Perfume for the gods

Almost two years ago, I relished giving a departmental seminar on a novel theory of smell by Luca Turin, which proposed that we smell molecules not by their shape, but by their vibrations. The seminar was largely inspired by this book, which then encouraged me to explore the fascinating literature on smell. Turin's theory was then largely discounted, although it predicted that dimethyl sulfide and dimethyl sulfide-d6 would smell different because of different vibrations of the C-H and C-D bonds. I tested this hypothesis myself and indeed could detect a slight difference in their smell. All ten of of my test subjects also could.

A critical editorial in Nature Neuroscience, based on an experiment conducted in Rockefeller University, dismissed the theory with what I thought was a little too much chutzpah. But now, in an article published in the Physical Review Letters, Turin's theory seems to receive support. I still have to read the details; not that the equations of quantum physics are exactly at the tip of my tongue, but still.

Turin has also come out with a book about smell and the science behind it. I just got a copy from Amazon and have started on it. One thing that you have to appreciate about the man is his fine perception of smell, as both science and art, as well as his wide-ranging knowledge. His descriptions of smell are sometimes poetry exemplified, and his ability to nail down a smell in the weirdest description is uncanny ("...smells like the breath of a newborn infant mixed with its mother's hair spray").

On the other hand, the science in the earlier book was sometimes pretty sketchy, and Turin's words about why the holy Angstrom is an appealingly natural unit are not entirely scientifically appealing. He says that the Angstrom seems very natural, because a C-C bond length is about 1 A. Well, a C-C bond length is 1.54 A, very different from 1 A as chemists will realise, and saying that a C-C bond length is 'about' 1 A is alarming. On a similar note, the difference between a C-C and a C=C is 'only' 0.12 A, and yet it makes a world of difference in the chemistry. As they say, chemistry (and biology) are worlds encapsulated within 0.5 A and 2kcal/mol.

Frankly, I have always thought that there's definitely much more to smell than shape. And as far as the difference in smell of deuterated compunds was concerned, I thought the vibration theory bore good weight. The problem is that smell is not quantifiable the way the effect of a drug is, through quantitative dose-response curves. I have to admit that SAR for smell looks even more bizarre than SAR for drugs, which is bizarre enough sometimes. The Nobel prize awarded to smell two years ago was really about the biology, and not about the molecular recognition part. So we definitely have a long way to go in deciphering smell. Smell is fascinating by any standards, no doubt about that.


  1. Order of magnitude, my dear fellow.

  2. Luca, I understand that, but the difference between 1 and 1.54 is a full 54%, and the difference in terms of chemistry is humungous (C-C vs C-H for example).
    If inflation rose from 1 to 1.1, would you say that it's about the same because it's the same order of magnitude? For economists, it would be a big deal because the increase is 10%.
    My point is, the significance of order of magnitude surely has to depend on context and purpose.

  3. Thanks Ashutosh. I'll tell you what:you suggest a better phrase, and I'll put it in the paperback :-)

  4. Think of odor SOR like insect resistance to a pesticide. Typically, a bug has many different routes of metabolism (P450, esterase etc...) that are operating on a pesticide in order to detoxify it. A tiny change in the rate of metabolism or enzyme affinity in a few of these routes can have the net affect of rendering the insect immune to the affects of the pesticide.

    The same can be said of odor. Consider the many (thousands?) receptors in the nose. If a structural change in a molecule alters the binding (Kd or kon, koff, equillibria or kinetics) of the substrate to a number of receptors by even a fraction of a percent, the overall odor (note) can be vastly different.

    I personally think that odors are fascinating and really, the only SOR data we have is purly empirical.

    Also, where drugs produce a physiological event, like the inhibition of an enzyme, that has physical consequences (i.e. lower levels of angiotensin), odor has a physical component and a mental component. The binding event generates a signal, or chord of signals, that is interpreted by our grey matter.

  5. Luca: Intriguing offer :-) Let me think of something and I will communicate it to you.

    Milo: I think that's a good way of thinking about it. If only we could quantify what changes in what event lead to what exact change in odor (eg., floral--->mint)

  6. A Hollywood version on the magic of smell has been released based on the book by Patrick Suskind - Perfume: The Story of A Murderer

  7. I can't seem to access the article on Nature News. Can someone give me the citation for the Phys.Rev.Let. article?

  8. Hirak: Can't wait to see it after seeing the trailer. Thanks!

    Tue: Brookes J. C., et al. Preprint, (2006).

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