Sniffing Out The Science Of Smell

There are hundreds of receptors in the human nose that can pick up thousands of odors with each sniff. But how do we make sense of the scents? Smell researchers Stuart Firestein and Donald Wilson discuss the complexities of olfaction and how the brain sorts out what the nose picks up.

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IRA FLATOW, host:

You're listening to SCIENCE FRIDAY from NPR. I'm Ira Flatow.

What will you remember about this summer which is vastly moving on, or any summer? How about the smells, the distinctive odors of the fresh cut grass, the barbecues, the chlorine from the swimming pool odors that may stay with us for the rest of our lives only to be recalled with the phrase: I remember that smell. What does that evoke in my mind?

What is about certain scents that when we smell them, we can we recall a memory or a feeling? And how does our nose work? How is the brain making sense of the dozens of different odors that we pick out each sniff? That's what we'll be talking about - the ABCs of odors and the brain interface with our nose, all kinds of stuff like that, and everything you wanted to know about smelling, I mean, this kind of smelling.

My guests to try and understand just what's going on there, let me introduce them. Stuart Firestein is a professor and chair in the Department of Biological Sciences at Columbia University. He joins me here in our studios. Welcome back to SCIENCE FRIDAY, Dr. Firesetein.

Dr. STUART FIRESTEIN (Biological Sciences, Columbia University): Thanks, Ira. Always a pleasure to be here.

FLATOW: Yeah. And Don Wilson, he's a research scientist at the Nathan Kline Institute and professor at NYU School of Medicine in New York. Welcome to science Friday, Don.

Dr. DONALD WILSON (Nathan Kline Institute; Child and Adolescent Psychiatry, New York University): Thanks, Ira.

FLATOW: Anything new under the sun in the science of - what do you call it, olfactional?

Dr. WILSON: We call it science of olfaction, the olfactory system.

FLATOW: Mm hmm.

Dr. FIRESTEIN: Oh my goodness, there's a ton of new things under the sun in the science of olfaction, from well, we're actually coming on to a 20-year anniversary that may be the most important, I think, moment in the modern era of olfaction, and that was the identification and cloning of a large family of receptors in our noses that mediate the sense of smell that act like a lock. If you think of it, odor is a key, and when they fit together, the brain is clued in to the fact that this odor is out there somehow. And this identification of this large, large family of genes, a thousand of them in many animals, as many as 450 in us, mediates this smell.

FLATOW: Wow. And that's so so that's sort of out of proportion to other things.

Dr. FIRESTEIN: Way out of proportion.

FLATOW: Way out of proportion.

Dr. FIRESTEIN: It's the largest gene family in the mammalian genome. The mammalian genome, typically, we think consists of about 25,000 genes. So in a mouse, it's about 5 percent of the genes and even in us, it's almost 2 percent. About one out of every 50 genes in your genome was devoted to your nose.

FLATOW: And why why is that?

Dr. FIRESTEIN: Yeah.

FLATOW: It is so important? I mean, we don't use our nose that much, do we? Unless, you know, as sight or whatever?

Dr. FIRESTEIN: Of course that seems to be the case.

FLATOW: Yeah.

Dr. FIRESTEIN: Although I think we use our nose a lot more than most people believe. The biggest problem with our sense of smell or the feeling that we don't have a good sense of smell is actually our bipedalism, the fact that we walk on two legs. And we have our noses stuck up here five or six feet in the air, when all the good odors are about eight or 10 inches off the ground. Or for example, as the case with other animals, they're more willing to put their nose where the odors are, shall we say, delicately.

(Soundbite of laughter)

FLATOW: And well, we've always heard that animals like let's pick out dogs, bloodhounds and things like that, that dogs are able to smell so much more sensitively than us in all different kinds of smells. Is that true?

Dr. FIRESTEIN: Well, it's a good question. I mean, I often say to people who ask me that question, if they have such a good sense of smell, why do they think they do that greeting thing that they do?

(Soundbite of laughter)

Dr. FIRESTEIN: You think you could do that from 10 feet away, you know?

FLATOW: Well, that's true. They get right up there and sniff you.

Dr. FIRESTEIN: Boy, they sure do.

FLATOW: So why do they need to be so close if they smell...

Dr. FIRESTEIN: Yes, well so some of this is behavioral, and a part of it, the another way to show that, I think, for humans, is that we actually have very sophisticated palate, for example, for food, much more than many other animals and we know that most of flavor is really olfaction.

FLATOW: Yeah.

Dr. FIRESTEIN: It's really the sense of smell, not just the four basic tastes.

FLATOW: Mm hmm.

Dr. FIRESTEIN: So when you put the odor in your mouth, when you put the source of the odor in your mouth close to your nose, you do

FLATOW: Right

Dr. FIRESTEIN: use your sense of smell.

FLATOW: Don Wilson, tell us what happens what is connected to our noses in the sensory? What goes on in the brain when we smell something?

Dr. WILSON: Well, it's actually really exciting because - so these you mentioned the ABCs of olfaction. I think that's a good analogy because these hundreds of different receptors that Stuart just mentioned essentially are recognizing different features of a molecule. You don't have - for most of odors, you don't have a receptor for that particular odor. You don't have a coffee receptor or a vanilla or a strawberry receptor. You have receptors that are recognizing small pieces of the molecules that you're inhaling, and the aroma of coffee, for example, is made up of hundreds of different molecules.

So what the brain then has to do is make sense of this pattern of input that's coming in: I've got receptors A, B and C activated when I smell this odor, and I've got receptors B, C, D and E activated when I smell this other odor. And what we've found is that what the brain is really doing with the olfactory cortex and the early parts of the olfactory system are doing is letting those features into what we and others would consider something like an odor object, so that you perceive now a coffee aroma from all of these individual features that you've inhaled. And, in fact, once you've perceived that coffee aroma, you really can't pick out that, you know, there's a really good ethyl ester in my Starbucks today or something - you really have an object that you can't break down into different components. So that's what the brain is doing.

And we know that part of that building of the object, that synthetic processing of all these features, is heavily dependent on memory. So you learn to put these features together and experience this odor the first time. So it's really a - in some ways, olfaction seems really simple. They suck a molecule up my nose and it binds to a receptor and so I must know what I've just inhaled. But, in fact, it's a fairly complex process where it's akin to object perception and other sensory systems.

FLATOW: Does the fact that it elicits such strong memories - you know, so you can a smell from 40 years ago or something. Is it because - are they close together, the centers for smell and memory in the brain?

Dr. WILSON: Well, in humans, it's - in some ways, the olfactory cortex is really enveloped by - embraced by parts of the brain that are important for emotion and memory. There are direct reciprocal connections between the olfactory system and the amygdala and hippocampus, these parts that are important for emotion and memory. So - and we think that as you're putting these features together to make this perceptual object, the brain and the cortex is also sort of listening to the context of which I'm smelling it, maybe the emotions that I'm having as I'm smelling it. And those can, in fact, we think can become an integral part of the percept itself. So it not only becomes difficult to say what the molecules were within that coffee aroma, but it also becomes difficult to isolate the emotional responses you're having with that same odor.

I would just like to put a caveat in there, that its also the case - although I never want to dis(ph) my favorite sensory system - it's also the case that you can hear music or see a picture and have a whole range of memories flood back. So it's not - the olfactory system may not be unique in that way that a single stimulus can evoke these memories and emotions. But in many ways, I may not be - you talked about the smells of summer. I may not really pay too much attention to the smells of summer, and then five years ago - five years from now, I smell an odor that maybe I didn't pay too much attention at one - when I initially inhaled it, and now I've got all of the other memories associated with that.

Dr. FIRESTEIN: I think one of the really interesting features of that memory connection - I think you'll agree with me, Don - is that in olfaction, the memories always tend to have a very strong emotional quality to them. That is, you smell something and you remember your grandmother's living room or your first day of school or your first lover or this or that. It's not like you smell something and remember a page of text or an equation or something that might come in...

FLATOW: Right. Right. Right.

Dr. FIRESTEIN: ...and they actually. So there's always a very strong emotional tinge to these memories.

FLATOW: Like you smell a pot roast in the hallway of an apartment building.

Dr. FIRESTEIN: That's right.

FLATOW: Right.

Dr. WILSON: That's right. And it comes right back to you, and remember your first lover.

Dr. FIRESTEIN: Yeah.

(Soundbite of laughter)

FLATOW: There you go, lover and pot roast. Okay. I can see the connection. Let's go to Sarah in Portland. Hi, Sarah.

SARAH (Caller): Hi. My question is for the doctor. I'm 60 years old. I live here in the Northwest. Always had a very sensitive - an acute sense of smell, worked making perfumes and things. In May of this year, I had a course of Rituxan, which is a monoclonal antibody, composed of human and mouse DNA. And my sense of smell, since then, has become like exponentially more acute, to the point it's a joke in my family. And so, I need to ask...

FLATOW: Wow.

SARAH: ...about that.

FLATOW: I don't know if we can answer the question. But it's a good one.

Dr. FIRESTEIN: What was the name of that stuff again?

SARAH: It's called Rituxan.

Dr. WILSON: Really?

SARAH: It's a monoclonal antibody treatment, in my case, for lymphoma, B-cell lymphoma. It was one of the first Genentech products.

Dr. WILSON: Oh, yes.

SARAH: And it's a combination of mouse and human antibody, you know, somehow.

FLATOW: Let me - while Stuart's writing down to take notes here, Don, do you have any suggestions for this?

Dr. WILSON: I'm afraid I don't know that there are some examples of individuals having these moments of extreme - or have periods of extreme olfaction. Unfortunately, it's more common to have a sudden loss of the sense of smell. I'd be totally speculating on why, you know...

SARAH: Well, you know, the speculation...

Dr. FIRESTEIN: Just enjoy it for now. Is it pleasant or is it...

SARAH: Well, it - taught me - you know, I sort of recovered and, you know, started going out in public. And all of a sudden, places that I would avoid, you know, like the soap aisle at the supermarket, just because it's too overwhelming - all of a sudden, was just, you know - I mean, I couldn't even get close to it. And so it's just made my, sort of, smell world much more vivid. And, oh, like my daughter came and she had a perfume on and she put a blanket around her and, like, six days later, I could still smell the perfume on the blanket.

FLATOW: Wait, could you smell things you had not smelled before?

SARAH: Yes.

FLATOW: Like?

SARAH: I can smell things like emotions on people, almost. You know, people's skin smells are much more informative. I mean, I hugged a nephew and I said to him, hmm, you know, familial but not sexually available. And I went, oh, my God. I can't believe I said that.

(Soundbite of laughter)

FLATOW: Wow.

SARAH: Yeah. So it's like I'm getting a level of information through my nose that is informing me about things I never did before.

FLATOW: Boy, the perfume people want to talk to you.

Dr. FIRESTEIN: Welcome to life as a dog.

SARAH: Exactly. Exactly. Well, I thought, welcome to life as a mouse.

FLATOW: Yeah, there you go. Thank you, Sarah. That's...

SARAH: You're welcome.

FLATOW: ...fascinating.

Dr. FIRESTEIN: It's remarkable.

SARAH: Okay. Bye-bye.

FLATOW: Bye-bye. Some things you just can't explain.

Dr. FIRESTEIN: No, we still can't. I mean, that is remarkable. It's very rare, as Don, to see an enhancement like that, more typically drugs, somehow rather cause a decrease in the sense.

FLATOW: Don, have you ever heard of anything like that?

Dr. WILSON: Yeah, you know, there's - Oliver Sacks has a - I think, has a chapter in one of his books where somebody essentially woke up and had the smell of a dog - didn't smell like a dog but smelled as a dog.

(Soundbite of laughter)

Dr. WILSON: And that - and it was really - he found it really remarkable, and then it eventually went away. Another sort of thing related to that on phantosmias, which are not that rare, where you will smell - you will have -essentially have an olfactory hallucination. Unfortunately, most of those are not pleasant, so it's not like, oh, I get lavender again today.

FLATOW: Hmm.

Dr. WILSON: But you - it's, you know, it's fecal or something like that. So they can really be sort of debilitating. As she was saying it, you know, this affects what store that she wants to go to. It can be - in some ways, we say that smell is, you know, not that important, but it can - when it goes wrong, it can have a fairly major impact on your life.

FLATOW: We're talking about smell this hour on SCIENCE FRIDAY from NPR. I'm Ira Flatow, talking with Stuart Firestein and Don Wilson. Let's see if we can get a phone call to Eric(ph) in Portland, Oregon. Hi, Eric.

ERIC (Caller): Hi, thanks for having me on. I lost my sense of smell here about 35 years ago from a blow to the head. And I lost it completely. I would have phantom smells, but they were not nothing really recognizable, just kind of strange like the taste of a penny, only in smell form.

But over time, I - little by little, some of my smell senses come back. And I was told by someone who wasn't a doctor, that there's a vestigial smelling organ in the back of your mouth, behind the little thing that hangs down there. I was wondering if your guests had ever heard of smell coming back after the olfactory nerve have been severed and if there's any - if there might be anything to do that organ that is in the back of your mouth.

FLATOW: Stuart? Don? Any...

Dr. FIRESTEIN: Well, it's certainly possible to regain your sense of smell after injury. It doesn't happen all the time. It's not guaranteed, but the primary sensory neurons that we call - the brain cells that are - they're actually brain cells in the very back of your nose which are the sensory neurons that pick up the odors. And they're true neurons. They're embryonically created at the same time as the rest of the brain, and they're just sort of shoved out from the skull where they are in contact with the environment, much like the cells in your retina are really part of your brain.

And like - or unlike most brain cells, of course, they are able to regenerate, to proliferate. You can make new ones. There's a population of what we call adult stem cells at the base of the olfactory tissue, and you can bud off brand-new neurons from that. And you do, even humans, throughout the course of your life.

So if you destroy the original neurons that you got, they can be replaced, depending on the nature of the accident, whether or not they can then send their cables, their axons, their connections back to the brain and do that appropriately. That's usually the thing that prevents you...

FLATOW: Hmm.

Dr. FIRESTEIN: ...from regaining your sense of smell. As to the organ in the back of your throat, I don't know anything about that one.

FLATOW: Don, any...

Dr. WILSON: No, not - I'm not - I don't think there's such a thing, but...

FLATOW: Well, Eric, you stumped the panel.

ERIC: Thank you very much.

FLATOW: Thanks for calling. 1-800-989-8255. Let me - in the couple of minutes we have left, what is the - is there a holy grail of smell? I mean, what you'd like to know that we don't know now? Let me ask you, Stuart, first.

Dr. FIRESTEIN: Well, actually, Don probably has a better answer for this, because I think what we've learned in the last two decades from the molecular biology...

FLATOW: Mm-hmm.

Dr. FIRESTEIN: ...with the discovery of these genes, has been remarkable. We have quite a good sense now, I think, of what goes in the front end of this thing. How, in a matter of what really only amounts to two synapses, two connections in the brain, from the olfactory epithelium to the cortex - which is what Don works on - we make a perception? That's really, to me, the great mystery right now.

FLATOW: Hmm. Don Wilson?

Dr. WILSON: Yeah, I'd have to agree. As I said in my last grant proposal...

(Soundbite of laughter)

Dr. FIRESTEIN: I hope they're listening down there at NIH.

(Soundbite of laughter)

Dr. WILSON: No, I think it's - I think there's really exciting things at both ends. I mean, we have essentially all these orphan receptors out in the nose that we don't really know what the ligands are for these different receptors and how we turn this percept into - or how we put - turn this pattern into a percept that we...

FLATOW: Well, could there be things like...

Dr. WILSON: ...can't predict (unintelligible)

FLATOW: ...this woman who says she could smell fear - so she could smell emotions on people? Can there be receptors for fear or something that - I don't know, that we don't know about?

Dr. WILSON: (Unintelligible) your physiology changes under different states. Hormones change - you know, fluctuate. Animals use those kinds of cues all the time. It may be something that we're missing out on. Maybe this relates back to the earlier segment on "Star Trek" on new things that we need to work on in the future.

But the other exciting thing about olfaction is that since it is so dependent on the ability of the brain to change, and memory is important directly for perception; olfaction is also an early biomarker for lots of different kinds of dimentia and disorders: schizophrenia, Alzheimer's, Parkinson's...

FLATOW: All right.

Dr. WILSON: And so there may be opportunities there to explore.

FLATOW: We'll have to get back to that. I want to thank both of you for taking time to talk with us. Fascinating.

Dr. FIRESTEIN: Ira, thank you.

FLATOW: You're welcome. Stuart Firestein...

Dr. WILSON: Thank you.

FLATOW: ...is professor and chair of the Department of Biological Sciences at Columbia. Don Wilson, research scientist at the Nathan Kline Institute and professor at NYU School of Medicine.

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