How Does Smell Work? Chemistry Read Directly by the Brain

Odour molecules must be volatile enough to reach the nose and soluble enough to dissolve in the mucus lining the olfactory epithelium, a patch of tissue high in the nasal cavity. There they bind to receptors on the cilia of olfactory sensory neurons. Humans have roughly four hundred working odorant receptor types, and the genes encoding them form the largest gene family in the mammalian genome, a discovery by Linda Buck and Richard Axel that won the Nobel prize in 2004. The crucial architectural fact is that each sensory neuron expresses only one receptor type, and all neurons expressing the same receptor project to the same small structure, called a glomerulus, in the olfactory bulb. A single odour molecule activates several receptors to different degrees, and a smell is therefore encoded as a pattern across many glomeruli rather than by any single detector, which is why four hundred receptors can distinguish an enormous number of odours, with one much-debated estimate putting the figure above a trillion.

Several features of the olfactory system have no parallel elsewhere:

• •It bypasses the thalamus, the relay station through which vision, hearing and touch pass before reaching the cortex, and projects directly to the olfactory cortex and from there to the amygdala and hippocampus
• •Those are the structures handling emotion and memory, which is the anatomical reason smell-evoked memories feel more emotional and more autobiographical than memories cued by words or images, an effect named after Proust's madeleine and demonstrated experimentally
• •Olfactory sensory neurons are exposed to the outside world and die and are replaced throughout life, which is unusual for neurons and made the system an early model for adult neurogenesis
• •Adaptation is rapid, so a smell fades from awareness within minutes of continuous exposure, which is why you stop noticing your own home
• •Retronasal olfaction, smelling from the back of the mouth while eating, supplies most of what people call flavour, since the tongue detects only a handful of basic tastes and the rest is smell
• •Naming smells is unusually difficult in most languages, and people asked to identify common odours frequently know the smell precisely while being unable to retrieve the word

Olfactory ability varies more between people than most senses. Specific anosmia, the inability to smell one particular compound while smelling everything else normally, is common and genetic, with the best-known case being the androstenone in some meats and the compound in coriander that makes it taste of soap to a minority. General loss of smell, anosmia, can be congenital or acquired through head injury, nasal disease, neurodegenerative conditions or viral infection, and it received far more public attention after becoming a recognised symptom of a widespread respiratory illness. Its consequences are underestimated: food becomes uninteresting, appetite and weight change, gas leaks and spoiled food go undetected, and rates of depression among people with anosmia are markedly elevated. Loss of smell is also an early marker in Parkinson's and Alzheimer's disease, frequently preceding other symptoms by years, which has made olfactory testing a research tool. Smell training, repeated deliberate exposure to a set of distinct odours over months, has evidence supporting partial recovery after viral loss.

How a receptor recognises a molecule remains partly disputed. The mainstream account is shape-based, treating receptors as binding sites that fit particular molecular structures, which explains a great deal and fails to explain some awkward observations, including molecules of very similar shape smelling completely different and molecules of different shape smelling alike. An alternative proposal holds that receptors detect molecular vibrations through electron tunnelling, which predicts that swapping hydrogen for its heavier isotope should change a smell, and experiments testing this have produced conflicting results and the theory remains a minority position. A separate open question is whether humans use chemical signals socially. Evidence that human body odour carries information about immune genotype, emotional state and relatedness is reasonably strong, while claims about specific human pheromones have not held up, with the compounds most often named in commercial products lacking good supporting evidence.

Smell detects actual molecules binding to around four hundred receptor types, each sensory neuron carrying just one type and all neurons of a type converging on one spot in the olfactory bulb, so an odour is encoded as a pattern rather than by a single detector. Uniquely among senses it bypasses the thalamus and projects straight to emotion and memory structures, which is why smells trigger memories so directly. Most of what is called flavour is smell from the back of the mouth, and loss of smell has serious and underrated consequences.