"I tell you, it is an animal," said the Bulldog. "Smell it for yourself."
"Smelling isn't everything," said the Elephant.
"Why," said the Bulldog, "if a fellow can't trust his nose, what is he to trust?"
"Well, his brains perhaps," she replied mildly.
"I object to that remark very strongly," said the Bulldog.
C. S. Lewis, "The Magician's Nephew"
We perceive the external world around us via five separate modalities: touch, vision, taste, sight and smell. All five are important in our being able to navigate the world (but, for the most part, not essential as proven by many people who are missing one or more off the list), and all five also have millions of years of evolution to thank for their development. However, smell and taste, which are inextricably linked, are the most basic of these senses. They are probably the evolutionary extension of a basic behavioural process called 'chemotaxis' that is demonstrated by motile single-celled and multicellular organisms. A chemotactically active cell or animal is able to sense the concentration gradient of a chemical and then move either toward or away from that stimulatory substance, depending on whether it is a food or toxin. Olfaction (the poncy name for the process by which smells are perceived) is an important enhancement of our experience of the world, but is as yet poorly understood. I'd advise anyone devoid of an interest in functional biology, anatomy or neuroscience to skip the first three headings; I get to the more interesting stuff after that...
The olfactory epithelium
We sense smell not via our nose, but via the olfactory epithelium, a thin sheet of pseudostratified epithelial cells that cover the roof of the nasal cavity, which is formed by the ethmoid and sphenoid bones of the skull. Air is drawn into the nasal cavity through the external nares (a.k.a nostrils) by the expansion of the lungs, causing the molecules contained within it (odorants) to pass over the olfactory epithelium. The anatomy of the nasal of passages is such that the air that enters the nasal cavity during normal breathing movements only superficially passes over this epithelium. When we 'sniff', we cause more of the indrawn air to come into contact with the roof of the nasal cavity, which is why sniffing intensifies the perception of a smell.
The olfactory epithelium is made up of millions of olfactory receptor cells, also called olfactory neurosensory cells, which are cellular extensions of the olfactory nerve. They are bipolar neural cells, that is to say they have two projections from the cell body: the dendrite, which carries information to the cell body from the surface of the epithelium; and the axon, which carries information away from the cell body toward the brain. The cell body rests within the epithelial layer with the dendrite projecting out of the layer into the nasal cavity where it forms a terminal knob. The knob has several long cilia radiating out of it that contain thousands of receptor protein molecules (or odorant binding protein) in their cell walls. These cilia, also called olfactory hairs, work to greatly increase the receptive surface area of a single olfactory receptor cell. Meanwhile, the axon of the cell projects in the opposite direction: through the portion of the ethmoid bone called the cribriform plate (cribriform, originating from the Latin 'cribrum' for sieve, meaning pierced by numerous small holes or sieve-like). They then synapse with the overlying olfactory bulb of the olfactory nerve.
The neural cells are surrounded by sustentacular cells, which are similar to the glial cells of the nervous system. The support cells secrete a thin mucus that acts as the medium within which odorants can dissolve into out of the inhaled air, allowing them to come into contact with the olfactory hairs coated by the mucus. There are also basal cells in the olfactory epithelium, which act as stem cells and are the source of new receptor cells. Olfactory receptor cells are one of the very few types of neural cells that are able to regularly renew themselves; each cell has a lifecycle of about 60 days.
The area of the olfactory epithelium is an indication of the importance of smell in an animal's environmental perception. The human olfactory epithelium is around 10cm2 in area; not very big, but then we don't rely on smell as a species. On the other hand dogs, who do rely on smell as their main sensory perception, can have an olfactory epithelium up to 170cm2 in size, with 100 times more receptors per square centimetres than humans (Bear et al, 2001). This is why bloodhounds have the impressive ability of being able to follow the scent of escaping felons even hours after they have been through an area. And to think they waste it on smelling each other's privates every two seconds.
Olfactory receptors
Smell is a very complicated topic to research; a single odour can be the result of a mix of hundreds of different chemicals. Each receptor cell expresses a single receptor protein that has been coded by a single gene, and this cell / receptor is able to respond to several different odours. The mathematics that result from all of this is quite complicated, but research suggests that, in humans, there are at least 1000 of these smell genes are expressed, and as odours are made up different proportions of different chemicals, it is estimated that the average humans is able to distinguish around 10,000 of these different chemicals using olfactory receptors. God knows how they came up with those figures; I'm just quoting them (Marieb, 2001). What I do know is that these receptors are incredibly sensitive, even in humans, who are relatively under endowed in the olfactory department. Some receptors need only a few molecules to be activated; another figure that I find quoted is a concentration of a few parts per trillion (Bear et al, 2001). The receptors are G-protein linked, and stimulation of the receptor results in an influx of sodium and calcium ions into the olfactory receptor cell, resulting in its depolarisation.
The response of receptor cells to odorants is, like other neuronal cells, variable depending on the conditions. There may not be enough of the odorant to stimulate an action potential; scavenger enzymes in the mucus layer may breakdown the odorant particles before they have a chance to bind to the receptor; or the receptor activation may cause an alternative signalling pathway to operate, preventing depolarisation. Even if a receptor does depolarise, it will eventually become adapted to the presence of the odorant and stop reacting to it. This is why, on encountering a strong smell that initially overwhelms you, after a few minutes you will fail to notice it any more. However, if you were to suddenly take a sharp intake of breath, you'd become aware of the smell again; the action of suddenly inhaling odorant-laden air exposes more of the olfactory epithelium to a greater amount of stimulus, which results in more action potentials.
Olfactory nerve
The olfactory nerve, also called cranial nerve I (CN I), begins with the olfactory bulbs overlying the cribriform plate. The olfactory bulbs are unique within the sensory nervous of the body; it is the only afferent nervous tissue in the body to analyse the information that it receives before it passes the information along to the thalamus, which is the area of the brain that determines the significance of all the other sensory inputs. The function of the olfactory bulbs is unclear, but it is likely that they segregate detected odours into broad categories that are independent of the strength of the odours detected. This organisation is achieved via thousands of spherical structures called glomeruli, each of which receives input from about 25,000 olfactory receptor cell axons. The organisational network of these glomeruli is mind-blowing; using molecular labelling techniques, scientist were able to demonstrate that, in mice, all the neurones expressing a particular gene (P2) throughout the entire olfactory epithelium all converged onto only two glomeruli in each olfactory bulb (Mombaerts et al, 1996). To those interested in such things, this discovery lead to all sorts of new theories about axonal pathfinding during embryological development.
These rudimentary organised signals then travel for further processing to two main areas: various different portions of the olfactory cortex in the frontal lobe via the thalamus, where smells are consciously identified and interpreted; and subcortically to the limbic system, which is the memory creating and associating portion of the brain which attaches and stimulates emotional responses to a smell. Individual smells are distinguished from each other using population coding. For example, Smell 1 and Smell 2 may be made up of the same three odorants: A, B, and C. So how does the brain tell the difference? With population coding, the brain can determine that Smell 1 is proportionally composed of 33% of each odorant. Smell 2 however is 5% A, 10% B and 85% C. Thus it is able to differentiate between the two. As for how the brain actually reads the information provided by the olfactory nerve... complicated. As with the rest of the sensory input to the cortex, it is assumed that there are neural spatial maps for smells, where an orderly arrangement of neurones identify any information received. As yet, there is no idea how one would go about reading this map. It is also thought that there is a temporal coding (the number of action potentials produced within a timeframe) aspect to how information is read, but again, little is known about this.
So... the interesting stuff
Smells are all around us, and it is probably true to say that life is made richer by them. They have a variety of functions and uses in many areas of life, both consciously and unconsciously. In fact, the olfactory bulb is the oldest part of the brain, and it'd probably be fair to say that the rest of the brain developed in order to interpret information picked up by the nose. Anyone who suffers from anosmia, whilst able to lead a relatively normal life, does miss out on some vital aspects of the world around us, not least the ability to detect a gas leak. Of course by the same degree, they also have a distinct advantage when it comes to such things as skunks or nappy changing. In fact, taking into account that 80% of odorants are of the unpleasant variety, it can be easily argued that they anosmics don't have it too bad.
Smell sensitivity
As with the rest of the senses, some people have a more accurate sense of smell than others. The young will have a better sense of smell than the old, with a peak in smell sensitivity seen in 6-10 year olds, and a significant decline seen in smell identification for those over the age of sixty. This is thought to be a result of age-related atrophy of the olfactory receptors, as well as viral damage to the olfactory epithelium. It has long been recognised that females have a better sense of smell than males, though why this should be, no one knows. Ovulating and pregnant women tend to have a more sensitive sense of smell than women who are in other stages of their menstrual cycle. I know that anyone smelling of stale tobacco smoke had better not come near me during at the beginning of my luteal phase; strong smells such as cigarette smoke and perfume make me nauseous to the point of vomiting. Speaking of tobacco smoke, smokers will have a decreased sense of smell in comparison to non-smokers, and this is also true of people who work in professions that expose them to large amounts of noxious odorants. My Dad's olfactory epithelium has taken great exception to his having to work with paraffin for years.
Particular odorants will also mean different things to different people, depending on their experiences. An odorant called androstenone can be variably described by different people as smelling of either sweat, sandalwood, urine, musk, or of nothing at all. Butyric acid will cause some people to recoil in disgust because it smells of vomit. To others it smells of the far less offensive substance, Parmesan cheese.
Evolutionary advantages of smell
There is a tendency to misunderstand the concept of 'evolution'; most people tend to imply that evolution is a process of improvement. Evolution actually has nothing to do with an organism becoming more advanced, and everything to do with it developing traits that make it more likely to survive in the environment that it inhabits. Evolving a sense of smell conferred an advantage over animals that didn't evolve a sense of smell. So, what are these advantages? Well, the detection of food for a start. This isn't so much true of humans of course (unless you're trying to track down an open kebab shop in London's East End at 4am), but go back a few steps on our evolutionary tree and you'll find primates for whom there were no kebab shops at 4am (or any other time) who needed to be able to track down their sources of sustenance using their noses rather than a telephone directory.
Then there's the detection of food that may cause harm by its consumption. It doesn't take a genius to recognise that drinking (or should that be 'eating'?) the bottle of milk that's been sitting in the fridge a couple of months now would be a bad idea for your digestive system. It just takes a couple of million years' worth of evolution. Along this road there have been organisms that couldn't detect the smell of off-milk (pyridine). They drank (ate. whatever) the off-milk. They died. They probably died before they were able to procreate and give birth to more organisms that couldn't detect the smell of pyridine. The organisms that were able to detect off-milk thrived, and now populate the planet. Hurrah for off-milk smell receptors!
Smell and memory
The unregulated connection of the olfactory bulb to the limbic system means that smell has the ability to provoke the most vivid of memories, without any conscious intercession. Caching a hint in the air of an odour can bring a sudden rush of memory of a long distant event to someone's mind, which is gone almost as soon as it's there, leaving them desperately trying to grab hold of the emotional sensations that flit across the mind's eye. My earliest conscious memory is from when I was 18 months old, of an accident that resulted in the loss of the tip of the third finger of my left hand. However, occasionally I catch a smell that takes me back to before even that, and a brief sensation of being held, safe, loved overwhelms me before disappearing back to whence it came. This type of memory is called an 'episodic memory'; it evokes a specific experience that comes unbidden on being exposed to the odour. The other type of memory associated with smell is 'semantic memory' is a memory that is connected with conscious thought, such as being asked to think of what chocolate smells like.
Smell doesn't always conjure up pleasant memories though; the smell of wood smoke and gunpowder is reminiscent for me to autumn days, clearing up leaves in the garden and building a huge bonfire for Guy Fawkes Night. A happy memory. To some, the smell of wood smoke and gunpowder may bring back the time they were badly burned on that 5th of November when they picked up a spent firework. Not a happy memory. Further to this, because smell is inextricably linked with taste, having a nauseous experience immediately following consumption of a food can often leave us unable to tolerate the smell of that food. One time as a child, I had risotto and a packet of ham cheddars before retiring to bed for the night. I awoke three hours later vomiting and grotty; a result of the flu rather than food poisoning. However, thanks to this quirk of evolution, my memory linked the waves of nausea (caused by an influenza virus) to my last meal. As a result, even a whiff of ham cheddars made me want to hurl from that day forth. I still don't like the damn things. It was also quite a large number of years before I was able to stomach risotto again. This reaction is called 'flavour aversion learning'; it requires very little experience (just the one meal in my case) and can last a very long time - aversions of fifty years duration have been reported. Evolutionarily speaking this is a good thing. An animal can't be a slow learner with regards to foods that are poisonous.
Smell and social interaction
Thanks to our genetics our individual smell is unique; a bloodhound can distinguish between fraternal twins, but not between identical twins. Humans can also distinguish between each other in terms of smell. A 6mth old child will show a clear preference for the smell of their mother's breast over a stranger's breast; in turn, a mother can distinguish between the smell of her own infant and that of others.
Another interaction commonly seen is the synchronisation of menstrual cycles in groups of females who spend a large amount of time together. It is thought that this occurs because of substances called pheromones (from the Greek 'pherin', to carry, and 'horman', to excite), which are chemicals released by organisms as an important signal for reproductive behaviours, the marking of territory, indication of aggression / submission, and identifying one individual out of many. Pheromones have been successfully studied in many animals, but their importance in human interaction is still less than clear. It has been clearly shown that women's menstrual cycle will shorten or lengthen when exposed to the body odours of another woman, but the reason that this should occur is unknown. Observed effects aren't even limited to the ordinary menstrual cycles; further studies have shown that pregnancy and lactation can also regulate the ovarian function of other females. In my first year at university I was living on an all female floor. I was the only person at the beginning of the year that was on the pill; within a month everyone else's cycles had synced to match mine. I did try to be amazed by the wonders of the inners working of the human being, but I was more pissed off by the fact that my living quarters had turned into some kind of hell never before experienced by man or beast for three days every month.
Smell and mate selection
Major histocompatibility complexes (MHCs) are an area of genes that have an important functions, the most well-known of which is immunological; essentially they code how the immune system distinguishes between 'self' and 'not-self'. In humans, this information is coded for on chromosome 6, contains over 200 genes, and is expressed as human leukocyte antigen (HLA) molecules that coat all the cells of the body to say "This is me. Do not attack." to the body's immune system. We each carry two sets of five separate HLA molecules, one set from our mother and one from our father. There are many, many variations of HLA molecules, and a variety in their mix confers an immunological advantage to an individual. It therefore makes sense that a female should seek out a partner whose HLA genotype differs from her own in order to avoid the dangers of inbreeding, thus helping to produce genetically fit children; any genetic deficiencies from one parent should be hopefully be compensated for by the other parent's HLA contributions. In mice, differences in MHCs (and thus potential mating partners) are detected by smelling a potential mate's urine. I'm pretty sure that this doesn't happen in humans. Of course, if it does, I've just discovered why it is I'm still single.
Research has yet to solve this mystery, but it is hypothesised that a female is able to (unconsciously) detect the compatible HLA profile of a mate from his body odour. This theory is certainly backed up in some studies into what attracts humans to other humans (Wedekind, Füri, 1997). But not all studies. Wedekind and Füri also demonstrated that women taking contraceptive pills switched to preferring odours of men with similar MHC (a behaviour also seen in pregnant mice.) A different study has suggested that women preferred odours matching the MHC of their fathers (Jacob et al, 2002); maybe Freud was onto something after all. All very confusing. Even more so when you consider that another study showed that women prefer men with similar facial features to themselves, and therefore a similar MHC (Roberts et al, 2005). I think it's fairly safe to say that no-one's really got a clue what's going on at the moment, and given the apparent fickle ways of women, probably never will.
Smell and emotion
Aromachology is the study of the effect of odours on the human body and mind. This is quite a diverse field of study, and a very profitable one, as anyone who produces perfumes or aromatherapy products will tell you. Smells can be used to subtly manipulate moods: lavender for restful sleep; rose for de-stressing; jasmine for countering exhaustion; and ylang ylang and patchouli to bring out the tiger in you.
However, it's not just good emotions that can be manipulated with smells. Fear is a very transmittable state; the average predator can smell fear (which results in the release of cortisol) a mile off. An animal that attacks a human is often encouraged further by the smell of fear that they have picked up being given off by the poor schmuck who decided to ignore the "Beware of the Dog" notice. However, it also goes the other way. Small animals whose single role in life it is to be food for other animals will have a fear reaction stimulated by smelling a predator. Studies indicate that cat odour and trimethylthiazoline (TMT; a synthetic compound isolated from fox faeces) will both induce a fear-related response in rodents presented with the smell saturated on a piece of cloth. This response includes freezing, avoidance, the release of cortisol, and, in some tests, risk assessment behaviour (Takahashi, 2005).
Smell and health
A while ago, there was a story in the press about dogs being used to 'sniff out' bladder cancer using a patient's urine sample. It's not just dogs that can do this; medical staff are also trained to recognise a disease by its smell. I can walk onto a ward and know instantly if there is someone currently being looked after that has had an upper gastrointestinal bleed; the blood's travels through a person's digestive system results in a black, tarry, and very, VERY smelly mess at the other end called melaena. The smell of it is indescribable, but if you've smelt it once, you'll never forget it. Incidentally, the heroine's name in (that pinnacle of film making) 'Total Recall' is Melina. It's not like I could take the film seriously to begin with; the last time I watched it I actually had tears of laughter rolling down my face.
There are lots of other diseases where the smell given off by the patient can lead to a diagnosis: the fruity, sweet, acid-pear breath of a diabetic patient in ketoacidosis; the smell of stale alcohol that seems to seep out of a drunk's pores; the fishy smell of bacterial vaginosis; the fetid, offensive odour of a lung abscess; the ammonia-laced aroma given off by those in liver failure; the faecal-tinted breath of a patient with bowel obstruction; and many more besides that I've only heard of, never experienced, such as the 'fresh-baked bread' of typhus and 'newly-plucked chicken feathers' of rubella. The reason that a person's body odour changes in disease is because there is an alteration in their normal physiology, resulting in an imbalance of the various amino acids, proteins and chemical compounds that are a necessity for, or a result of, all the processes that keep us alive. For instance, the sweet smell on the breath of hyperglycaemic diabetics is caused by an excess of ketone, an amino-acid breakdown product of proteins that are being burnt off as a fuel by the body.
Financial rewards of smell
Smell is a financial goldmine that is now, with the progress of research and technology in the area, starting to reap profitable rewards for years of hard effort. Although, this is not completely true as perfumers have been reaping the financial rewards for centuries. Perfumes are usually oily extracts of various substances that, when sprayed on the skin, disolves into the natural skin oils to produce a long-lasting scent. This is why a fragrence may smell different on different people; we all have our own individual natural skin oils.
A sixteenth century book of cosmetics, "Les secrets de Maistre Alexys le Piedmontois" promises that a particular fragrance recipe will make a woman attractive, not for a day, not for a week, but forever. A bold claim, especially when you take into account the recipe is "a young raven taken from its nest, fed hard-boiled eggs for 40 days, killed, and then distilled with myrtle leaves, talcum powder, and almond oil." (Ackerman, 1990) Yum. Edgar Allen Poe must be spinning in his grave. Of course, if you think the ravens had it bad, spare a thought for the Ethiopian Cats that have their anal sacs regularly scrapped out for the civet (a musk) that they produce. Ouch. Beavers (castoreum) and East Asian deer (musk) don't have it too good either. All of these substances are used to make up the smell of a fragrance; perfumes are complicated things to mix, with top notes (the main smell), middle notes (the underlying symphony to the top note) and base notes (which carry the perfume and makes it linger). How many notes, and their mixture, is reflected in the price of the perfume; a fake CK One may smell the same as the real thing when you take a cursory sniff, but it wouldn't last very long. The hypothesised reason for the human obsession with the anal contents of some animals is because animal musks are very similar to human testosterone - one of the hormones that is responsible for sexual behaviour.
The sperm whale has it slightly easier; it produces an oily substance in its stomach called ambergris to protect the stomach itself from the sharp backbones and beaks of the cuttlefish and squid, respectively. Ambergris is the perfect fixative for fragrances in perfumes, and while most perfumes today use a synthetic fixative, most of the more expensive varieties still use the original. While ambergris can just be removed from the stomach of the whale, the preferred form is of ambergris that has passed through the whale's digestive system and become semi-fossilised in the ocean; it's not easy to get a reliable supply, and so natural ambergris fetches a high price. The good news for the digestive tracts of animals across the world is that, thanks to a lot of research in the area, many fragrance notes are now synthetic; the first perfume to contain a primarily synthetic fragrance was Channel No. 5, with a top note that is based on an aldehyde.
Another huge source of revenue is in the creation of artificial flavourings; since the tongue is only able to discern sweet, salty, bitter, sour, and umami most of our tasting of a food comes from smelling it. Artificial flavourings are, despite consumer fears, everywhere. They are often used to back-up an existing flavour, for example, in strawberry yoghurt, but can also be used as a complete replacement for a flavour. The smells of food are already used by supermarkets to manipulate customers into spending more money; my local Sainsbury's redirects air from the bakery to the entrance of the store in an effort to make you more hungry when shopping. I wouldn't mind so much, except it works. Bastards. Fragrances could also be a cash cow (excuse the pun) for agriculture; there are numerous opportunities for the use of synthetic odorants in the fields of animal husbandry and pest-control. As yet, there has been little exploration of these markets, but it's only a matter of time; all it needs is a biotech company to catch the scent in the air of the potential profits....
References
- Ackerman D, 1990, "A Natural History of the Senses", 1st edition, Phoenix
- Bear MF, Connors BW, Paradiso MA, 2001, "Neuroscience: Exploring the Brain", 2nd edition, Lippincott Williams & Wilkins
- Gilbert AN, Firestein S, 2002, "Dollars and scents: commercial opportunities in olfaction and taste", Nature Neuroscience; 5:1043-1045
- Jacob S, McClintock MK, 3, Zelano B, Ober C, 2002, "Paternally inherited HLA alleles are associated with women's choice of male odor", Nature Genetics; 30:175-179
- Laing DG, Doty RL, Breipohl W, 1991, "The Human Sense of Smell", 1st edition, Springer-Verlag
- Marieb EN, 2001, "Human Anatomy and Physiology", 5th edition, Addison Wesley Longman
- McClintock T, Sammeta N, 2003, "Trafficking prerogatives of olfactory receptors", Neuroreport; 14(12):1547-1552
- Mombaerts P, Wang F, Dulac C, Chao SK, Nemes A, Mendelsohn M, Edmondson J, Axel R, 1996, "Visualising an olfactory sensory map", Cell; 87:675-686
- Roberts SC, Little AC, Morris Gosling L, Perrett DI, Carterd V, Jonese BC, Penton-Voakf I, Petriea M, 2005, "MHC-heterozygosity and human facial attractiveness ", Evolution and Human Behavior; 26:213 - 226
- Takahashi LK, Nakashima BR, Hong H, Watanabe K, 2005, "The smell of danger: A behavioral and neural analysis of predator odor-induced fear", Neuroscience & Biobehavioral Reviews; 29(8):1157-1167
- Wedekind C, Füri S, 1997, "Body odour preferences in men and women: do they aim for specific MHC combinations or simply heterozygosity?", Proceedings: Biological Sciences; 264(1387):1471 - 1479
|
