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  • The fragrance that you will smell, you will never be able to smell this way again.

  • It’s a fragrance called Beyond Paradise,

  • which you can find in any store in the nation.

  • Except here it’s been split up in parts by Estée Lauder

  • and by the perfumer who did it, Calice Becker,

  • and I'm most grateful to them for this.

  • And it’s been split up in successive bits and a chord.

  • So what youre smelling now is the top note.

  • And then will come what they call the heart, the lush heart note.

  • I will show it to you.

  • The Eden top note is named after the Eden Project in the U.K.

  • The lush heart note, Melaleuca bark note -- which does not contain any Melaleuca bark,

  • because it’s totally forbidden.

  • And after that, the complete fragrance.

  • Now what you are smelling is a combination of --

  • I asked how many molecules there were in there, and nobody would tell me.

  • So I put it through a G.C., a Gas Chromatograph that I have in my office,

  • and it’s about 400.

  • So what youre smelling is several hundred molecules

  • floating through the air, hitting your nose.

  • And do not get the impression that this is very subjective.

  • You are all smelling pretty much the same thing, OK?

  • Smell has this reputation of being somewhat different for each person.

  • It’s not really true.

  • And perfumery shows you that can’t be true,

  • because if it were like that it wouldn’t be an art, OK?

  • Now, while the smell wafts over you, let me tell you the history of an idea.

  • Everything that youre smelling in here

  • is made up of atoms that come from what I call

  • the Upper East Side of the periodic table -- a nice, safe neighborhood.

  • (Laughter)

  • You really don’t want to leave it if you want to have a career in perfumery.

  • Some people have tried in the 1920s

  • to add things from the bad parts, and it didn’t really work.

  • These are the five atoms from which just about everything

  • that youre going to smell in real life, from coffee to fragrance, are made of.

  • The top note that you smelled at the very beginning,

  • the cut-grass green, what we call in perfumery -- theyre weird terms --

  • and this would be called a green note,

  • because it smells of something green, like cut grass.

  • This is cis-3-hexene-1-ol. And I had to learn chemistry on the fly

  • in the last three years. A very expensive high school chemistry education.

  • This has six carbon atoms, so "hexa," hexene-1-ol.

  • It has one double bond, it has an alcohol on the end,

  • so it’s "ol," and that’s why they call it cis-3-hexene-1-ol.

  • Once you figure this out, you can really impress people at parties.

  • This smells of cut grass. Now, this is the skeleton of the molecule.

  • If you dress it up with atoms, hydrogen atoms --

  • that’s what it looks like when you have it on your computer --

  • but actually it’s sort of more like this, in the sense that the atoms have a certain

  • sphere that you cannot penetrate. They repel.

  • OK, now. Why does this thing smell of cut grass, OK?

  • Why doesn’t it smell of potatoes or violets? Well, there are really two theories.

  • But the first theory is: it must be the shape.

  • And that’s a perfectly reasonable theory in the sense that

  • almost everything else in biology works by shape.

  • Enzymes that chew things up, antibodies, it’s all, you know,

  • the fit between a protein and whatever it is grabbing, in this case a smell.

  • And I will try and explain to you what’s wrong with this notion.

  • And the other theory is that we smell molecular vibrations.

  • Now, this is a totally insane idea.

  • And when I first came across it in the early '90s, I thought my predecessor,

  • Malcolm Dyson and Bob Wright, had really taken leave of their senses,

  • and I’ll explain to you why this was the case.

  • However, I came to realize gradually that they may be right --

  • and I have to convince all my colleagues that this is so, but I’m working on it.

  • Here’s how shape works in normal receptors.

  • You have a molecule coming in, it gets into the protein, which is schematic here,

  • and it causes this thing to switch, to turn, to move in some way

  • by binding in certain parts.

  • And the attraction, the forces, between the molecule and the protein

  • cause the motion. This is a shape-based idea.

  • Now, what’s wrong with shape is summarized in this slide.

  • The way --I expect everybody to memorize these compounds.

  • This is one page of work from a chemist’s workbook, OK?

  • Working for a fragrance company.

  • He’s making 45 molecules, and he’s looking for a sandalwood,

  • something that smells of sandalwood.

  • Because there’s a lot of money in sandalwoods.

  • And of these 45 molecules, only 4629 actually smells of sandalwood.

  • And he puts an exclamation mark, OK? This is an awful lot of work.

  • This actually is roughly, in man-years of work, 200,000 dollars roughly,

  • if you keep them on the low salaries with no benefits.

  • So this is a profoundly inefficient process.

  • And my definition of a theory is, it’s not just something

  • that you teach people; it’s labor saving.

  • A theory is something that enables you to do less work.

  • I love the idea of doing less work. So let me explain to you why -- a very simple fact

  • that tells you why this shape theory really does not work very well.

  • This is cis-3-hexene-1-ol. It smells of cut grass.

  • This is cis-3-hexene-1-thiol, and this smells of rotten eggs, OK?

  • Now, you will have noticed that vodka never smells of rotten eggs.

  • If it does, you put the glass down, you go to a different bar.

  • This is -- in other words, we never get the O-H --

  • we never mistake it for an S-H, OK?

  • Like, at no concentration, even pure, you know,

  • if you smelt pure ethanol, it doesn’t smell of rotten eggs.

  • Conversely, there is no concentration at which the sulfur compound will smell like vodka.

  • It’s very hard to explain this by molecular recognition.

  • Now, I showed this to a physicist friend of mine who has a profound distaste

  • for biology, and he says, "That’s easy! The things are a different color!"

  • (Laughter)

  • We have to go a little beyond that. Now let me explain why vibrational theory has

  • some sort of interest in it. These molecules, as you saw in the beginning,

  • the building blocks had springs connecting them to each other.

  • In fact, molecules are able to vibrate at a set of frequencies

  • which are very specific for each molecule and for the bonds connecting them.

  • So this is the sound of the O-H stretch, translated into the audible range.

  • S-H, quite a different frequency.

  • Now, this is kind of interesting, because it tells you

  • that you should be looking for a particular fact, which is this:

  • nothing in the world smells like rotten eggs except S-H, OK?

  • Now, Fact B: nothing in the world has that frequency except S-H.

  • If you look on this, imagine a piano keyboard.

  • The S-H stretch is in the middle of a part of the keyboard

  • that has been, so to speak, damaged,

  • and there are no neighboring notes, nothing is close to it.

  • You have a unique smell, a unique vibration.

  • So I went searching when I started in this game

  • to convince myself that there was any degree of plausibility

  • to this whole crazy story.

  • I went searching for a type of molecule, any molecule,

  • that would have that vibration and that -- the obvious prediction

  • was that it should absolutely smell of sulfur.

  • If it didn’t, the whole idea was toast, and I might as well move on to other things.

  • Now, after searching high and low for several months,

  • I discovered that there was a type of molecule called a Borane

  • which has exactly the same vibration.

  • Now the good news is, Boranes you can get hold of.

  • The bad news is theyre rocket fuels.

  • Most of them explode spontaneously in contact with air,

  • and when you call up the companies, they only give you minimum ten tons, OK?

  • (Laughter)

  • So this was not what they call a laboratory-scale experiment,

  • and they wouldn’t have liked it at my college.

  • However, I managed to get a hold of a Borane eventually, and here is the beast.

  • And it really does have the same -- if you calculate,

  • if you measure the vibrational frequencies, they are the same as S-H.

  • Now, does it smell of sulfur? Well, if you go back in the literature,

  • there’s a man who knew more about Boranes than anyone

  • alive then or since, Alfred Stock, he synthesized all of them.

  • And in an enormous 40-page paper in German he says, at one point --

  • my wife is German and she translated it for me --

  • and at one point he says, "ganz widerlich Geruch,"

  • an "absolutely repulsive smell," which is good. Reminiscent of hydrogen sulfide.

  • So this fact that Boranes smell of sulfur

  • had been known since 1910, and utterly forgotten until 1997, 1998.

  • Now, the slight fly in the ointment is this: that

  • if we smell molecular vibrations, we must have a spectroscope in our nose.

  • Now, this is a spectroscope, OK, on my laboratory bench.

  • And it’s fair to say that if you look up somebody’s nose,

  • youre unlikely to see anything resembling this.

  • And this is the main objection to the theory.

  • OK, great, we smell vibrations. How? All right?

  • Now when people ask this kind of question, they neglect something,

  • which is that physicists are really clever, unlike biologists.

  • (Laughter)

  • This is a joke. I’m a biologist, OK?

  • So it’s a joke against myself.

  • Bob Jacklovich and John Lamb at Ford Motor Company,

  • in the days when Ford Motor was spending vast amounts of money

  • on fundamental research, discovered a way

  • to build a spectroscope that was intrinsically nano-scale.

  • In other words, no mirrors, no lasers, no prisms, no nonsense,

  • just a tiny device, and he built this device. And this device uses electron tunneling.

  • Now, I could do the dance of electron tunneling,

  • but I’ve done a video instead, which is much more interesting. Here’s how it works.

  • Electrons are fuzzy creatures, and they can jump across gaps,

  • but only at equal energy. If the energy differs, they can’t jump.

  • Unlike us, they won’t fall off the cliff.

  • OK. Now. If something absorbs the energy, the electron can travel.

  • So here you have a system, you have something --

  • and there’s plenty of that stuff in biology --

  • some substance giving an electron, and the electron tries to jump,

  • and only when a molecule comes along that has the right vibration

  • does the reaction happen, OK?

  • This is the basis for the device that these two guys at Ford built.

  • And every single part of this mechanism is actually plausible in biology.

  • In other words, I’ve taken off-the-shelf components,

  • and I’ve made a spectroscope.

  • What’s nice about this idea, if you have a philosophical bent of mind,

  • is that then it tells you that the nose,

  • the ear and the eye are all vibrational senses.

  • Of course, it doesn’t matter, because it could also be that theyre not.

  • But it has a certain --

  • (Laughter)

  • -- it has a certain ring to it which is attractive to people

  • who read too much 19th-century German literature.

  • And then a magnificent thing happened:

  • I left academia and joined the real world of business,

  • and a company was created around my ideas

  • to make new molecules using my method,

  • along the lines of, let’s put someone else’s money where your mouth is.

  • And one of the first things that happened was

  • we started going around to fragrance companies

  • asking for what they needed, because, of course,

  • if you could calculate smell, you don’t need chemists.

  • You need a computer, a Mac will do it, if you know how to program the thing right,

  • OK? So you can try a thousand molecules,

  • you can try ten thousand molecules in a weekend,

  • and then you only tell the chemists to make the right one.

  • And so that’s a direct path to making new odorants.

  • And one of the first things that happened was

  • we went to see some perfumers in France --

  • and here’s where I do my Charles Fleischer impression --

  • and one of them says, "You cannot make a coumarin."

  • He says to me, "I bet you cannot make a coumarin."

  • Now, coumarin is a very common thing, a material,

  • in fragrance which is derived from a bean that comes from South America.

  • And it is the classic synthetic aroma chemical, OK?

  • It’s the molecule that has made men’s fragrances

  • smell the way they do since 1881, to be exact.

  • And the problem is it’s a carcinogen.

  • So nobody likes particularly to -- you know, aftershave with carcinogens.

  • (Laughter)

  • There are some reckless people, but it’s not worth it, OK?

  • So they asked us to make a new coumarin. And so we started doing calculations.

  • And the first thing you do is you calculate the vibrational spectrum

  • of coumarin, and you smooth it out,

  • so that you have a nice picture of what the sort of chord, so to speak, of coumarin is.

  • And then you start cranking the computer to find other molecules,

  • related or unrelated, that have the same vibrations.

  • And we actually, in this case, I’m sorry to say,

  • it happened -- it was serendipitous.

  • Because I got a phone call from our chief chemist

  • and he said, look, I’ve just found this such a beautiful reaction,

  • that even if this compound doesn’t smell of coumarin,

  • I want to do it, it’s just such a nifty,

  • one step -- I mean, chemists have weird minds --

  • one step, 90 percent yield, you know, and you get this lovely

  • crystalline compound. Let us try it.

  • And I said, first of all, let me do the calculation on that compound, bottom right,

  • which is related to coumarin, but has an extra pentagon inserted into the molecule.

  • Calculate the vibrations, the purple spectrum is that new fellow,

  • the white one is the old one.

  • And the prediction is it should smell of coumarin.

  • They made it ... and it smelled exactly like coumarin.

  • And this is our new baby, called tonkene.

  • You see, when youre a scientist, youre always selling ideas.

  • And people are very resistant to ideas, and rightly so.

  • Why should new ideas be accepted?

  • But when you put a little 10-gram vial on the table in front of perfumers

  • and it smells