Biology 202
1999 First Web Reports
On Serendip

The ability to take a chemical sample of the environment and interpret that sample has long been a skill of earth dwelling life forms. We don't tend to think of the sense of smell as a mechanism that analyzes physical specimens. It is sort of a repulsive notion, considering some of the undesirable substances we are forced to smell every day. But, just as we cannot feel a book without touching it, we cannot smell an orange without guiding some orange molecules up our noses. The capacity that humans divide into smell and taste has a single evolutionary precursor. This was a common chemical sense that enabled single-celled organisms to identify food and alert themselves to the presence of harmful substances. While it is among the oldest and most universal senses employed by living creatures, science has been slow to understand it. One roadblock to knowledge progression has been the inherent difficulty in experimenting with the chemical senses. Delivering precisely timed and quantitatively accurate amounts of chemical stimuli to receptors is a technological challenge, but often necessary in the study of olfaction (1). While in many animals, the chemical senses play the most important role in perception and survival, in humans they are less involved in behavior than sight or hearing. This relative insignificance is another reason why olfaction has received scientific short shrift. It has been comparatively neglected by our culture as well--the English language does not include a sufficient vocabulary for describing odors. It is very difficult to verbally depict an odor to an individual who has never encountered it. Our understanding of smell is ever increasing, and while some big questions remain, others are continually being answered.

The olfactory epithelium of each of the two nasal passages in humans is a 2.5 square centimeter patch containing about 50 million sensory receptor cells (3). The reception of the odorant and the beginning of sensory signal transduction occurs in the olfactory cilia, which are hair-like extensions of the receptor neurons (10-20 cilia per neuron). The neurons have a turn-over rate of about 40 days (3). On the opposite side of the cilia, within the epithelium, the neurons form axons which penetrate the cribiform bone in bundles and synapse with neurons in the olfactory bulb (2). Via the olfactory tract, (cranial nerve I), olfactory information travels to the primary olfactory cortex without first passing through the thalamus. This bypass is unique to olfaction, and is thought to reflect the early development of the olfactory system in the evolution of vertebrates (2). Odor information is widely distributed among other brain areas for conscious recognition of odors.

The average human being, it is believed, can recognize up to 10,000 odors (2). So, how do we use the aforementioned equipment to accomplish this? Smelling starts with receptor proteins located on the cilia, which recognize and bind odorant molecules, and in turn stimulate the cell to send signals to the brain. The proteins can be seen as locks that are "opened" by the molecular odorant keys. In the early 1990's, researchers found that there are about 1000 separate receptor proteins on mouse, and assumedly human, olfactory neurons. That's 1 percent of the genome of the mouse! (3) This enormous number of genes is evidence of the profound importance of smell to animals. The riddle presented by this information is, if the number of odors we can recognize far exceeds the number of receptor proteins--by a ratio of at least 10 to 1 (2), how does the brain know what the nose is smelling? Richard Axel of Columbia University found that a given olfactory neuron can make only one or a few receptor proteins, and that neurons are distributed randomly on the epithelium with respect to their odorant receptors. Where the axons reach the olfactory bulb, however, sorting takes place based on receptor type. So, the olfactory bulb is an organized spatial map of receptor information.

"The brain is essentially saying something like, 'I'm seeing activity in positions 1, 15, and 54 of the olfactory bulb, which correspond to odorant receptors 1, 15, and 54, so that must be jasmine,' Axel suggests." Most odors consist of mixtures of odorant molecules. Therefore, other odors would be identified by different combinations. (2)

Thus, while our visual system integrates information from only three kinds of receptors (corresponding to the primary colors) to make sense of all the perceivable colors, the olfactory system must perform calculations on combinations involving any of 1000 receptors.

Humans may have an olfactory sense that they don't even know about, an ability to sense chemical signals emitted by other people. While the information would be received through the nose, a different organ within the nasal cavity, separate from the olfactory epithelium, would serve as the sensory apparatus (see paper title). That the structure exists in humans in not in question. It is called the vomeronasal organ (VNO) and is found in most four-limbed species (4). The VNOs are narrow sacs that lie on either side of the nasal septum, well below the olfactory epithelium. In most mammals, the VNO detects sex pheromones that indicate sexual readiness in potential mates, as well as other types of pheromones. For example, a whiff of the right airborne chemicals emanating from a female mouse may immediately illicit mating behavior in a male mouse (2). The VNO has its own pathway to the brain. In rodents, VNO signals bypass the cerebral cortex, (where conscious awareness lies) and head to parts of the brain that control reproduction and maternal behavior (2). So, the rodents have no conscious awareness of their second olfactory system. Researchers believe the VNO is a much more primitive structure that works in a different way than the main olfactory system. While they know it's different, they are still uncertain about how it works. While we know that other animals have functioning VNOs, it's less clear that they work in humans.

There is recent evidence, however, indicating that humans do indeed have the ability to sense and give off pheromones. A unique study at the University of Chicago has provided some of the first scientific proof of human pheromones. In the spring of 1998 psychology professor Martha McClintock published the results of an experiment on women's menstrual cycles (5). She had already done a study on female rats where she discovered that exposure to one set of airborne pheromones significantly shortened the rats' cycles, while another set lengthened them (2). In the new study, she wanted to find out whether there are similar opposing pheromones in humans. The re searchers wiped pads (which had been placed under women's armpits for 8 hours) under the noses of female subjects. They found that "compounds donated by women in the late follicular phase (the early portion) of their menstrual cycles accelerated the preovulatory surge of luteninizing hormone (LH) of recipient women, and shortened their menstrual cycles." (5) They also found that "compounds from the same donors, but collected later (at the time of ovulation) had an opposite effect, delaying the LH surge of recipients and lengthening their menstrual cycles." (5) These results indicate that the long observed phenomenon of women living in close quarters developing synchronized menstrual cycles can be explained by the recognition of pheromones by the VNO.

I question the adaptive purpose of this and other possible types of human pheromones. It is fairly clear why sex pheromones evolved in lower animals. In many lower species, the female is only fertile during certain isolated time periods. It would advantageous for the female to be able to broadcast this information in some way to attract males, and equally beneficial for the males to have a device that can interpret the signal. But why isn't the pheromone-sensing mechanism a conscious one? Many species, including pheromone bearing ones, have ways of signaling temporary fecundity via visual and consciously perceived odor signals. Because the VNO signals bypass the cerebral cortex, they are sensed unbeknownst to the sniffer. Why this is advantageous, I am not sure. Back to the human question. The adaptive reason for the menstrual cycle synchrony in women is not clear to me. Alternatively, I can see a reason for pheromones signaling to men that a certain stage of the cycle has been reached, since sex is more likely to be fruitful during some parts of the cycle than during others. I would expect that such pheromones exist, though proving their existence would be a challenge. Olfaction, as ancient as it is, provides a great challenge to those who wish to study it. Its capabilities, inciting memories; stimulating hormones; detecting odors with exposure to only a few molecules, (some species can do this) are amazing. As we gain a greater understanding of the brain, we will continue to make strides in understanding the complex mechanism behind the sense of smell.

WWW Sources

2)Howard Hughes Organization's Page on the Human Senses

3) John C. Leffingwell, Ph.D. olfaction website

4) Site on the Vomeronasal Organ

5)U. of C. News Release on Pheromone Study

6) Monell Chemical Senses Center

7) Scientific American Article by Philip Morrison, "The Silicon Gourmet"

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