René Descartes said ‘I think, therefore I am’. The knowledge of one's own existence is the only certainty which each human has, the rest of what we understand about the universe is comprised of mental models based on input from our senses. Smell is often described as the most mysterious or the least understood of our senses. In the light of the very significant advances in our understanding over the last two decades, I would argue that the latter is not the case. Smell is certainly the oldest of our senses since it is present in even the most primitive living organisms and, throughout evolution, has played a crucial role in survival and development of species. Our understanding of the chemical mechanisms of odour detection in the nose has advanced enormously since Buck and Axel's discovery in 1991 of the gene family coding for the olfactory receptor proteins. The mysteries of smell revolve around the complexity of the combinatorial detection system and the neuroprocessing that converts the physical input into the mental image which we call smell. Unlike vision where we have three primary colours, each corresponding to a specific wavelength of the electromagnetic spectrum, there are no fixed reference points in odour. When we describe a smell, it is always in relation to other things that elicit a similar mental impression. We might describe one sample as smelling like roses and another as smelling like rotten eggs but neither of these is a fixed reference point. Odour exists as a continuum in a multi-dimensional mental space, and all we can do in describing a new odour is to relate it to known points in that ‘odour space’. Odour classification is merely an attempt to map out regions within that space. Many parts of the brain are involved in converting the chemical stimulus in the nose into the mental odour percept, and some of these brain regions are strongly linked to memory and emotion. Thus an odour can trigger memories or influence emotional states before the subject is consciously aware of smelling it. In humans, the role of smell has extended from a survival tool, giving us information about changes in the chemical environment, through a desire to mask unpleasant odours, into a source of pleasure and artistic expression in the form of perfumery.

The chemistry of fragrance is a fascinating subject because of its breadth and the diversity of other disciplines that impinges upon it. The fragrance industry has ancient roots. For example, a perfume factory discovered on Crete dates back to 2000 B.C., and Egyptian tomb paintings often portray scenes involving the use of perfumes. In those days, the ingredients of perfumery were extracted from plant and animal sources, and plant extracts still provide many of the key notes in perfumery. Our understanding of how nature produces such an array of intricate chemical structures has grown over the last century and the natural products chemist now works alongside botanists, biochemists and molecular biologists in seeking to further our knowledge of biosynthesis. I never cease to be amazed by the variety of terpenoids that nature makes from a single precursor, isopentenyl pyrophosphate. The modern perfumery industry relies heavily on ingredients synthesised by chemists. The feedstocks include natural extracts such as pinene and petrochemicals such as isobutylene. The complexity of fragrance molecules, the performance and cost constraints of perfumes for household applications and the need to use synthetic routes that do minimal harm to the environment all combine to present a significant challenge for the process chemist. Success in this undertaking requires close collaboration with the chemical engineers who will design the process plant used in manufacture. The first generation of synthetic fragrance ingredients were exact copies of natural counterparts, such as the coumarin, vanillin and heliotropin used in ‘Jicky’ (1889), but non-nature-identical materials were given a boost in 1921 with the success of Chanel 5 which used small amounts of novel aldehydes to add a unique top note to the rose and jasmine oils in the heart of the fragrance. Designing novel fragrance ingredients is another very significant intellectual challenge and there are many parameters that must be taken into account. It is not sufficient just to produce a pleasing odour, the price must also be acceptable and the substance must be stable to the components of the consumer goods into which perfume is incorporated. These include acids as strong as hydrochloric, bases such as sodium hydroxide and oxidants like sodium hypochlorite and peracetic acid. The material should also be safe to use and should biodegrade easily in sewage treatment plants. Structure/activity relationships are important tools, and these bring the fragrance chemist into contact with mathematicians such as statisticians and computer modellers. Attempts to understand the relationship between molecular structure and odour brings us to the forefront of current scientific research. At least nine Nobel Chemistry Prize winners have mentioned fragrance chemistry in their Nobel Lectures and eight Nobel Prizes have gone to scientists working on the biochemistry and molecular biology of the class of receptor proteins to which the olfactory receptors belong. In 2004, the Nobel Prize for physiology/medicine went to Richard Axel and Linda Buck for their work on identifying the genes responsible for the olfactory receptor proteins which are the basis of our sense of smell. Linda Buck used this discovery to confirm that smell is a combinatorial sense, with each receptor responding to a range of odorants and each odorant stimulating a range of receptors. The 2012 Nobel Prize for chemistry was awarded jointly to Robert Lefkowitz and Brian Kobilka for their work in elucidating the structure and mechanism of action of G-protein coupled receptors, the class to which olfactory receptors belong. Chemists trying to understand the implications of these two great breakthroughs in our understanding of olfaction must be prepared to work at the frontiers between chemistry, molecular biology, neuroscience and psychology. Albert Einstein said: ‘The most beautiful thing we can experience is the mysterious. It is the source of all true art and science’. We have come a long way in our understanding of fragrance but there is still plenty of mystery to provide us with intellectual challenge and beauty.

The object of this book is to review our current state of knowledge of the chemical aspects of the sense of smell, from the volatile compounds of nature to our man-made odorants that complement them; our understanding of how the nose detects odorants and produces an electrochemical signal which is translated into a mental image; and to touch on the role of this chemical sense in living organisms and in particular in humans and its contribution to our way of life and our well-being. Throughout the book, the emphasis will be on the human sense of smell, but the sense in other species will be included in order to clarify the subject or to provide the context.