Pod Insights Daniel and Kelly's Extraordinary Universe The science of taste and smell (with Steven Munger) About this episode Daniel and Kelly talk to Dr. Steven Munger about phantom smells, stinky shirts, careers as a "nose", and more.
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Transcript 11,337 words · 15 speakers
Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.
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2:40 Daniel Whiteson? All right, so I have a follow up question there. First of all, am I correct in interpreting your answer as 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?
2:55 Daniel Whiteson? That may be a stretch. I'm taking that as a yes, and we're moving on.
3:12 Daniel Whiteson? Hi, I'm Daniel. I'm a particle physicist, and I remember the first time I smelled California.
3:18 Kelly Weinersmith? Hi, I'm Kelly Leersmith. 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 Chacos. But I did end up leaving, but I don't remember the smell. What was the smell of California?
3:42 Daniel Whiteson? And now I'm worried the smell is wind from other people's feet.
3:46 Kelly Weinersmith? Well, that doesn't sound very nice. No wonder so many people are leaving California.
3:49 Daniel Whiteson? 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.
4:24 Kelly Weinersmith? 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.
4:29 Daniel Whiteson? And what is the smell of the ocean? What are we smelling in the ocean? Is it fish? Is it algae? Is it fish poop? What's going on there?
4:38 Kelly Weinersmith? It's probably algae, diatoms. Yeah, I don't know. Maybe I don't want to know. Maybe I enjoy it more not knowing.
4:47 Kelly Weinersmith? What is your favorite scent?
4:49 Daniel Whiteson? My favorite scent? 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.
4:58 Kelly Weinersmith? That's good.
4:58 Daniel Whiteson? You know, when you start cooking something delicious and that smell hits you, I'm like, mm. Sometimes I feel like they should make a perfume, you know, because if I wanted to date with a lady and she smelled like onions and garlic and olive oil, I'd be like, yum.
5:10 Kelly Weinersmith? Married.
5:11 Daniel Whiteson? In a very wholesome way.
5:12 Kelly Weinersmith? Right, right, right. Here's the ring. Yeah, that is a good smell. Zach 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.
5:25 Daniel Whiteson? There you go. And so what are your favorite smells, Kelly?
5:28 Kelly Weinersmith? I 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 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.
5:51 Daniel Whiteson? 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.
5:59 Kelly Weinersmith? Oh, that's fantastic. Life is really good sometimes.
6:03 Daniel Whiteson? Life smells amazing.
6:05 Kelly Weinersmith? 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.
6:14 Daniel Whiteson? I'm very glad your life doesn't stink.
6:16 Kelly Weinersmith? 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.
6:39 Kelly Weinersmith? Today's show, we have Dr. 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.
6:47 Speaker 07 Thanks so much. Really enjoy the invitation.
6:50 Kelly Weinersmith? I'm excited that I get the chance to chat with you again. We've interacted a couple of 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.
7:02 Speaker 07 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.
7:12 Kelly Weinersmith? Yes, yes. Back when I used Twitter, we met Steve. We had a question for him for our book Soonish, and we've been in touch since.
7:17 Daniel Whiteson? So Steve, got to ask, do your family and your kids describe your work as a professor of everything stinky and delicious?
7:24 Speaker 07 No, they don't, or at least they haven't until this point, but...
7:29 Kelly Weinersmith? 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?
7:39 Speaker 07 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 30 years. We know what cells in the nose, which cells in the tongue detect odors and tastes. 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
8:23 Speaker 07 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 odorants, or single taste molecules, except, yeah, if you sit there eating 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 it 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.
9:05 Daniel Whiteson? And so for vision, we have something of a cartoon understanding, or 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 up 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 macroscopically what happens from when that cotton candy molecule hits your nose or your tongue? What's going on?
9:30 Speaker 07 Of course, it depends a little bit on whether you're talking about vertebrates or invertebrates. There are amazing amounts of similarities in the organization, but a lot of the molecular players are quite different.
9:41 Daniel Whiteson? Do invertebrates like cotton candy?
9:45 Speaker 07 Most insects and others like sugars. They're attracted to at least certain types of sugars and they will avoid compounds that we perceive of as 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, in 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 mucus 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.
10:26 Speaker 07 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 cell. Those nerve cells then send messages back through the skull. To the brain where they interact with ourselves at the brain and create this process.
10:46 Daniel Whiteson? So folks like me who are not adept at chemistry, I want to understand what you mean when you say recognize those molecules. Like I'm imagining some molecule 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?
11:06 Speaker 07 Exactly. So we 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 odors, there's not a particular receptor just for this molecule and just for that molecule. In humans, we have about 400 of these receptors. In rodents, it could be 1,000, 1,500, depending on the species. But even with those numbers, you could imagine
11:50 Speaker 07 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 to 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
12:32 Speaker 07 the way those receptors in the 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.
12:44 Daniel Whiteson? 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.
13:24 Speaker 07 Absolutely. You got it.
13:26 Kelly Weinersmith? 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 than vision? And does the brain process it in different ways?
13:38 Speaker 07 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 odorants of pizza is. You smell the pizza and your brain, a certain number of receptors are activated by those odor molecules that come from the pizza you're 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 do it in my head because there can be overlaps.
14:12 Daniel Whiteson? Especially if you're a baby in Iceland and they like rotting fish pizza, right?
14:17 Kelly Weinersmith? My PhD involves a lot of rotting fish.
14:19 Speaker 07 Oh, yeah, we're just in Iceland this summer for a conference, which is, I did not eat in any of the rotting fish while we were there, though.
14:26 Kelly Weinersmith? I'd avoid it, too.
14:27 Daniel Whiteson? Beautiful country, though. Beautiful country, wonderful people.
14:29 Speaker 07 Oh, it's stunning, stunning.
14:31 Daniel Whiteson? So Steve, you know that there's a common like philosophy question, which is also a staple in dorm rooms at 3am, 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 qualia of seeing red, or the qualia 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 Mary in the red room philosophical study about smell and taste?
15:12 Speaker 07 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 cilantro. Some of you might really like cilantro and like sort of that green grassiness of it, the brightness of it that it can add to foods. And others might hate it and say, nope, that's soapy. That ends up being most likely a genetic difference in one particular odor receptor that seems to be changed in its responsiveness to those soapy odor components. Those people
15:55 Speaker 07 who get the grassiness as the primary bit versus get the soapiness as 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. There are also what we, a variety of other genetic variants we call specific anosmia's. And these are ones where you may have a mutated odor receptor that is the primary receptor for a particular compound, and you just can't smell it, and someone
16:34 Speaker 07 else can. So endocrinone, 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 could put a big bat in front of my nose, I have no idea it's 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 rotundone, which is a black peppery odorant. And there were maybe 20% of the people in
17:18 Speaker 07 that room that could not actually tell the differences between the wine, even though in that case I could, and it was quite pronounced peppiness. 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 opsin that actually shifts the wavelength response a little bit. And then, so in that case, you can imagine two people seeing slightly different shades of green, but still saying, no, that's the grass on.
17:54 Daniel Whiteson? 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.
18:12 Speaker 07 A colleague of mine, Doron Lantz, had once made the statement, no one is normosmic. We all differ. There are 400 potentially active odorant receptor genes in the human, and all of us probably have one or two, or maybe more, that are mutated in such a way that that changes the way that we respond to the molecules that those receptors would normally respond 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
18:56 Speaker 07 with each other, perceive the world around them, or have sort of underlying long-term off-tastes, or fecal smells, or other things that their brain is constructing. Those are the ones where I'd 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 what I'd put as specific anosmia.
19:20 Kelly Weinersmith? So you mentioned wine. I enjoy wine, but when I read the descriptions on the back, I call bull 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 the minority or the majority of not being able to appreciate a complex flavor profile?
19:40 Speaker 07 I don't know if you are in the minority majority. I can't say that I am certainly as hugely skilled as people that do that professionally. But part of it is also training. I mean, certainly a sommelier or winemaker or brewmaster, 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 currant 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.
20:24 Speaker 07 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 has. They're trying to make it a common language using more descriptive things rather than saying islamal acetate or whatever other chemical name you might want to come up with. The other thing that people who are really skilled at is they practice a lot. This is a attention to detail. This is memory. This is like learning a language. All those aspects go into it too, that allow you to sort of focus on.
21:04 Speaker 07 So if you get someone who trains you that, okay, these six wines all have this flavor characteristic and those six wines 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 well. So I think it's more practice than anything.
21:21 Kelly Weinersmith? I need to switch jobs.
21:24 Daniel Whiteson? I think that probably also tells us something about the experience of these smells. You know, you're training somebody to recognize the certain responses. You're helping distinguish between black pepper and currant 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.
21:43 Speaker 07 Yeah, which is an interesting contrast with taste in some ways, and that taste is much more innate.
21:51 Speaker 07 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 roast coffee or IPA beer or Belgian Indive 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 means spit it out and sweet means go ahead and ingest it. There's
22:36 Speaker 07 an energy source there.
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24:45 Kelly Weinersmith? All right, so here we have a question from a listener that actually inspired this whole episode. So let's go ahead and listen.
24:52 Speaker 10 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 detect 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 stupid kids. But I have this question.
25:37 Speaker 10 I was hoping you could help me out and figure out, why are we able to detect poison as bitter? Thank you very much.
25:47 Speaker 07 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 bitter are also aversive to a lot of other animals, even if they're not using the same protein molecules to detect them that mammals aren't. 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
26:32 Speaker 07 you would not like them. No one would like them. Put in the 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 the coffee shop, 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 bitter. I like dark roasted coffees and I like highly hopped beers and it's appealing to me, but
27:14 Speaker 07 if I took those compounds up 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 perception. They're found all over the body. Bitter receptors are in the gut, they're in the heart, they are in the thyroid gland.
27:52 Speaker 07 And there's a lot of question of 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 endogenous 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?
28:25 Daniel Whiteson? All right, so I have a follow up question there. First of all, am I correct in interpreting your answer as 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?
28:37 Speaker 07 That may be a stretch.
28:41 Daniel Whiteson? 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?
29:04 Speaker 07 That's a very common question. The answer is quite conclusively no.
29:08 Daniel Whiteson? Oh, man.
29:09 Speaker 07 So I'll give you an example. So the sweet taste receptor, this is a protein, it's actually a protein complex called T1R2, T1R3, two members of 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 sites, different way. So synthetic sweeteners like aspartame, so the blue packet, saccharin, the pink packet, sucralose, 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.
29:51 Speaker 07 Lead, one reason the kids eat lead paint is lead acetate tastes sweet and that activates that same receptor. So all of those compounds are giving you a perception of sweet. Because they turn on that receptor. That same receptor is in your gut. And specifically in a population of cells called enterantagene L cells that are involved in glucose responses, allowing your metabolic systems to respond to the ingestion of a 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 that's sitting on the inside surface of your intestine.
30:36 Speaker 07 That triggers a response that elicits amongst other things peptide hormone called GLP one, glucagon like peptide one, which probably everybody now knows about because of Ozempic and Wegovy, which is basically mimics that peptide. And that peptide 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.
31:21 Speaker 07 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.
31:34 Kelly Weinersmith? So Daniel and I, while 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?
31:48 Speaker 07 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, as you sniff, that would be called that ortho nasal olfaction. Or as you're chewing food or drinking drink, odor molecules that volatiles can come up back through your throat and enter your nasal cavity that way. We call that retro nasal olfaction from the back.
32:20 Kelly Weinersmith? And volatile just means it goes into the air?
32:22 Speaker 07 And volatile just means it's light enough to go in the air.
32:25 Kelly Weinersmith? Okay.
32:25 Speaker 07 But the receptors are all in the nose. In lower primitive mammals, you're going to have also another variant called the vomeronasal organ. This is part of the accessory olfactory system that can not only respond to some volatile chemicals, but also peptides can serve as olfactory stimuli there.
32:44 Kelly Weinersmith? So the vomeronasal organ, when snakes are sensing their environment, they stick it into the vomeronasal organ to like, figure out scent trails. Is that right? Can we go a little more into detail about what that does?
32:54 Speaker 07 Yes. So snakes doing it a little differently. It tends to require contact. In mice and rats, the mouse will generally stick its nose right in whatever that odor source is, whether it's the glandular secretions of a mate, or a pool 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 vomeronasal organ, which is just adjacent to the nasal cavity, there's a blood vessel that will sort of pump those molecules into the organ where they can interact with these specialized olfactory neurons. And 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
33:39 Speaker 07 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 variety of compounds that can be perceived of as bitter. 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 papilla, some of the bumps in your tongue. And they're also in the soft palate, in my favorite German word, the Geschmackstrifen, which is the taste strip, which a bunch of taste buds in the soft palate. And then there are also some in the pharynx, in the throat.
34:24 Speaker 07 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 are detecting chemicals. The third chemical sense is known as chemisthesis. And chemisthesis 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 hijack
34:52 Speaker 07 Sensors for temperature or pain or vibration. So capsaicin in a hot chili pepper, menthol in mint, sanchul in Szechuan peppercorns. These are going to basically be the actually current chemicals that make this 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.
35:26 Daniel Whiteson? Did you say there was one that triggers a sense of vibration?
35:29 Speaker 07 Yeah, the sanchul in Szechuan peppercorns, which are actually flower buds, gives you this little tingling aspect to it.
35:35 Daniel Whiteson? I see, so it's different from capsaicin. It's not a warmth.
35:38 Speaker 07 It seems to have a bit of a warmth aspect to it as well. So some of these can be working across, but they're compounds in ginger and compounds in eucalyptus and all these types that will do this type of thing.
35:48 Daniel Whiteson? And is the chemical mechanism the same, the sort of lock and key structure, the same for all these different kinds of experiences?
35:56 Speaker 07 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 charged particles fly across the brain. So they're not triggering an intracellular biochemical cascade. They're actually changing the electrical properties of the cells directly. So just different families of proteins. But they do all come together, and this all comes together in the brain, and that's what we call flavor. So flavor is smell plus taste. You can bring chemistasis into that. You can also impact flavor by sight.
36:41 Speaker 07 For example, if either you remember Crystal Pepsi or any of these clear colas that came out a number of years ago, the one of the problems was, is you looked at it, you expected a seltzer or a Sprite or whatever 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 flavor is perceived. But one of the big term
37:15 Speaker 07 Confusions is how I'd say the general population uses the word taste versus how we as taste and 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
37:57 Speaker 07 lime, if you're not looking at the color of it, is not because one is sour and one's not sour, they're both sour, but one has a different complement of odorant molecules than the other that gives it a subtly different perceptual flavor.
38:11 Daniel Whiteson? 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 suite of receptors there? For example, to make it 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 spray it against your nose, would you notice anything?
38:45 Speaker 07 Basically, no, there's not. I mean, people often, if you ever looked at turbinado 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 that 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, and my guess is it wouldn't be anything specific, because that would be a molecule that would probably impact every single receptor. It might just give you a background blur.
39:26 Kelly Weinersmith? So if you had to lose your sense of taste or your sense of smell, which would you rather lose?
39:32 Speaker 07 Smell easily.
39:33 Daniel Whiteson? Wow.
39:34 Kelly Weinersmith? Really?
39:34 Speaker 07 And that's not because in any way diminish, I don't want to lose either of them.
39:39 Kelly Weinersmith? Yeah, yeah.
39:40 Speaker 07 People who I would say I would probably rather lose sight or 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 was 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 the whole life.
40:24 Daniel Whiteson? Wait, so soft foods are unpleasant without taste? Is that what you're saying?
40:28 Speaker 07 Yeah, there's something about without having that taste, but it's just purely the texture impact, the yogurts and cottage cheese. I mean, not that I want to eat cottage cheese anyway, but
40:43 Speaker 07 all of these things are just very difficult. So usually the 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 multi-sensory in other ways that help to offset some of those losses. We say that for people with smell disorders. Exploring different spices, adding textures, adding color to your food to make it more palatable, enjoyable, you're never going to a 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
41:26 Speaker 07 their sense of smell because of the spices.
41:29 Daniel Whiteson? So you're saying crunchy blue cottage cheese is a better experience than white soft cottage cheese?
41:36 Speaker 07 Yeah, but that's a low bar.
41:42 Kelly Weinersmith? Let's take a break and we'll come back and talk more about smell and taste.
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42:52 Speaker 08 Hey, it's Nile Rodgers, host of "Before the Moment", a Lincoln original series. I'm driving across the country, meeting some of today's most fascinating artists. We're exploring the stories before the moment that changed everything. This week, I'm joined by my friend, John Legend. How does music actually enter your mind?
43:14 Speaker 12 I'm not sure why or how the music comes to me, but I think people who love music and write music, our brains are just filled with music. Like, we have listened to so much music. We've been a part of so much music. I think of the story that I want to tell, the mood that I want to create with the music, start playing chords, see where they lead me.
43:35 Speaker 08 Sometimes, I'm just not even thinking about music, right? And I hear this little thing, and I go, "Oh, that could be this."
43:45 Speaker 12 You know, you just have to be ready for when the inspiration hits.
43:49 Speaker 08 Yeah. Experience "Before the Moment", a Lincoln original series, on the iHeartRadio app, YouTube, or wherever you get your podcasts.
44:07 Daniel Whiteson? 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.
44:31 Speaker 07 Exactly. So 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 they're temporarily, like just having a head cold where you're just clogged up and so the odor molecules can't get to where they need to go. Sometimes it's because of shorter or longer term damage. Everything from viruses to inhaled toxins or pollutants, sinus or nasal disease that may cause inflammation,
45:15 Speaker 07 allergies, head trauma, early stages, Alzheimer's, Parkinson's, and other neurological, neuro and neurogenerative diseases.
45:25 Daniel Whiteson? Exposure to the swamps of Virginia.
45:27 Kelly Weinersmith? Daniel, if I could just interrupt you, are those things like messing up the shape of the receptors or messing up the connection between the neurons that talk to your brain? Or maybe it's a combination of these things?
45:38 Speaker 07 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.
45:53 Speaker 07 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-19. So we'd known for a long time that a variety of viruses, common coronaviruses that could cause common cold, rhinoviruses, adenoviruses, influenza, they could, in some people, will lead to temporary or permanent smell loss. In COVID, it was really striking how many people were losing
46:35 Speaker 07 their sense of smell very rapidly, and a large number of them, probably about 10%, may never recover that Oh my god. smell 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 that are providing support to
47:18 Speaker 07 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. It attacks 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. Wow. But in other people, the damage is extensive enough that that does not seem to be the
48:00 Speaker 07 case. But it is a sort of indirect attack by the virus on the olfactory neurons rather than the neurons themselves being dead. Other viruses may work differently, but it is that peripheral. Damage, that's the issue. Now, we do also know that in a small number of people, there seem to be true taste effects and even chemisthesis effects. You may have seen videos of people saying, oh, yeah, here's I'm chewing an onion or I'm gonna just shove garlic into my mouth, not perceiving it at all. We don't know why or how the virus was affecting taste or chemisthesis. Those losses did seem to be temporary. I'm not aware of long-term losses in those senses.
48:41 Kelly Weinersmith? 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?
48:47 Speaker 07 That actually is very common. So we think of smell disorders, we can break them into two different categories. One, we call quantitative disorders. So there's really a reduction or a complete inability to detect or perceive odors. And the others are qualitative, somewhat changing the quality of the smell. And we can break those into two different groups. Parasmia is distorted smell. So I'm gonna, you put a flower in front of your nose, you smell and it smells like garbage. And that's, you can imagine, not good. Fantasmia 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 parasmia, there are unpleasant smells as well.
49:32 Daniel Whiteson? You mentioned fecal phantoms earlier that I have to follow up on.
49:36 Speaker 07 Yeah, fecal 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 anosmia, no ability to smell, or hypoasmia, reduced smell. And that sense of smell is coming back. But during that time, parasmia or fantasmia emerges. And while we don't absolutely know the cause, it may be as the system's trying to rewire itself, or the brain is, is getting missignals or creating signals, looking for them when they aren't fully coming from the nose. So that is unfortunately pretty common.
50:19 Daniel Whiteson? And why don't we understand the cause? What's hard about these studies is that we're talking about humans and brains and you can't just do whatever experiments you want?
50:27 Speaker 07 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. Lose your 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, parasmia and phantasmia, we can't measure them in any objective way. We have tools to measure smell loss, there are a variety of psychophysical tests that
51:08 Speaker 07 we can do that can allow us to quantify how sensitive you are to particular others. With parasmia and phantasmia, we are entirely relying on the patient being able to describe it and sort of relate. We just don't have the tools to investigate it nearly as well as for smell loss.
51:29 Kelly Weinersmith? You mentioned that the phantom smells tend 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?
51:48 Speaker 07 I think it's both of those that you gave, what I'd say is probably the leading hypothesis about it, that avoiding bad is more important. So it's sort of false to that, but there's really no evidence to support it, it just is the one that seems to make most sense. But yeah, we just don't know.
52:05 Daniel Whiteson? 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 super noses. And also that their noses get tired, so they can only work for a few hours during the day, and then have to spend the rest of the day on the beach recovering from all this, you know, difficult smelling work. Are these people real, or is the whole thing a scam? And how does your nose get tired?
52:34 Speaker 07 They are real, yeah. Generally, their professional term is a nose. Professional nose and much like we were talking about earlier about Somiers 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 of is what we call 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 over saturate a particular information
53:16 Speaker 07 channel in the brain and it will dial down the gain and you become 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 thing. 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 sort of 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.
53:58 Daniel Whiteson? 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?
54:24 Speaker 07 There's no good evidence of human pheromones. And by pheromone, specifically mean a odor chemical that's given off by one member 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.
54:44 Speaker 07 Use those, but certainly smells can affect our interactions with each other. You talk about to young mothers who lose their sense of smell. One of the things they'll bring up very early is that, you know, my baby's head. I love smelling his hair after you got to wash yourself. 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 pheromones in that way.
55:25 Speaker 07 But similarly, it can be your friend had the Nilla Wafer experience and that triggered, you know, intensity. Maybe you're around frying bacon all the time or 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.
55:45 Daniel Whiteson? Eagle lagoons cause people to get depressed, you're saying?
55:47 Speaker 07 Yeah, exactly.
55:48 Daniel Whiteson? Wow.
55:49 Speaker 07 So, yeah, those aspects are very real.
55:51 Kelly Weinersmith? When I was in college, I remember in my evolutionary psychology class, learning about these studies where like men wore shirts. And then the women smelled the shirts and then rated which men were the most attractive. But that's not pheromones. Has that study since been debunked or was there something else that they were picking up on?
56:06 Speaker 07 There certainly are questions about the extent of that. I mean, certainly the concept of women's menstrual cycles coordinating in dorms and things like that. That may be smell related. I'd say they haven't always been replicated to the sense, so.
56:24 Kelly Weinersmith? I thought that one was fairly debunked that it's more like a statistical. You're just going to overlap 25% of the time by chance or something.
56:30 Speaker 07 Yeah, exactly. But it's also not something I think a lot of people are spending a lot of time studying at the moment, so.
56:36 Daniel Whiteson? And if we have some understanding of the chemical mechanism of this, can we make progress towards things like recording scents digitally and then manufacturing them? 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? So I could like email somebody a smell?
56:56 Speaker 07 There are a lot of efforts in this area. And you can imagine artificial noses being used as sensors for all sorts of things. By security types of questions, they put them in fields to know when the crops are ready to harvest, or if there's been an infestation, things like that. A lot of these could be more specialized. You would 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 could have a sensor, a wand that you could wave over someone to detect that, that would be a miracle.
57:40 Speaker 07 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 it over a borneo forest and collect all the volatiles coming off a particular group of plants, or whatever. Take those back, use modern biochemical chromatographic mass spec types of techniques to define not only every single molecule, but also its relative concentration, which is very important.
58:24 Speaker 07 And then they can recapitulate these. They can do this chemically, but then can you also, yeah, send it along to have a production apparatus on the other end of that email that then 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.
58:47 Daniel Whiteson? So I could email California to Kelly so she can also enjoy the scents of the ocean and the floral notes?
58:53 Kelly Weinersmith? You know, I'm gonna try to be nice and not mention that right now you'd probably be sending me the smell of burning homes.
58:58 Daniel Whiteson? Oh.
58:59 Kelly Weinersmith? But Virginia's got some perks, man.
59:02 Speaker 07 Yeah, this seems like maybe a running.
59:05 Kelly Weinersmith? Yeah, this is a running debate.
59:07 Daniel Whiteson? 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?
59:30 Speaker 07 I would think it would be more ubiquitous than other senses. There are chemicals everywhere. The universe's 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 that 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
1:00:15 Speaker 07 completely distinct from each other, those two families, it's not a single evolutionary origin of the odor receptors across those different phyla, but the arrangement of what the sensory neurons look like, how they're arranged, connected to the brain, and how they arrange is actually remarkably similar. And those have independently evolved. 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.
1:00:54 Daniel Whiteson? Do aliens like cilantro? A question we don't yet have an answer to.
1:00:59 Kelly Weinersmith? 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 ask you weird questions because of what you do.
1:01:09 Speaker 07 Okay, I don't remember that.
1:01:11 Kelly Weinersmith? 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.
1:01:19 Speaker 07 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 this 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, taste loss that associated with COVID. It brought a
1:01:59 Speaker 07 greater attention and understanding of the broader population about how impactful these disorders can be. But we still have a long way to go, 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 is has a smell or taste disorder has a place to go to get diagnosed, perhaps identify an 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
1:02:44 Speaker 07 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, or 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 present, but also clinical studies looking at diagnostics 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
1:03:27 Speaker 07 cycle, if you have other types of disorders, so that you can have a baseline 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 help people every, whether it's with a disorder or whether it's for people who chefs,
1:04:07 Speaker 07 wine makers and who 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.
1:04:17 Kelly Weinersmith? Awesome. Well, congrats on the new center.
1:04:19 Speaker 07 Thank you.
1:04:20 Kelly Weinersmith? 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 szechuan.
1:04:34 Kelly Weinersmith? So yeah, thank you so much for coming on the show.
1:04:36 Speaker 07 Thanks so much for having me. It was fun.
1:04:45 Kelly Weinersmith? Daniel and Kelly's Extraordinary Universe is produced by iHeartRadio. We would love to hear from you.
1:04:50 Daniel Whiteson? We really would. We want to know what questions you have about this extraordinary universe.
1:04:56 Kelly Weinersmith? We want to know your thoughts on recent shows, suggestions for future shows. If you contact us, we will get back to you.
1:05:03 Daniel Whiteson? We really mean it. We answer every message. Email us at [email protected] .
1:05:10 Kelly Weinersmith? Or you can find us on social media. We have accounts on X, Instagram, Blue Sky, and on all of those platforms, you can find us at D and K Universe.
1:05:19 Daniel Whiteson? Don't be shy. Write to us.
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