Correction: Molecular Vibration-Sensing Component in Human Olfaction

Abstract

Whether olfaction recognizes odorants by their shape, their molecular vibrations, or both remains an open and controversial question. A convenient way to address it is to test for odor character differences between deuterated and undeuterated odorant isotopomers, since these have identical ground-state conformations but different vibrational modes. In a previous paper Proc Natl Acad Sci USA 108:9, 3797-802) we showed that fruit flies can recognize the presence of deuterium in odorants by a vibrational mechanism. Here we address the question of whether humans too can distinguish deuterated and undeuterated odorants. A previous report (Keller and Vosshall (2004) Nat Neurosci 7:4, 337-8) indicated that naive subjects are incapable of distinguishing acetophenone and d-8 acetophenone. Here we confirm and extend those results to trained subjects and gas-chromatography [GC]-pure odorants. However, we also show that subjects easily distinguish deuterated and undeuterated musk odorants purified to GC-pure standard. These results are consistent with a vibrational component in human olfaction.

Molecular recognition in olfaction

“…Since smelling peaks as they come out of a gas chromatograph is a difficult skill, a peak capture method invented by Christina Zelano was used, akin to preparative GC but on a microscale. The results conclusively showed an odour character difference perceptible by untrained subjects [75]. One of us (LT) was a subject and reports that the odour difference was very marked insofar as the musky odour character was absent from the nominally perdeuterated samples, replaced by a harsh (often described as waxy) burnt-candle smell.…”

“…Modification of the fingerprint region, by contrast, is most easily achieved by deuteration of part or all the hydrogens contained in the odourant. As we have seen, it has been shown that flies [87,122], honeybees [88,90], and humans [75] can tell hydrogen from deuterium odourants. Remarkably, a connection between fingerprint and functional group regions was also found when flies who had been trained to avoid deuterium odourants also avoided nitriles and vice versa, suggesting that the -CD stretch and -CN stretch, both around 2150 cm −1 were being confused by the flies [87].…”

“…The effect of deuteration on C-H(D) bond lengths is essentially undetectable by neutron diffraction [73], and many effects previously attributed to small differences in C-D vs. C-H bond lengths are likely instead due to differences in noncovalent interactions between H and D atoms themselves [74]. There is no question that polarisability, and thus hydrophobicity, of deuterated compounds is slightly lower: they exit a hydrophobic gas-chromatography (GC) column very slightly earlier than their hydrogen counterparts [75]. However, the magnitude of this effect should be seen in context: the GC column needs to be several tens of meters long to achieve even incomplete separation of isotopes.…”

“…The ability of humans to distinguish isotopes by their odour has proven highly controversial [58,75,99], and there is no settled view. However, in insects the evidence that isotopes can be distinguished by smell is much stronger, as shown above.…”

Status of the Vibrational Theory of Olfaction

“…These flies were also trained to react to specific levels of deuterated vs. natural abundance species through application of negative electronic stimulus in a similar T-maze. A generalization experiment was also performed showing that Drosophila trained to avoid 1-octanol vs. d 17 -1-octanol were able to generalize some characteristics and showed selective avoidance for ACP vs. Gane et al [88,89] examined the VTO through two tests employing both trained and untrained human subjects. Furthermore, great effort was expended to address the concern of impurities; assuring GC-level purities of all odorants, even those purchased at high purity.…”