Smell column - primary reception not so well understood

I’m not a specialist in smell research by any means, but my understanding is that the idea of “smell primaries” hasn’t really had much currency for quite some time now. If you want evidence just look to the gazillion dollars that fragrance and flavour companies spend every year trying to come up with new synthetic odorants – a burden they could be quickly relieved of if we could produce any smell sensation on the basis of just 7 primaries.

I think the honest answer about smell reception at this point in time is that it remains poorly understood. Various “Shapist” (lock-and-key) models are the most widely accepted, but their predictive value has proven to be completely dismal – another thorn in side of the fragrance and flavour R&D budgets.

“Vibrationist” theories have been proposed from time to time, most recently in the form of an inelastic electron tunnelling model devised by the biophysicist Luca Turin. The guys is not well liked in smell research circles, and vibration theory has not been well received, but he has done a terrific job of enumerating all of the many inadequacies of current lock-and-key theories of smell reception.

I guess wikipedia is as good a place to start as any, if you’re curious.

Interesting. I’m not an expert in olfaction either, but I hadn’t heard the vibration model. There’s an interesting article in Nature neuroscience by Keller and Vosshall published in 2004 that seems to systematically eviscerate the model though. Here are the major findings–

I find this article pretty convincing at first glance. I think the vibrational model is cool, but it kind of defies the way signal transduction appears to work in any other sensory modality. As far as I can tell, the lock-and-key model is a better (though certainly imperfect) model. The fact is, structural biology is hard, and I suspect we simply don’t know enough about odorant receptors to design molecules well against them at this point.

I could be wrong.

Agreed that any lock-and-key model with any predictive value is going to have to be monstrously complicated, and is just beyond our capability right now.

My main issue with the tiny Keller and Vosshall study is that they used naive subjects that weren’t screened for their smelling acuity. We already know that there’s huge variation in natural acuity (i.e. many chefs and perfumers are absolute freaks compared to the rest of us, esp. after years of training), and Turin himself never claimed that the key differences in odorant character are massive. The previous animal studies using isotopes seemed to suggest that acuity might play a very important role in whether we find experimental support for vibration theory.

As an aside, I seem to remember Turin raising one point in his book that I found particularly interesting – namely, seeing as how receptor antagonists seem to be so common, how come an obvious one has never been encountered for smell reception? (E.g. A molecule that, when sniffed, prevents us from smelling a specific odorant.)

In any case, I don’t really want to be an apologist for vibration theory. My main issue with the staff report was in regards to the notion of smell primaries, as well as primary and secondary odorants, which to my knowledge enjoy very little evidence or support.

Again, I’m not in this field–I’m not even in pharmacology–but a quick PubMed search turned up some stuff that suggests that selective antagonism of olfactory receptors does occur.

Just abstracts this time (I still have a stack of papers to read for my real research, ugh)…

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](Olfactory receptor antagonism between odorants - PubMed)

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](http://www.ncbi.nlm.nih.gov/pubmed/15069207?ordinalpos=16&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)Again, I suspect that part of the issue here is the sheer complexity of the olfactory system in terms of receptor diversity. I might not expect there to be a blanket olfactory receptor antagonist, given how many olfactory receptors exist. And, as these abstracts indicate, odorants themselves may act as agonists at some receptors and antagonists at others, meaning that the perceived odor of a given mixture of volatile compounds is a complex odor code derived from a great deal of interference between competing odorants. As a result, maybe we have identified odorant antagonists :wink:

Oh no worries. I’m glad you exposed me to it; as I said, I’d not heard of it. Olfaction is sort of the least popular sensory modality in terms of neuroscientific investigation, and I think it’s due for a closer look. God knows I’m sick of hearing about visual cortex…

Link to column.

I enjoyed that article, well written Fierra.

I’ve seen Luca Turin speak and he gives a fantastic lecture. I suspect his vibrational theory would be better received coming from someone else - he has the type of salesman charisma that makes scientists nervous. Anyway, he uses some knockout examples that are covered in the wiki article anosmia linked to. The borane one in particular was memorable, he searched the literature for a compound that had the same vibrational stretch as a S-H bond, not many do as it is a relatively empty region of the spectrum, and came up with a borane, a million miles away in structure from a thiol. Hey presto, the borane smells sulfurous.

The lock and key terminology seems a little unfortunate to me. It’s a very classical metaphor to be applying to an area as poorly understood as olfaction.

I guess we should give up on the dream of an aerosol can full of doo-doo antagonist. Back to lighting matches . . .