54 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS 4. LEARNED VERSUS INATE RESPONSES TO ODORS From Aristotle's proposal (47) that the various categories of animals might be arranged on a graded scale of complexity or perfection with man at the top, came the general ac- ceptance that all animals could be ranked on a single continuous dimension known as the scala nat•rae. However, such a "phylogenetic scale" is inconsistent with contempo- rary views of animal evolution. Hodos and Campbell (48) commented, "Comparative psychologists have failed to distinguish between data obtained from living representa- tives of a common evolutionary lineage and data from animals which represent di- vergent lineages. Only the former can provide a foundation for inferences about the phylogenetic development of behavior patterns." Primates evolved as a special branch of the insectivore line, e.g., shrews, moles and hedgehogs, dating back more than 60 million years. Over this period of time, carnivores and rodents have followed inde- pendent and different courses of development from the primate line and from each other. Consequently, from the aspect of the evolution of primate characteristics, com- parisons such as rat-cat-man are meaningless. The rodent olfactory system can be com- pared to man's because they are basically similar despite the fact that there is no phylogenetic relationship. A clue to patterns of evolution in the human lineage could be gained from a comparison among living insectivores, prosimians, Old World monkeys and man. It was for this reason that special importance was accorded to recent work (11-16) pertaining to the influence of vaginal odors of female rhesus monkeys on the sexual behavior of the male rhesus. The proposed existence of a primate phero- mone sparked interest in the search for human pheromones. Before discussing the putative rhesus monkey pheromone and its implication for hominids, let us briefly review some recent knowledge and thoughts relevant to learned responses to odor. The pheromone concept implies that learning and/or prior experience with odorants do not play an essential role in its effect. However, it is now generally recognized that the original definition of pheromone is misleading, even for insects. The olfactory sti- mulus is not always simple (49) and insect behavior may be more plastic or modifiable by previous experience than heretofore suspected (50). In other words, an insect's response to pheromones is not necessarily programmed by genetics. Since mammalian behavior is infinitely more complex and more flexible, responses to pheromones are intricate, variable and often experience-oriented (51). Because of the strong de- pendence on experience, Bronson (51) has proposed the term s/gna///ng rather than re- /eas/ng for those odors yielding an immediate effect on mammalian behavior. Mam- malian responses to sex pheromones are far more easily modified by early associations than has been supposed (52,53). Similar to avian imprinting, there often appears to be a sensitive period for olfactory imprinting (54). Early experiences with artificial odorants, ranging from cage shavings to arbitrarily selected perfumes, have modified sexual behavioral preferences, eating, aggression, exploration, etc., in lower animals (53). For example, weanling rat pups showed a preference for citral subsequent to in- jecting their lactating mothers with this chemical. Not unexpectedly, there is a paucity of information pertaining to the sense of smell in human neonates. Newborn infants respond to sensory stimuli and their suckling behavior changes on presentation of various odorants (55). Suckling ceased or decreased in frequency on exposure to iodoform, anise or peppermint oils in approximately the same percentage of children as was observed in rabbits, kittens and puppies. Russell (56) reported the existence of olfactory maternal attraction in a recent study on human neonares. Sleeping infants were presented with breast pads previously worn by breast-feeding mothers. Two-day

PHEROMONES (OLFACTORY COMMUNICATION) 55 old subjects showed essentially no response. At two weeks they exhibited general arousal with little attendant discrimination between their mother's pad and those of strange mothers. At six weeks of age, six of the ten infants tested could identify the ma- ternal odor from that of a stranger. In an earlier and independent investigation (57), a differential response was shown six days after birth. The source of these odors is not known with certainty. The response may be due to a true maternal odor or, as demonstrated in other primates (58), originate in odors placed on the mother by the neonate. In either instance, olfactory cues generate behavioral responses in infants. The ontogenetic implications are fascinating. For example, would the putative maternal odor or similar odor "imprinted" between one and six weeks give rise to a behavioral response later in the adult? Regarding the effects of odor on developing Homo sapiens, Bieber (59) stated, "The sense of smell is the primary sensory modality in the heterosexual development of heterosexual responsivity." Furthermore, it has been suggested (60) that olfaction may play a crucial role in the establishment of sexual identity. An interesting study (61) has demonstrated that adult male hamsters undergo a dra- matic change toward the female's vaginal secretion when its presentation was followed by lithium chloride poisoning. The secretion, which is sniffed and ingested by the male, contains a substance that specifically affects sexual motivation which does not depend on previous experience. Surprisingly, hamsters form aversions to the vaginal secretion when it has been followed by a single experience with poisoning. The experiments sug- gest that adult mammals' responses to sex pheromones are much more easily modified by experience than has been supposed. The olfactory system, in consort with limbic structures, served to free animal behavior from the rigidity of inborn reflex mechanisms mediated by the hypothalamus, e.g., temperature regulation and the au- tonomic control of cardiovascular and digestive systems. As a result, not only are specific, genetically programmed pheromonal effects made possible, but also those associated with past life experiences. The sexual behaviour of the male rhesus monkey to an odorant emitted by the female tended to support the belief held by some scientists and laymen (62-64) that specific, naturally occurring body odors ("pheromones") may have previously unsuspected influences on social and sexual behaviors of man. Michael and Keverne (ll-14) reported that male rhesus monkeys are strongly attracted to and copulated with estrogen-treated females, presumably on the basis of olfactory cues. A series of low molecular weight aliphatic acids, i.e., acetic, propionic, isobutyric, butyric and iso- valeric, were proposed to be the active components of the vaginal secretions (15). The acid mixture, when substituted for the vaginal secretions, was said to have similar stimulatory effects on the males. In view of the basic importance of these findings to a general theory of primate behavior, Goldfoot and co-workers (17,18) performed addi- tional evaluations of the effects of vaginal material on the male rhesus sexual behavior. Their detailed st•udy failed to support the conclusions drawn from previously published work, that is, vaginal secretions and aliphatic acids essentially were without effect on the males. The significant procedural differences between the two groups of investiga- tors lie in Michael et al's practice of prior selection of males and on specific experiences provided them which, in effect, trained the males to respond to the odor cues (18). Al- though a clearer picture will emerge after further experimentation, the effect of associative learning in the rhesus monkey rather than a pheromonic phenomenon ap- pears to best explain the evidence accumulated to date.