimpanzees, gorillas, and orangutans, our closest relatives. And what about us? A research team at the University of Utah in Salt Lake City has championed the cause of the human vomeronasal organ for more than a decade. Physiologist Louis Monti-Bloch, now at Pherin Pharmaceuticals in Mountain View, California, and his colleagues have documented the location of the vomeronasal organ's outlet in humans: a tiny pit just a couple of centimeters up the inner wall of the nostril. They've pioneered equipment that confines puffs of airborne chemicals to that area, south of the smell sensors in the olfactory epithelium. They have tested odorless human-derived substances that reportedly cause electrical discharges in the region of the vomeronasal organ pit and that change blood pressure, heart rate, hormone levels, and mood.

Their findings haven't exactly been embraced. No one disputes the presence of the intra-nostril pit. But critics say there's no good evidence of an active nerve pathway from the pit to the brain.

In any case, you may not need a vomeronasal organ to sniff out a pheromone. Preti and Wysocki think the general sense of human olfaction may well have taken over specialized chores relegated to the vomeronasal organ in other species. In addition to a freezer stocked with sweat, urine, spit, and worse, Preti keeps a long list of body-secretion compounds that could prove to govern effects on physiology or mood. He has a list of diseases that may someday be diagnosed by volatiles from the breath or the body. And with his boss, Monell director Gary Beauchamp, he is developing the idea of the odor print: the notion, first proposed by the late biologist Lewis Thomas more than 25 years ago, that body odor bears a signature of immune-system proteins as unique as a face or a fingerprint. There's some evidence that people can recognize odor prints even when they aren't aware of smells. One recent study suggests odor prints may even influence our choice of spouses. "It should be everywhere on the body," says Preti. "But of course my favorite area is the armpit."



Read "The Sniff of Legend" (Discover, April 1994) by Karen Wright, about pheromones and the search for the human equivalent of the vomeronasal organ.

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