The five senses (sight, hearing, taste, smell and touch) developed in living organisms as a means of giving them information about their environment. Chemoreception was probably the first of the senses to appear and is present in very simple, primitive species. The basic mechanism for detection of chemical signals from outside these primitive organisms is probably the basis of the senses of smell and taste which we and other higher animals possess today. Nature does not discard systems that work, but develops, adapts and refines them. This might give us clues about the receptor mechanism, since it probably began to evolve as a means by which aquatic organisms could detect water soluble chemicals. For most animals, the chemical senses are the ones on which they rely most heavily; it is only some groups of birds and a few primates that depend more on sight than on smell and taste. Despite the importance of the chemical senses, we understand very little about them. It is surprising that relatively little research into the chemical senses has been carried out, but encouragingly this is changing and many groups around the world are now beginning to take up the challenge and are already making significant headway.

The receptors used to detect odorants are similar to those used to detect hormones and, indeed, to those used in vision. Therefore, any increase in our knowledge of smell and taste receptors could also benefit our understanding in other fields, even though this is more advanced than our understanding of olfaction at present. Apart from the academic interest, there are obvious commercial reasons for increasing our understanding. For example, it is of particular interest

is to be able to predict the odour of new molecules without having to prepare and evaluate them, and thus save time and money in the search for new perfume ingredients.

Perfumes were originally made entirely from natural chemicals; the essential oils, absolutes and concretes that could be obtained by extraction from vegetable or animal sources. With the introduction of organic synthesis in the nineteenth century, a variety of odorants became available as products of the chemical industry. Many of the early synthetic fragrance materials were the products of serendipitous discovery. For example, it was during his work on explosives that, in 1888, A. Baur discovered that certain nitrobenzene derivatives pos­sessed musk-like odours. Advances in techniques of separation, pur­ification and structural determination enabled more and more of the secrets behind the odour of natural perfume ingredients to be unlocked, and these discoveries paved the way for the synthesis of analogues. Thus, the provision, by serendipity and imitation, of a large palette of perfume chemicals (as opposed to multicomponent natural oils and extracts) with defined odour properties made possible the search for structure-activity relationships (SARs) and the rational design of odorants.

In this chapter, I review firstly some of the theories that have been developed about olfaction, secondly the current state of knowledge regarding the physiology and biochemistry of olfaction, and then I indulge myself in some philosophical considerations regarding mental discipline and scientific method and the apparently too frequent lack of both in approaching an understanding of how our sense of smell works.

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