Restoring the sense of smell to COVID-19 patients

Jean Mary Zarate: 00:04

Hello and welcome to Tales From the Synapse, a podcast brought to you by Nature Careers in partnership with Nature Neuroscience.

I’m Jean Mary Zarate, a senior editor at the journal Nature Neuroscience. And in this series we speak to brain scientists all over the world about their life, their research, their collaborations, and the impact of their work.

In episode nine, we meet a researcher at the forefront of research into olfactory loss, who is developing implants that may help patients whose sense of smell has been affected by COVID 19.

Thomas Hummel: 00:44

My name is Thomas Hummel. I work at the smell and taste clinic at the department of otolaryngology of the Technical University of Dresden in Germany.

So it’s a sub-unit of the department of otolaryngology. We, because I’m a medical doctor, I specialize in smell and taste disorders since a long time. Since about, like about 30 years I’ve been working in the sense of smell. And since about 20 years, or a little bit longer, I see patients with smell and taste disorders.

We are a relatively small unit, about, between five and 15 people. We recruit many students, and we try to diagnose people with olfactory loss and counsel them in terms of therapy.

And we also at the same time, apart from the clinical research that we do because we want to see where smell and taste disorders come from and how they develop, we also do research in the physiology of the chemical senses, that includes like gustation, trigeminal sensitivity in the nose, and olfaction.

So, gustation is sweet, sour, bitter taste functionality. Trigeminal functionality is in the nose. It’s like burning, biting, stinging, cooling. These are all trigeminal sensations.

And olfaction, this is what we normally perceive as odors. But odors, they are typically a very complex thing you know, they, many other things contribute to these percepts.

And this all we try to investigate further. Not just here but also within the group of a very highly international group in the chemical senses.

So I guess as soon as you start to work in the chemical senses, you are automatically connected to many other people in different countries because there are so few people who take care about that.

Different when you work in cardiovascular diseases. You just look around the corner and there’s somebody who works on cardiovascular disorders. In the sense of smell it is different. You look around the corner, and there’s nobody.

Thomas Hummel: 03:04

I got into the area of chemical senses with my thesis, because I started in Erlangen, which is in Bavaria in Germany, close to Nuremberg.

And I was interested in the senses. Actually my wife brought me into that. I was one of her participants in one of her studies. And she was, her thesis was the first to investigate electrophysiological equivalence of the sense of smell, like looking at EG-related compounds.

And she needed subjects and she sort of hired me and I was one of her victims in that study. And I gladly obliged and then got interested in that. And my supervisor Gerd Kobal, he was one of the pioneers in that area. And I did my thesis with him on trigeminal sensitivity. So on pain basically in the nasal cavity, and from there on also worked in a sense of smell and so like. So I broadened in many, branched out in different areas.

Thomas Hummel: 04:16

As a child, I have no background in, no special background in the chemical senses. I think I behaved like most children. So being interested in everything, and nothing.

So this was my interest in the sense of smell only developed later. And sort of, I think this is how life is. You know, you start something and then you have to make decisions. You go left or you go right and you take a left.

And next time you take a right and in the end you end up somewhere you know This is what happened to me.

And I always had fun doing what I’m doing and at least I found it interesting. Hope this would be, maybe it’s also of some use to others. So that's where I come from.

Thomas Hummel: 05:04

The olfactory system, or the sense of smell basically, has a couple of different, at least two different pillars.

One is the olfactory system. That’s the, in a sense, the perception of odors. That resides in the nasal cavity and the top of the nasal cavity in the roof of the nasal cavity, just more or less between your eyes.

So there are about five square centimetres up there that contain olfactory receptors.

And the odor molecules that get up there in the nose, they make contact with these receptors.

First, you have to penetrate the mucus that is on top of the mucosa. That’s why it’s called mucosa, because there is mucus.

And they penetrate that, make contact with the receptors. And with a little bit of luck, they activate these receptors. And if there are enough of these receptors activated, this produces a sensation.

Because then the signals are transmitted to the olfactory bulb. That is a first relay station in the brain that is very important for olfactory processing.

It’s about like 12 millimetres long, and about 10 millimetres thick.

So it’s a little sausage that’s lying there. As a German I always like to make the comparison to sausages.

So then the odors activate this olfactory bulb. And if enough of these activations take place, then the odorous activation is then further transmitted into other parts of the brain.

What’s happening at the level of the olfactory bulb is that there is a pattern is produced. So if we perceive, let’s say vanilla. Vanilla is not just activating one vanilla cell inside, a cell type inside the cavity.

But in the olfactory mucosa, in the smell epithelium, the vanilla activates a couple of different receptor types. They produce a pattern, and the pattern is then transferred to the olfactory bulb.

And vanilla, when we perceive vanilla, behind that is the perception of a pattern that can be overlapping with other odors. But it’s a specific pattern. And this is why, when it’s about olfactory coding, we have about, probably about 400 different receptor types that are developed in the olfactory epithelium.

And some of them are activated by one odor, and some of them are activated by others.

And because it’s about pattern recognition, these 400 receptors (if you think about the combination of these different receptors), they can code for almost an infinite number of odorants that we can have an audience that we can perceive. Not name, but we can perceive them, and possibly also differentiate them.

In real life, probably we have much less odors that really matter. That’s actually a bit of an unresolved question, how many odors matter in our lives.

There’s one estimate from a study from Munich where they looked at foods and how many odors are important in foods, and it’s about 250.

So surprisingly few that really are important. On the other hand, we can perceive theoretically billions of different odorants.

So it's really quite diverse when it comes to that. But in real life, possibly, it's not so many odors that we need, or at least that we perceive consciously.

So this was one pillar of olfaction.

The other pillar is the trigeminal sense. That’s mediating, this is like mediating their trigeminal nerves, they mediating the other parts of the nasal cavity and their mediating sensations like coolness or stinging or burning or pungency.

That’s also part of the olfactory precept. So each odor that we have, odor that we perceive, also is sort of composed of an olfactory component, it’s probably the largest component, a larger component and a trigeminal component That’s a smaller part of it.

But it’s always in there. So when you think about Cinnamon, cinnamon is this beautiful, deep smell of cinnamon, but at the same time, there is a little bit of a, slight little bit of tingling in there in the cinnamon, and this is trigeminal sensation

Thomas Hummel: 09:39

When people lose their sense of smell this can have a number of different causes, like the most frequent cause is aging.

So as we get older, we, our sense of smell goes down typically. Of course there are exceptions to that. But typically we lose our sense of smell. And this is then, that's the major cause.

So if you look at people older than 80, like estimates are like half of them, or at least one third of them have no sense of smell.

This loss is gradual with time, so many people do not even recognize it, because it's a gradual loss. So (and you don’t compare yourself to as you age). I don’t compare myself, not to my students, because they…I compare myself to my wife.

So she's the same age. And as we age together probably our sense of smell was much better 30 years ago, but does not really matter, you know?

As long as we are in synchrony, she’s my peer group. So as long we are in synchrony, it’s all good. So this is why many people lose the sense of smell, and they do not even recognize it. So that’s one major cause.

The second major cause affecting olfactory loss is sinonasal disease. It is chronic rhinosinusitis with and without polyps, that’s a chronic inflammation, typically leads also to olfactory loss.

It's a gradual loss also over months and years. And at one point, it’s recognized or it’s not recognized. Then there are other causes like-post viral olfactory loss, after viral infection, or COVID, 19, which is a major driver currently of olfactory loss. It affects also younger people.

Then you have post-traumatic olfactory loss, head trauma. So thee stronger the head trauma, the more severe the head trauma, the more likely that you lose a sense of smell

Then you have neurodegenerative disease. So if you have Parkinson's disease or Alzheimer's disease, like a very early sign of that is olfactory loss.

And then you have numerous other causes of olfactory loss that is myasthenia gravis, or like drug-induced olfactory loss, or a couple of other causes.

But the major causes are aging, chronic rhinosinusitis, post viral olfactory loss, also including COVID-19, post traumatic olfactory loss, and then neurodegenerative diseases like neurological disorders.

Thomas Hummel: 12:25

The olfactory implant, the idea is fairly old. Also, I don’t know when it had been first mentioned, but I think implants that have been around for a long time, and as you see they are performed on a daily basis in the auditory system, where people receive cochlear implants.

And they also, first experiments and results also on visual implants, they work quite well, seem to be quite well working, at least in the auditory system.

They are extremely helpful to many people, not to all people, but to many people.

And the basic idea is that you have a sensor that is, in our case, the sensor would be in the nasal cavity. In the case of the cochlear implant, it’s close to the ear

And then you sense the sound, or you sense the odor. And then in our case, the odor would activate in the sensor a certain pattern, and this pattern is then transferred to the brain.

And the first realization, we will transfer that to the olfactory bulb.

There would be a wire going, or several wires going to the olfactory bulb, and in the olfactory bulb we will produce a pattern of activation. It could be like different sides of the olfactory bulb could be activated. Or could be activated with different amplitudes or with different strengths or with different durations, so that you produce a pattern that makes sense to the olfactory bulb and the olfactory bulb then miraculously does something with that signal and transfers it into the brain.

And the brain then does something with that signal. It’s basically, it’s similar things happening in the auditory system. You have a sensor that sort of senses the sounds, and the sounds, they are the signal is then transferred to the brain and the brain is doing something with this signal.

And in the end, we perceive like speech or we perceive like when people say hello, we can, we get the basic pattern and our brain can make sense out of this pattern. It requires some training also.

So you need to adjust to this signal. And then after some time, you can make sense of the signal and you can understand when people greet you and say hello, Also more complex sentences. And so this could make sense.

Thomas Hummel: 14:50

We are the very beginning. That's a project that's funded by the European Union. A couple of other parts of the team we are just one group within a team, there are people in Lyon. Moustafa Bensafi, he's the head of this is the leader of this group. Then there are people in Grenoble, And they also work with us. They work on senses. And people in Milano and in, in Thessaloniki, and in other places, and we collaborate together, and try to come up with a system that could make sense.

If you want to have a meaningful, effective implant, you want this implant to produce meaningful odors. And in theory, it’s possible.

There’s also first studies that indicate that we can with electrical stimulation, we can produce, we can elicit meaningful odors. There’s one elegant work by Eric Holbrook from Harvard, and when you stimulate the olfactory bulb through the bone, and three out of his five patients, they had sensations they were odor-like sensations.

And this is the one of the bases that encourages us to pursue this idea that with electrical stimuli, we can trigger odors, we can elicit odors in the brain.

How it will pan out in the end we do not really know. But also the parts that are needed for that system, they are available. So the senses are there. Based on the principle of the deaf in established cochlear implants. Could be similar implants also performed inside the nasal cavity. So they could be connected to the olfactory bulb, and there could be, we could elicit a pattern.

And this pattern then might make sense to the brain and we would be able to perceive potato chips at the end of the day.

If it does not happen, if you only perceive something smoky. Regardless of what I present to you like whether it’s vanilla, or potato chips or a piece of steak, then it would not be so useful.

But that’s something we will have to find out. And I think at the moment many people are quite positive that this can be something that could be helpful or see in daily life. And then this would make sense.

Jean Mary Zarate: 17:36

Now that’s it for this episode of Tales From the Synapse. I’m Jean Mary Zarate, a senior editor at Nature Neuroscience. The producer was Dom Byrne. Thanks again to Professor Thomas Hummel. And thank you for listening.