J. Soc. Cosmet. Chem., 29, 47-58 (February 1978) Pheromones (olfactory communication) STANLEY K. FREEMAN * International Flavors & Fragrances (R&D) Union Beach, NJ 07735 Received February 25, 1977. Presented at Annual Meeting, Society of Cosmetic Chemists, December 7, 1976, New York, New York. Synopsis In view of the intimate relationship between the olfactory and limbic systems, OLFACTORY COMMUNI- CATION could be involved in various aspects of reproductive physiology in man. The PHEROMONE CONCEPT implies that learning and/or prior experience with odorants do not play an essential role in its ef- fect. Recent evidence suggests that associative learning rather than a pheromone phenomenon should be seriously considered in the interpretation of certain features of primate behavior mediated by the sense of smell.' 1. INTRODUCTION Pheromones, substances used in communication between members of the same species, probably originated about two billion years ago when the first simple cells externally secreted chemical signals for the purpose of aggregation. It is not unreason- able to assume that this mode of communication was continued a billion years later with the emergence of the first eucaryotes or nucleus-containing cells(1). Chemical communication in single cell organisms is believed to be a necessary prelude to the evolution of multicellular organisms. Haldane (2) speculated that communication among single cell organisms was the direct lineal ancestor of intercellular communica- tion, i.e., hormone function. On the other hand, it has been suggested recently (3) that chemocommunication among aquatic animals could have originated in a transition from hormones to pheromones. Only minor evolutionary changes are required com- pared to the major modifications necessary to enable an olfactory system to function in air. In the latter case, odorants must be altered to become volatile, suitable organs must be developed for odorant production, etc. Observations of both marine and terrestrial animal behavior indicate that chemical communication occurs in most animal phyla. The term pheromone emerged from the diligent and ingenious investigation of Karlson and Butenandt (4) in 1959 on the sex attractant of the silkworm moth, and referred to chemicals liberated by an insect that induce immediate behavioral responses in another insect of the same species. Insect physiologists call these *Deceased March 10, 1978. 47

48 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS substances releaser pheromones. Because this designation is too restrictive for the considerably more complex mammalian systems, the concept of primer pheromones was introduced. These substances produce endocrine changes, e.g., the release of re- productive hormones into the bloodstream, causing physiological changes in the recipient animal. Striking examples of behavioral effects brought about by this mode of chemical communication may be seen in female mice: 1. Pregnancy block frequently occurs when a recently impregnated mouse is exposed to the odor of a male of a strain different from that of the stud male, while exposure to males of the same strain as the stud male does not prevent implantation [Bruce Effect (5)] 2. A decrease of reproduc- tive capacity of the animal occurs when the odor of other mice increases its corti- costerold production [Ropartz Effect (6)] 3. Estrus is suppressed and pseudo- pregnancies develop when four or more female mice are grouped together in the absence of a male [Lee-Boot Effect (7)] and 4. The estrous cycle is induced and ac- celerated in grouped females by exposure to an odorant present in the urine of male mice [Whitten Effect(8)]. Although pheromones may be classified as olfactory or oral according to their site of reception, the overwhelming majority found in the world of insects and mammals are volatile and airborne compounds that are olfactorily sensed. More than two hundred chemicals have been characterized from insects that mediate overt sexual behavior and modify mating behavior (9). In contrast, relatively few mammalian pheromones have been isolated and identified, although many are known to exist. Pheromones have been identified in those species with specialized scent glands, e.g., Marmoset monkey, Mon- golian gerbil, European rabbit, blacktail deer, and pronghorn antelope (10). A sex at- tractant was reported to be present in the female rhesus monkey (11-16), but a recent study (17,18) did not support this claim. Pheromones in fish may play a role in terri- torial defense, attraction and recognition of the other sex, parents or off-spring, and guidance of fish migrating upstream to their spawning sites. However, the only phero- mones known with certainty are the alarm substance which elicits a fright reaction (19), and substances which induce exploratory feeding behavior (20). The following discussion basically will pursue two approaches in the multifaceted aspects of olfactory communication in primates. First, it will be shown in Section 2 that anatomical and clinical evidence suggests that pheromones could be involved in the mediation of behavior. Second, in Section 3 a brief will be presented for the role of learning and/or prior experience as an alternative to the pheromone concept. 2. OLFACTORY PATHWAYS 2.1 OLFACTORY EPITHELIUM AND OLFACTORY BULB Lucretius wrote (21), "You may readily infer that such substances as agreeably titillate the sense (of smell) are composed of smooth round atoms. Those that seem bitter and harsh are more tightly compacted of hooked particles and accordingly tear their way into our senses and rend our bodies by their inroads." Many and diverse odor theories have since been proposed, crossing a spectrum from reasoned conjecture to implausi- ble speculation. Actually, we have no more than a limited understanding of the mechanism underlying olfaction. It is generally accepted that the olfactory and taste systems in all vertebrates, including man, conform to the same basic plan. In contrast with the cells of the taste mucosa, which are highly specialized cells related to skin