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Response to Doty 2025, predicting odor from structure is useful.

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This paper responds to Doty's 2025 review, arguing that despite the view of odors as cognitive constructs, recent advances enable practical, predictive modeling of odor perception from chemical structure, suggesting the field has progressed beyond earlier limitations in mapping odor space to physicochemical properties.

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Doty (Odors as cognitive constructs: history of odor classification and attempts to map odor percepts to physical and chemical parameters. 2025. Chem Senses 50:bjaf022) provides a thorough historical review of odor classification but underestimates recent advances in quantifying odor space. He argues that odor qualities are cognitive constructs that do not map well to physicochemical properties. While odor is indeed cognitively mediated, practical and predictive rules for olfaction exist and continue to improve. Therefore, we suggest that Doty's historical review should be read not as a eulogy for physicochemical modeling, but as a historical baseline that the field is now surpassing.

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  • 10.1093/chemse/bjaf022
Odors as cognitive constructs: history of odor classification and attempts to map odor percepts to physical and chemical parameters
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  • Chemical Senses
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Attempts to map odor percepts to physical and chemical parameters have a long and challenging history. In contrast to color vision, where three classes of photoreceptors respond to the same stimulus property (wavelength), ~400 classes of olfactory receptors are available to respond in a non-linear non-additive fashion to ~5000 different chemical parameters. Theoretically, millions of permutations between structural elements of chemicals and their smells are possible, and some chemicals with different structures have the same odor and vice versa. Importantly, the same odor quality can come from multiple environmental objects and most odors depend upon the synthesis of a complex melody of volatile chemicals that individually can have dissimilar smells. At the individual receptor level, both agonists and antagonists within a mixture can impact receptor function. Hence, it is perhaps not surprising that no universal relationship between odor quality and underlying physical or chemical dimensions analogous to spectral wavelength for vision or air pressure waves for hearing has yet been identified. This review provides a historical account of psychological odor categorization, attempts to map odor percepts to physiochemical parameters, and attendant pitfalls. It concludes that perceived odor qualities may be best viewed as cognitive constructs with attendant variability due to individual experiences, linguistic processes, and biologic factors that do not map well to universal physiochemical dimensions.

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