Ep 153 Alpha-Gal Syndrome: A tick bite gone bad

Speaker 1 This is exactly right.

Speaker 3 Be honest, how many tabs do you have open right now?

Speaker 4 Too many?

Speaker 2 Sounds like you need Close All Tabs from KQED, where I, Morgan Sung, Doom Scroll so you don't have to.

Speaker 4 Every week, we scour the internet to bring you deep dives that explain how the digital world connects and divides us all.

Speaker 7 Everyone's cooped up in their house. I will talk to this robot.

Speaker 9 If you're a truly engaged activist, the government already has data on you.

Speaker 10 Driverless cars are going to mess up in ways that humans wouldn't.

Speaker 11 Listen to Close All Tabs, wherever you get your podcasts.

Speaker 12 We all have that piece.

Speaker 14 The one that's so you you've basically become known for it. And if you don't yet, fashionistas, you'll find it on eBay.

Speaker 14 That Mew Mew red leather bomber, the Custo Barcelona cowboy top, or that Patagonia fleece in the 2017 colorway.

Speaker 14 All these finds are all on eBay, along with millions of more main character pieces backed by authenticity guarantee. eBay is the place for pre-loved and vintage fashion.
eBay, things people love.

Speaker 17 I'm a kid, so am I going to surprise you with a poster board I need for the science fair tomorrow? Probably, but can you get up to 40% off back to school essentials on Uber Eats? Definitely.

Speaker 17 So order on Uber Eats and get up to 40% off.

Speaker 12 Exclusions May Apply. Check out for availability.

Speaker 18 Hi, my name is Winnie.

Speaker 18 And I'm an ecologist. In the summer of 2018, my husband and I moved to northeast Missouri for his job.
In early August, we decided to go for a hike at a nearby conservation area.

Speaker 18 We had about a mile left in the hike when we heard rustling in the brush beneath some big oak trees. It turned out to be a red-tailed hawk with a broken wing.

Speaker 18 In order to bring the bird to the nearest wildlife veterinarian located in Columbia, Missouri, we needed to get the bird to our car.

Speaker 18 So my husband gave me his overshirt. While he distracted the hawk, I tossed the shirt over the bird's head to calm it down, and we safely carried the bird back to our car.

Speaker 18 It was like a 90-minute drive to Mizzou Veterinary Hospital, and before long, we noticed that our feet and our ankles were really itchy. About halfway to Columbia, we had to stop for gas.

Speaker 18 So that's when I pulled down my sock and I saw what looked like thousands of tiny grains of sand moving across my ankles. At the time, I was convinced that these were chiggers.

Speaker 18 With very few options for how to remove them, we continued on our mission to get the hawk to the veterinary hospital. The staff stabilized and treated the animal, and we drove back home.

Speaker 18 After that day in 2018, my husband and I avoided areas that were trigger-prone, particularly between April and September when they're the worst.

Speaker 18 We also used repellent sprays and we treated our clothes and shoes with permethrin to deter sugars.

Speaker 18 It's worth noting that we had also been warned about lone star ticks.

Speaker 18 These are really common in Missouri and they're common even in urban and suburban areas and they're also really aggressive feeders.

Speaker 18 So we were really careful not to get any ticks and it turns out that sugar treatment and tick treatment for clothes and repellents, they're the same thing.

Speaker 18 One evening in October of 2022, we made a meal with hamburger. It was noteworthy because we didn't eat much meat and it was a special treat for us.

Speaker 18 Later that night, I woke up violently ill and I was certain that I had gotten food poisoning.

Speaker 18 At some point while I was dry heating into a bucket, I realized that my ankles and my palms were insanely itchy and covered in hives. The hives quickly spread to my torso, legs, arms, and scalp.

Speaker 18 I was struggling to breathe and I remember feeling that numb feeling in my entire body. You know the feeling when you get Novocaine at the dentist? It was like that, but everywhere.

Speaker 18 I wasn't thinking entirely clearly, but I do remember taking two Benadryl, waiting about five minutes, panicking, and then taking two more Benadryl.

Speaker 18 While I waited for the hives to go away, I remember trying to figure out how and why food poisoning could cause hives. The next day, I arranged to see an allergist.

Speaker 18 He sent off a bunch of blood tests and one of them came back positive. It was for AlphaGal.

Speaker 18 As an ecologist, I knew about AlphaGal. I had friends with AlphaGal, I have coworkers with AlphaGal.
It's something that we're aware of in the ecology world, at least in Missouri.

Speaker 18 But I do remember being really angry. I was angry because my husband and I had been so careful not to get any ticks or chiggers since that first incident in 2018.
But then I remembered.

Speaker 18 I remembered those chiggers.

Speaker 18 And in hindsight, they had to have been seed ticks or tick larvae. We probably had walked into a bed of these seed ticks and we were probably bitten by hundreds of them.

Speaker 18 Also, it wasn't until the doctor told me the results of those tests that I realized a lot of the last four years really just sort of fell into place.

Speaker 18 You see, sometimes I had, I had noticed that my ankles and my arms would get really itchy for no apparent reason.

Speaker 18 In hindsight, it was usually after I had like jello or soup that was made with beef broth. Fast forward to the present, in 2023, we moved to Minnesota.

Speaker 18 As an ecologist, I like to keep an eye out for all sorts of different organisms, and I note how their ranges are changing. Just last month, I found a lone star tick on my dog.

Speaker 18 Neither she nor I have been to Missouri for over a year. So, those little ticks, those little lone star ticks, they are moving their way north.

Speaker 12 Winnie, thank you so much for sharing your story with us. We really appreciate it.
And, like, my gosh, what a strange

Speaker 12 thing this is.

Speaker 15 I know.

Speaker 23 Thank you so much for being willing to go through all of that with us and with all of our listeners.

Speaker 15 We really appreciate it.

Speaker 12 Yeah.

Speaker 12 Hi, I'm Erin Welsh.

Speaker 15 And I'm Erin Allman Updike.

Speaker 12 And this is this podcast will kill you.

Speaker 26 And today we're getting real weird.

Speaker 27 Really weird because we're talking about AlphaGal syndrome, aka red meat allergy.

Speaker 12 As given to you by the bite of a tick.

Speaker 31 By the bite of a tick.

Speaker 32 It's so weird, Aaron.

Speaker 15 Yep.

Speaker 12 It is. It is very bizarre.
It feels like something out of a sci-fi novel that's that's like, you know, near future, and the world is about to collapse because climate change and farming and whatever.

Speaker 12 And so then a rogue scientist introduces this thing into ticks that causes everyone to be vegetarian. Yeah, you get the

Speaker 15 liked it a lot.

Speaker 33 I would watch that movie, honestly.

Speaker 12 I would, yeah, I would absolutely watch that movie and probably fall asleep halfway, but that's my, that's my jam.

Speaker 35 Yeah, it's uh, I'm really excited for it.

Speaker 36 It's going to be a really really fun episode.

Speaker 38 Yeah, I have so many.

Speaker 39 It's so weird. It's so weird.

Speaker 15 Yeah.

Speaker 12 And we'll get into all of that weirdness

Speaker 15 later on.

Speaker 12 But first, we've got some other business to take care of.

Speaker 40 We do.

Speaker 41 It's quarantining time, as always.

Speaker 12 So what are we drinking this week?

Speaker 43 We're drinking Gal Pal.

Speaker 15 You know, just your little Gal Pal.

Speaker 15 Gal Pal.

Speaker 15 You're also a Gal Pal.

Speaker 45 It's a delicious beverage.

Speaker 47 Of course, it is made with none other than Beef Eater gin.

Speaker 15 Not sponsored.

Speaker 12 Not sponsored, but

Speaker 12 we can't pass up that name, that branding.

Speaker 48 As well as passion fruit and lemon lime soda.

Speaker 49 It's a really refreshing gin bev.

Speaker 15 Yeah. Gal pal is.
It's great.

Speaker 12 Yeah.

Speaker 12 And check it out because we'll be posting the recipe for Gal Pal, the quarantini, as well as gal pal, the placebarita on our website, this podcastwillkillyou.com, and all over our social media channels.

Speaker 12 So if you're not following us there, you really should be because we're coming out with some pretty stellar content, if we do say so ourselves.

Speaker 15 And we do. We do say so ourselves pretty much every week.

Speaker 15 We do.

Speaker 51 If you check out our website, you will also find a lot of other really great content that we tell you about every single week, including transcripts from all of our episodes, which I believe you can now find as well on Apple podcasts.

Speaker 45 Speaking of Apple podcasts, are you subscribed?

Speaker 21 Because you should be to make sure that you're helping support the show.

Speaker 15 It really helps us to double check that you are subscribed and haven't accidentally been unsubscribed, which happened to me, in fact, from our own podcast.

Speaker 55 And anyways, back to our website.

Speaker 43 You can find transcripts.

Speaker 56 You can find merch.

Speaker 42 We have a whole bunch of merch.

Speaker 22 We have new merch and we have a few items left from some of our old merch.

Speaker 15 So if you wanted to get your hands on things that you thought we were out of, double check because we might just have it there.

Speaker 12 Limited stock.

Speaker 15 Uh-huh.

Speaker 59 We've also got links to Bloodmobile, who does the music for all of our episodes.

Speaker 44 We've got a Goodreads list.

Speaker 30 We've got a bookshop.org affiliate account.

Speaker 60 We have the sources from all of our episodes.

Speaker 48 Oh, my goodness.

Speaker 19 This podcast will kill you.com. Check it out.

Speaker 12 I don't think we have any other business, do we?

Speaker 15 No.

Speaker 12 Okay, well then let's get started because I feel like we have a lot of ground to cover when it comes to this bizarre thing called Alpha Gal syndrome.

Speaker 61 We do, we do, we do.

Speaker 15 Let's get into it right after this break.

Speaker 11 Hi, I'm Morgan Summ, host of Close All Tabs from KQED, where every week we reveal how the online world collides with everyday life.

Speaker 62 There was the six-foot cartoon otter who came out from behind a curtain.

Speaker 10 It actually really matters that driverless cars are going to mess up in ways that humans wouldn't.

Speaker 12 Should I be telling this thing all about my love life?

Speaker 63 I think we will see a Twitch stream or president maybe within our lifetimes.

Speaker 4 You can find Close All tabs wherever you listen to podcasts.

Speaker 65 Top reasons your dog wants you to move to Ohio.

Speaker 64 Amazing dog parks to stretch your legs. All four of them.
Dog-friendly patios. Even gourmet hot dogs loaded with the good stuff.
Bone appetite.

Speaker 64 And Ohio has so many high-paying jobs, you'll be top dog in no time. Jobs in technology, engineering, science, advanced manufacturing, and more.
The career you want and a life you'll love.

Speaker 65 Have it all in the heart of it all.

Speaker 64 Go to callohiohome.com.

Speaker 63 This is where projects come to life.

Speaker 63 Our showrooms are designed to inspire with the latest products from top brands curated in an inviting, hands-on environment, and a team of industry experts to support your project.

Speaker 63 We'll be there to make sure everything goes as planned, from product selection to delivery coordination. At Ferguson Bath Kitchen and Lighting Gallery, your project is our priority.

Speaker 62 Discover great brands like Kohler at your local Ferguson showroom.

Speaker 15 Alpha Gal syndrome is, at its core, a food allergy.

Speaker 45 And allergies are a hypersensitivity response to a very specific

Speaker 15 thing.

Speaker 69 Most allergies usually are a hypersensitive response to a protein.

Speaker 45 So, that right there is the first of so many places where the story of alpha-gal syndrome is so much weirder than just a food allergy.

Speaker 13 Because, in this case, it's an allergy to a specific sugar, alpha-gal.

Speaker 42 And alpha-gal, of course, has a much more complicated chemical name.

Speaker 21 It's galactose alpha13 galactose.

Speaker 12 It's really hard to search for because I didn't want to have to put in the little alpha sign every time I searched.

Speaker 73 Actually, I never thought about if you just type alpha, does Google also recognize alpha as the word alpha?

Speaker 15 You know?

Speaker 12 Probably.

Speaker 15 I don't know.

Speaker 15 And I don't know enough about SEO or whatever.

Speaker 12 Anyway. Oh, gosh, no.

Speaker 48 In any case, galactose alpha 1, 3, galactose alpha gal so this is a short sugar it's a oligosaccharide it's just a couple of sugar molecules linked together in a specific way and alpha gal syndrome is when people develop an allergy to this particular sugar And like we already mentioned, this food allergy is also different than most food allergies because it develops after an initial exposure, not to a food, but to a tick.

Speaker 25 So I figured to understand the story of AlphaGal, to understand this weird food allergy, we first have to kind of take a step back and understand allergies more generally, like how do allergies, food allergies usually work?

Speaker 32 So an allergy at its core, like I said, is a hypersensitivity reaction, which basically means it's your body overdoing it in response to some kind of exposure, and that exposure is usually a protein.

Speaker 76 So in the case of food allergies, it's proteins that we eat.

Speaker 60 And adverse reactions to foods can come in a lot of different types and flavors.

Speaker 68 We already covered this season, celiac disease, which is an adverse food reaction to specific proteins in gluten.

Speaker 78 Some types of adverse reactions are classified as allergies, and these are usually what are called IgE-mediated allergies.

Speaker 23 And IgE-mediated allergies are the types of allergies that you probably think of if you think of a food allergy.

Speaker 15 You probably think of, most classically, peanuts.

Speaker 75 So someone who's allergic to peanuts might develop hives and then throat swelling and then anaphylaxis, difficulty breathing, after exposure to peanuts.

Speaker 68 At its core, what's happening here is that our body is mistaking a food protein, like a peanut protein, for a pathogen and then mounting an immune response to this perceived threat.

Speaker 13 But it's doing that in a weird way by making these antibodies called IgE antibodies.

Speaker 15 So

Speaker 52 to understand allergies, we then also have to understand what the heck is an IgE antibody.

Speaker 12 Can I ask a question real quick?

Speaker 15 Please.

Speaker 79 Why

Speaker 12 proteins?

Speaker 30 Ooh, good question.

Speaker 71 I don't have an exact answer to that, except that proteins tend to be be more immunogenic.

Speaker 15 Okay.

Speaker 71 So it's similar with like vaccines.

Speaker 23 A lot of times, if we try and develop a vaccine against just carbohydrates or sugars that we could also target on the outside of a pathogen, that doesn't tend to last as long.

Speaker 30 So we usually then link it to a protein, like for example, tetanus toxoid.

Speaker 52 And then we'll link carbohydrates to that protein to generate a better immune response.

Speaker 26 But I don't know why proteins tend to be more immunogenic.

Speaker 82 Yeah, it's a good question.

Speaker 12 It's interesting.

Speaker 15 Okay. Yeah.

Speaker 12 And so I feel like maybe this is jumping ahead.

Speaker 15 Okay.

Speaker 15 You said

Speaker 12 when, when you are exposed to something that triggers this IgE response,

Speaker 12 the IgE response is because your body is thinking that this is a pathogen,

Speaker 12 but this response is kind of out of control and really bad

Speaker 12 and can be much worse for you than a a pathogen, than a potential pathogen could be.

Speaker 15 Totally. Potentially.

Speaker 12 Yeah.

Speaker 12 So

Speaker 12 I don't know what my question is there.

Speaker 12 Why would that happen? Like, why, why would that be an evolved response?

Speaker 15 Yeah, this is a great question.

Speaker 44 Like, why did allergies evolve is a bigger question than I can.

Speaker 12 Maybe that'll be something that we address in our two-parter.

Speaker 78 100%.

Speaker 71 But what part of your question is getting at is like, why IgE?

Speaker 72 Like, why is this response so weird?

Speaker 79 So let's talk about what IgE is and why the response with IgE antibodies can be so severe.

Speaker 23 So antibodies, I feel like we've talked a lot about on this podcast in various time points, but antibodies are one of our immune systems ways of having a very specific response.

Speaker 48 So antibodies are the things that we make, say, for example, when we get a vaccine, to then be able to specifically target and fight off one particular, say, virus or something, right?

Speaker 26 Our antibodies can very precisely identify one particular protein, for example, or carbohydrate sugar on a particular virus.

Speaker 75 And then when we're exposed to that again, our antibodies bind to those antigens that they can identify, and they act like a flag.

Speaker 23 They alert our immune system.

Speaker 15 Hey, come over here.

Speaker 52 I found something that shouldn't be here, right?

Speaker 72 And then we do our immune response thing.

Speaker 57 Most of the time when we talk about antibodies, or at least on this podcast, when we have, we haven't mentioned the different types, but in vaccines and those kinds of antibody responses, our body is usually making IgM and IgG antibodies.

Speaker 52 There's other ones that are like in the context of our guts and our immucosal membranes called IgA.

Speaker 79 And then there's IgE antibodies.

Speaker 15 And these are created in the same basic way as all of our other antibodies in response to one particular protein.

Speaker 39 They're very, very specific.

Speaker 54 And it's our B cells, the same cells that are making these antibodies.

Speaker 22 It's thought that evolutionarily this antibody response, IgE, evolved mostly to respond to parasites and protozoan pathogens and maybe even venoms like snake venom.

Speaker 78 And what IgE does is it doesn't just serve as a flag the way that something like IgG does.

Speaker 22 IgE is an antibody that hangs out attached to some of our other immune cells, like called mast cells and our basophils.

Speaker 48 That part's less important, but basically, IgE is attached.

Speaker 83 It's not free-floating, it's attached to these other white blood cells.

Speaker 45 And when they find the antigen that they're targeted for, they grab onto it.

Speaker 81 And what that does is it triggers these cells that they're attached to to kind of almost burst open and spew forth a ton of highly reactive, super inflammatory stuff.

Speaker 23 Really quick, all of a sudden, it's like a boom immune response rather than like a flag.

Speaker 43 Hey guys, everyone come over.

Speaker 85 And then that response takes some time.

Speaker 15 Right.

Speaker 12 It's kind of like scorched earth policy.

Speaker 34 Exactly.

Speaker 15 Yes. It's like something's here.
Blah! Just destroy it all. A little reactive, maybe.

Speaker 12 Like, let's take a moment. Let's breathe.
Let's just see, do we need to do this? Are there less extreme responses that we can come up with? No. Apparently not.

Speaker 22 IgE is like my toddler last night when I told him he needed to come out of the bath.

Speaker 15 Yeah.

Speaker 15 100%.

Speaker 43 So in a food allergy like a peanut allergy, our body is inappropriately recognizing a peanut protein and then it's mounting weirdly this IgE response to it.

Speaker 35 That process is called sensitization.

Speaker 59 That has to happen first.

Speaker 71 You have to be exposed to something.

Speaker 23 Your body does kind of a weird thing by deciding that it's going to make IgE antibodies against that protein.

Speaker 82 And our immune system doesn't ever forget things.

Speaker 72 So it holds on to those IgE antibodies, just waiting in the wings.

Speaker 52 And then the next time that we eat a peanut, those antibodies are already there.

Speaker 81 And they're like, we found the invader.

Speaker 60 And they do their scorched thing.

Speaker 56 They bind to that peanut protein.

Speaker 19 All of those mast cells expel tons of inflammatory material.

Speaker 52 And then you have the symptoms of that allergic reaction.

Speaker 52 And that is what we see in alpha-gal syndrome, except for a few pretty important details.

Speaker 59 So again, alpha-gal, it's a sugar, a carbohydrate.

Speaker 36 And already, that's a little bit weird.

Speaker 19 We are mounting a massive immune response to an oligosaccharide.

Speaker 73 Why is this particular sugar so immunogenic?

Speaker 22 Well, it turns out that this particular sugar is found pretty universally attached to proteins and lipids on cell membranes of, it seems like most all, many, many different types of cells throughout the body of pretty much every mammal except for humans and apes and old world monkeys.

Speaker 12 Oh, yeah, we'll get into it.

Speaker 27 I know. I cannot wait.

Speaker 23 I know, Erin, that you're going to get into a lot more detail about AlphaGal and the antibodies that we make against alpha-gal from an evolutionary context.

Speaker 15 But just for some context on alpha-gal.

Speaker 75 So we do not make this sugar in our bodies.

Speaker 1 We happen to make from infancy.

Speaker 30 antibodies against this particular alpha-gal sugar.

Speaker 76 The same way that people who, like me, are blood group O, make antibodies against the A and B sugars that make blood groups A, B, and O that are attached to our red blood cells.

Speaker 16 So the antibodies that we make and have circulating around us are IgG antibodies.

Speaker 38 I like to think of them as like normal ones, even though they're all normal.

Speaker 26 That's a terrible descriptor, but you know what I mean?

Speaker 56 They're just like free-floating. They're not doing much.

Speaker 15 Right.

Speaker 42 We can eat all the bacon that we want and it doesn't trigger any kind of immune response, even though we have these IgG antibodies floating around.

Speaker 75 Now, we cannot take a pig heart and transplant it into a human body.

Speaker 68 It so happens that this particular sugar is one of the major barriers to transplantation of animal organs into humans.

Speaker 52 But we can eat bacon, be exposed to it through our guts and do just fine, unless we can't enter the tick.

Speaker 15 Oh, gosh.

Speaker 12 Yep. It's so weird.

Speaker 15 It's so weird, Erin.

Speaker 28 So when I talked about how food allergies work, the first step that I went through was sensitization, right?

Speaker 61 There has to be a period of sensitization where our body sees these antigens and goes, ooh, something's weird here.

Speaker 21 I'm going to make antibodies against it.

Speaker 20 And in AlphaGal syndrome, that sensitization to AlphaGal, it doesn't happen from food.

Speaker 22 It happens from a tick bite.

Speaker 15 Ticks, of course, are our little six to legged, depending on life stages, blood feeding friends.

Speaker 59 These are obligate blood feeders throughout their whole life cycle, and they have to stay attached for a pretty long time, like hours to days, in order to get a full blood meal.

Speaker 23 And while they do this, just like our friend the leech, They spit a whole bunch of their saliva into our bodies to help with things like anticoagulation and anesthetizing us so that we don't notice them and we're not bothered by them.

Speaker 15 can hang out for a long time.

Speaker 12 Tick saliva is kind of a magical substance.

Speaker 15 Same way lynch saliva is, right?

Speaker 12 Exactly. And I feel like tick saliva, I know people are working on it, but I do feel like there are some amazing opportunities in tick spit.

Speaker 32 I agree.

Speaker 44 I was reading about like the siolome, they call it the

Speaker 15 saliva microbiome. So cool.

Speaker 12 I love it. I love when there's a new word for microbiome for a different part of

Speaker 20 a different area, a different area.

Speaker 52 So, what happens in alpha-gal syndrome is that during blood feeding, some species of tick, somehow, some way, introduce alpha-gal into our bodies, directly into our bloodstream or our lymphatics while they're blood feeding.

Speaker 69 And for some people,

Speaker 75 this triggers that sensitization, the development of those IgE antibodies against that specific sugar, alpha-gal.

Speaker 52 That is how sensitization happens.

Speaker 23 Often, but not always, when people develop alpha gal, they report like one specific tick bite that they had a more severe local reaction to.

Speaker 15 So they'll get like a large red welt that's super itchy, and this reaction will last like a lot longer or be a lot more extreme than other tick bites that they might have had in the past.

Speaker 43 And then what happens is that on re-exposure to alpha-gal, like the next time that somebody eats bacon, because alpha-gal is all over any meat products that you're eating, now their body has all of this IgE waiting and it goes, whoa, whoa, whoa, this is that highly virulent pathogen I have to respond to.

Speaker 45 It binds to it.

Speaker 52 Those mast cells degranulate.

Speaker 60 They release all of their super inflammatory stuff.

Speaker 23 And you get this massive immune response, aka allergy.

Speaker 15 That's how alpha gal works.

Speaker 12 Well, Erin, I have a few questions here.

Speaker 56 Well, Erin, I thought that you might.

Speaker 15 Okay.

Speaker 12 We know that this is multiple tick species all over the world.

Speaker 15 That

Speaker 15 this is happening.

Speaker 12 And so it's clearly not related to certain tick species or like tick phylogeny.

Speaker 15 Yeah, it's it was surprising to me how many different genera of ticks, like totally unrelated species of ticks across the whole globe can end up causing this.

Speaker 12 Right. Which suggests like, can any tick be

Speaker 12 a culprit in this? Can any tick induce this allergy? So where is, like, what is the trigger from the tick?

Speaker 15 Yeah.

Speaker 41 That's a great question.

Speaker 23 It's the trigger is alpha gal.

Speaker 71 The question is, where is this alpha gal coming from?

Speaker 15 Right.

Speaker 12 Is it coming from a previous blood meal?

Speaker 12 Does that mean, but I also couldn't find, I did a little bit of digging and I couldn't find any relationship between life stage of the tick that bit someone and because you would think, okay, now I'm just getting nitty-gritty, but let me when ticks are first born or when ticks first hatch from their little eggs, they haven't eaten, they haven't taken any blood meals.

Speaker 12 And so those larvae, if they bite you and they do bite you, like the seed ticks,

Speaker 12 will that still induce alpha gal response? It can. Exactly.
So like what the heck is going on?

Speaker 91 Right.

Speaker 42 So that's, that's the question is what the heck is going on?

Speaker 59 Where is this alpha gal coming from?

Speaker 56 For a long time, we really didn't know.

Speaker 23 Like you said, was it coming from a previous blood meal that just was still there?

Speaker 61 And so the ticks spit a little bit into us.

Speaker 23 Was it something that's in the tick?

Speaker 56 It seems like it is coming from the ticks themselves.

Speaker 91 There was a paper

Speaker 12 coming from inside the house.

Speaker 12 It doesn't really work in this context, but

Speaker 15 we try, though.

Speaker 12 We try.

Speaker 3 Be honest, how many tabs do you have open right now?

Speaker 4 Too many?

Speaker 2 Sounds like you need Close All Tabs from KQED, where I, Morgan Sung, Doom Scroll so you don't have to.

Speaker 4 Every week, we scour the internet to bring you deep dives that explain how the digital world connects and divides us all.

Speaker 7 Everyone's cooped up in their house. I will talk to this robot.

Speaker 9 If you're a truly engaged activist, the government already has data on you.

Speaker 10 Driverless cars are going to mess up in ways that humans wouldn't.

Speaker 11 Listen to Close All Tabs, wherever you get your podcasts.

Speaker 64 Top reasons data nerds want to move to Ohio. High-paying careers for business researchers, analysts, project managers, and more.
So many jobs, you can take your pick.

Speaker 45 What else does the data say?

Speaker 77 How about a bigger backyard, a shorter commute, and a paycheck that goes further?

Speaker 64 So crunch the numbers and our world-famous pickles.

Speaker 81 It all adds up.

Speaker 64 The career you want and a life you'll love.

Speaker 65 Have it all in the heart of it all.

Speaker 64 Dive into the data at callohiohome.com.

Speaker 63 This is where projects come to life.

Speaker 63 Our showrooms are designed to inspire with the latest products from top brands curated in an inviting hands-on environment and a team of industry experts to support your project.

Speaker 63 We'll be there to make sure everything goes as planned, from product selection to delivery coordination. At Ferguson Bath, Kitchen and Lighting Gallery, your project is our priority.

Speaker 62 Discover great brands like Kohler at your local Ferguson showroom.

Speaker 76 There was a paper from 2019 in Frontiers in Immunology that found evidence of alpha-gal in ticks, even ticks that had not fed on other mammals, like ticks that were fed on human blood.

Speaker 15 And they weren't able to find alpha-gal in unfed ticks.

Speaker 85 So it was only after at least partial blood feeding that they were able to find alpha gal that was reactive to these anti-alpha gal antibodies.

Speaker 36 And they found this in multiple different tick species, including the one that most commonly causes alpha-gal syndrome in the U.S., Amblyoma americanum.

Speaker 52 Now, what's really weird is that we still don't know how the tick is making this alpha-gal because ticks don't have the enzyme, just like humans don't have the enzyme that other mammals use to make alpha-gal, ticks don't have that enzyme.

Speaker 81 So what that means is that there has to be either some other chemical pathway that they're using to make alpha gal,

Speaker 22 or is it one of their microbes?

Speaker 41 Is it something in the tick microbiome, like say, a commensal or another pathogen like a rickettsia or something that is making alpha-gal inside the tick and then it gets into the salivary glands and then the tick is spitting it into us.

Speaker 78 That level, we don't know.

Speaker 56 So like we know it's coming from the tick.

Speaker 51 We know it's coming from tick saliva, but we don't know how the ticks are making it and why.

Speaker 87 Like why are ticks making this weird sugar?

Speaker 15 Like what?

Speaker 12 Why, why does anyone make this weird sugar? Because so I spent a lot of time. I was hoping you would answer that question, Erin.

Speaker 12 Well, no, I mean, the question that I am trying to answer is why don't we make it? But instead, I never really considered why would we?

Speaker 15 Why would we? Yeah. Why do we? Yeah.
I don't know.

Speaker 12 Don't know.

Speaker 84 So it's very very weird and like we mentioned there's a lot of different tick species that can cause this in the us amblyoma americanum is the most common in australia it's exodes holocyclis also called the paralysis tick we have to do tick paralysis and if you drive we do we do

Speaker 88 but also things like exodes ricinus uh rifficephalus bursa hyaloma species like so many different species across again the entire globe, North America, South America, Australia, Europe, Africa, everywhere where there is tick and you shall find

Speaker 12 red meat allergy from tick bites.

Speaker 48 Yep, including in some species like Exodes scapularis, people have found alpha-gal in the saliva, but we have yet so far to see alpha-gal syndrome develop in people after exodes scapularis bites, as far as we know.

Speaker 15 Asterisk, who knows what will happen.

Speaker 30 But what does actually alpha-gal syndrome look like?

Speaker 44 We haven't even talked about what the symptoms are,

Speaker 20 aside from being like, allergy.

Speaker 15 And it turns out that this also gets a little bit weirder than just your typical quote-unquote food allergy.

Speaker 12 Of course.

Speaker 26 Of course.

Speaker 68 So the symptoms of Alpha Gal syndrome can, of course, vary, but they often start with GI symptoms that might include things like abdominal pain, nausea, or vomiting.

Speaker 82 They can also include skin symptoms like hives or what are called urticaria.

Speaker 25 And hives, if anyone has never had them or never seen them, they're a very classic allergy association.

Speaker 48 They're these like red, irregularly shaped, slightly raised, kind of puffy looking welts that you can get kind of anywhere across your whole body.

Speaker 15 They can be big, they can be little, there can be a combination of different sizes.

Speaker 71 And they're usually super, super itchy, hives are.

Speaker 86 And then you can also get angioedema, which means swelling, edema, swelling of the face, especially the lips and the mouth.

Speaker 36 And then the most severe reaction is anaphylaxis.

Speaker 42 And we think of anaphylaxis as that not being able to breathe, right? Airway constriction because of swelling and edema.

Speaker 83 But anaphylaxis is actually a widespread response.

Speaker 45 It's not local to just the respiratory system.

Speaker 84 So what's happening in anaphylaxis is widespread vasodilation of blood vessels and then constriction of your respiratory system, of like your bronchioles.

Speaker 26 And that can lead to hypotension, so low blood pressure, and eventually shock and death. Anaphylaxis is very, very scary and a serious emergency.

Speaker 58 And a pretty high proportion, something like 60% or some studies cite even more people report very severe reactions, including anaphylaxis with AlphaGal syndrome.

Speaker 12 And so this, those suite of symptoms there are found in other food allergies. In alpha gal, it's just delayed.

Speaker 48 Yeah, that's the other weird thing that sets AlphaGal apart from most other food allergies is that these symptoms usually develop hours, three to six hours after exposure to the allergen in question, which is mammal meat usually.

Speaker 22 Not minutes.

Speaker 76 And most other food allergies happen after a matter of minutes and peak even in like 10 to 20 minutes after exposure.

Speaker 56 So I knew you were going to ask.

Speaker 31 I asked, why the heck is there this delay?

Speaker 51 Yeah.

Speaker 69 Unsurprisingly, we don't entirely know, but it's thought that it's not necessarily something like weird about

Speaker 71 alpha-gal or this allergy in specific, but it's just a delay in the circulation of this antigen.

Speaker 85 So the sugar itself, AlphaGal, it's not just like a free-floating sugar.

Speaker 23 It's not like a carbohydrate that's like, you know, what makes up your breads or something.

Speaker 51 These are sugars that are attached to proteins and lipids.

Speaker 37 They're glycoproteins and glycolipids.

Speaker 90 And so they enter the system, they enter your body a little bit more slowly.

Speaker 23 But we can see really quick onset reactions in someone with alpha-gal syndrome if they're exposed to alpha-gal via the bloodstream.

Speaker 23 And this we saw in the case of cetuximab, which is an antibody, a monoclonal antibody.

Speaker 15 I think you'll probably talk about it, Aaron,

Speaker 15 that happens to have some alpha-gal on it or in it, in that medication.

Speaker 22 And people who were exposed to that, who they didn't know that they had AlphaGal, but they did, their response was much more rapid on the order of minutes and peaked within 20 minutes, which is more like what we would expect with other food allergies.

Speaker 15 Okay.

Speaker 78 It's so weird, Aaron.

Speaker 43 So I want to like just reframe it again as like, okay, so what are we actually talking about?

Speaker 15 What is AlphaGal syndrome overall?

Speaker 76 AlphaGal syndrome is just like a food allergy, except that it's a tick bite and not a food that causes that initial sensitization.

Speaker 54 It's a sugar and not a protein that you're reacting to.

Speaker 20 It's a delayed, like three to six hours later, allergic response rather than an immediate one.

Speaker 48 And it often can develop later in life, but it can develop at any point in life.

Speaker 33 And most food allergies develop during childhood after just a few exposures rather than like like a lifetime of being able to tolerate it.

Speaker 52 And now all of a sudden you can't.

Speaker 86 Oh, and just so that I don't forget, re-exposure to ticks, like getting more tick bites after you've already developed Alpha Gao syndrome seems to heighten the sensitivity even more so that people have renewed worse reactions or are like never able to tolerate meat again.

Speaker 86 Whereas if people can not get any tick bites for a number of years, they might be then eventually able to tolerate meat again at some point in the future.

Speaker 15 Right. Okay.

Speaker 15 Okay. I have a few questions.
Great. Give them to me.

Speaker 12 Are there other carbohydrates that trigger food allergies in people?

Speaker 15 It's a great question.

Speaker 25 I tried to find some more like specific details on this.

Speaker 79 Not really that I can see.

Speaker 32 There certainly can be carbohydrates that you have adverse reactions to, but an IgE-mediated allergy response like this, no.

Speaker 21 This is pretty unique.

Speaker 12 Okay. And then another question is, if every tick has the potential, more or less, I know some more than others, has the potential to cause alpha gal syndrome.

Speaker 12 Does every person then have the capacity to develop alpha gal syndrome?

Speaker 15 I love your question, Darren.

Speaker 15 Such a good one. No idea.

Speaker 23 We have no idea what it is about one person versus another that predicts why someone would develop Alpha Gal syndrome after exposure to a tick and another person wouldn't.

Speaker 51 Like same tick could bite two people.

Speaker 22 One could develop it and one could not.

Speaker 15 Why?

Speaker 78 We don't know.

Speaker 48 And what's really weird too is that a lot of times, like with allergies, food allergies and respiratory allergies, we often see this kind of like triad.

Speaker 55 It's called an atopic triad, where you have like allergies, asthma, eczema.

Speaker 52 These are all kind of things that share similar immunologic pathways.

Speaker 20 And so you might expect that someone with one food allergy is more predisposed to have other food allergies because again, it's this like hypersensitivity response.

Speaker 19 But a lot of times people with Alpha Gal syndrome don't have any other allergies.

Speaker 22 They don't have any other food allergies.

Speaker 15 They don't have any other respiratory allergies. So it's like, we really don't know right now, like why, why? Yeah.
Right.

Speaker 15 Who? We don't know.

Speaker 12 Ah, it's just, it's so weird. Like, what? Is it just that it's this, the alpha gal is coming into your body in a weird way?

Speaker 15 Like it's a weird way for sure.

Speaker 54 But like, is every amblyoma Americanum tick bite doing that?

Speaker 86 Probably, maybe.

Speaker 35 We think it's probably a threshold thing.

Speaker 30 Like, maybe everyone develops some degree of these IgE antibodies, but not everyone is going to then have AlphaGal syndrome, like respond in this severe way to exposure to AlphaGal in their meat.

Speaker 32 Because there is also degrees, right?

Speaker 88 Alpha-Gal is a sugar on so many mammalian products, not just meat.

Speaker 46 It's also found in dairy at lower levels, but most people don't have reactions to dairy and some people do.

Speaker 56 It's also found in things like gelatin, which means that it's in a lot of pharmaceuticals.

Speaker 79 And so for some people, there's a really wide range of stuff that they now can't tolerate.

Speaker 81 And for other people, they can tolerate all of those things just fine.

Speaker 27 And it's really only like bacon or like pork product or like red meat, like beef.

Speaker 70 And so it's a really like wide variation.

Speaker 33 And so there's probably a lot that's like thresholds, like how much IgE do you have?

Speaker 56 How much did you make?

Speaker 69 How recent was it?

Speaker 71 You know, all of that kind of stuff.

Speaker 12 I remember talking with someone who had alpha-gal syndrome and they could eat cured meats, but not like a hamburger.

Speaker 15 Interesting. Yeah.

Speaker 71 Yeah. And is that just volume?

Speaker 33 Like, when you eat a hamburger, do you just eat a lot more of it than you do with a cured meat?

Speaker 25 I don't know.

Speaker 12 Or is somehow the carbohydrate more degraded in cured meats? Like, exactly.

Speaker 15 Right. I do.
I don't know. I don't know either.

Speaker 45 There's a lot. It's so, so, so, so interesting.

Speaker 15 So, oh, yeah.

Speaker 15 Aaron, tell me

Speaker 56 everything.

Speaker 23 Like, I know you're going to talk about this sugar.

Speaker 30 Like, where did it come from?

Speaker 38 Why do some mammals make it?

Speaker 79 Why do we not make it anymore?

Speaker 19 How did this come to be?

Speaker 15 And then also, like, how did we figure this out? Because,

Speaker 15 yeah.

Speaker 75 You know what I did not realize is how recently we figured it out.

Speaker 57 Cause I feel like when we were in Panama, it was the thing.

Speaker 15 Everyone, everyone had it. Everyone had had it.
Everyone had it. Yeah.
Yeah.

Speaker 79 But it was like very new at the time.

Speaker 15 Yeah.

Speaker 12 Yeah. Let's let's get into some of this, these questions and take a quick break and then we'll begin.

Speaker 12 Erin, like you mentioned, we learned about this, I think, pretty recently.

Speaker 12 The first time that I learned about the fact that you could become allergic to red meat following a tick bite, I was so confused. Like, I had no idea.

Speaker 12 I think it was 2013, and I had just started field work in Panama for my PhD research on ticks and climate change. And

Speaker 12 for all of you listeners out there right now, I'm wearing my Smithsonian t-shirt that has little larval ticks all over it. I love it so much.

Speaker 12 Actually, they have eight legs, so they must not be larvae, even though they look like they're not.

Speaker 15 No, I think they're nymphs or adults. They're big.

Speaker 12 They're big, but they look, I don't know. Some look like there's an adult.
I think it's nymphs. Also, okay, anyway, we don't need to get into it.

Speaker 34 She's wearing a tick shirt, guys.

Speaker 15 She'll take that occasion.

Speaker 12 It's one of my favorite shirts.

Speaker 12 But yeah, so in 2013, a professor who was also in Panama reached out to me and was like, oh, I heard you're working on ticks. Have you heard of a red meat allergy following a tick bite? I have it.

Speaker 12 A few other researchers who have spent a lot of time doing field work in this area have also have it, and it could be a cool project.

Speaker 12 And I didn't end up pursuing it as a project because probably I was scared of like the immunology aspect of it.

Speaker 12 But over the, I probably should have, but over the next few years that I worked there, every field season, people would come up to me and say, oh, I just got diagnosed with this red meat allergy.

Speaker 12 I ate a hamburger and nearly died. Yep.
Or, hey, I think my allergy is getting better. I can eat salami now.
Like there are so many people, Aaron.

Speaker 12 It definitely seems like central Panama is a hotspot, but maybe it's just that everywhere is sort of a hotspot for red meat allergy.

Speaker 15 But it really was like a lot of people. The people that we hung out with like got bit by a lot of ticks, let's be honest.

Speaker 21 We all did.

Speaker 12 Yeah, exactly. I mean, yeah, thousands and thousands I would catch every day.

Speaker 15 Yeah.

Speaker 12 So anyway, but every time I learned of someone new who had developed the allergy, I would do some like light Google scholaring to try to answer the three main questions that I had.

Speaker 12 What the heck is going on in this allergy? How the heck did people discover the connection to tick bites? And why the heck does this happen? Yeah.

Speaker 12 And so, Aaron, you just took us through the first question. And so I'm going to try to take on those other two, starting with the how.
Like how was AlphaGal syndrome first recognized?

Speaker 12 So the syndrome itself has no doubt been around for longer than people have recognized it.

Speaker 12 That professor that I mentioned had developed it, I believe, in the early 1990s, and there is apparently unpublished work from the state of Georgia in the late 1980s that mention the potential of a red meat allergy in association with tick bites, but it took a series of kind of unusual events at opposite ends of the earth for the connection to be made between tick bite and red meat allergy.

Speaker 12 On the one end of the earth was Dr. Cheryl Van Noonen, an immunologist who was working at an allergy clinic in Sydney, Australia.

Speaker 12 She noticed what seemed like an unusual number of people coming to the clinic complaining that they had recently developed an allergy to red meat with a delayed onset of symptoms that involved things like tongue swelling, throat constriction, respiratory distress, and all the other sort of suite of symptoms that you you mentioned.

Speaker 12 What's an unusual number, you might ask? Like, when did this start to stand out? So between 2003 and 2007, 25 patients, seven men, 18 women, reported this allergy.

Speaker 12 And I'm sure that she and her collaborators ruled out many other potential causes, but ticks seemed like a strong possibility from the beginning, with 24 of the 25 patients reporting a history of having bad local reaction to tick bites.

Speaker 12 And the areas, like the regions where these patients resided, were known to be quote-unquote endemically infested with several tick species.

Speaker 12 In 2007, Van Noonen authored an abstract, the first academic publication, linking the red meat allergy to a tick bite from the tick Ixodes holocyclis.

Speaker 12 While Van Noonen was drawing her own conclusions down under,

Speaker 12 other researchers in the U.S. were on a different trail, but one that would lead them to the same strange allergic reaction.
In 2004, trials were underway to test a cancer drug called

Speaker 12 ceteximab.

Speaker 15 Ceteximab.

Speaker 12 Cetuximab.

Speaker 12 No wonder I didn't recognize it when you first said it, because I've only read it and I didn't try to say it in my head.

Speaker 12 But they were testing this cancer drug to see if it was safe for FDA approval.

Speaker 12 But researchers were noticing that in some patients, this medication was causing a hypersensitivity reaction, particularly those patients residing in a handful of states in the southern US.

Speaker 12 The reactions could be quite severe, pretty quick onset anaphylaxis that would have you on the floor, and had even resulted in death for a few.

Speaker 12 So the pressure was on to find out what was causing this.

Speaker 12 Researchers Christine Chung, Thomas Platts-Mills, Scott Commons, and others were tasked with solving the problem, and they quickly narrowed in on an IgE response to a carbohydrate antigen called alpha-gal.

Speaker 12 So that answered one question they had, which was like, what were people's immune systems reacting to with this drug? But it still left an important one unanswered. What was triggering this reaction?

Speaker 12 Like why alpha-gal?

Speaker 15 Right.

Speaker 12 The first clue came from alpha-gal itself.

Speaker 12 As you mentioned, Erin, this antigen is found in tissues of non-primate mammals and some primate mammals with some notable exceptions like humans, apes, and old world monkeys.

Speaker 12 And so the researchers thought that maybe we should look for patients who have had allergic reactions to beef and then map where they live.

Speaker 12 And the story goes, according to the Radiolab episode on this, that the researchers then took out their map of beef reactions and compared it to as many other maps that they could find, just like overlaying other distribution maps, you know, other disease maps, other, like all sorts of environmental exposures, whatever.

Speaker 12 And one map in particular stuck out, which was the distribution of Rocky Mountain spotted fever cases. Could this allergy be triggered by a tick bite?

Speaker 12 They interviewed the patients with the beef allergy, confirmed to be IgE antibodies to AlphaGal, and found that more than 80% of them had been bitten by a tick before experiencing symptoms.

Speaker 12 This finding, combined with the report from Australia, was more or less the solid proof that they needed to suggest that tick bites were triggering an allergy to red meat, specifically the alpha-gal antigen.

Speaker 12 And fascinatingly, it was different tick species and on opposite ends of the world. And also just like found around the same time.
I think that part is also amazing.

Speaker 79 It's so, so, so weird that it happened, especially like the satuximab thing and then the figuring that out and the like Australia thing.

Speaker 83 Like to do it all, it's so weird.

Speaker 34 Like the serendipitous, I guess.

Speaker 12 Erin, I feel like I need to throw in this well actually

Speaker 15 here. So please.

Speaker 12 This is not for you, but the tick species that you mentioned that is thought to be primarily responsible for alpha gal syndrome here in the U.S.

Speaker 12 is the lone star tick, Amblyoma americanum, which actually very, very rarely transmits the causative agent of Rocky Mountain spotted fever.

Speaker 12 And so the fact that the maps line up for Rocky Mountain spotted fever and alpha gal, it really just seems coincidental to some degree.

Speaker 12 It might just be overlapping distributions of the Rocky Mountain spotted fever ticks

Speaker 12 or tick and yeah. But I was just like, wait, that doesn't

Speaker 12 like am I understanding?

Speaker 37 Similar distributions of all of those tick species.

Speaker 15 Yeah.

Speaker 12 But anyway, I had, I am sorry, I had to.

Speaker 12 But once those reports came out, first Van Noonen in 2007 and then Commons and Platts Mills in 2008.

Speaker 12 Platz Mills, by the way, developed the red red meat allergy during this research through a tick bite. But it seemed like following these reports, the allergy was everywhere.

Speaker 12 All you had to do was look. France, Spain, Germany, Switzerland, Sweden, South Korea, Japan, Central America, South Africa, and more every year, worldwide distribution.

Speaker 15 Yeah.

Speaker 12 The fact that this stranger-than-fiction allergy to red meat triggered by a tick bite was discovered on two different continents across the globe within a few years of each other is pretty incredible.

Speaker 12 Is it coincidence?

Speaker 15 Maybe.

Speaker 12 But is it serendipitous? Maybe.

Speaker 12 But some of the researchers have also hypothesized that exposure to ticks has been steadily on the rise over the past few decades in some regions where the allergy is common as a result of increasing numbers of mammalian hosts like bandicoots in affected regions of Australia and white-tailed deer in the southeastern U.S., in addition to habitat encroachment.

Speaker 12 So we're basically just like

Speaker 12 more, we're encountering ticks more readily.

Speaker 15 Classic.

Speaker 12 And more

Speaker 12 are there to encounter. Exactly.
Yeah.

Speaker 12 And as for what the future may hold, I'll leave that to you, Erin, except to say that as the climate continues to change, impacting the range of tick species, as we continue to encroach into these habitats, I'm sure we'll just see more and more of this allergy develop.

Speaker 37 The ticks are just trying to save us all from eating too much meat.

Speaker 15 Yeah.

Speaker 15 Thank you, ticks.

Speaker 12 We appreciate you.

Speaker 15 Yeah.

Speaker 12 But for now, let's turn back in time to get at the second question that I mentioned at the top of this. Like, why the heck does this happen evolutionarily?

Speaker 12 So, like you mentioned, Aaron, humans react to alpha-gal because we don't produce it ourselves. And so we recognize it as non-self and we attack it.
Pretty standard issue, immune stuff, right?

Speaker 15 Yeah.

Speaker 12 And that inability to produce alpha-gal makes us outliers among mammals.

Speaker 12 Of all mammal species, catarines, which includes old world monkeys and apes, including humans, are the only ones who can't make alpha-gal, who don't make alpha-gal.

Speaker 12 That means that other primates like New World monkeys, lemurs, lorises, and tarsiers, not to mention cows, pigs, dogs, mice, etc., all produce alpha-gal.

Speaker 12 We also continuously circulate antibodies against it.

Speaker 12 Alpha-Gal is, in fact, the most abundant natural antibody in humans, making up about 1% of immunoglobulins.

Speaker 45 That's so bizarre, Aaron.

Speaker 12 It's so bizarre. And so it seems like this kind of a big deal.
Yeah. And so what makes this different? Like, why? Why us? Or why not us, rather?

Speaker 12 And that's the question that researchers have been trying to figure out for decades now. Looking at which species make alpha-gal and which species don't, two things stand out.
Number one,

Speaker 12 since the ability to produce this is so widespread among mammals, including both placental and marsupial mammals, it's clear that catarines once produced alpha gal like all other mammals and lost the ability at some point.

Speaker 15 Okay.

Speaker 12 And number two, that point was around 28 million years ago, before the old world monkeys and apes diverged.

Speaker 15 Okay, that makes sense.

Speaker 12 What happened 28 million years ago to cause such a big shift, resulting in both the loss of the ability to make alpha-gal and the production of antibodies against it?

Speaker 35 Right.

Speaker 42 And like, did that happen like all of a sudden or was it?

Speaker 15 Yeah.

Speaker 23 Because all, you're saying all catarines make antibodies against alpha-gal.

Speaker 15 Yes. Okay.

Speaker 27 Right.

Speaker 12 So what, what happened?

Speaker 15 Yeah.

Speaker 12 How does a deadly disease sound?

Speaker 15 Well, sounds like, sounds like right up our alley is how it is.

Speaker 15 Right up our alley.

Speaker 12 This carbohydrate will kill you.

Speaker 12 Some researchers, namely Yuri Galili, who has done a tremendous amount of work on alpha-gal, have proposed that around 28 million years or so ago, a highly virulent pathogen or pathogens, I've seen airborne enveloped viruses suggested and also sepsis-causing bacteria suggested.

Speaker 12 Some pathogen swept through old world primates on the Eurasia-Africa landmass, killing those who produced alpha-gal and sparing the very few who didn't, who would over the next generations increase in number.

Speaker 12 And there seems to be some debate as to the cause or causes, like was it a pathogen? Was it climate? Was it a mix of both?

Speaker 12 But there does seem to be a sharp decline in old world primate populations during this time, almost leading to extinction, like overall, but I think also extinction of certain species.

Speaker 12 But why would not producing alpha-gal help protect you from severe infection or death? That's where things get super interesting.

Speaker 12 Because it turns out that mammals aren't the only species to produce alpha-gal.

Speaker 12 In fact, some viruses, bacteria, and parasites do, or they bind to host-produced alpha-gal to gain entry into their host cells.

Speaker 12 E. coli, species of Klebsiella, Plasmodium species, some of which cause malaria in humans, mycoplasma, causative agent of tuberculosis, salmonella, trypanosoma, leishmania, C.

Speaker 12 diff, mosquito-borne viruses. I mean, a lot of pathogens either produce or use alpha-gal in some capacity, and also microbes that aren't pathogenic to us.

Speaker 12 For instance, some members of our gut microbiome may produce alpha-gal, which triggers this constantly elevated antibody response, which could then protect us from things like malaria.

Speaker 12 And some people are looking at this in terms of an actual mechanism for how we can shape our gut microbiome to boost our immune system, like adding in more bacteria that produce alpha-gal as a way to raise those antibody levels and neutralize any invading malaria parasites.

Speaker 15 What?

Speaker 12 It's so cool because there does seem to be this association between gut microbiome, alpha-gal production, anti-gal antibodies, and then malaria susceptibility.

Speaker 12 And so I love it because I'm like, oh, is this the first time that I've actually seen the microbiome, like a mechanism yeah for the microbiome instead of just functional right it's not just like what are these bacteria it's like what is the function of this and how is that interacting with our

Speaker 12 it's direct links instead of there's an association which is also really important but at the same time it's exciting to see like this sort of concrete pathway of logic yes love it

Speaker 12 AlphaGal can also provide some insight into blood types in disease. People who have type B or type AB blood seem to be less susceptible to alpha-gal syndrome

Speaker 12 because the B, like me,

Speaker 12 because that B antigen that they produce is very similar, apparently, structurally to alpha-gal. And so their bodies see it as more like self.
And so they're not as liable to attack it.

Speaker 27 Yeah. I've heard too that

Speaker 42 you have more specific anti-gal proteins, anti-alpha-gal proteins, whereas people who are O or A

Speaker 52 have like less specific ones that bind to maybe B and alpha-gal and like a are just a little bit messier.

Speaker 12 It's messy, it's just a little more efficient.

Speaker 15 Yeah, there you go.

Speaker 12 Yeah, painting with a broad brush.

Speaker 15 But

Speaker 12 researchers have also genetically engineered mice to knock out the alpha-gal producing gene and found some fascinating results, with knockout mice being more protected against some pathogens, like SynV virus or syndbis virus, and less protected against others like herpes simplex type 2.

Speaker 15 Huh. Yeah.

Speaker 55 Interesting.

Speaker 12 And then there's the genetic engineering of pigs to not produce alpha-gal, so-called gal-safe pigs, which I love because it makes them not only safe to consume for people with alpha-gal syndrome, but also it opens the doors for xenotransplantation, transplanting pig organs into humans, which, as you mentioned, Erin, previously could not be done in part because or in major part because of this alpha-gal

Speaker 12 carbohydrate.

Speaker 83 It's wild that this

Speaker 15 particular carbohydrate, like this little sugar, is that important.

Speaker 15 I know. Right.

Speaker 89 Like it was one of the major, I mean, it still is one of the major barriers to animal organ like transplant into humans.

Speaker 71 And so now with the development of these pigs, like it's,

Speaker 31 it's so, it's so fascinating, Aaron.

Speaker 12 I think the thing that surprised me the most about doing this episode is that I had never heard of alpha gal before 2013.

Speaker 12 And I since then have never heard about it outside of the context of alpha gal syndrome. Same.

Speaker 12 But this is one of the most important

Speaker 12 components of like our life, of our immune system in terms of anti-gal, in terms of other animals. And it just plays so many more roles than

Speaker 12 preventing you from eating meat.

Speaker 15 Right.

Speaker 48 Than just alpha gal syndrome, which is also very like interesting and important and cool.

Speaker 15 Yeah.

Speaker 12 It's wild.

Speaker 12 The other big takeaway from this, I think, and that is very obvious, is that the story of AlphaGal is still very much unfolding. And the tick-borne allergy is really just a part of it.
Yeah.

Speaker 12 I mean, I was going down.

Speaker 12 so many rabbit holes in terms of autoimmune diseases and alpha gal, whether there are people who do produce alpha gal and how they respond to different pathogens, because it really is just like a simple frame shift mutation.

Speaker 12 So we still have the gene. It's just like, is not exposed to it.

Speaker 15 It just doesn't work. Yeah.
Right.

Speaker 12 And then blood types and association with different diseases. Let's do an episode on that.

Speaker 12 I mean, but every answer that I found or every partial answer that I found just led to a million more questions.

Speaker 12 And so now I'll end this with a question for you, Erin, which is, where are we today with Alpha Gal syndrome?

Speaker 37 Oh, I can't wait to tell you all about it right after this break.

Speaker 40 According to the CDC in the US,

Speaker 15 there were over 110,000 cases of AlphaGal reported between 2010 and 2022. And most of those are the latter half of that 12 years.

Speaker 15 Okay.

Speaker 48 Which is somehow both way more than I expected, but also likely a gross underestimate because AlphaGal syndrome is not a notifiable disease.

Speaker 45 And the estimates of prevalence globally really, really range.

Speaker 38 And I think will likely change drastically over time, and not just because numbers are actually changing.

Speaker 23 But the estimates that I saw right now

Speaker 16 in places where we have prevalence estimates range between in Germany, four cases per 100,000 people to 13 cases per 100,000 people in Virginia, which is a part of the U.S.

Speaker 37 that has a higher number of cases than a lot of other parts of the U.S.

Speaker 33 and 113 per 100,000 people in the Sydney Basin in Australia.

Speaker 15 Wow. Okay.

Speaker 40 Right. So, like, really big variation.

Speaker 46 And a lot of that has to do with both tick species and where those ticks exist, how much people are interacting with ticks, right?

Speaker 36 Like, if you're in a big city, you're not probably going to be interacting with ticks as much as if you're in a more rural area, et cetera.

Speaker 70 But also, where are we looking? Like, where are we looking for this?

Speaker 48 Because, like we said, if you're looking for it, you'll find it.

Speaker 20 And cases are on the rise without a doubt.

Speaker 77 For example, in the US in 2017, there were just over 13,000 new cases diagnosed.

Speaker 37 There were nearly 19,000 cases diagnosed in 2021.

Speaker 12 Wow.

Speaker 27 Yeah.

Speaker 61 And what's really mind-blowing is that in studies where they have looked at like larger populations, just like checking for people who might have IgE, those allergy-associated antibodies against alpha-gal, in some populations, they found up to 20% of people who who had IgE antibodies against AlphaGal.

Speaker 54 But by no means does that mean that all of those people have AlphaGal syndrome.

Speaker 22 So there's still a really big open question of like, what is that threshold?

Speaker 56 Like, how much IgE do you have to have?

Speaker 38 And why are some people reacting and developing Alpha-Gal syndrome and some people aren't?

Speaker 12 Do levels of IgE correspond directly with that allergic response?

Speaker 12 Or can some people have like two people have the same levels of IgE and one person has anaphylaxis and the other person does not react whatsoever?

Speaker 44 Yeah, it's a great question.

Speaker 26 It does seem to be that the levels do matter in terms of what your response is.

Speaker 28 Okay.

Speaker 20 There still isn't a very clear, like, for example, diagnostic threshold of like, okay, this is the value which you have Alpha Gauss syndrome versus this is the value where you don't.

Speaker 26 That is still a little bit like up for debate, it seems like.

Speaker 15 Okay.

Speaker 15 Yeah.

Speaker 50 But it does seem to correspond where higher levels, more response, and like repeat tick bite, those levels go up.

Speaker 44 And like you mentioned, Erin, as with all, I think ever of our vector-borne disease episodes, there's a lot that is probably contributing to this rise in incidence and prevalence.

Speaker 68 This includes things like changes in the distribution of ticks in the U.S., especially increases in things like deer populations and other mammal populations in other parts of the globe that are really great hosts for ticks, but also our exposures to ticks, things like land use change, deforestation, blah, blah, blah, climate change, everything that changes the way that we interact with ticks and other tick hosts is going to affect any kind of tick-borne disease, including alpha-gal.

Speaker 15 But also things like getting better at recognizing and diagnosing this, because One of the things that we, I always try and talk about, like, well, where's the current research or where's the research going?

Speaker 23 And for a disease like AlphaGal, that is still so brand new in the scheme of what medicine understands about this disease to begin with, like we just figured out this existed a couple decades ago, not even like 20 years ago.

Speaker 33 So we're still very much writing that story of like, where do we go with AlphaGal syndrome from here?

Speaker 15 And right now,

Speaker 46 We need people to know that it exists because a recent survey by the CDC from 2022 found that 42% of healthcare providers in their particular study hadn't heard of Alpha-Gau syndrome.

Speaker 15 They didn't know about it.

Speaker 23 Wow. And I will say that that was just a survey of primary care providers.

Speaker 71 So it was like pediatricians,

Speaker 21 internists and family practice physicians, and then NPs and PAs.

Speaker 44 And rates of knowledge are probably much higher among, say, allergists or even GI specialists that people might get referred to for their GI symptoms.

Speaker 71 But that is still a pretty important knowledge gap to kind of highlight.

Speaker 15 Absolutely.

Speaker 61 We've talked a lot on this podcast about like delays in diagnosis and things like that.

Speaker 70 And these are very severe reactions.

Speaker 41 So this is like pretty significant.

Speaker 12 Yeah.

Speaker 12 Yeah.

Speaker 43 So I think that's one of the biggest areas of like, how to make everyone know about it.

Speaker 13 Maybe make a podcast.

Speaker 15 Maybe we can help.

Speaker 12 Solution.

Speaker 22 And in truth, there is, there is so much that is still unknown in terms of what is the next big research area.

Speaker 15 It's everything.

Speaker 23 Like, why do some people mount this response and others don't?

Speaker 29 What really is that IgE threshold and what's causing it in some people?

Speaker 32 What other treatment options might exist besides just never eating any kind of mammalian meat again?

Speaker 48 How can we desensitize people like we might do for other food allergies? Can we do that?

Speaker 45 Is it just avoidance of tick bites or is there anything else?

Speaker 44 What are all the different tick species that can cause this?

Speaker 52 How many have we not yet discovered?

Speaker 71 How is it going to change with things like climate change?

Speaker 91 How are these ticks making AlphaGal to begin with?

Speaker 15 Right.

Speaker 12 Right. There are so many different questions and different opportunities for research into this from so many perspectives to make it super integrative research.

Speaker 12 Like it's, it's a really incredibly open field with a lot of opportunity to understand too, like

Speaker 12 something that is so universal in across mammals, except for a handful.

Speaker 82 Except for us and a handful of our cousins.

Speaker 54 It's, yeah, it is really, really

Speaker 37 an interesting disease and such a weird and wacky mechanism.

Speaker 21 I also am dying to know everyone who's listening, like, had you heard of Alfegao syndrome?

Speaker 31 Because I never know with things like this, if it's like

Speaker 23 everyone knows about it at least a little bit, or if we really are just that weird, where like we've been talking about it since like 2013, because so many people in Panama had it.

Speaker 47 Right.

Speaker 56 And like, it's not that normal.

Speaker 90 And there was that Radiolab episode so many years ago, but like, how, had you heard of this?

Speaker 22 How much did you know about this?

Speaker 15 Right.

Speaker 15 I really want to know.

Speaker 12 Do you have this?

Speaker 30 Do you have this?

Speaker 12 Because we have had a lot of people reach out to say, I am allergic to red meat thanks to a tick bite.

Speaker 15 What's going on here?

Speaker 56 And how long did it take to get diagnosed?

Speaker 15 Because it seems like there's a pretty big gap in diagnosis.

Speaker 22 But yeah, I have so many more questions, Erin.

Speaker 12 I think that we all do. And so let's direct people to the best source of where they can try to answer those questions, which is

Speaker 12 a million sources.

Speaker 12 I truly do have like a million sources here. I want to shout out just a few.
So there's one by Commons and Platz Mills from 2009 that goes into sort of anaphylaxis syndromes relating to alpha-gal.

Speaker 12 Then there are a couple of interesting papers about sort of the evolutionary significance of alpha-gal. One by Galile from 2019, as well as a handful of many more actually.

Speaker 12 And this paper goes into how viruses may have led to the loss of alpha-gal production and the rise in alpha-gal antibodies.

Speaker 12 And then there's a paper by Rodriguez and Welsh from 2013, no relation as far as I'm aware, titled Possible Role of a Cell Surface Carbohydrate in Evolution of Resistance to Viral Infections in Old World Primates.

Speaker 12 And there's so many more, including the paper on this pig that's been, on the pigs that have been engineered to not produce alpha-gal. Amazing.

Speaker 12 And a paper about how dogs can actually develop alpha-gal syndrome, possibly.

Speaker 31 What?

Speaker 40 Even though they make alpha-gal?

Speaker 12 Yeah, I found a paper from 2019 about how tick bites can induce anti-alpha-gal antibodies in dogs.

Speaker 15 Wow.

Speaker 12 Really strange.

Speaker 15 It is really wild.

Speaker 15 I also had quite a lot of papers for this episode.

Speaker 82 Probably some of the same ones, Erin, that you read and mentioned.

Speaker 37 Some of the early reports from like 2009 from Van Noonen,

Speaker 38 as well as an early one from Commons et al.

Speaker 53 from 2009 in Journal of Allergy and Clinical Immunology.

Speaker 47 The one from Van Noonen was in the medical journal of Australia.

Speaker 22 I also had update ones from both of those authors. There's like so many.

Speaker 37 The really interesting paper from 2019 was by Chris Bell et al.

Speaker 23 in Frontiers and Immunology.

Speaker 32 That was Discovery of Alpha Gal-containing Antigens in North American tick species believed to induce red meat allergy.

Speaker 46 That one was super interesting.

Speaker 41 And then I had a bunch as well about allergies and allergic responses in general.

Speaker 68 If you want more details on like how food allergies work and IgE and all of that kind of stuff.

Speaker 26 As always, we'll post the list of our sources from this episode and every one of our episodes on our website, this podcastwillkillyou.com, right under the episodes tab.

Speaker 15 You can find it there.

Speaker 12 Thank you again so much, Winnie, for sharing your story with us. We appreciate it so, so much.

Speaker 74 We really, really do.

Speaker 15 Thank you.

Speaker 13 Thank you also to Bloodmobile for providing the music for this episode and all of our episodes.

Speaker 12 Thank you to Tom Breifogel and Liana Squalachi for our amazing audio mixing.

Speaker 48 Thank you to Exactly Right Network and everybody there.

Speaker 12 And thank you to you listeners. We hope that you enjoyed this and are like, wait, what?

Speaker 15 Wait, what? Do you have questions?

Speaker 12 I'm sure you do. Send them our way.
We can ponder them together.

Speaker 15 Yeah, because we have them too. Yeah, we do.

Speaker 45 And as always, a special shout out to our patrons.

Speaker 91 Thank you so, so much for your support.

Speaker 33 It means the world to us.

Speaker 45 If you would like to support the show in other ways, there are a lot of ways that you too can support the show.

Speaker 23 Just listening this far is a great way to show support.

Speaker 51 So thank you again for doing that.

Speaker 42 You can also tell a friend if you haven't told all of your friends about us, help spread the word.

Speaker 44 We love to have new listeners.

Speaker 46 You can write a review on your favorite podcast channel or rate us. That also helps, gets us up in the charts, which helps other people find us.

Speaker 26 There's lots that you can do and we really appreciate all your support.

Speaker 12 Yeah, we do. Well, until next time, wash your hands.

Speaker 49 You filthy animals.

Speaker 3 Be honest, how many tabs do you have open right now?

Speaker 4 Too many?

Speaker 2 Sounds like you need close all tabs from KQED, where I, Morgan Sung, Sung, Doom Scroll so you don't have to.

Speaker 4 Every week, we scour the internet to bring you deep dives that explain how the digital world connects and divides us all.

Speaker 7 Everyone's cooped up in their house. I will talk to this robot.

Speaker 9 If you're a truly engaged activist, the government already has data on you.

Speaker 10 Driverless cars are going to mess up in ways that humans wouldn't.

Speaker 11 Listen to Close All Tabs, wherever you get your podcasts.

Speaker 65 Top reasons your dog wants you to move to Ohio.

Speaker 60 Amazing dog parks to stretch your legs.

Speaker 64 All four of them. Dog-friendly patios.
Even gourmet hot dogs loaded with the good stuff. Bone apetee.
And Ohio has so many high-paying jobs, you'll be top dog in no time.

Speaker 64 Jobs in technology, engineering, science, advanced manufacturing, and more. The career you want and a life you'll love.

Speaker 65 Have it all in the heart of it all.

Speaker 64 Go to callohiohome.com.

Speaker 93 Today's episode is brought to you by Toyota.

Speaker 93 The Toyota Certified Used Vehicle Sales Event is full of great surprises, like a wide selection of low-mileage models all backed by Toyota, with warranties that start on the date of purchase.

Speaker 93 Because when it comes to quality, the best new cars make the best used cars.

Speaker 94 So don't miss your chance. Find your certified Toyota today.
But hurry, these great offers end November 3rd. Toyota Certified Used Vehicles Sales Event, where every surprise is a great one.

Speaker 94 Inventory may vary by dealer, participating dealers only. Comprehensive and powertrain or limited warranties.
See TCUV Warranty Supplement, ToyotaCertified.com or your Toyota dealer for details.