New study contradicts Luca Turin's theory?

[purplebird7]

I'm still in here, reading this discussion.
Thank you, Redneck Perfumisto, for mediating the various communications and maintaining Decorum on the Forum.

As far as 100% synthetic perfumes go, I doubt I could correctly detect one. Even after smelling all of the ingredients in the Note Identification Project, I might be able to identify the presense of a particular natural ingredient but not the absence of all of them.

[surreality]

not always.

not saying turin is wrong, but if someone goes around telling everyone something that is OBVIOUSLY false, such as "pulp fiction had john travolta and danny glover" or columbus was on the may flower, or chuck yeager was the first man on the moon or....whatever...

You are confusing statements of fact like "john travolta and danny glover were in pulp fiction", with scientific or philosophical hypothesis. The two types of statements - facts and hypotheses - are not the same.

when they ARENT onto something, people will argue with them, loudly.

If a scientist or philosopher is so far off base as to be obviously wrong they usually garner no attention whatsoever, and their theories or ideas die a quick, silent death.

[helo darqness]

OK, I find myself agreeing with both of you here. Generally, people will try to ignore the folks who are so far off base that they're not making sense. To borrow the book title from the now-famous physics phrase, "not even wrong". E.g., the 6000 year-old Earth people (who are the flat Earthers of the 21st century). The trouble is, when those folks use politics to bring that junk into science, then we have to make a big fuss, like it or not. But trust me, if they were just holding meetings and whatnot and not trying to make everybody else listen to that stuff, they would be totally ignored.

But you're probably also right, h_d, in that it's a bit different on the internet. People seem more willing to just say whatever they think (), and people are also more willing to talk back honestly to anything they disagree with. I personally love that aspect of web culture, since it promotes more vigorous discussion of ideas. When all parties are open to changing their minds based on the evidence, and everything is up for discussion without preconditions, huge progress can be made toward understanding.

beachroses - I know what you're saying about those purely synthetic frags. I find them difficult to wear, sometimes - I almost dread putting them on.

you would be surprised how publicly vocal people are in the politic-religion thing. i live in NYC, but i know people are like this everywhere, people scoff at me for siding with science. its big online because its a more efficient medium.

[Redneck Perfumisto]

LT claims that his company has used his thoery to come up with as non cancer-causing replacement for coumarin. When I read Burr's book, I was rooting for Turin's theory just because it would, by definition, replace millions of man hours of apparently near-random molecule creation, making possible the a flood of new scents.

BTW, I hane only the barest-bones understanding of any of this, but I do remember reading that Buck had to retract at least part of her research because nobody has been able to duplicate it.

Second things first - you're right - Buck did have to retract a paper, but it was not the Nobel stuff specifically. Here are some links about the retraction:

http://www.boston.com/news/local/art...racts_a_study/

http://www.nytimes.com/2008/03/07/sc...7retractw.html

http://fangzhouzi-xys.blogspot.com/2...-rebuttal.html

http://www.msnbc.msn.com/id/23505769/

From the latter:

The University of Tokyo’s Hitoshi Sakano, an expert on olfactory neurons who did not play a role in Buck’s research, told Nature that the retraction would probably have only a minor effect on the field. Other researchers have corroborated some of the paper's results using other techniques, he said.

So no big setback for the mainstream theories of olfaction.

Back on your first point... Yes, I think everybody wants to make medicinal and olfactory chemistry predictable. Luca Turin is just doing what everybody else is - he's simply choosing his own path. But I personally expect no "miracles" from any kind of rational odorant discovery, any more than we're getting them in rational drug discovery. This kind of prediction is simply difficult, no matter how you do it. I think people are getting better at both drugs and odorants. But even in drugs, now, we are not at the point where you put the disease in one end of the computer and a card with a structure pops out the other. The reason there is perennial funding for anything having to do with drug discovery is that it simply ain't solved. So what percentage of the millions of man-hours can be saved is really up for grabs, in my opinion, but I would be skeptical of ideas claiming to save them all, as much as I would be of such a claim in drug discovery.

You can get a good sense of Turin's work, and the molecules he's making, here:

http://www.flexitral.com/research/Rational_odorants.pdf

As an aside, there's a good, recent summary of his position on the pros and cons of vibration there. More importantly, he actually talks about his reasoning on his recent molecules there. Some of it I had guessed by looking at his patents and viewing his TED lecture, but other parts were new for me and very interesting. He's rather open about his strategy, so I don't feel like I'm spilling any beans here. What he's doing is a baby step in rational odorant design, but it's a very profitable one. I the words of a horse-racer, he's got a method for calling the ponies, and he's showing it off. I don't blame him. Everybody with any kind of predictive method wants to do that, and, as the song goes, "money talks". It seems that he's basically found a method for reliably finding things that smell the same. I don't know how other people feel about that, but personally, I think it's impressive, no matter how it's done. First of all, it's profitable. He's finding new molecules that are olfactively close to known moneymakers, but with structural tweaks that remove known bugaboos. And it would seem that he's doing it by (1) getting structurally close using what tend to be (but are perhaps not guaranteed to be) olfactively neutral operations, and (2) making sure that the IR shows the new molecule to be some kind of a spectral ringer for the one he's copying. Apparently, the combination of these two things works pretty well in finding new molecules. Is the IR part necessary? That's a big question. If it is, then I think it is could almost be taken as evidence of a relationship of some kind (not saying what) between odor and the vibrational spectra of odorants. If it's not, then it's superfluous, as many contend the vibrational idea to be.

I find it all very interesting. I do think it's important for people not to get the idea that odorant design isn't already quite rational by standard methods. For example, one of my loves, Cosmone, in Givenchy Pi Neo. It's a big macrocyclic musk, in a patent on a bunch of other big macrocyclic musks. It features a carbonyl in a big ring, a methyl group two carbons away, and a double bond on the far side of the ring. These are just combinations of things that are present in known macrocyclic musks. Two are essential - the big ring and the carbonyl - and the others are known features that are not always present, thus optional. I wouldn't say that they're olfactively neutral operations - maybe just olfactively safe in musks. But the point is that this molecule was obviously rationally constructed. And if you look at the patent, you can see that the folks were synthesizing nice molecules that all looked like potential winners.

Now let's say you wanted to be rational about molecules like that. If you knew what receptor Cosmone was hitting, then I would certainly put my money on normal methods of receptor binding stuff as a way to predict things that would work there. If we really understand it, then Cosmone should be a nice hit there, and we should find others like it that also look good. My money would also say that the subset of hits that pop out should pinpoint a variety of olfactively neutral operations, possibly including some new ones. Then my question would be, for some subset of molecules that look good from a binding standpoint, is there any correlation between anything vibrational and either (a) what we learned from normal binding studies, and (b) actual percieved odor? To me, that's a potential acid test for vibration. If vibration calls the winners there, or even seems to show some relationship to something, then something is probably up. If it's ambiguous, then it's one more reason to think that vibration is superfluous.

Scientifically, I think everybody's goal is - or should be - to kill vibration. The question is, when do you say it's dead? We have to be careful about calling things dead - the history of science is filled with healthy giants who suddenly collapse and dead ideas that rise like Lazarus.

And we even have to be careful about the ideas that we don't favor. Just as when we favor an idea, and should immediately seek out its weak points, likewise when we oppose an idea, we should oppose its most favorable forms, and give it every chance to make its case.

As a rather extreme example, the creationists don't believe Jesus rode dinosaurs. They believe Adam rode dinosaurs (or, to be fair, that he could have). It's actually an important distinction in their theory, because they use Noah as the linchpin of their explanation why dinosaurs don't exist today. Fortunately, the currently accepted disproof of that hypothesis covers both special cases.

Don't get me wrong - I don't see vibration as anything like that. I see it more like some minority positions in chemistry, physics, or astronomy. Often such positions get more support from the public than they do from other scientists, because the public will (and I think rather fairly) give the benefit of the doubt, whereas other scientists have already made up their mind for the most part. I think people would be surprised how fast most scientists will change their minds when good, solid, convincing evidence, backed up by a solid explanation, comes along. But I'm still a huge believer in Carl Sagan's dictum that extraordinary claims demand extraordinary evidence.

[Redneck Perfumisto]

you would be surprised how publicly vocal people are in the politic-religion thing. i live in NYC, but i know people are like this everywhere, people scoff at me for siding with science. its big online because its a more efficient medium.

Ouch. I probably spend too much time around scientists, many of them religious in one way or another. We don't usually see that. But I'll avoid straying too far into those forbidden topics here.

[Redneck Perfumisto]

As far as 100% synthetic perfumes go, I doubt I could correctly detect one. Even after smelling all of the ingredients in the Note Identification Project, I might be able to identify the presense of a particular natural ingredient but not the absence of all of them.

Then I simply MUST send you some CK Crave. At a low dose, it's possible to convince oneself that there's citrus in there. But use a bit more, and it's clear that this stuff ain't found in nature!!!

No, seriously, you're absolutely right. The human nose has some definite limits. There are likely some kind of natural ingredients in my Crave, but I would never know for sure without real analysis. I think the best one could get human-wise would be a trained perfumer sniffing out the main ingredients. As you say, presence is detectable, but not the absence of sufficiently small amounts.

[xiikzodz]

The fundamental problem with the vibrational theory is that nobody actualy attempts to verify it. Among the people who try hardest not to verify this theory is Luca Turin himself. Apparently he keeps mistaking salon talk about fashionable fragrances with proper research. Theories are not being promoted through any propaganda or campaign but they are verified through systematic research.

Odorants are substances with numerous properties. One can measure these using various techniques. It so happens that different measurable properties are not at all independent. Because of underying quantum level structure substances similar in some way frequently are similar in some other. Simplified shape or vibrational spectrum are such properties. They sometimes indicate similarities in the way substances smell and sometimes not. For both there are numerous counterexamples found (though only few people agree to have ever taken vibrational/shape theory seriously and they frequently shy the results).

To give an analogy. One group of people claims "the fastest road cars are red" (vibrational theory) the other "the fastest cars are those with largest engine" (shape theory). Everyone sober will see the faults in both "theories". Alas, both groups may struggle write books and mock at one another endlessly because many Ferraris are red and Ferraris are fast and on the other hand indeed supercars have large engines. Obviously the size of the engine and the colour of the car don't really hit on the target. So it is apparenty with the human nose.

[Advocate]

The fundamental problem with the vibrational theory is that nobody actualy [sic] attempts to verify it.

You mean, aside from:

http://vosshall.rockefeller.edu/repr...sshall2004.pdf

http://chemse.oxfordjournals.org/cgi...tract/21/6/773

http://linkinghub.elsevier.com/retri...08814600002879

http://www.flexitral.com/research/review_final.pdf

http://linkinghub.elsevier.com/retri...59438808001037

http://journals.cambridge.org/abstra...22215100067281

http://books.google.com/books?hl=en&...bXLVDAAioaaN7E

http://nthur.lib.nthu.edu.tw/dspace/...87654321/30403

http://d.wanfangdata.com.cn/NSTLQK_NSTL_QK7700978.aspx

et cetera . . . .

[kbe]

Since there is no definitive and ultimately proven work that moves any theory of how smell works to the fact column I find Dr. Turin's vibrational theory to be the one I think will prove to be correct.

[xiikzodz]

And the list above is the best proof for my claim. Appart from works completely irrelevant to vibrational theory listed above the research goes in the direction of falsifying the vibrational claim.

Lets do it one by one:

You mean, aside from:

http://vosshall.rockefeller.edu/repr...sshall2004.pdf

Falsification of some single Turins claim on carbon chain lengths. Has nothing to do with theory verification. Points out holes in the theory. The authors admit to go into vibrational theory reluctantly, so to say, motivated by the medial mess about olfaction triggered by Turin.

http://chemse.oxfordjournals.org/cgi...tract/21/6/773

Existence of hypothetical possibility of detecting vibrations by a human nose. Obviously has nothing to do with verification of any theory.

http://linkinghub.elsevier.com/retri...08814600002879

Labouring under assumption vibrational theory is feasible the authors seek parameters for certain aromatics (i.e. almonds).

http://www.flexitral.com/research/review_final.pdf

Assumes the theory is right and illustrates what it is therefore good for. (The link died with the company but I remember the paper.)

http://linkinghub.elsevier.com/retri...59438808001037

Perfectly irrelevant. It is a nice formal approach to the olfactory problem. The authors propose a metric (distance) on the space of all possible chemical substances as a mean of comparing them and, in turn, comparing their smells. (By the way it is the atrticle on which I actualy based my previous claim.)

http://journals.cambridge.org/abstra...22215100067281

I daresay putting this link on the list must have been an act of deficiency in sobriety. This one, however informative an possibly useful, has in its intention absolutely nothing to do with veryfying ANY theory.

http://books.google.com/books?hl=en&...bXLVDAAioaaN7E

Informs about the state of the art (you didn't expect a textbook to veryfy theories, did you?). Neither challenges nor attemps to prove anything. Just lists partial results from those few articles we all know...

http://nthur.lib.nthu.edu.tw/dspace/...87654321/30403

Toolbox (software) potentialy helpful in veryfying the theory in question what anyone gifted with the ability of reading sees immediately.

http://d.wanfangdata.com.cn/NSTLQK_NSTL_QK7700978.aspx

Link's dead and I failed to guess which paper it was.

et cetera . . . .

Spot on. There are many papers of the kind. Thanks for providing me with the support for my claim and saving me from looking for those links. I have some 150 articles on olfacion on my drive but most of them are hard to find anywhere online...

[xiikzodz]

Perhaps I should explain my point to avoid further development in the direction of flooding everything with papers on olfaction. I read for living and I think I might put some light on the whole "scientific conspiracy against Turin".

In my opinion, the idea is fantastic. Turin's contribution to it which is picking up proper pieces of the puzzle and putting them in logical places is remarkable. Really an inspiring story. Now in science, if you have a fine idea (which Turin had) you define the problem assemble a lab and start working. Putting together a lab suitable to some novel approach is a piece of hard work and there is always a danger that once the lab is ready the theory is proven rubbish. In certain age it is a risky business. You don't won't to end up with work of your life being crap. Furthermore, lab assembling and lab work is hard and leaves little time for sniffing at bottles and mocking at perfumers. Turin therefore smartly chose another way. He challenged the whole scientific world with his unbaked theory. To it the scientific world responded by ignoring Mr Turin. And rightly so. Why risking all the mess with labs grants and whatnot for someone else's benefit? This escalated Turin's resentment and eventualy the whole matter started to be discussed in places like this forum.

But there is a nice way out. If one believes in something one should pursue it sometimes at some cost. Mr Turin seems to believe in the theory, it is an extremely good hunch, so he'd rather do finaly the job right and work on it hard in the lab. Explaining the sense of smell throough the inelastic tunneling would be a delightful result. I daresay it would puzzle quite some people for quite some time. Starting with the question of an evolutionary path of development of such a mechanism. I would realy love to read some proper papers about such things.

[Advocate]

Before we get to the heart of the matter, I apologize for not giving my first post the time that it deserved. I was taking a break from my day job, and I thought that a few minutes spent with Google Scholar would be all that would be necessary.

As I understand your point, it is that Luca Turin came up with the vibrational theory and, to date, no one has tested it. ("The fundamental problem with the vibrational theory is that nobody actualy [sic] attempts to verify it.") Now, if I have misunderstood that point, please correct me.

That assertion is plainly false. The vibrational theory has been tested experimentally numerous times, with some experiments seeming to confirm it, and some experiments seeming to disprove it. This evening, I easily found two examples. First, Dr. Turin himself tested his theory and described his experiment in his 1996 article in Chemical Senses: http://chemse.oxfordjournals.org/cgi...tract/21/6/773. Here is a second article on an experiment conducted by others testing Dr. Turin's theory: http://www.sciencedirect.com/science...8197c8e0516693.

It is nice that you "read for a living." I do, too, and I suspect many other Basenotes members do, too, so that seems a rather weak appeal to authority. Nevertheless, it beats digging ditches, doesn't it?

I was confused to read you debunking a "scientific conspiracy against Turin." I do not recall that being postulated in this thread prior to you mentioning it. Since you surrounded those words with quotation marks, I assume that you were quoting a specific post. If you could provide a link to that post, then I would greatly appreciate it, because I confess that I suspect it is merely a straw man.

I was intrigued to read that you have assembled a collection of approximately 150 scholarly articles on this subject. I (and probably many others like me) would appreciate it if you would share that collection with us. If you would be willing to zip those articles into a compressed archive and send it to me, then I would be happy to privately message my email address to you.

I look forward to further discussion on this topic. However, I would appreciate it if ad hominem attacks on me ("deficiency in sobriety") and Dr. Turin ("sniffing at bottles and mocking at perfumers") could be avoided.

[xiikzodz]

Testing a theory is fine but frequently leads to no verification. The Fermat Last Theorem has been tested on unimaginable large number of triples and yet verified with a proof long after that.

Here we have the following situation. We know from the tests that the vibrational theory alone cannot model the human sense of smell properly. On the other hand, it is still quite possible and supported by some other tests that the tunneling mechanism takes part in olfactory recognition. If so then we come to the hard work thing and a potential breakthrough in biophysics.

My interest in olfaction had its peak around the year 2000. I was involved in an information theory project on insect olfaction (NASA paid for such things). We have assumed some kind of receptor mechanism in olfaction and studied spike trains which is the information on the level of the brain activity. Thus the collection of the papers on olfaction. I'm afraid I can't zip them and share with others without violating the copyrights frequently owned by rather large subjects. The only hope would be to link them in case they existed somewhere online. For people who are really interested it will probably suffice to locate some large academic library go to journals in biophysics and take the bibliography listed in the Axel & Buck for a good start.

I am glad ad hominem attacks here are not suffered. Turin's sniffing at bottles and mocking and perfumers I fail to consider as such as it is a mere fact to which he eagerly consents himself. I appologize for anything else offensive in my posts. I suppose I tuned a bit too much into the Turin's way of presenting the subject. I agree it is inacceptible.

The phrase "scientific conspiracy against Turin is a quote from one of the papers you have kindly listed.

I wrote I read for living not to exhibit authority but to express personal involvement in the subject. You may avoid bad music but if your job is to review the market you will have to suffer all kinds of rubbish.

[pluran]

It's interesting to find out who's funding these "studies". The die-hard opponents of Turin's theory are primarily large corporations who stand to lose tens/hundreds of billions if it is ever proven correct. Which it most likely will be.

[xiikzodz]

Large companies don't bother about theories. In most normal countries (ecept Japan for instance) you can't patent them so once it is published a big company hires people to apply it and they're back in business. The real sufferers would definitely be those who live from collecting and (pre)processing raw materials. Those thousands of women picking up rose petals for example.

Still one more technical thing about research. Theories never really proove right once and for all. It has been mentioned in the thread before. The life span of a theory is from the moment it has been accepted to the moment something new contradicts it. But the work sometimes, actualy quite frequently, won't just dissolve into oblivion. It is because the contemporary science is about models. We have a theory when we claim to have understood something truly and fully. Model is something different (and Turin chose to mix the two notions as he pleases). Having a model we don't claim to know the fundamental mechanism but we claim to have a tool giving the right answers regardlessly to the actual process underlying the studied phenomenon.

The notions of a model and a theory are slightly different understood by different people (and in mathematics they have utterly different though related meaning) but the thing I wrote above is quite universal.

Now Turin has a problem. His vibrational theory is obviously not a model yet. For one thing, it so far models nothing, and we already know it for sure does not model a human nose (see Vosshall). It would become a proper, and in fact a brilliant, model if there were conditions given under which the spectra alone give the right answer. Otherwise we have a model which works only in casa it works which is a tautology.

The vibrational theory is also not a theory. To be such it has to be accepted by the scientific world. Not long ago (remarkably two millenia after the rise of Pythagoreans) scholars believed in dragons and mermaids and that the birds of paradise were legless (see the latin name of the Greater Bird-of-paradise, Paradisaea apoda - legless). Now scientists are far more skeptical and it takes slightly more that persuasion and a bunch of examples to settle a proper theory. In fact Turin made a fool of himself by using publicity for the purpose and it will be hard to get this thing back into serious consideration.

Strategicaly Turin is left with no choice but creating a proper model (af a human nose) having inelastic tunneling as one of its components. There is nothing diminutive in creating a model. The greatest theory in biophysics is called Hodgson-Hutchin Model and the most acurate theory humans have ever invented is called Standard Model and being currently exposed (CERN) to a series of tests which might prove it wrong and the textbooks might have to be rewritten.

[Aiona]

The thing that I find very troubling is that I was taught in grad school that you had better make an "airtight" case or else you would have to expect fellow scholars to "rip you to shreds" (and this wasn't even a scientific discipline!), yet scientists (and those in biology seem to be the worst offenders) don't seem to have any qualms about dismissing the ideas of others out of hand when there is so much evidence against their own. If Redneck P. is right, there is no reason for any one theory to be viewed as anything more than an educated guess at this point, given that there is evidence against their idea as well as a compelling competing notion. If you want to make a case, then make it as strong as possible, It's possible that two theories can both explain 99% of the evidence, but only the right one can explain 100%, and this is something too many scientists these days don't seem to understand.

UPDATE: If you got to pubmed.com and search for sense of smell, you find interesting stuff like:

"No two roses smell exactly alike, but our brain accurately bundles these variations into a single percept 'rose'. We found that ensembles of rat olfactory bulb neurons decorrelate complex mixtures that vary by as little as a single missing component, whereas olfactory (piriform) cortical neural ensembles perform pattern completion in response to an absent component, essentially filling in the missing information and allowing perceptual stability. This piriform cortical ensemble activity predicts olfactory perception."

Nat Neurosci. 2008 Dec;11(12):1378-80. Epub 2008 Nov 2.

http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

That subject fascinates me at the moment. How the brain can categorize.

Currently Aiona Jr. can see a picture of a tiger, and without my ever having said anything about felines, he points to it and says, "Cat."

Colors are another matter. I can't get him to consistently tell me a color.

'Makes me think of when I did my surgery rotation, and the radiologist on call said, "Yep! It's appendicitis!" I said, "How do you know?" And he goes, "How can you tell a cat is a cat?" I said, "It has a tail." He said, "lots of things have tails." I said, "It has a pointy nose." "You mean like a dog?" And he went on for some time, baiting me. And then he said, "That is appendicitis. I know it, as I know what a cat is." And now I know too.