Daniel and Kelly’s Extraordinary UniverseThe science of taste and smell (with Steven Munger)
Daniel and Kelly talk to Dr. Steven Munger about phantom smells, stinky shirts, careers as a "nose", and more.
All right, So I have a follow up question there. First of all, am I correct in interpreting your answer is saying that bitter tastes are learned tastes and therefore more sophisticated, And therefore we have scientific evidence that dark chocolate is better than white chocolate, for example.
That may be a stretch.
I'm taking that as a yes, and we're moving on.
Hi.
I'm Daniel. I'm a particle physicist. And I remember the first time I smelled California. Hi.
I'm Kelly wider Smith. I'm a parasitologist. And I remember the first time I felt the wind on my feet as I put on my sandals when I got to California for my PhD interview, And I remember thinking, I'm never going to leave here because it was snowy and cold and miserable in Ohio, and I just loved that I could wear my chockos. But I did end up leaving. But I don't remember the smell. What was the smell of California?
And now I'm worried the smell is wind from other people's feet.
Well, that doesn't sound very nice, and I wonder so many people are leaving California No.
I used to visit my grandfather in Los Angeles when I was a kid, and I remember walking out of the airplane into Los Angeles and smelling it, and in my memory it's got sort of floral notes to it and a little bit of sea salt or a little bit of something from the ocean, because I learned in this interview you can't actually smell salt, but there's definitely something about California. And when I returned later to interview for a job, I remember getting off the airplane, this time in Orange County and having that same scent memory transporting me back to my childhood in those summers in Los Angeles and being like, hey, this could be a place I live. I like it here.
Yeah, I remember when we lived in Santa Barbara. I did love the smell of Santa Barbara. But I think that's mostly the smell of the ocean.
And what is the smell of the ocean. What are we smelling in the ocean? Is it fish? Is at al g Is it fish poop? What's going on there?
It's probably algae dia. Tom's Yeah, I don't know. Maybe I don't want to know. Maybe I enjoy it more not knowing what is your favorite scent?
My favorite sent that's a great question. I'm not sure what my favorite is. But up there is the smell of onions and garlic in olive oil. You know, when you start cooking something delicious and that smell hits you, I'm like, hmm. Sometimes I feel like they should make up perfume, you know, because if I want on a date with a lady and she smelled like onions and garlic and olive oil, I'd be like.
Ye, marry in a very wholesome way, right right, right, here's the ring. Yeah, that is a good smell. That always laughs because whenever he cooks I come in and go, oh, it smells great. He's like, every time you say it smells great, it's the same thing. And I'm like, well, I'm consistent. It just still smells great. I love it.
There you go, And so what are your favorite smells?
Kelly love the smell right after a rain, and I think that has something to do with bacteria and some other stuff. I don't need to know. It just smells great. And then I'd love the smell of rosemary. One of the things that I loved about the place that I lived in Davis, California. Is that there was a rosemary bush and every day before i'd go to school, I'd pull a bit off and snap it and smell it before I went out. And then lavender and eucalyptus. Those are very relaxing smells for me.
We have a whole hillside that's been colonized by a rosemary bush, and when the sun hits it in the afternoon, that wafts over. It's like overpoweringly amazing.
Oh, that's fantastic. Life is really good.
Sometimes life smells amazing.
Sometimes it does. It didn't in grad school when I was jumping into dump trucks full of dead fish. But there have been plenty of good smelling parts of my life and I'm in one of them now, which is great.
I'm very glad your life doesn't stink.
Thanks. Yeah, I'm glad your life doesn't stink either.
Yeah.
So on today's show, we have my friend Steve Munger. He is an expert on smell and taste, and I have asked him all sorts of stupid questions in the like five plus years that I've known him, and I am super excited to do that again today. So let's go ahead and bring Steve on the show. Today's show we have doctor Stephen Munger. He's professor and co director of the Center for Smell and Taste Disorders at the University of Virginia. Welcome to the show.
Thanks so much, really join the invitation.
I'm excited that I get the chance to chat with you again. We've interacted a couple times about all sorts of weird smell and taste topics, and I'm excited to bring to our listeners your sort of weird knowledge on smell and taste, weird and wonderful.
Thanks. Yeah, it was one of those instances back in the day when Twitter was a lot more about finding each other and getting interesting information. So it's a good result.
Yeah, yes, yes, Back when I used Twitter, we met Steve. I had a question for him for our book soonish and we've been in touch since.
So, Steve, You've got to ask do your family and your kids describe your work as a professor of everything stinky and delicious?
No, No, they don't, or at least they haven't until this point.
But I always love getting the chance to ask you about smell and taste stuff. And let's start with sort of a very basic question, how well do we understand smell and taste? Like, do we understand it microscopically?
We do, I would say we're still a bit behind vision and hearing as far as our understanding of a lot of the basic biology of it. But it's come a long way, especially in the last thirty years. We know what sells in the nose, which sells in the tongue, detect odors and taste. We have a good sense of everything from the protein receptors on their surfaces to the way they connect to the brain and start to organize signals, so that we can actually make sense of our detection of all those chemicals that are in our food or in our environment. But it's still a lot left to be worked out, particularly in the way that one distinguishes different types of odors or tastes, or conversely puts them together, because of course, you don't really encounter single odor molecules, which we call odorant or single taste molecules, except yeah, vicetherian cotton candy, you're getting pretty much pure sugar, But usually you're encountering them as mixtures. A flower has hundreds of different compounds that you're smelling at the time foods have tastes and odors that your brain is trying to put those signals together. So how we pull apart the different components and then put them back together so our brain can make sense of them and we can then react in an appropriate way. There's still a lot of questions in those areas.
And so for vision, we have something of a cartoon understanding, at least I do of how this works. You know, photons hit these proteins in your eye, they get absorbed, they flip some switch, they send a signal of your optic nerve. Your brain gives you an experience of a color. Do we have an analogous picture for smell and taste? Can you walk us through microscopically what happens from when that cotton candy molecule hits your nose or your tongue. What's going on?
Of course, it depends a little bit on whether you're talking about vertebrates or in vertebrates. There are amazing amounts of similarities in the organization, but a lot of the molecular players are quite different.
Do invertebrates like cotton candy.
Most insects and others like sugars are attracted to at least certain types of sugars, and they will avoid compounds that we perceive of is bitter. But how they do that can be a little bit varied. If we think of smell, what we're working with are millions of cells in our case and sort of the roof of the nasal cavity. These are neurons nerve cells that have one end projecting out into the environment, basically within a mucous layer within your nasal cavity. So when you sniff something or when odors come back from your throat while you're eating and get up into that nasal cavity, they bind with receptor molecules that fit into the family known as G protein coupled receptors. So these are ones that recognize the odor molecule and then initiate a biochemical cascade within the cell that changes the electrical activity of that sell. Those nerve cells then send messages back through the skull to the brain where they interact with nerve cells of the brain and create this process.
So folks like me who are not adept to chemistry, I want to understand what you mean when you say recognize those molecules, Like I'm imagining some molecules sticking up above the mucus and another molecule comes along, and if they have the right sort of shape and electrons in the right places, they can bind together. Is that what's happening, Like they're interacting chemically.
Exactly, So we'd call it docking or binding, where the odor molecule actually fits within a pocket that is formed by the protein strands of the receptor and causes a conformational change. The receptor protein changes its shape, which allows it basically to flip a switch inside the cell, so it's working across the membrane to initiate this cascade. And then one interesting thing about how we perceive ots, there's not a particular receptor just for this molecule and just for that molecule. In humans, we have about four hundred of these receptors. In rodents could be one thousand, fifteen hundred, depending on the species. But even with those numbers, you can imagine that would be a pretty limited repertoire of chemicals you could detect if it was really that one to one thing. What it turns out to be is that each receptor generally can recognize a number of different molecules. Oftentimes they may even be chemically distinct in their structure, and each individual odorant molecule can bind two multiple receptors, and so what you're getting is really a pattern of activation. The molecule A may turn on receptors one, five, and six, molecule B may turn on receptors three, five, and six, and that, because of the way those receptors and cells that express them are connected to the brain, gives you different patterns of activation that you then learn to associate with molecule A or molecule B.
So let me see if I'm understanding The picture I was imagining before was something sort of like a lock and key mechanism, where you know, the dog poop molecule floats up and connects with something in my nose and is able to connect in and activate that and as you say, actually change the shape of that which triggers some signal down the brain. But now you're telling me that, like, there are lots of different keys that can turn that lock, and that one key also can turn multiple locks, so that everything in our environment can turn on several signals, and that each signal can actually be turned on by several different kinds of things. So dog poop and cat poop might turn on the same signal, but they also might turn on a different combination of signals.
Absolutely, you got it.
Yeah, So you know when I look around my room, there's lots of different wavelengths, lots of different colors hitting my eye. Is smell more complicated vision? And does the brain process it in different ways?
I don't know if i'd say it's more complicated, but it is a little different, particularly because there's a bit of a learning aspect. You're not born knowing what the utterance of pizza is. You smell the pizza and your brain certain number of receptors are activated by those odor molecules that come from the pizza your sniffing, and you learn that that pattern of activity means pizza, while another one that may have some but not all of the molecules in common means rotting fish. And you know what to do with the mind because there can be.
Overlaps, especially if you're a baby in Iceland and they like rotting fish pizza.
Right, My PhD involves a lot of rotting fish.
Yeah, just in Iceland. This summer for our conference, which is fout, I did not eat in any of the rotting fish there though.
Beautiful country, the beautiful country, wonderful people.
Yes, oh it's stunning, stunning.
So, Steve, you know that there's a common philosophy question which is also a staple in dorm rooms at three am, which is like, when I see red, do you see the same red? How do we know? And what you just said suggests a similar question about pizza, like when I'm smelling pizza, is somebody else experiencing the same thing? And my understanding is that the qualitya of seeing red, or the quality of experiencing that signal from your nose is something we don't have a great philosophical handle on. We don't know how to compare. We can't experience somebody else's internal subjective experience. Is there an equivalent question for smell? You know? Is there this sort of marry in the red room philosophical study about smell and taste?
I think from a practical point of view, you can say, indeed, people have different perceptions of the same odor mixture, and one of the classic ones is slantro. Some of you might really like slantro and like sort of that green grassiness, of a brightness of it that it can add to foods, and others may hit it and say nope, that's soapy. That ends up being less likely a genetic difference in one particular odent receptor that seems to be changed in its responsiveness to those soapy odor components. Those people who get the grassiness as the primary b versus get the soapiness is the primary odor component, are differing in the ability of their odor receptors in their nose to respond to that array of chemicals. So the chemicals are the same, but the way someone's perceiving it, and of course the way that impacts their interest in ingesting that changes quite a bit. They're also what we hit a variety of other genetic variants we call specific anosmias, and these are ones where you may have a mutated odent receptor that is the primary receptor for particular compound and you just can't smell it and someone else can't. So endosternone, which is a pig pheromone from male pigs, but there are related chemicals in it they're using cleaning products and other things, is a classic of that. There are a lot of people, myself included. You can put a big vat in front of my nose. I have no ideas there, and there are other people like my wife who get even remotely close to it, and you know, oh my god, that's awful. And there are those types of genetic differences. We did a thing with a bunch of winemakers recently and spiked identical wines, one unspiked one with another compound called rotundo in, which is a black peppery odorant, and there were maybe twenty percent of the people in that room that could not actually tell the differences between the wine, even though in that case I could, and it was quite pronounced pepperiness. From that respect, there are differences now that is a little different than what you brought up with the are we seeing the same red wavelength getting the same perception of what red is? Although if I recall, there is a fairly common mutation in the green cone option that actually shifts the wavelength response a little bit in that and so in that case you can imagine two people seeing slightly different shades of green. But still I go, that's the grass on.
And so as somebody who is director of a center on smell disorders, would you categorize somebody who can't appreciate cilantro as having a variant or like an issue, like a disorder. I mean, this is something we need to treat. All these folks out there are like missing out on one of the joys of life.
Colleague of mind Doron lance At once made the statement, no one is norma osmic. We all different. That there are four hundred potentially active odent receptor genes in the human and all of us probably have one or two or maybe more that are mutatd in such a way that that changes the way that we respond to the molecules that those receptors would normally spawn to. So we're all seeing something a little different. And I do think that that is distinct from people who have a smell or taste loss, or distortions or phantoms that disrupt their ability to really more globally interact with food, interact with each other, perceive the world around them, or have sort of underlying long term off tastes or equal smells or other things that their brain is constructing. Those are the ones where I put them into the category of disorders, as opposed to we have blondes and brunettes and blue eyes and brown eyes and that's more of what I've put a specific in osmia.
So you mentioned wine. I enjoy wine, but when I read the descriptions on the back, I call both. When I read the back, I'm like, what percent of people who drink wine can taste all of the notes that are listed on the back? Am I in my or the majority of not being able to appreciate a complex flavor profile.
I don't know if you are in the minority majority. I can't say that. I am certainly is hugely skilled as people that do that professionally, But part of it is also training. I mean, certainly a summer or winemaker or brewmaster or whatever generally going to have a pretty functional sense of smell and taste in order to be able to get most of the signals that they want to be able to perceive. But the ability to sort of pull out strawberry and lead pencil and black current and whatever others. Part of that is because there's been a standardization of the naming of certain odor perceptions. In the context of wine, beer has its own beer wheel, coffee has its own coffee wheel, so that when someone says lead pencil, they are describing pretty close to the same odorant molecules present there that someone else is. They're trying to make it a common language using more descriptive things rather than saying Islam molassatype or whatever other chemical name you might want to come up with. The other thing that people are really skilled is they practice a lot. This is a attention to detail, This is memory, This is like learning the language. All those aspects go into it too, that allow you to sort of focus on. So if you get someone who trains you that, Okay, these six ones all have this flavor of characteristic and those six ones do not, it becomes a lot easier to start to pick them out, and then once you've done that, it's easier to recognize it as well. So I think it's more practice.
Than anything I need to switch jobs.
I think that probably also tells us something about the experience of these smells. You know, you're training somebody to recognize as certain responses. You're helping distinguish between black paper and current and whatever. There must be a lot sort of in the neurobiology of smell behind you know, the actual chemistry of the receptors as well.
Yeah, which is an interesting contrast with taste in some ways. And that taste is much more innate. You give babies sugar, they're going to smack their lips, and if they're old enough, they're going to smile and they're going to want to eat more. You give them something that's plain bitter compound, they're going to scrunch up their face and put their tongue out and try to sort of spit it out. And they're born with that. I mean, we learn over time to give context to that. We learn that in some cases bitterness is not definitely poison. If it's our French rose coffee or our ipa beer or Belgian and dive or whatever it might be. We learn that we can appreciate that as part of a complex flavor profile in a safe way, but innately bitter being spitted out and sweet meaning go ahead and adjust it. There's an energy source.
There, all right. So here we have a question from a listener that actually inspired this whole episode. So let's go ahead and listen.
Hi, Daniel and Kelly. I had a question growing up and going into the woods. I was always told that if you put a plant in your mouth and it's bitter, spit it out, because it's likely poisonous as an adult. This raises questions in my mind, why are poisonous plants bitter? Did humans evolve the taste of bitterness exclusively to the tech poisonous plants? But then you got the question of coffee is bitter and we all know how that goes in the morning, But how bitter is too bitter to be poisonous because we know everything in moderation. And then there's the did the boy scout leader just tell me this because he didn't want to see what all of us were trying to put in our mouth because we were super kids. But I have this question. I was hoping you could help me out and figure out why are we able to detect poison as bitterer?
Thank you very much. We think that the sense of bitterness has evolved in order to avoid toxins. That seems to be common that compounds that we would perceive of as bitder are also aversive to a lot of other animals, even if they're not using the same protein molecules to detect them that mammals are. So that's very common. But obviously we can learn in context that bitterness may also be something that can be attractive if it's put together with other things that we like. Coffee is a good example. There are a lot of compounds in coffee, including caffeine, that on their own are bitter and you would not like them. No one would like them. Put in the kind of coffee, not only do you have the appealing aroma of coffee, the pharmacologic buzz of the caffeine. The fact that you enjoy going to the coffee shop with your friends is a part of a ritual every morning. The fact that you don't see a bunch of dead people laying around that coffee shops they've just been poisoned. All these things give you context that tells you that in that particular situation, the bitterness is positive and a lot of people learn to like better. I like darker roasted coffees and I like highly hopped beers. That it's appealing to me. But if I took those compounds in and of themselves, out of that context, I wouldn't. So that's definitely the case. It's interesting that both for the receptors that respond to sweet and umami or savory tastes amino acid tastes as well as to bitter tasting compounds They're not restricted to the taste cells of the mouth, the ones that actually lead to taste receptions. They're found all over the body. Bitter receptors are in the gut, they're in the heart, they are in the thyroid gland. And there's a lot of question if are these proteins potentially responding to ingested toxins and then allowing for some sort of physiological protective response if you start to build up too much, or could they be just repurposed in a way that allows the same protein to respond to indigenous signaling molecules within the body and also be used when it's connected up to the taste system, to be used for detecting bitter tastes.
All right, follow up questions there. First of all, am I correct in interpreting your answer is saying that bitter tastes are learned taste and therefore more sophisticated, and therefore we have scientific evidence that dark chocolate is better than white chocolate for example.
That may be a stretch.
I'm taking that as a yes, and we're moving on. My real question is a comment on the idea of having smell receptors in the gut and in the heart. And other places in your body as it relates to the experience of smell. Is there a possibility that we are experiencing those flavors in our gut or in other parts of our body and it's contributing to our experience. Are we tasting inside our body?
That's a very common question. The answer is quite conclusively no.
Oh man.
So I'll give you example. So the sweet taste receptor, this is a protein. It's actually a protein complex called T one R two T one R three two members the type one taste receptor family. These in the mouth. They are responding not only to sugars, but to anything that you perceive of as sweet. It actually activates this protein complex. It has lots of different binding sides differently, so synthetic sweeteners like aspertain so the blue packet saccharin, the pink packet, sucrolos, the yellow one proteins that are found in a number of tropical berries and fruits that are highly potent, thousands of times more potent than sugar. Lead. One reason the kids eat lead paint is lead acetate taste sweet, and that activates that same receptor. So all of those compounds are giving you a perception of sweetness because they turn on that receptor. That same receptor is in your gut and specifically in a population of cells called ntraantigrin l cells that are involved in glucose responses, allowing your metabolic systems to respond to the ingestion of the sugar load. So let's go back to cotton candy. You eat that cotton candy, the sugar goes through your digestive system down into your small intestine. Those glucose molecules now interact with the sweet taste receptor, the sitting inside surface of your intestine. That triggers a response that elicits, amongst other things, a peptide hormone called glp one glucagun like peptide one, which probably everybody now knows about because of ozembic and govi, which is basically mimics of that peptide, and that pep pi can then act on the brain, It can act on the pancreas to adjust the insulin release and satiety and things like that. So the receptor is mediating that physiological response in the gut, it's mediating the detection of taste in the mouth. But why is it not giving you taste in the gut. It's because the nerves that connect that part of the gut to the brain go to a different area than the nerves that connect the part of the tongue. So how you are detecting it is the same. It's the same lock in those two different places, but the doors that they are in are very different.
So Daniel and I will asking you questions have been alternating between saying smell and taste, and we haven't been consistent, But those are different. How does our body respond to smell and taste differently? Or is it okay that we're being sort of loose with those terms.
No, I think it's something we do want to distinguish, and maybe it's good to briefly define them explicitly. So smell is going to be at least in humans. The detection of volatile chemicals, whether coming through the nares of your nose the front, or as you sniff, that would be called that orthonasal faction, or as you're chewing food or drinking drink. Otor molecules that volatize can come up back through your throat and enter your nasal cavity. That way, we call that retro nasal olfaction.
From the back, and volatile just means it goes into.
The air, and volatile just means it is light enough to go in the air. Okay, the receptors are all in the nose. In lower primitive mammals, you're going to have also another variant called the vomer and nasal organ. This is part of the accessoril factory system that can not only respond to some volatile chemicals, but also peptides can serve as olfactory stimuli.
There So the vomero nasal organ. When snakes are sensing their environment, they stick it into the romero nasal organ to like figure out cent trails. Is that right? Can we go a little more into detail about what that does?
Yes, so snake's doing it a little differently. It tends to require contact in mice. In rants, the mouse will generally stick its nose right in whatever that odor source is, whether it's the glandeurth, secretions of a mate or a fool of urine or what might be. These are often social signals that can be sex or aggression, pheromones or predator cues or such. There's within the vomer a nasal organ, which is just adjacent to the nasal cavity. There's a blood vessel that will pump those molecules into the organ where they can interact with these specialized olfactory neurons in that goes back to a slightly different part of the brain. Humans don't have that organ, so it's a little bit different. So you have all those and those are all located in the nose and they project to specific areas of the brain. Taste is very specifically the detection of non volatile compounds like sugars and salts, and acids and amino acids and a variety of compounds that can be perceived of the spinner. They activate cells that sit within taste buds for the most part, which are basically just little onion like collections of cells, and those are on the tongue, certain taste papillo, some of the bumps in your tongue, and they're also in the soft palate in my favorite German word, the geschmack Strifen, which is the taste strip, which a bunch of taste buds in the soft pealet and then there also are some in the varyingx throat. Those are connected to different parts of the brain. Specifically to the brain stem, and that's carrying taste information. There's a third chemical sense both smell and taste or detecting chemicals. The third chemical sense is known as chemisthesis, and chemos thesis is one you probably haven't heard the name of, but you've experienced, and that is when chemicals that are often in spices or herbs will sort of hijacked sensors for temperature or pain or vibration. So capsayasin and a hot chili pepper, menthol in, mint, santial in, sesshue, peppercorns, these are going to basically be naturally current chemicals that make this is generally trigeminal nerve sensors feel like they've been activated. So capsaicin makes it feel like there's warmth there even though there's no change in temperature because it's turning on a heat receptor. Menthol is cooling because it's turning on a cold sensitive receptor.
Did you say there was one that triggers a sense of vibration.
Yeah, the sansial in such one peppercorns, which are actually flower bites, give see this little tingling aspect to it.
I see, So it's different from capsas and it's not a warm.
It seems to have a bit of a warmth aspect to it as well. So some of these can be working across but their compounds in ginger and compounds and eucalyptus and all these types of that will do this type of thing.
And is the chemical mechanism the same, the sort of lock and key structure the same for all these different kinds of experiences.
They are, although in these cases they're primarily attaching to ion channels, which are proteins that can be bound by an external chemical But then they open up and they let charge particles fly across the rent, so they're not triggering an intracellular biochemical cascade. They're actually changing the electrical properties of the cells directly. So just different families proteins, but they do all come together in this all comes together in the brain, and that's what we call flavor. So flavor is smell plus taste. You can bring chemosthesis into that. You can also impact flavor by site. For example, if either you remember crystal pepsi or any of these clear colas that came out a number of years ago. One of the problems was is you looked at it, you expected a seltzer or a sprite or whatever or not, and then you drank it and there was a real disconnect between your expectation and what your taste and smell was telling you. So sometimes those visual cues temperature, and other things can impact how your flavors perceive. But one of the big term confusions is how I would say the general population uses the word taste versus how we face as smell scientists use it. When we as scientists use it, we mean just those limited sweet, sour, salty, bitter, umami tastes happening in the mouth. Patient comes they've lost their sense of smell. They may say, I can't taste anything. It all tastes really flat. If you were to test them with putting sugar on their tongue or salt on their tongue, it probably would work really well. But what they've lost is the complexity of flavor that comes from the odors that arise from those foods. The ability to distinguish a lemon from a lime if you're not looking at the color of it, is not because one is sour and one's not sour the most sour, but one has a different complement of ettererant molecules than the other that gives it a subtly different perceptual flavor.
You distinguish smell and taste in terms of whether or not the things can volatilize. Is that just because it determines where it lands, like on your tongue or on your nose, or is there fundamentally different sweet receptors there? For example, to make a concrete is there a smell of salt? Like salt doesn't volatilize. You're sitting in front of a crystal of salt. You can't receive any salt molecules on your nose. Obviously, you lick it, you taste it, But is there a smell of salt if you could like pulverize the salt and sprayed against your nose, would you notice anything?
Basically, no, there's not. I mean people often if you ever looked at Terminado sugar, you know that's a raw sugar. This hasn't been really refined. It has an aroma to it, but that's sort of the leftover molasses and stuff. If you were to get pure sucrose or pure sodium chloride, and you do, there are no contaminants. They're really not going to give you a smell. I mean, if you could somehow create a spray of individual sodium chloride molecules, I guess there wouldn't be anything specific, because that would be a molecule that would probably impact every single receptor. Wow, I'd just give you a background blur.
So if you had to lose your sense of taste or your sense of smell, which would you rather.
Lose smell easily?
Wow?
Really?
And that's not because any way just diminished. I don't want to lose either of them. Yeah, people who I would say I would probably rather lose sight, er hearing than smell or taste. Once again, I don't want to lose any of them. The reason that I put taste at sort of the top of the list of not wanting to is because the people who really cannot taste, it's much less common than people losing the sense of smell. I've actually met someone who actually born without a sense of taste, and one thing that they sort of routinely describe is just how hard it is to eat. I mean, even to swallow food. Everything becomes very texturally driven in the mouth, so soft foods are really hard to get down and it just seems like a real challenge for them for whole life.
Wait, so soft foods are unpleasant without taste, is that what you're saying.
Yeah, there's something about without having that taste, but it's just purely the texture impact. The yogurts and cotta cheese. I mean, not that I want to eat cottage cheese anyway, but oh, these things aren't just very difficult. So usually what they will do is they'll try to add texture to it, which is to make any time with a sensory loss, if you can make things multisensory in other ways that help to offset some of those losses. We say that for people with smell disorders, explore adding different spices, adding textures, adding color to your food to make it more palatable, enjoyable. You're never going to hundred percent offset the loss of the ability to smell the aromas, but you can get it closer. A lot of South Asian food oftentimes are very popular with individuals who have lost their sense of smell because of the spices.
So you're saying, crunchy blue cottage cheese is a better experience than white, soft cottage cheese.
Yeah, but that's a low Baruch.
Let's take a break and we'll come back and talk more about smell and taste.
So this helps me understand a question I wanted to ask, which was about what happens when we get a cold and our nose is plugged up and things taste like cardboard. So I'm guessing now from your answers before that my taste hasn't changed because I can still put my tongue on things, but my sense of smell has decreased, and so my flavor experience has changed. So I can still technically taste things when I have a cold, but I'm not getting the full experience exactly.
You're losing You're having diminished flavor perception while your taste is the same. But that's being technically how we use it as opposed to the way most people would colloquially describe it. So that's having diminished taste. But yes, taste and smell are differentially affected. There are a variety of reasons that people could lose sense of smell, sometimes very temporarily, like just having a head cold where you're just clogged up and so the outer molecules can't get to where they need to go. Sometimes it's because of shorter or longer term damage, everything from viruses to inhale toxins or pollutants, sino nasal disease. It may cause inflammation, allergies, head trauma, early stages Alzheimer's, Parkinson's, and other neurological generative diseases.
Exposure to the swamps of Virginia Daniel.
If I could just intruct it, are those things like messing up the shape of the receptors, are messing up the connection between the neurons that talk to your brain, or maybe it's a combination of these things.
They differ. So for example, loss of smell is one of the earliest signs of what we call idiopathic or typical Parkinson's disease, even before some of the motor symptoms. While we don't know exactly how it's happening, what seems to be the case is areas of the brain that are affected by Parkinson's. Some of the earlier areas to be affected are ones that are important for dealing with smell, So that's happening in the brain, not in the periphery within the nose. Contrast that with COVID nineteen, so we'd known for long time that a variety of viruses, common coronaviruses that can cause common cold, rhinoviruses, abnoviruses, influenza, they could in some people will lead to temporary or permanent smell loss. In COVID was really striking how many people were losing their sense of smell very rapidly, and the large number of them, probably about ten percent, may never recover that spell that they lost, which is really hard for them to deal with. But we do know something about how that virus is causing this disruption. And so in the tissue in your nose where those sensory neurons are sitting that detect the odors, that's called the olfactory epithelium, there are other cells there that support those neurons actions. There are supporting cells called sustentacular cells that are sort of balancing the environment. They may be putting out certain molecules in the area. They're providing support to the whole tissue. There are glandular cells, there are stem cells that are allowing the tissue throughout your life to constantly regenerate. It turns out that the virus doesn't directly attack the sensory neurons tacks the supporting cells and the stem cells, and in some people that attack, that disruption of those cells is going to be temporary enough the cells, some of them, survive. The neurons aren't damaged indirectly enough to not be able to recover. Maybe the neurons are wiped out, but the stem cells are intact and they're able to regenerate the tissue in a few days or weeks. But in other people the damage is extensive enough that that does not seem to be the case. But it is a sort of an indirect attack by the virus on the olfactory neurons, rather than the neurons.
Themselves be dead.
Other viruses may work differently, but it is that peripheral damage that's the issue. Now we also know that in a small number of people there seem to be true taste effects and even chemosthesis effects. You may have send videos of people saying, oh, yeah, I'm chewing an onion, or I'm going to just shovel garlic into my mouth, not perceiving.
It at all. We don't know why or how.
The virus was affecting taste or chemosthesis. Those losses did seem to be temporary. I'm not aware of long term losses in those senses.
So I have a friend she lost her sense of smell, and then when it came back, she was smelling things that weren't there. Is that common and what causes that?
That actually is very common. So if we think of smell disorders, we can break them into two different categories. One we'd call quantitative disorders, So this really a reduction or complete inability to detect or perceive odors, and the others are qualitative someone changing the quality of the smell. And we can break those into two different groups. Parosmia is distorted smell. So someone put a flower in front of your nose, you smell, and it smells like garbage, and that's you can imagine not good. Phantosmia is the perception of smells when nothing is there. I smell smoke, I smell sometimes luckily those are pleasant smells, but more often, like with the prosmea, they are unpleasant smells as well. Well.
You mentioned fecal phantoms earlier that I have to follow up on.
Yeah, equal smells, garbage smells are ones that are very common. These often not exclusively, but often will come sort of as the system is trying to potentially repair itself. We see someone's getting they've lost their sense of smell, so they have an osmia with no ability smell, or hyposmia reduce smell, and that sense of smell is coming back. But during that time, parosmia or phantosmia emerges. And while we don't absolutely know the cause, it may be as the system's trying to rewire itself whenever the brain is getting miss signals or creating signals looking for them when they aren't fully coming from the nose. So that is unfortunately pretty common.
And why don't we understand the cause? What's hard about these studies is it that we're talking about humans and brains and you can't just do whatever experiments you want.
I think there are a couple of reasons. One is that the senses of smell and taste were very much neglected from a medical point of view for many, many years. The loser sense of smell, you go to the doctor if they even knew anything about it, because they don't get taught about it in medical school to any meaningful extent. They might say, oh, that's too bad, You're just gonna have to live with it. Or nothing we can do about it and sort of getting passed off of that there wasn't a lot of attention to it. The other is, for those qualitative disorders parosmi and phantasmia, we can't measure them in any objective way. We have tools to measure smell loss, the variety of psychophysical tests that we can do that can allow us to quantify how sensitive you are to particular odors. With parosmia and photosmia, we are entirely relying on the patient being able to describe it and sort of related. We just don't have the tools to investigate it nearly as well as for smell loss.
You mentioned that the phantom smells tend to to be like garbage or feces. Is there any hypothesis for why bad smells are what comes first? Does it represent anything about, like, you know, evolutionarily, smells that clue us into the presence of like disease causing agents are more important, so we put those online first, or who the heck knows?
I think it's both of those that you gave. What I'd say, it's probably the leading hypothesis about it that avoiding bad is more important, So it sort of faulse to that, but there's really no evidence to support it, just as the one that seems to make more sense. But yeah, we just don't know.
And what about on the other end of the spectrum. I remember hearing when I visited a perfume factory once in France that there are people who are like super smellers, and you know, their job is to like distinguish these smells and design new perfumes. And there's like a very small number of these supernoses. And also that their noses get tired, so they can only work for a few hours during the day and then that's spend the rest of the day on the beach recovering from all this, you know, difficult smelling work. Are these people real? Oh's the whole thing a scam? And how does your nose get tired?
They are real? Yeah, Generally their professional term is a nose professional nose. And much like we were talking about earlier about Sammie's and others, they've been trained. They certainly have a good sense of smell. They probably are if we look on the bell curve, they lean towards the better end of those abilities. But they've also really learned to recognize all these things. But the reason that they get tired is what we call it adaptation or desensitization and habituation, depending on where along in the nose and brain this happens. But basically, when you're having something stimulated over and over, you can sort of oversaturate a particular information channel in the brain and it will dial down the gain and come less. So you have to take breaks. Even when we're smell testing people, we work in breaks within it so that they don't get sort of overwhelmed and saturated, so they're attuned to the next Like you all experience adaptation. You go into a bakery and smell the cookies and the breads and everything, and then you're there for a few minutes and it just there goes away. You don't really notice it anymore. Part of that is the gain of the system being down. Part of that is your brain attending to novel stimuli and all of that. I don't know if they head out to the beach, probably most of them are in Paris or Geneva, but yeah, there's a real physiological reason that they need to have those breaks.
Well, I used to know a guy who lived downwind from the Nilla wafer factory in Houston, and he said he had to move away because he was gaining weight because it just made him eat all the time. And it makes me wonder about the sort of subconscious effect of smells. I mean, are there smells that affect our behavior that we don't consciously experience? Are there, for example, human pheromones that you know attract you to somebody or not. Do perfumes actually do that to people?
There's no good evidence of human fairmonts. And by a pheromone specifically mean a odoor that's given off by one number of a species, that acts on another member of a species to change its behavior, or some physiological response like a hormonal response. We don't use those, but certainly smells can affect our interactions with each other. You talk about two young mothers who lose their sense of smell. One of the things they'll bring up very early. So you know my baby's head, I love smelling his hair after you got to wash your stuff. There definitely is a link between smell and emotion and sort of that bonding and all those types of things. Romantic partners will often talk about enjoying the smell of their partner and things like that, But these are not innate triggering fair aomones in that way. But similarly, it can be if your friend had the nil away for experience and that triggered you know, intensity, maybe around front baking all the time, whatever it is. But people who live near hog farms that have these large pools to deal with the waste. There are a lot of studies about the increased depression.
Ecal lagoons cause people to get depressed or saying.
Yeah exactly wow, so yeah, those aspects are very real.
When I was in college, I remember in my evolutionary psychology class learning about these studies where like men wear shirts and then the women smelled the shirts and then rated which men were the most attractive. So that's not pheromones. Has that study since been debunked or was there something else that they were picking up on?
There certainly are questions about the extent of that mean. Certainly the concept of women's menstrual cycles coordinating in dorms and things like that that may be spell related. I would say they haven't always been replicated to the sense.
So I thought that one was fairly debunked. That it's more like a statistical you're just going to overlap twenty five percent of the time.
By chance or something.
Yeah, exactly. It's also not something I think a lot of people are spending a lot of time studying at the moment.
And if we have some understanding of the chemical mechanism of this, can we make progress towards things like recording sense digitally and then manufacturing them. You know, can I create an artificial nose with all of these receptors, write down the signals and then create something which puffs out those molecules on the other side, or I could like email somebody a smell.
There are a lot of efforts in this area, and you can imagine artificial noses being used as sensors for all sorts of things, biosecurity types of questions. They put them in fields to know when the props are ready to harvest, or if there's been an infestation, things like that. A lot of these it could be more specialized. You'd certainly love to have. You know, there's a lot of evidence that the aromas that an individual gives off if they have cancer or if they have some other disease might be unique. If you could identify those chemicals there are dogs that have been trained, although that's really hard to make a regular part of it because just the amount of training and how you have to go through that. But if you can have a sensor a wand you could wave over someone to detect that, that would be a miracle. But there's also commercial ways for trying to replicate this with food or with other types of aromas you might like to recapitulate. For example, a lot of the flavor houses now will usually go around and sample things. They put a dome to capture the odor headspace over a plate of food at a particular food truck that you like, or you put over a borneo forest and collect all the volatives coming off a particular group of plants or whatever. Take those back, use modern biochemical chromatographic mass spect types of techniques to define not only every single molecule but also its relative concentration, which is very important, and then they can recapitulate these. They can do this chemically, but then can you also send it a lot long to have a production apparatus on the other end of that email that that can then puff it out. People have been trying that to various degrees for decades now, and I think the technology is catching up to be able to do that in a much more sophisticated way.
So I could email California to Kelly so she can also enjoy the sense of the ocean and the floral notes.
You know, I'm going to try to be nice and not mentioned that right now, you'd probably be sending me the smell of burning home. But Virginia's got some perks. Man.
Yeah, this seems like maybe a running.
This is a running debate.
So my question is, I hope a question you haven't heard before, which is about smell and taste on other planets. Given the usefulness of smell and taste and our knowledge of the evolutionary history on Earth, what do you think the chances are that aliens, when they evolve on their planets smell and taste or don't smell and taste. How likely do you think this is to be ubiquitous to life in the universe.
I would think it would be more ubiquitous than other senses. They are chemicals everywhere the universes, chemicals just arranged in different forms, and so being able to sense that is really integral. You look at unicellular organisms, whether they're bacteria, protozoans or whatnot. They can all sense the chemicals around them. These are fundamentally primitive forms of smell and taste. So yeah, I think that is clearly going to be a thing. Whether it is put together the same way then we have. It's interesting that while the receptors in a fruit fly and a human, the receptors for odors and for tastes are molecularly completely distinct from each other those two families. It's not a single evolutionary origin of the odor receptors across those different phila, but the arrangement of what the sensory neurons look like, how they're arranged connected to the brain, and how they arranged is actually remarkably similar. And those that independently evolve, so there seem to be some strategies that have benefited from that conservation or at least limited repertoire of options, while other ones are free to to sort of evolve independently and come up with more than one solution to the problem.
Do aliens like cilantro a question we don't yet have an answer to.
Maybe one day, all right. As someone with anxiety, I'm still dwelling on the fact that I called your research weird at the beginning. What I meant was, I asked you weird questions because of what you do.
I don't remember that.
Oh good, good. So then the lead in is you just started this new center for smell and taste disorders. Tell us a bit about your new center that you're co directing.
Well, thanks for that opportunity. It's something that we've seen over the last decades that there's a huge need for. And what that need is we have massive underserved population of people that are experiencing the disorders, but the amount of research that's going into trying to better diagnose them, better support them, and eventually better treat them is really small. One of the small bright spots of COVID was because of the prevalence of smell loss and taste loss that associated with COVID. It brought a greater attention and understanding of the broader population about how impactful these disorders can be. But we still have a long way goo and we don't want to lose the momentum of that knowledge and appreciation from it. So the center is really trying to areas within its mission, and one is patient care, So being able to make sure that someone who has a smell or taste disorder has a place to go to get diagnosed, perhaps identifying underlying cause that might be treatable, as well to get support such that they better understand how to improve the palatability of the food, how to be safer with gas leaks and fires and spoiled food and things that they may be hard to detect, how to get emotional or therapeutic support if they're being depressed, which is very common, where's changing their social relationships. We also want to facilitate research, and that's everything from the very fundamental building blocks of smell and taste and how it works, so that we can better understand how it may not work when it's spent, but also clinical studies looking at dignostics and treatment. One of the studies we're doing right now is trying to answer a very simple question is how much does your sense of smell normally vary morning versus night day to day, if you're pregnant during menstrual cycle, if you have other types of disorders, so that you can have a base line to understanding. So if you're going to get your sense of smell regularly tested, do you actually know what's just normal variation versus an actual pathologic change that needs to be dealt with. So we want to train doctors and scientists in this field to a better degree than is often the case. And then we want to reach out to the community education and engagement to kill people every whether it's with a disorder or whether it's for people who chefs, mind makers, and who or not that are using smell and taste as part of their livelihood and how they make their way through the world, to help them better understand that as well.
Awesome, Well, congrats on the new center. I learned a lot today. I think I'm going to appreciate the next piece of food that I eat even more and appreciate how complex it is. I love that we learned the thing about vibrating. The next time I go to a Chinese restaurant, I'm definitely going to order something with extra session one. So yeah, thank you so much for coming on the show.
Thanks so much for having me. It is fun.
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