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      The search for human pheromones: the lost decades and the necessity of returning to first principles

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      Proceedings of the Royal Society B: Biological Sciences
      The Royal Society

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          Abstract

          As humans are mammals, it is possible, perhaps even probable, that we have pheromones. However, there is no robust bioassay-led evidence for the widely published claims that four steroid molecules are human pheromones: androstenone, androstenol, androstadienone and estratetraenol. In the absence of sound reasons to test the molecules, positive results in studies need to be treated with scepticism as these are highly likely to be false positives. Common problems include small sample sizes, an overestimate of effect size (as no effect can be expected), positive publication bias and lack of replication. Instead, if we are to find human pheromones, we need to treat ourselves as if we were a newly discovered mammal, and use the rigorous methods already proven successful in pheromone research on other species. Establishing a pheromone relies on demonstration of an odour-mediated behavioural or physiological response, identification and synthesis of the bioactive molecule(s), followed by bioassay confirmation of activity. Likely sources include our sebaceous glands. Comparison of secretions from adult and pre-pubertal humans may highlight potential molecules involved in sexual behaviour. One of the most promising human pheromone leads is a nipple secretion from the areola glands produced by all lactating mothers, which stimulates suckling by any baby not just their own.

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          Most cited references71

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          Scientific method: statistical errors.

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            An Agenda for Purely Confirmatory Research.

            The veracity of substantive research claims hinges on the way experimental data are collected and analyzed. In this article, we discuss an uncomfortable fact that threatens the core of psychology's academic enterprise: almost without exception, psychologists do not commit themselves to a method of data analysis before they see the actual data. It then becomes tempting to fine tune the analysis to the data in order to obtain a desired result-a procedure that invalidates the interpretation of the common statistical tests. The extent of the fine tuning varies widely across experiments and experimenters but is almost impossible for reviewers and readers to gauge. To remedy the situation, we propose that researchers preregister their studies and indicate in advance the analyses they intend to conduct. Only these analyses deserve the label "confirmatory," and only for these analyses are the common statistical tests valid. Other analyses can be carried out but these should be labeled "exploratory." We illustrate our proposal with a confirmatory replication attempt of a study on extrasensory perception.
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              Genetic variation in a human odorant receptor alters odour perception.

              Human olfactory perception differs enormously between individuals, with large reported perceptual variations in the intensity and pleasantness of a given odour. For instance, androstenone (5alpha-androst-16-en-3-one), an odorous steroid derived from testosterone, is variously perceived by different individuals as offensive ("sweaty, urinous"), pleasant ("sweet, floral") or odourless. Similar variation in odour perception has been observed for several other odours. The mechanistic basis of variation in odour perception between individuals is unknown. We investigated whether genetic variation in human odorant receptor genes accounts in part for variation in odour perception between individuals. Here we show that a human odorant receptor, OR7D4, is selectively activated in vitro by androstenone and the related odorous steroid androstadienone (androsta-4,16-dien-3-one) and does not respond to a panel of 64 other odours and two solvents. A common variant of this receptor (OR7D4 WM) contains two non-synonymous single nucleotide polymorphisms (SNPs), resulting in two amino acid substitutions (R88W, T133M; hence 'RT') that severely impair function in vitro. Human subjects with RT/WM or WM/WM genotypes as a group were less sensitive to androstenone and androstadienone and found both odours less unpleasant than the RT/RT group. Genotypic variation in OR7D4 accounts for a significant proportion of the valence (pleasantness or unpleasantness) and intensity variance in perception of these steroidal odours. Our results demonstrate the first link between the function of a human odorant receptor in vitro and odour perception.
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                Author and article information

                Journal
                Proceedings of the Royal Society B: Biological Sciences
                Proc. R. Soc. B
                The Royal Society
                0962-8452
                1471-2954
                April 07 2015
                April 07 2015
                April 07 2015
                April 07 2015
                : 282
                : 1804
                : 20142994
                Affiliations
                [1 ]Department of Zoology, University of Oxford, Tinbergen Building, South Parks Road, Oxford OX1 3PS, UK
                Article
                10.1098/rspb.2014.2994
                4375873
                25740891
                26f03f46-4016-4126-8602-b7e8e494891c
                © 2015
                History

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