]. Soc. Cosmetic Chemists, 21, 99-106 (Feb. 4, 1970) Primary Odor Correlated with Molecular Shape by Scanning Computer JOHN E. Auoo}•v., Ph.D.* Presented May 8, 1969, New York City Synopsis--The human sense of smell is probably based on distinct primary ODORS. An experimental method is described for identifying and mapping out the chemical extent of one of the primary odors, represented by the sweaty odor of ISOVALEmC Acre and its homologs and isomers (to which certain persons are specifically "odor-blind"). The production of this primary odor is shown to require the carboxylic acid functional group, in conjunction with a limited range of MOLECVI, AR S}•APES and sizes. • Silhouette photographs of scale molecular models are rapidly scanned and compared by a television camera linked to a COMPU•:}m. A correlation coefficient as high as 0.8 has been obtained between molecular shape and odor quality. A survey is being planned with the objective of identifying all the primary odors, which may eventually reach 20 to 30 in number. Some implications of this "olfactory code" for cosmetic chemistry are briefly discussed. INTRODUCTION In 1962, two papers describing the stereochemical theory ot5 oilac- tion were published (1, 2). At that time just seven primary odors were described. Several years have since passed and it seems appropriate now to review progress in this subject. In short, there have been three main advances. The first rigorous experimental method has been developed 15or identi15ying a human pri- mary odor (3-5). A computer procedure has been adapted 15or relating odor quality to molecular shape (6). Furthermore, it has proved nec- essary to raise the limit on the probable number o15 primary odors, from seven to perhaps nearer 27 (7). * Western Regional Research Laboratory, Agricultural Research Service, U.S. Depart• ment of Agriculture, Albany, Calif. 94710. 99

100 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS These three principal trajectories are described in the cited references. In the present article the main results are sketched, and some opinions are offered on how these findings may eventually influence cosmetic chemistry. IDENTIFICATION OF THE "SWEATY" PRIMARY ODOR The French physicist Marcel Guillot has many acquaintances in the perfumery industry. He himself is totally unable to smell the macro- cyclic musks, although his sense of smell appears otherwise satisfactory. On inquiry, he found that many creative perfumers and essential oil chemists are aware of some personal "blind spot" as regards a particular odor. He mentioned macrocyclic musks, steroid musks, benzyl salicy- late, methyl ionone, and farnesol, plus a few others (8). With remark- able insight, he suggested that these "anosmies partielles" may corre- spond with a deficiency for the affected person in the nerves signalling the corresponding "odeurs fondamentales." Hence, the systematic study of odor-blindness, or "specific anosmia," should lead to an enumeration of the "primary odors" of the human sense of smell. Although Guillot's suggestion was made 20 years ago, there seems to have been no attempt to exploit it until very recently (3). The research work in this laboratory required close attention to detail, but was not inherently difficult (4). A newly-reported example of odor-blindness, that to the sweaty odor of isobutyric acid, was studied. About 2% of the people are unable to smell this compound until the concentration is elevated approximately 50 times compared with the normal detection threshold for the average observer. The defect is specific, because these same people have no problem detecting other, unrelated odors. Here a word of warning should be interpolated. It is necessary to take quite extraordinary precautions as regards the olfactory purity of the isobutyric acid sample. Any trace of impurity can be smelled by the anosmic observers, even though it may not show up on the gas chromato- graph. This point is liable to be imperfectly appreciated by critical re- viewers or intending experimenters in the field of chemical constitution/ odor quality relationships. An expert perfumer of the author's acquaint- ance was frequently surprised at the changes in the odors of many sup- posedly familiar lower fatty acids following meticulous purification. The results for isobutyric acid are illustrated in Fig. 1. A group of 86 normal observers had personal detection thresholds distributed in a roughly bell-shaped curve. Meanwhile, the panel of 10 specific anosmics (found by screening an entire staff of 400-plus) exhibited thresholds more