EMILY KWONG, BYLINE: You're listening to SHORT WAVE...
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KWONG: ...From NPR.
AARON SCOTT, HOST:
Heya (ph), flavor friends. Aaron Scott here with the newest episode in our Taste Buddies series. It's all about the science behind the wonderful things that tickle our tongues. So there is this story among scientists who study taste. Back in 1931, a chemist by the name of Arthur Fox was working with a chemical called PTC, or phenylthiocarbamide, which is similar to toxic compounds found in some poisonous plants. So Arthur was pouring some of the powder into a bottle, when some puffed up into the air.
MASHA NIV: And then his colleague, who was next to him, told him - what's going on? That's very bitter. But he did not feel that it's bitter at all. He didn't feel the taste.
SCOTT: This is Masha Niv, a biochemistry professor at The Hebrew University of Jerusalem.
NIV: And so he was very curious about it - how come the same compound tastes better for his friend, but is tasteless for him? And they started running this, like, voting experiment. And, actually, I think it's even an example of a very early crowd science experiment.
SCOTT: This was, of course, an earlier era, when it was totally cool for scientists to taste whatever random chemical they are working with and to enlist their friends, family and peers to do the same. Fortunately, PTC turned out to be safe, at least in very small doses. So these days, Masha uses PTC on strips of paper to run a similar experiment with her students.
NIV: What I do is I put a little bit of these strips in different small paper envelopes, and so that makes the people in class think that they are getting different papers because it comes from different sources. And then I ask, OK, so all together, place it on your tongue, try to taste it, and then tell me - which paper did you get? Who got the paper without any taste, and who got the paper with the terrible, terrible taste?
SCOTT: So you make them think that it's different pieces of paper with different compounds on it?
SCOTT: It's a fun trick, and it helps illustrate there's a lot more to bitter than meets the eye - or the taste bud, as the case may be. For example, for sweet things, there's only one type of taste receptor. For bitter, there are 25 of them. It's a giant family of bitter receptors that we're only beginning to understand.
NIV: I'm very interested in it because it's so complex, and I think that it got a bad name in terms of toxicity. So the way I think about it - it's not that bitter is toxic, but bitter says, pay attention.
SCOTT: So today on the show, we pay attention to bitter. What makes it so complex? What does it have to do with our immune system? And what are bitter taste receptors doing elsewhere in our bodies, like in the lungs? I'm Aaron Scott, and you're listening to SHORT WAVE, the daily science podcast from NPR.
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SCOTT: So to begin, SHORT WAVE producer Berly McCoy sent me some of the PTC strips like Masha hands out so I could play along like one of her students.
NIV: So if you're alone, you can just take one strip of paper and place it on the tongue.
SCOTT: So I'm putting this piece of paper in my mouth, and I'm sucking on it, and all I taste is paper.
NIV: OK. So you are probably a non-taster, which means that you got the non-taster version from both your mother and your father because people in the same family will tend to be - to have the same - you know, the tasting or not tasting.
SCOTT: I have to admit - I'm a little sad about this. I love bitter things, and now I'm kind of wondering - what am I missing out if I'm a non-taster of this bitter compound? What does that mean about how I taste things?
NIV: OK. So this is an excellent question because, actually, humans have 25 different types of bitter taste receptors. And this particular compound that you now tasted is recognized - or in your case, not recognized - by only one member of this family of bitter taste receptors, which still lets you feel bitter taste of other compounds - you still do feel bitterness of coffee and so on, but feeling the bitterness and liking the bitterness is not exactly the same. It's really, like, complex.
SCOTT: I like that.
NIV: Don't be sad, it's (laughter)...
SCOTT: OK (laughter). So don't lament that. Don't lament my inability to taste PTC.
SCOTT: OK. So why is bitter so complex? I mean, why do scientists think we evolved this ability to taste bitter things in the first place?
NIV: So bitter, as the common paradigm says, it has to protect from poisons or, as I try to say, it has to alert us so that we decide whether something is poisonous for us or not. Because, in the world around us, there are plants, and there are insects, and there are lots of natural chemical compounds around us, and we kind of need these receptors to say, OK, it's something new. Let's first be a little bit careful about it - a little bit averse to it. So this is the one possible reason.
SCOTT: Right. Right. Because not all bitter is bad. I mean, there are good bitter compounds too - or, well, at least I hope so, given how much some of us love things like coffee and, for me, you know, those herbal tinctures that you buy at the health food store that other people find gross. Maybe it's because I can't taste that bitter in them. But can you talk about the good flip side of bitter?
NIV: Yeah. So I think two kind of, I guess, lines of evidence for the good of bitter - one is that there is self-medication by some animals. So they are looking for specific herbs to chew on and to eat, and it is often connected to bitterness of these things that they are seeking. And another very connected issue is that many pharmaceutical drugs are bitter, and so one could think that there are perhaps antidiabetic, anti-inflammatory effects of bitter compounds which are also represented in pharmaceutical drugs. So this we need to find out.
SCOTT: And maybe somewhat linked to this - I read this really interesting thing that we have bitter receptors not just in our tongues, but in other parts of our body, too, right? And I'm not sure if that means that they're necessarily tasting or if they're just receiving, basically, these compounds. But, Masha, can you tell us more about where these rogue bitter taste receptors are and what they're doing?
NIV: OK. I'm not sure I can tell you what they are doing because not everything is clear...
NIV: ...But I just - for sure, they're not tasting. So one example, maybe related to the respiratory system or the upper airways - one really interesting finding - persistent infections are more common - now, you're going to be sorry again that you're a non-taster.
SCOTT: Oh, no.
NIV: They are more common than people who are non-tasters. And so they found that these receptors, when they're in the nose and the upper airways, they respond also to molecules that are released by bacteria. Basically, it's a way of chemical communication between bacteria, and so the bitter taste receptors are, like, listening in to these chemical cues between bacteria, and then the reaction is a release of molecules that can kill the bacteria. But if you have the non-taster version, then it doesn't work, and then there is more chance for, you know, persistent infection.
SCOTT: Great. Lucky me. Anyway, so I want to pivot to a tool you've developed called BitterPredict. You previously built this giant database of known bitter compounds, and then BitterPredict uses that database to create, basically, a decision tree that helps you predict if new compounds will be bitter or not. Why is it helpful to have this tool?
NIV: So there are several motivations. One of the reasons is that many drugs are bitter. When you're talking about pediatric drugs for children, the bitter taste is really a big problem in the sense that they don't adhere to taking the drug that they were prescribed if it's too bitter. And so far, the way it was being done is you develop the drug, and then, when it's already in clinical trials, or even when it is approved, then it turns out that actually it's very bitter, and it's a problem, and you need to change the formulation. And so it's really an inefficient way of doing that. So with...
SCOTT: And it also seems like why we end up with those super syrupy, sweet cough syrups and things...
SCOTT: ...'Cause the other option, I'm guessing, is you mask the bitterness with lots and lots of sugar.
NIV: Exactly. What we can do is predict the bitterness of drugs. Even when it's just a hypothetical structure of a molecule that we're just thinking of synthesizing, based on the formula, we can already predict if it might be intensely bitter. The next step is to develop inhibitors of bitterness.
SCOTT: Yeah. Yeah. And speaking of taste inhibition, it's my understanding that you are studying the loss of smell and taste for individuals who have had COVID-19, too.
NIV: So, yeah, so we - I've been studying this for the last two years, actually, and I wanted to know whether maybe different taste modalities are impacted in different ways in COVID-19. So, like, taste umami, sour - and if that would have been the case, that would have given us a hint at, you know, the mechanism of the impairment because the cells are separate for the different taste modalities. However, it turned out that they are impacted altogether, so we still don't know a lot about the mechanism, but about 10% of people who lost smell or taste still have this problem half a year and longer. But we do - we did find that taste recovers more quickly than smell, and usually you don't have taste impaired once the smell has recovered.
SCOTT: So what has this taught you about why taste is so important to our lives and well-beings?
NIV: I think it's really important because the senses of taste and smell maybe were not considered a major - it's not like sight and hearing, right? You are not considered disabled if you have these problems and nobody can see that you have it, right? It's very, like, subjective - a lonely feeling. So it was really important to show that it's a really, really common problem, and it has a huge effect on appetite and on emotional well-being.
SCOTT: Masha Niv, thank you so much for opening our taste buds to bitter.
NIV: Thank you so much.
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SCOTT: So if bitter whet your appetite, we have several more episodes from our Taste Buddies series, focused on salty, sour and umami. You can find them wherever you get your podcasts. This episode was produced by Berly McCoy, edited by Stephanie O'Neill and fact-checked by Margaret Cirino. The audio engineer was Natasha Branch. I'm Aaron Scott. Thanks for listening to SHORT WAVE from NPR.
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UNIDENTIFIED PERSON #1: I've got this little vial. It's filled with all these test strips. I just pulled one out, and I'm going to put it on my tongue. Hmm. Mmm. Mmm. Oh, my God. No, that's bad. I'm a taster. I kind of suspected that, actually.
UNIDENTIFIED PERSON #2: OK, it's on my tongue. I can taste it. It's pretty gross. It tastes like nail polish remover.
UNIDENTIFIED PERSON #3: Tasting the PTC strip. Oh. Oh, no. Mmm mmm. Not good (gagging). That's bad. That's really bad.
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