Luca Turin

A major prediction of Turin's vibration theory of olfaction is the isotope effect: that the normal and deuterated versions of a compound should smell different due to unique vibration frequencies, despite having the same shape. A 2001 study by Haffenden et al. showed humans able to distinguish benzaldehyde from its deuterated version.[10]

However, experimental tests published in Nature Neuroscience in 2004 by Keller and Vosshall failed to support this prediction, with human subjects unable to distinguish acetophenone and its deuterated counterpart.[11] The study was accompanied by an editorial, which considered the work of Keller and Vosshall to be "refutation of a theory that, while provocative, has almost no credence in scientific circles." It continued, "The only reason for the authors to do the study, or for Nature Neuroscience to publish it, is the extraordinary -- and inappropriate -- degree of publicity that the theory has received from uncritical journalists."[12] The journal also published a review of The Emperor of Scent, calling Chandler Burr's book about Turin and his theory "giddy and overwrought."[13] However, tests with animals have shown fish and insects able to distinguish isotopes by smell.[14][15] Biophysical simulations published in Physical Review Letters in 2007 suggest that Turin's proposal is viable from a physics standpoint.[16]

The vibration theory received possible support from a 2004 paper published in the journal Organic Biomolecular Chemistry by Takane and Mitchell, which shows that odor descriptions in the olfaction literature correlate more strongly with vibrational frequency than with molecular shape.[17]

In 2011, Turin and colleagues published a paper in PNAS showing drosophila fruit flies can distinguish between odorants and their deuterated counterparts. Tests on drosophila differ from human experiments by using an animal subject known to have a good sense of smell and free from psychological biases that may complicate human tests.[18] Drosophila were trained to avoid the deuterated odorant in a deuterated/normal pair, indicating a difference in odor. Furthermore, drosophila trained to avoid one deuterated odorant also avoided other deuterated odorants, chemically unrelated, indicating that the deuterated bond itself had a distinct smell. The authors identified a vibrational frequency that could be responsible and found it close to one found in nitriles. When flies trained to avoid deuterated odorants were exposed to the nitrile and its non-nitrile counterpart, the flies also avoided the nitrile, consistent with the theory that fly olfaction detects molecular vibrations.[19]

Two years later, in 2013, Turin and colleagues published a study in PLoS ONE showing that humans easily distinguish gas-chromatography-purified deuterated musk in double-blind tests. The team chose musks due to the high number of carbon-hydrogen bonds available for deuteration. They replicated the earlier results of Vosshall and Keller showing that humans cannot reliably distinguish between acetophenone and its deuterated counterpart, with 8 hydrogens, and showed that humans only begin to detect the isotope odor of the musks beginning at 14 deuteriums, or 50% deuteration.[20] Because Turin's proposed mechanism is a biological method of inelastic electron tunnelling spectroscopy, which exploits a quantum effect, his theory of olfaction mechanism has been described as an example of quantum biology.[21]

In response to Turin's 2013 paper, involving deuterated and undeuterated isotopomers of the musk cyclopentadecanone,[20] Block et al. in a 2015 paper in PNAS[22] report that the human musk-recognizing receptor, OR5AN1, identified using a heterologous olfactory receptor expression system and robustly responding to cyclopentadecanone and muscone (which has 30 hydrogens), fails to distinguish isotopomers of these compounds in vitro. Furthermore, the mouse (methylthio)methanethiol-recognizing receptor, MOR244-3, as well as other selected human and mouse olfactory receptors, responded similarly to normal, deuterated, and carbon-13 isotopomers of their respective ligands, paralleling results found with the musk receptor OR5AN1. Based on these findings, the authors conclude that the proposed vibration theory of olfaction does not apply to the human musk receptor OR5AN1, mouse thiol receptor MOR244-3, or other olfactory receptors examined. Additionally, theoretical analysis by the authors shows that the proposed electron transfer mechanism of the vibrational frequencies of odorants could be easily suppressed by quantum effects of nonodorant molecular vibrational modes. The authors conclude: "These and other concerns about electron transfer at olfactory receptors, together with our extensive experimental data, argue against the plausibility of the vibration theory." In commenting on this work, Vosshall writes "In PNAS, Block et al…. shift the "shape vs. vibration" debate from olfactory psychophysics to the biophysics of the ORs themselves. The authors mount a sophisticated multidisciplinary attack on the central tenets of the vibration theory using synthetic organic chemistry, heterologous expression of olfactory receptors, and theoretical considerations to find no evidence to support the vibration theory of smell."[23] While Turin comments that Block used "cells in a dish rather than within whole organisms" and that "expressing an olfactory receptor in human embryonic kidney cells doesn't adequately reconstitute the complex nature of olfaction...", Vosshall responds "Embryonic kidney cells are not identical to the cells in the nose .. but if you are looking at receptors, it's the best system in the world."[24] In a Letter to the Editor of PNAS, Turin et al.[25] raise concerns about Block et al.[22] and Block et al. respond.[26] A recent study[27] describes the responses of primary olfactory neurons in tissue culture to isotopes and finds that a small fraction of the population (<1%) clearly discriminates between isotopes, some even giving an all-or-or -none response to H or D isotopomers of octanal. The authors attribute this to "hypersensitivity" of some receptors to differences in hydrophobicity between normal and deuterated odorants.

Turin filed one of the first patents for a semiconductor device made with protein.[28] Turin's recent work focuses on the relevance of his olfaction theory to more general mechanisms of G-protein coupled receptor activation. In an article[29] in Inference Review, he proposed that the electronic mechanism was a special case of a more general involvement of electron currents in GPCRs. A 2019 preprint[30] argues that the highest-resolution x-ray diffraction structure of rhodopsin,[31] considered the ancestor of all GPCRs, contains the elements of an electronic circuit. He has also reported detection of non-equilibrium electron spins in Drosophila by their radiofrequency emissions,[32] though this is described as a "work in progress".

In 1988, Turin began work at the lab led by neuroscience researcher Henri Korn at the Pasteur Institute. There, Turin and his colleague Nicole Ropert reported to their superiors that they believed some of Korn's research on neurotransmitters was based on fabricated results.[33] After Turin made a formal request that the CNRS investigate the allegations, he was told to find work outside France; Ropert was also asked to leave.[34]

Korn was awarded the prestigious Richard Lounsbery Award in 1992 and became a member of the National Academy of Sciences in the U.S. and the French Academy of Sciences.[35] Then in 2007, re-analysis of Korn's data by Jacques Ninio in the Journal of Neurophysiology showed serious anomalies that suggested the results were indeed fabricated.[33]