Dr. Stuart Firestein is the Chair of Columbia University's Department of Biological Sciences. His colleagues and he study the vertebrate olfactory receptor neuron as a model for investigating general principles and mechanisms of "signal transduction" — the ways in which chemicals, such as neurotransmitters, hormones, and peptides with membrane receptors, exert their influence in the brain and nervous system. He hypothesizes that the olfactory neuron is uniquely suited for these studies since it is designed specifically for the detection and discrimination of a wide variety of small organic molecules, i.e. odors.
Question: What is the difference between taste and flavor?
Stuart Firestein: So taste really refers to four, really five I suppose sensitivities and that’s sweet, sour, salt, bitter, the four well known ones and a relatively new taste sensation called umami, at least new in the west. It’s been known in Asian cuisines for quite some time, since at least the early 1900s when it was first discovered by a Japanese biochemist and umami is actually the taste of glutamine. I should say umami is a Japanese word that means savory and it’s actually the taste of the molecule glutamate, which is an amino acid. We’re all made of 20 amino acids. One of them is glutamate, so lots of us have glutamate in them, other animals, plants and so forth. You find very high concentrations in meat, but also in many vegetables and fruits like tomatoes for example. It’s a taste that has come to be recognized in the west at least largely I think because of the influx of Asian cuisine over the last couple of decades and so we now recognize it and we recognize there is a molecular process for sensing umami as well, which I’ll talk about in just a moment. So those are the four or rather, the five tastes, sweet, sour, salt, bitter and umami.
Flavor is another animal altogether in a way. Flavor is what we call a hedonic sense in that it is really a combination of several different senses, the five tastes, but also in a very important contribution from your olfactory or smell system. In fact, it’s estimated that about 85% of what we perceive of as flavor is really olfactory. It’s the sense of smell, which is why of course when you have a cold food doesn’t seem very appealing because you don’t smell it or you don’t smell much of it and then you’re left with just sweet, sour, salt, bitter and umami. Also important are things like temperature, so some foods taste correct at one temperature and taste not so good at another temperature. Also important is mouth feel. You don’t like a food that you don’t expect to be slippery or slick to be slick or slippery and of course carbonation and things like that make some beverages better or worse, so all of those things come together and give us this, as I say, hedonic sense of flavor and that’s much more complex than either taste or olfaction on its own.
Question: What is happening on a neurological level when we taste?
Stuart Firestein: So now we can talk about the molecular events that give you this sense of flavor. We’ll start I think just to be organized if you will then with the easier one, which is taste, sweet, sour, salt, bitter and umami and those occur on your tongue. They’re specialized cells that exist in various places on your tongue. Actually I should point out that more than 90% of the tissue of your tongue has nothing to do with taste. The taste cells, the cells that are sensitive to these various tastes occupy a really relatively small part of your tongue, but there are various sorts of either receptors or what we call channels, which are able to bind to, which are able to grab a hold of things like salt ions, sodium in particular or sweet molecules like sugars or bitter molecules or sourness, which is a question of what we call PH, which is due to hydrogen ions and they’re able to grab a hold of these particular kinds of particles and when they do so they signal through the cell, through the rest of the taste cell. They set up a change in the electrical properties of that cell and that is what is transmitted to the brain through a somewhat complicated pathway, a series of different cells all hooked together that go to a particular portion of your brain and when one of those cells is active your brain says this is salty or that’s bitter or this is a bit sour and so that is how at least those tastes, those very basic tastes are transmitted to your brain.
Now along with that when you chew food up your sense of smell becomes very important. Our sense of smell is mediated by tissue way up in the nether reaches of the nasal cavity way back up in our nose. It’s a thin tissue, a very thin we call it an epithelium, but that just means a very thin tissue that lines a bone way up in your nose here and it has cells in this tissue, which are sensitive to various odors. Now there are two ways odors can make it into our nose. One is by sniffing them up and that’s done of course and that is how we smell things in the room or outside or here or there, but we don’t have such a good sense of smell that way. Well I should make a more careful statement. It’s generally thought that humans don’t have a good sense of smell, but actually we do have quite a good sense of smell when tested carefully.
The biggest problem with our sense of smell is that we walk on two legs and all the good odors are 8 or 10 inches off the ground and we have our noses stuck up here at 5 or maybe 6 feet if you’re lucky in the air where we just don’t come into contact with odors and of course we don’t do certain behaviors that other animals that we think are more sensitive to smells do. I always joke that dogs are supposed to have a great sense of smell, but frankly that greeting thing they do doesn’t really look like a great sense of smell to me. I think you could do that from 10 feet away rather than putting your nose right there as it were, but in any case other animals are willing to put their noses where the odors are more than we are. The one exception to that is in the area of flavor and indeed humans have a very, very discriminating palate when it comes to food, much more than many other animals and the reason for that appears to be that as we chew our food we set up a pressure gradient, an air pressure gradient and we release the molecules in the food that are odor molecules and they go up the back of our throat through what is called unfortunately a name called the retro nasal pathway, which just means back of the nose really, but in any case this retro nasal pathway takes the odor molecules that are released by chewing the food and pushes them up the back of the nose and right directly onto to the epithelium in the back of your nose and this is why we then include olfaction as part of flavor because we get a great deal of the sense of flavor, the quality of a flavor of a substance from the olfactory input.
Question: Is there a way someone might try this at home?
Stuart Firestein: There is a simple experiment you can do at home to prove this to yourself. Take a jelly bean of any old flavor at all. I always find it works best with grape or cherry, but any old flavor at all will do. Hold your nose and put the jelly bean in your mouth while you hold your nose. Continue holding your nose and then chew up the jelly bean, but don’t swallow it. Your sensation will be if you think about it, will be of a kind of a gloppy sweetness, that is your sweet receptors on your tongue will be working and you’ll know it’s sweet and your feel or touch receptors all in your mouth will catch the texture of it, but it won’t have any of that cherry or grape flavor. Then after you’ve chewed on it for a little while and while it’s still in your mouth just open your nose and actually breathe out. It’s even more effective if you breathe out and I guarantee that you will be shocked to find that suddenly the flavor of grape or cherry or lime or whatever it is appears as if out of nowhere and that I think is a clear demonstration that it’s really in your nose that you catch much of the flavor.
Question: Is olfaction a more primitive or sophisticated sense?
Stuart Firestein: So olfaction is quite a remarkable sense actually. It’s often called the most primitive sense, the ability to detect chemicals in the environment and of course in biology the word primitive has a kind of a funny connotation. On the one hand you might say primitive meaning well the simplest or the most rudimentary, which is the typical meaning of the word primitive, but in biology of course because things happen over evolutionary time the more primitive something is the longer it has had to evolve and become better if you will, more perfected if you will and so this idea that the olfactory sense is the most primitive may also make it in some ways that most sophisticated.
Question: How does olfaction work on a neurological level?
Stuart Firestein: The olfactory sense works by having this thin tissue lining the region of your nose way up at the top with a set of cells which are called olfactory sensory neurons. The important thing there is they are true neurons, that is brain cells. They’re like the cells in your brain inside your skull, but they’ve kind of been pushed out into the top of your nose where they have the ability now to come into contact with odors in the environment or odors in food as I just mentioned to you. These cells express… Maybe that is a bad word. Let me go back on that if I may. These cells have the remarkable ability to detect and discriminate among a tremendous variety and number of chemical compounds out there in the world, which we call odors. There are at least 10,000, maybe 100,000 of them. There is certainly 10,000 identified odors because this is what we can find in the catalogs of flavor and fragrance companies and these are mostly only the good odors. There is probably another 10,000 bad smelling odors as well and then many new odors are created every day.
Most odors are small molecules. They’re what we call organic molecules in that they’re made up of carbon, but they’re relatively small. They’re volatile. They float around the air and they come up into your nose and can be trapped on the surface of these specialized neurons, olfactory sensory neurons, trapped by receptors that are on the surface of these cells. These receptors can be thought of as a kind of a lock and key mechanism at least to a first approximation. If you imagine that the receptor is a lock then a key is the odor molecule and if the odor molecule has the right shape it fits into the lock and activates the cell. It tells the cell I’ve found something that fits my receptor and I’ll change my electrical qualities and signal the brain that I’ve found a molecule that fits. On the other hand you might have another receptor shaped like this and this molecule won’t fit in it, but this molecule fits nicely and so we’re able to discriminate between different odors based on their shape and other chemical properties that make them either bind to or not bind to, fit or not fit into one of these receptors or locks. What is remarkable about the olfactory system is the number of locks that we make, the number of receptors.
So in a mouse or a rodent or a dog there are nearly a thousand different types of these proteins, of these receptors on the surface of all these cells, these millions of cells in your nose. Each one of those protein receptors, each one of those locks if you will, is encoded by a gene in your genome. Even in humans we have fewer receptors, but we still have quite a large number, about 450 of them, so let me put that in a little bit of perspective. We have about 25,000 genes that make up our whole genome. The whole plan for what we are is 25,000 genes in our genome, so that means and that is typical of most mammals. A mouse or a rat is about the same, so in humans that means that nearly 2% of the genes in our genome are devoted to our sense of smell, devoted to making these receptors. That is about 1 out of every 50 genes. In a mouse or a rat it’s almost 5% or about 1 out of every 30 genes devoted to making receptors in your nose. So clearly there is an evolutionary commitment to the sense of smell if you will.
Question: Why is understanding olfaction important, beyond telling us how we smell?
Stuart Firestein: One of the important things I’d like to say about these receptors is that they belong to a family of receptors that are also similar to them. They’re called G protein-coupled receptors, but that’s not so important to actually have the name for them, but there are a large number of these receptors beyond the olfactory receptors, about another 400 of them in our genome and they do very, very important things. These are also receptors for serotonin, for dopamine, for acetylcholine and for many molecules that float around in your brain and do important things, for various hormones and many other substances in your body, molecules in your body that have to be detected by other tissues.
So this is important because one of the reasons we study olfaction—aside from the fact that we think it’s a very cool sense and a very cool ability—is that we feel if we learn something about these receptors in olfaction we’ll know something about them elsewhere too. We’ll learn how to design drugs that fit directly into these receptors and don’t have as many side effects as current drugs do. So we consider it a kind of, if you will, a model system, because what olfaction does is molecular recognition. It recognizes molecules and really every cell in your body, every cell in your brain and every cell in every organ in your body is busy recognizing molecules and responding to them whether they’re hormones that float through the blood or drugs or metabolic byproducts or a variety of other substances. We are, in the end, chemistry.
Question: Are olfactory signals processed in your brain in a similar fashion to visual or auditory signals?
Stuart Firestein: So the olfactory neurons once they bind this odor molecule and change as I say, their electrical quality, the voltage if you will, across their membrane this signal is transmitted to the brain down a long cable-like structure called an axon, which most brain cells have. It goes through a very thin bone and into a region of your brain called the olfactory bulb, a very small chunk of your brain that actually hangs under the bottom of your brain just kind of behind your eyes if you will. And there they make a connection with another set of neurons, so a connection that we call a synapse and they make a connection with another set of neurons, which then transmits the message to the next step in the brain.
So the first step, the first relay station is the olfactory bulb and from there the signal is sent mostly to an area, specialized area of cortex, of brain cortex called the piriform cortex. Now this pathway is unusual because the other senses typically from the primary tissue—the retina or the auditory, the hair cells of the auditory or the cochlea—send their signals first to a tissue in the center of the brain, an organizing region in the center of the brain called the thalamus. And there the signals are sorted and standardized and then moved out into specialized area of the cortex—the visual cortex at the back of your brain, the auditory cortex on the side of your brain—for further processing and presumably building up into a perception. I’m waving my hands a bit here because we really don’t understand so much about those processes yet, although we’re beginning to.
The olfactory system is a bit unusual in that way in that it does not go through the thalamus. At some point later in the progress of olfactory information there is an offshoot of some of the fibers that do go to thalamus, but it’s rather minor. So instead in the olfactory system you go from the sensory neurons to this olfactory bulb structure where there is a synapse with another kind of cell. It’s called a mitral cell—and those mitral cells take in information from lots of different sensory neurons and decide what is being smelled out there, because of course most of the time we don’t smell a single molecule, we smell a blend of molecules. Usually a complex blend of molecules and so pulling that all apart is at least partly the job of these mitral cells to which the olfactory sensory neurons make a connection. The mitral cells then make some decisions, if you will. They integrate information and they have an axon also, a long cable that goes to this area of the brain called the piriform cortex where they synapse, make connections with yet another cell.
So what is remarkable about this in the olfactory system is that from the outside world to cortical tissue, which is the highest level of brain tissue we have, there are only two synapses, two connections, one between the sensory neuron and the cells in the olfactory bulb and then between these olfactory bulb cells, the mitral cells and those in the piriform cortex.
In any other system you wouldn’t be anywhere yet. In the visual system you’d still be in the retina after two synapses. You wouldn’t have even gotten to the inner retina let alone to the thalamus or to the visual cortex, which is six or seven synapses away. The same thing is true of auditory system and many other sensory systems including taste by the way, the actual taste system. There are at least three, four, five synapses to get you to cortical tissue whereas the olfactory system has this very immediate access to the cortex.
Question: Why are taste and smell so closely linked with our memory?
Stuart Firestein: The connection between taste, smell and memory is a very curious one. It’s well documented. We’ve all had the experience. There are interesting quirky things about it. Why there is such a connection or how it exactly works is not so well known, but we get hints from the nature of it.
So we’ve all had the experience of course, this so called "Proustian" experience. You know there is a famous passage in Marcel Proust’s "Remembrance of Things Past" in which he tastes a Madeline cookie and a sip of lemon tea and this vivid memory from 40 years earlier, from his childhood 40 years earlier—coming home from church and having this lemon tea and a Madeline cookie at his aunt’s house—just comes back to him and perfectly vivid, as if it were right there in front of him and he writes several pages about that and then goes onto write what, 40 volumes or some crazy thing, about 7 volumes I think it actually is of memory, of memories. So that’s maybe the extreme example, but we’ve all had that experience where we smell something or we taste something and some memory quite vivid comes back, usually from quite some time ago.
Now one of the things we can note about those memories is they’re always emotionally laden somehow or another. You don’t smell something and remember a page of text or an equation or a phone number or something useful like that. You always remember something like grandma’s living room, the first day of school. You know one of the most recognizable smells in America is the smell of crayons, Crayola crayons. So you know that brings right back, you can imagine that smell and you’re right back in school somehow or another. So it’s always something emotional, your first lover or some event like that. So that is one important thing about it. It seems to have an emotional content rather than an informational content if you will, for these memories.
The other is that they are long-lasting. We recall things from many, many years ago and they’re extremely vivid. Now the ones that involve taste—which I remind you again also involve olfaction really—we call them taste aversions because you have the sense that it’s taste and it’s in your mouth, but this is just a trick by the way, your brain is playing on you. If you’ve done the jelly bean experiment you’ll know that the flavor is due to your olfactory system and yet the experience of flavor is unquestionably still in your mouth. This is just some little trick your brain plays on you because it thinks that is where it should taste things. So we call them taste aversions. These are very interesting and we’ve all had this experience too. We eat some food. A few hours later we get sick from it and that’s it. We just can’t even think about eating it again. This is also very, very interesting kind of learning, which is very uncommon.
For one, it’s one-trial learning. You eat something. You get sick from it. You’re done with it. It lasts for an extremely long time, typically years, sometimes the rest of your life. You just don’t want anything to do with whatever it was that made you sick, peanut butter or lobster or whatever it was you know. And most remarkably this memory can be formed with several hours of delay, which is very uncommon. Usually in order to make... and this works for other animals well, not just people. You can induce a taste aversion in a mouse or a rat or a dog or anything. They get them normally, but you can also induce them. And you can do them with hours of delay, so you can taste the food. You can eat the food and then you get sick on it four or five, six hours later and that’s... You could have even eaten things in between that and it doesn’t matter. Your aversion will be to what you tasted then that made you sick. And as I say that is true for other animals as well, so it’s one-trial learning. It’s extremely long-lasting. It’s a very stable, intense memory and it can be formed with significant delay in it.
There is a great instance of this I have to say. A researcher named John Garcia I believe is his name. Several years ago he was... I forget where he was, but at some university in I believe California, in any case in the West. And there was a problem with coyotes predating on sheep, so sheep farmers were up in arms. The coyotes were killing off their sheep and they wanted to go out and shoot all the coyotes, which would have also been a bad idea because it’s part of a whole ecosystem, et cetera, et cetera. So Garcia came up with this idea that maybe he could get the coyotes to leave the sheep alone and he did it by using taste aversion, so he took a few sheep carcasses, dead sheep and he laced them with a chemical called lithium chloride. Now if you eat something with lithium chloride in it you will get dreadfully ill. You’ll get terribly sick, miserable nausea and all the rest of that, but you will not die from it and so these coyote
would come and eat these sheep. Then they’d go back to their burrow and they would spend a miserable night being sick from the sheep and that was it. They just didn’t want anything to do with sheep after that and you had these coyotes that just they’d find something else to eat, whatever it was. I’ll go kill something else, but I’m not messing with sheep anymore, so it was effective actually.
Question: Why do some things taste good and some things taste bad?
Stuart Firestein: The question of why we decide that something tastes good or doesn’t taste good or is disgusting even somehow, is being... I would say this is an area that is being researched... a lot of effort is being put into research in this area and we don’t really understand it. It’s particularly interesting because it’s clearly a combination of nature and nurture. It’s one of the great places to study this question of nature versus nurture if you will.
There are some things that seem to just simply disgust us in a very, very instinctive deep kind of way that seems to be built into the organism and there are other things that we clearly learn to find either good or bad. We use foods as rewards and as punishments. There are very important sociological and cultural issues about food and these are clearly learned and yet there are other things about it that are clearly inside of us. Indeed, think of the word disgust. The root of the word disgust, gust is the word we use for taste, which is gustatory, the gustatory system or gustation is the scientific word for the sense of taste. And so we think of something as "disgusting" because it repels us.
Where it comes from or how it exactly works I have to say is still one of the great unknowns and of course there are huge cultural differences as well as to what is acceptable and unacceptable in the way of food and taste, flavor. So it’s a very interesting question. And it’s one of those interesting questions because it’s not just science. It’s anthropology as well and cultural studies. It’s one of those kind of interesting interdisciplinary kind of places where people of all sorts of stripes are interested in it.
Questions: Why are you so interested in language and smell?
Stuart Firestein: I can ask you to close your eyes and imagine the color red or imagine a lemon or imagine the color yellow and you won’t have much trouble doing that. It’s pretty easy to sort of bring up some image of this, but if I ask you to conjure the smell of a lemon most people find that extremely difficult to do—even though if I then with you blindfolded put a lemon under your nose you’d go "lemon." I mean there would be no question about being able to identify it, but conjuring is a bit more difficult. And there are people who think—and I think they’re probably right—that at least some of this has to do with the way we name odors and to some extent flavors and the language we use for it.
For example, we have no primary terms for odors. We say it’s fruity. It’s woody. It’s amber. We don’t have a word like red or blue or green that just means the color, you know. We don’t have C, middle C, which means a certain sound or something like that. We use words that are borrowed from other places and so the linguistics of olfaction I think are at least in some way or another reflect both the difficulty sometimes of remembering odors or the difficulty of conjuring them, why it is some people are better at it than others. Perfumers and chefs seem to have more language associated with odors. They’re good a describing odors in all kinds of ways that you and I would never think of.
Question: How many different distinct scents can the best nose in the world actually smell and record in one sniff?
Stuart Firestein: This is a very interesting question this notion of how analytical our sense of smell is you might say. And there is some classic work done by a fellow named David Lang in Australia in which he showed that if he takes four odors let’s say, four fairly common odors that you would have no trouble identifying and puts them in little bottles, the fluids in little bottles. One after another puts them under your nose, you’ll say that’s banana, that’s lavender, whatever the four are and then he blends them together in ways that he doesn’t tell you, so he puts two of them together and puts it under your nose and you can identify quite easily which two he has put in, in any random way. Then he puts three of them together and it becomes much more difficult to figure out which three of the four are in there. And by the time he puts four in there, there is no way you know, so actually the experiment is done with six otherwise you’d know if it was just the four, so once you hit three or four odors in a blend you have a great deal of difficulty analytically determining what are the things that made up that now essentially new perception of a particular odor, of the blend. And that’s true not only as it turns out for amateurs, but normal people, but also for perfumers and well trained chefs and fragrance artists. They’re not too much better.
Recorded September 22, 2010
Interviewed by Andrew Dermont