I am sad. And upset. And angry and hurt and all of those lovely emotions. Why? Because I was looking forward to telling you the story of an exciting theory, one that combines the mysterious (our sense of smell) with the strange (quantum mechanics). Alas, as I was reading into it, I stumbled over the perfect anti-paper. It had everything I didn´t want to see. The misgiving, multiple use of the word “claim” , the discrediting data, experimental and theoretical. And I could feel my blood pressure start to rise, much like when I discuss the refugee crisis in Europe with a bunch of bigots. Then I thought that it would actually be a great story to tell nonetheless. It gives an insight into how emotions in science and the “underdog bias” can have a huge effect on our research.
It’s something we do every day. When we enter the kitchen, hug a loved one, and stop to literally smell the flowers. It’s something we do with occasional pleasure, and other times with quite some discomfort. Yet, it´s an absolute mystery. I’m talking about our olfactory sense, our sense of smell. It is not as strong as that of a bloodhound. Nonetheless it’s essential. I fondly remember a lab experiment, when I had eaten some almond Christmas cookies and walked into the lab. One of my colleagues took one single sniff and started screaming at the top of his lungs: ”ALMONDS, I SMELL ALMONDS! SOMETHING IS LEAKING CYANIDE GAS! EVERYONE SAVE THEMSELVES!”
A hilarious mistake, but if the gas leak had actually been the case, his nose would have saved our lives. Cyanide gas is incredibly toxic and was possibly used by the famous chemist Gilbert Lewis to commit suicide. (Being nominated 35 times for a Nobel Prize and never winning it will do that to you.) Smell is important. But no one really understands how olfaction works on a molecular level.
One idea revolves all around shape. It´s the usual hand-in-glove model, the key-in-lock theory, the every-Jack-has-his-Jill idea. Linda Buck and Richard Axel were awarded the Nobel Prize for discovering our olfactory receptor genes in 1991. They discovered about a thousand of them. Only one receptor can be expressed per neuron. This means the hand-in-glove model requires one receptor for one molecule. I dare you to go out and smell 1001 different pure chemical solutions. The 1001st will be different, too. How is that possible? Another problem is: there are many smells with similar shape, but completely different smells. Left-turned Carvone smells of spearmint, the right-handed version of caraway. Same molecule, different smell. There’s also the mirrored question: Why are there completely different molecules that all smell the same, like the 75 chemicals that all smell like almonds, cyanide gas being one of them? What the heck, shape theory?!
The Shapists, the majority of scientists confident in the hand-in-glove model, have a theory to overcome these problems. It’s still the hand-in-glove, but with small adaptations:
- Mirrored chemicals, like carvone, have mirrored receptors.
- Instead of complete molecules, chemical groups have receptor pockets. For example ethanol, will have an hydroxyl (-OH) receptor and an ethyl (C2H6) receptor. Together, they enable us to smell the alcohol we enjoy in our G&T and other alcoholic beverages, C2H6
But can this theory really account for perfume descriptions of such awe-striking intricacy as the following?
I do not have access to old samples of Magie, but Lancôme’s revived “Collection” version smells plausible, i.e., a plush, elegant, and some- what dry aldehydic chypre in the classic French manner. It brings to mind a pouting model, hands on hips in opera gloves, wearing a hat, a spencer jacket, and a pencil skirt, with her feet at right angles to each other as if she were going up a ski slope. (Luca Turin)
I don´t know how something can smell like a pouting model, but Luca Turin, the author of the above perfume description, could. When he wasn´t obsessing over perfumes, he worked in a chemistry lab. And he disagreed with the Shapists. To oppose their theory, he revived the vibrational theory of olfaction. It was developed in 1928 by a chemist named Malcom Dyson. His experiments led him to notice that when he added heavier atoms to a given chemical structure, it would alter the smell. This could be due to heavier atoms vibrating at a different frequency than lighter ones. In the lab, we use infrared light to detect the vibrations, but I have yet to find someone with a laser in their nose. So, unable to explain the physics of his theory, Dyson’s idea faded into obscurity, like so many other ideas before it.
Then Turin hit the stage. A biophysicist by training, he was studying electron flow in proteins, while sniffing at perfume bottles and writing perfume guides in his past time. At some point he must’ve had enough of leaving his hobby at home and dragged it into the lab. His new twist to Dyson’s theory: he brought quantum mechanics into the mix. Quantumbiology is incredibly exciting, but due to the fact that quantum states HATE warm, wet environments, few people ever apply it to biological problems. Many that do, like Turin, face hostility. Turin placed his bets on quantum tunneling. The vibrational energy of our smelly molecule fits between the energy levels in our receptor. This allows an electron to jump through the receptor to trigger “ACTIVATE” in our olfactory neuron. The strange quantum aspect here is that the electron doesn´t physically pass through the receptor. It simply disappears at point A and reappears at point B. A group of mathematicians could find no physics-based problems with this theory. They dubbed it the “Swipe Card Model”. The molecule has to fit and vibrate at the correct frequency to activate our sense of smell. Turin tried to prove his theory by again using heavy atoms. He added heavy hydrogen atoms (called deuterium) to a molecule and took a sniff to tell whether there was a difference between one with normal hydrogen. Is there a difference? He´s adamant there is. Fruit flies agree. They were trained to hate one smell and love the other agree with him, proving that a difference is noticeable.
Since then, the theory has turned into a scientific war zone. Fruit flies can’t explain the sense of smell in humans! The human study failed to replicate the study! The latest attack of the Shapists was a paper by Block, published 2015, in which they called the entire vibrational theory “an implausible claim”. Ouch. They took the time to produce olfactory receptors on kidney cells and measured their activation to a smell. They were unable to detect a difference in activation between normal musk and heavy, deuterated musk. As a biochemist, I can tell you that this entire project took them years. You don´t just express receptors on kidney cells in a matter of weeks. The Shapists, as much as they dislike the vibrational theory, put in quite an effort to disclaim it. Block accuses Turin of using impure chemical solutions in his smelly tests. Turin hits back that the odor solution Block used was an equal to his in the way it was produced. If his solutions are impure, so are theirs. The discussion, led through letters sent to the journal PNAS is pretty nasty, to be honest. (Read up on the scientific mudfight HERE http://www.pnas.org/content/112/25/E3154.full (Turin) and HERE http://www.pnas.org/content/112/25/E3155.full (Block’s reply)!) Though Turin kept fighting, it seemed after the Block paper, that all was lost. Alas! It seems to simply have been just another battle in the olfaction war. Just a few weeks ago, a team from Trento, Italy headed by Marco Paoli found a different pattern of activation in live honeybees between the two chemicals!
I’m willing to bet that the Shapists are writing furious letters once more, angry with the fact that once again insects were used to beat their theory. (This is where I quietly cheer on the Trento team, because I believe in using simple models before complex human models, too. Also, that’s where my bee-studying friend from Bees on Crack is from! Go Team Trento!) But in total, this entire discussion has turned into something bigger than just a discussion of controversial results. We are the audience to a public struggle between David and Goliath. Turin is the typical underdog, fighting the scientific establishment. It’s hard not to cheer him on – but we shouldn’t jump to conclusions, simply because we like a rebel. We have the scientific method to determine the winner, which require a rational discussion and presentations of facts. Alas, this entire war has turned into something so emotional, that I wouldn’t want to touch it with a 10-foot pole in the lab. But it also shows us: scientists are humans, and we do get attached to our theories. And so, if the vibrational theory of olfaction does hold true, it will have to wait for, as Max Planck once said, “its opponents to die off.” It’s your turn to pick which side you’ll be on.