An artificial nose

The renown olfaction researcher Stuart Firestein praises himself for not having excellent smell. Strange perhaps for someone who tries to understand how our noses and brains perceive odors. “Not at all”, said the professor during a colloquium he gave at the Kluyver laboratory last month. “My lab can be very stinky. It is good that I’m not overly sensitive to odors.”

Firestein was invited by Prof. Luuk van der Wielen to give a guest lecture about his research on vertebrate olfactory receptor neurons. For all those who had watched his 2012 TED talk about ignorance – “not to confound with stupidity” – it came as no surprise that he enjoys spurring his audience with jokes. According to Firestein, scientists talk way to much about what they know, whilst the things they don’t know are what really matter. He likes to cite James Clerk Maxwell, saying “Thoroughly conscious ignorance is the prelude to every real advance in science.”

One thing many scientists in Firestein’s research field are ignorant about, though maybe without consciously realising it, is the function of mucus in odor perception. Whilst trying frantically for decades to decipher the role of olfactory receptor neurons, the specific research topic about mucus had pretty much been ignored by olfaction researchers. During his lecture Firestein said that he would like to work on this topic together with TU Delft.

Why do you think snot is important for smelling?

Firestein: “When we measure the threshold concentration needed for a chemical to be picked up by neurons, it appears that the concentration is ten times higher when we do such experiment in a Petri dish then when we do it using a live animal. People attributed that difference to the fact that a different technique had been used.”

Couldn’t that be the explanation?

Firestein and Van der Wielen start laughing. “Really, believe me, scientists have been sweeping this topic under the rug. The mucus traps chemicals. I think it functions like the lens of an eye. Or like hair on skin that help you feel little insects walking on the skin of your arm.”

Why do you want to work together with TU Delfts bioprocess engineering group on this matter?

Firestein: “Our expertise is complementary. The idea of our collaboration is to bring our fields together; psychophysics and the physiology of the body (my two fields) and Van der Wielen’s field, the physics of transport phenomena.”

Prof. Van der Wielen, as a bioprocess engineer, you focus on technologies that are relevant for industries, like the oil industry and the pharmaceutical industry. This is something completely different.

Van der Wielen: “I believe it is important to sometimes look outside one’s usual research domain. It can lead to new insights. We once did a research on wine gums. We tried to find out how these sweets obtained the right elasticity. It shouldn’t be to snotty but not to hard either. That research helped me understand how the grains in a gas chromatograph (a machine used to separate or analyse gasses and liquids, red. TvD) shrink and expand which ultimately leads to the demise of the gas chromatograph.”

What should we make of this collaboration?

Van der Wielen: “We will start off with a student project. The student will focus on the extremities of the olfactory receptor neurons, the cilia, that stick into the mucosa. He will thus make some kind of devise with lots of mucus, an artificial nose if you want. You cannot take out a little piece of a real nose and use that as the mucus will evaporate. It is really quite complicated. The idea is to put that artificial nose under a fluorescence microscope and see how olfactory molecules are transported through the mucus and trapped at places. It all has to do with transport phenomena in the end. Just like the wine gum research. As a matter of fact the student will first do numerical studies using a model from the wine gum research.”

Prof. Firestein, what do you find fascinating about olfaction?

Firestein: “It is the only sensory system that has no spatial distribution in the brain. Vision, touch and sound are all spatially distributed in brain. Our brain recreates special maps to process these senses. But how does our brain create an image of chemicals? It is not as if we process aldehydes in the left brain half and ketones in the right. Olfaction is sort of a puzzle. Puzzling also is its extreme sensitivity. We can smell the difference between one carbon atom. Heptyl acetate gives you the distinguishing odor of pear while hexyl acetate, which has one carbon atom less, will give you the odor of banana. How  the hell can we distinguish molecules that differ only one atom?”

During your speech you also mentioned your fascination for the connection between memory and odors.

“Yes this is well described. When we are emotional our olfactory senses are higher. That explains how odors can bring up memories. One of my post docs, Ricardo Aranedo, stimulates brain tissue with odor. He then looks at the synapses. Do they strengthen or weaken? When he adds adrenaline he sees that the connections strengthen.”

What can we do with that knowledge?

“It can help us gain insights in how to forget, which is interesting for people who suffer from posttraumatic stress disorder. We can learn a lot from sheep here. We humans can’t tell sheep apart, yet apparently nor can they. Not by sight that is. They do it by smell. The first thing a sheep does after it has given birth is lick the calve and the placenta. Every lamb has a very distinctive scent. But within a couple of months she forgets the odor. How do sheep do this? I’m thinking of applying for a grant with a proposal entitled ‘How do sheep forget?’ Though I’m not sure generals will get the meaning of that straight away.”