30th anniversary of an era-shifting olfactory study


Thirty years ago today—on April 5, 1991—Linda Buck and Richard Axel ushered in the modern era of olfaction with the publication of “A novel multigene family may encode odorant receptors: a molecular basis for odor recognition.”

Buck and Axel were the first scientists to crack the genes for odor receptors (comprising 3% of human genes, responsible for some 400 receptors).

As cognitive scientist Ann-Sophie Barwich writes in her recent history of the science and philosophy of smell: “Olfaction, a minor footnote in the history of science, was catapulted into mainstream research.” (Smellosophy: What the Nose Tells the Mind; Harvard, 2020). Buck and Axel received the Nobel Prize in 2004 for their odor-reception research.

RIFM Senior Scientist Mihwa Na, PhD, was drawn to the Research Institute for Fragrance Materials in part because she had researched the interaction between fragrance molecules and human and animal olfactory receptors at the molecular level for her degree.

“Buck and Axel laid a critical foundation in answering the question: How does the sense of smell work?” said Dr. Na. “The sense of smell is initiated when an odor molecule binds to an odor receptor, located in the olfactory sensory neurons in the nose.”

“Buck and Axel identified the family of genes for these odor receptors, which are responsible for the first step in the sense of smell,” Dr. Na continued. “Their work also revealed how humans can recognize myriad odors using only approximately 400 receptors, through the ‘combinatorial code.’”

Combinatorial code means that a single odor receptor detects numerous odor-producing molecules, or “odorants,” and that multiple receptors recognize a single odorant. Additionally, different odorants are recognized by various combinations of receptors. Even slight alterations in an odorant structure, or a change in its concentration, can change its “code,” and thus, how it smells to us.

Thanks to the combinatorial code, some researchers suggest that humans may distinguish as many as a trillion shades of smell (see Bushdid et al., 2014).

RIFM Scientist Nikaeta Sadekar, PhD, leads RIFM’s efforts in related work to study odor thresholds in humans. Odor thresholds are the lowest concentration levels at which a person can detect a smell in their immediate environment.

“The process of smelling is an enjoyable, even memory-building experience,” Dr. Sadekar said. “Smelling an old book or getting a whiff of something we associate with a special time—such as pumpkin spice or a bouquet of flowers—is part of what gives color to life.”

“We have identified our next step in our odor threshold work,” Dr. Sadekar continued. “We are building a list of fragrance ingredients to evaluate, based on criteria associated with the ingredients’ volume of use and physical-chemical properties.”

“We know that if you can smell something, that does not mean your exposure to it is necessarily high. Fragrances are known to be effective at extremely low levels. By improving and sharing our understanding of odor thresholds, we hope to provide a science-based foundation for enjoying fragranced products.”

Related: Ask a RIFM Scientist: If I can smell it, is it safe?