Support for NPR and the following message come from the William and Flora Hewlett Foundation. Investing in creative thinkers and problem solvers who help people, communities, and the planet flourish. More information is available at Hewlett.org. You're listening to Shortwave from NPR. If you've tried alcohol, you might remember the first time as some rebellious choice or as part of some holiday ritual like champagne at New Year's. Or it could have been by accident. I had mine in the middle of winter, somewhere around this time of year. I was only about eight or nine and a snowstorm had hit the tiny town I lived in along Washington State's border with Canada. The power had been knocked out and the house was freezing. So my mom gathered me and my brother and my sister and gave us a tiny sip of cognac to keep us warm. Telling it now, it kind of feels like something out of a novel, but if you're Katie Wu, that first sip can also be pretty mundane. I vaguely remember taking that little errant sip of wine at some dinner party my parents had when I was a kid. I don't think that did anything to me except make me go, I'm spitting this out. Years later, Katie finally tried another drink because I was a very, very, very well-behaved high schooler. And I sort of already knew what was coming because I had watched my parents get extremely red and goofy and sweaty and warm every time they went out and had sake or red wine. I knew what was likely in my future. Like clockwork, when Katie started to sip that drink in college, her face bloomed red. I would compare myself to a human stop sign or if Rudolph's nose was the entirety of my face, like truly the warmth blooms from my cheeks and then spreads all over and even starts to creep down my neck. You can see it from across the room. Yeah, for me, it gets splotchy. You know, like I notice like I have the splotch on my arm or on my legs or something. Yeah, it's almost like a weird allergic reaction. Yes. I once had a friend like accidentally walk past me and touch my face just incidentally and he pulled his hand away like he had just touched a hot tea kettle and he literally went, whoa, your face is so warm. This happens because she and I get what's commonly called Asian flush or Asian glow when we drink. Katie is just one of what researchers estimate to be about half a billion people with the condition. Now, not everyone who has it will experience it in the same way. A lot of people will have redness not just in their face, but a little bit all over the body. Some people will start to sweat. Some people will actually start to feel a little bit nauseated. Other people will even get a little bit dizzy. For me, my top symptoms are definitely redness, warmth in the face and tons of nausea and dizziness. As a staff writer for the Atlantic, Katie wrote an article on the topic. She mentions that mostly East Asian people have this reaction, hence the name. The kind of nitty gritty of this is honestly poison is building up in your body. One of the kind of natural breakdown products of alcohol is this compound called aldehydes and they occur in a bunch of different forms. But for people with Asian glow or alcohol flush, they lack the molecular machinery to break down those toxic aldehydes and so they're kind of sitting there with poison stewing in their tissues for a lot longer. And aldehydes in the body don't just come from alcohol. They also build up naturally as part of your metabolism. So why would evolution make it so that some people, a pretty sizable amount, can't properly break down aldehydes? Today on the show, Katie shares how this biological process goes haywire and one theory as to why it might have been a powerful tool for some of our ancestors to survive disease. I'm Regina Barber and you're listening to Shortwave from NPR. Support for NPR and the following message come from the William and Flora Hewlett Foundation, investing in creative thinkers and problem solvers who help people, communities, and the planet flourish. More information is available at Hewlett.org. Okay, Katie. So Asian glow affects half a billion people, including you and me. And it's because of a genetic mutation we both have, right? Yeah. And what is just wild about that is it is one of the most common genetic mutations out there. And science has actually nailed it down to a single change in a single gene, aldehyde dehydrogenase 2. And so everything is kind of in there in the name. It dehydrogenates aldehydes, which effectively means it is in its functional form breaking down these toxic aldehydes. But for people with a mutation, they make basically a broken copy of this aldehyde detoxifying machine. And so the aldehydes build up. I will say that, you know, because all of us carry two copies of every gene in our body, most people are actually heterozygous, which means they carry one normal copy and one broken copy. That's the case for most people with this condition. But the effect is dominant, which means even if you have just one broken copy, you're generally going to experience some of those symptoms and they can get actually pretty bad. What are aldehydes? Like why are they so toxic? Right. So aldehydes in short are carcinogens. They are these pretty toxic compounds that can actually do direct damage to DNA and proteins if they sit around too long in your cells. They will, you know, cause literal mutations in our genetic code. And that's really not great. Yeah. And so everyone has two copies of a gene, right? Like one from each parent. We just talked about that. What would happen if you had two copies of this genetic mutation and you're not processing this alcohol at all? Right. To have absolutely no functional copies of this gene means that any time that you accumulate aldehydes in your body, whether it's because you're drinking or just living as a normal human who is producing aldehydes is a normal part of metabolism. The aldehydes are not really going to go away very quickly, which means more damage to DNA, more damage to proteins. Your cells are just going to be kind of living in a rougher state of things, more stressed, more damage, more opportunity for things to go awry. One possible way to sort of think about it is like if you picture a sink that's draining and what you want to do is get rid of all the poison in the sink by fully draining it and the faucet is running. There is no way to totally shut off your aldehyde faucet because your body is constantly metabolizing something. People who have two normal copies of aldehyde dehydrogenase have a completely unstop sink. The stopper is totally lifted. And if you are heterozygous, you have just one defunct copy. It's lowered maybe halfway, but rotter is still dribbling through. If you've no functional copies, you've basically plugged that sink. But then when you're drinking, it's like right, right, right. Yeah. I mean, when you're drinking, it's like you've not only got the faucet dripping, but you've got like a gallon jug that you're also just pouring into the sink. And so how does the body get rid of these aldehydes if there is a buildup? Right. So there are some backup systems in place, other ways that the body can get rid of aldehydes, but they have traditionally been thought of as backup systems, secondary, maybe not as effective. So it's not like the poison will build up and suddenly you will just dissolve into a sludge of aldehydes and you will cease to exist. Eventually, this will all break down. But basically, you can think of it as people with this mutation sort of stewing in poison a little bit longer than people who have functional copies of this aldehyde cleanup system. And in your article, you write that by one line of evolutionary logic, I and other sufferers of so-called alcohol flush shouldn't exist. What's your reasoning there? Yeah. I think the main thrust of that argument is just that it is absolutely bizarre that there are so many flushers around today. Half a billion people, that is absolutely bonkers for a mutation that not only makes it difficult to drink, but raises your baseline risk of a bunch of health conditions that are not benign. Esophageal cancer, certain kinds of cardiovascular disease. This is not a fun thing to have. I mean, you are basically walking around as a human that has a lot more poison sitting in their tissues, which isn't generally something that evolution selects for. Now that we've gotten that out of the way, let's swing positive like your article does. So recently, an NYU microbiologist, Harin Darwin, and her colleagues reported their findings that people with this mutation might be especially good at doing something else, right? Right. So if you sort of spin this story the other way, it's not why are there so many people with this broken gene walking around? It's what might have made that version of this gene super useful to our ancestors in the past. And one possible answer to that is it might have helped us fight off a bunch of different infectious diseases. And I kind of love the logic here, right? We know that there is a kind of poison component to this story. Having this buildup of aldehydes in our body is bad for our tissues, but aldehydes are such a kind of all-purpose toxin that the idea is they could be harming microorganisms that wanted to hurt us as well. And so maybe our bodies just kind of wised up to the system and they were like, okay, we're making all of this toxic trash. Maybe that can actually be useful for defending ourselves, which has to come into play really often. Specifically related to tuberculosis. Yeah. So one of the most intriguing possibilities is that this could have been useful against ancient outbreaks of tuberculosis. And that's actually a really compelling idea, because we know that tuberculosis or TB has been one of the greatest infectious killers in history. If there was even a slight advantage to carrying this mutation, if it meant that people were even slightly better at suppressing bacterial growth or spreading fewer of the bacteria to others, then that might have been enough to help this mutation sort of build up in the population and reach some of the numbers that it did today. And we should also note that this work is currently under review at the Journal of Science. So it hasn't actually been given peer review a thumbs up yet, right? Yeah, exactly. And there was a note in your article, I remember that you said that this is a hypothesis, right? It might not have helped TB. So we should just be a little cautious about kind of making that connection. I think that's absolutely right. The TB idea, I think is a really compelling possible example. It is tricky to prove though, right? And we know that, for instance, aldehydes can kill TB in the laboratory. That is super compelling, but it doesn't necessarily mean that TB is what drove this mutation to prominence thousands of years ago. A lot of experts who weren't involved with the work told me infectious disease writ large probably was a huge influence here, because there's evidence that aldehydes are bad, again, not just for our tissues, but a ton of bacterial cells. Maybe they could have even been bad for parasites or viruses, which also have to have proteins and genetic material to function. So even if it ends up not being TB specifically, or it ends up being TB, but also a bunch of other stuff, that still points to a possibility that infectious disease is what was kind of in the background, making a bunch of us flush when we drink alcohol today. Thank you, Katie, for validating my struggle and showing that there might be a positive to it. Yeah, I mean, what I kind of love is that this story gives me a reason to be a little bit proud of this mutation. Whereas I always had to be like, oh, yeah, I'm getting read again. I'm sorry, like I'm that person. But you know what? I feel like it's something that you can wear proudly as a badge from now on if you choose to. Oh, I'm going to. Thank you so much for coming on our show. Of course, anytime. This episode was produced by our showrunner Rebecca Ramirez and edited by Burley McCoy. Britt Hansen, check the facts. And Gillie Moon was the audio engineer. Beth Donovan is our senior director and Colin Campbell is our senior vice president. I'm Regina Barber. Thank you for listening to Shortwave from NPR. Support for NPR and the following message come from the William and Flora Hewlett Foundation. Investing in creative thinkers and problem solvers who help people, communities and the planet flourish. More information is available at Hewlett.org.
