Speaker 1: Hi. My name is Winnie and I'm an ecologist. In
Speaker 1: the summer of twenty eighteen, my husband and I moved
Speaker 1: to northeast Missouri for his job. In early August, we
Speaker 1: decided to go for a hike at a nearby conservation area.
Speaker 1: We had about a mile left in the hike when
Speaker 1: we heard rustling in the brush beneath some big oak trees.
Speaker 1: It turned out to be a red tailed hawk with
Speaker 1: a broken wing. In order to bring the bird to
Speaker 1: the nearest wildlife veterinarian located in Columbia, Missouri, we needed
Speaker 1: to get the bird to our car, so my husband
Speaker 1: gave me his overshirt while he distracted the hawk. I
Speaker 1: tossed the shirt over the bird's head to calmb it down,
Speaker 1: and we safely carried the bird back to our car.
Speaker 1: It was like a ninety minute drive to Missoo Veterinary Hospital,
Speaker 1: and before long we noticed that our feet and our
Speaker 1: ankles were really itchy. About halfway to Columbia, we had
Speaker 1: to stop for gas, so that's when I pulled down
Speaker 1: my sock and I saw what looked like thousands of
Speaker 1: tiny grains of sand moving across my ankles. At the time,
Speaker 1: I was convinced that these were chiggers. With very few
Speaker 1: options for how to remove them, we continued on our
Speaker 1: mission to get the hawk to the veterinary hospital. The
Speaker 1: staff stabilized and treated the animal, and we drove back home.
Speaker 1: After that day. In twenty eighteen, my husband and I
Speaker 1: avoided areas that were chigger prone, particularly between April and
Speaker 1: September when they're the worst. We also used repellent sprays,
Speaker 1: and we treated our clothes and shoes with permethrin to
Speaker 1: deter chiggers. It's worth noting that we had also been
Speaker 1: warned about lone star ticks. These are really common in Missouri,
Speaker 1: and they're common even in urban and suburban areas, and
Speaker 1: they're also really aggressive feeders. So we were really careful
Speaker 1: not to get any ticks. And it turns out that
Speaker 1: chigger treatment and tick treatment for clothes and repellents, they're
Speaker 1: the same thing. One evening in October of twenty twenty two,
Speaker 1: we made a meal with hamburger. It was noteworthy because
Speaker 1: we didn't eat much meat and it was a special
Speaker 1: treat for us. Later that night, I woke up violently ill,
Speaker 1: and I was certain that I had gotten food poisoning.
Speaker 1: At some point, while I was dry heating into a bucket,
Speaker 1: I realized that my ankles and my palms were insanely
Speaker 1: itchy and covered in hives. The hives quickly spread to
Speaker 1: my torso, legs, arms, and scalp. I was struggling to breathe,
Speaker 1: and I remember feeling that numb feeling in my entire body,
Speaker 1: you know, the feeling when you get novacine. At the
Speaker 1: dentist it was like that, but everywhere. I wasn't thinking
Speaker 1: entirely clearly, but I do remember taking to benadryl, waiting
Speaker 1: about five minutes panicking, and then taking two more benadryl
Speaker 1: while I waited for the hives to go away. I
Speaker 1: remember trying to figure out how and why food poisoning
Speaker 1: could cause hives. The next day, I arranged to see
Speaker 1: an allergist. He sent off a bunch of blood tests
Speaker 1: and one of them came back positive. It was for
Speaker 1: Alpha gal. As an ecologist, I knew about Alpha Gal.
Speaker 1: I had friends with Alpha Gal, I have coworkers with
Speaker 1: Alpha gal. It's something that we're aware of in the
Speaker 1: ecology world, at least in Missouri. But I do remember
Speaker 1: being really angry. I was angry because my husband and
Speaker 1: I had been so careful not to get any ticks
Speaker 1: or chiggers since that first incident in twenty eighteen. But
Speaker 1: then I remembered. I remembered those chiggers, and in hindsight,
Speaker 1: they had to have been seed ticks or tick larvae.
Speaker 1: We probably had walked into a bed of these seed ticks,
Speaker 1: and we were probably bitten by hundreds of them. Also,
Speaker 1: it wasn't until the doctor told me the results of
Speaker 1: those tests that I realized a lot of the last
Speaker 1: four years really just sort of fell into place. You see,
Speaker 1: Sometimes I had I'd noticed that my ankles in my
Speaker 1: arms would get really itchy for no apparent reason. In hindsight,
Speaker 1: it was usually after I had like jello or soup
Speaker 1: that was made with beef broth. Fast forward to the present.
Speaker 1: In twenty twenty three, we moved to Minnesota. As an ecologist,
Speaker 1: i'd like to keep an eye out for all sorts
Speaker 1: of different organisms, and I note how their ranges are changing.
Speaker 1: Just last month, I found a lone star tick on
Speaker 1: my dog. Neither she nor I have been to Missouri
Speaker 1: for over a year. So those little ticks, those little
Speaker 1: lone star ticks, they are moving their way.
Speaker 2: North, Winnie, thank you so much for sharing your story
Speaker 2: with us. We really appreciate it, and like, my gosh,
Speaker 2: what a strange yeah thing this is.
Speaker 3: I know, thank you so much for being willing to
Speaker 3: go through all of that with us and with all
Speaker 3: of our listeners. We really appreciate it. Yeah. Hi, I'm
Speaker 3: Aaron Welsh and I'm Erin Allman Updike.
Speaker 2: And this is this podcast will kill you.
Speaker 3: And today we're getting real weird, really weird, because we're
Speaker 3: talking about alpha gal syndrome aka red meat.
Speaker 2: Allergy, as given to you by the bite of a tick.
Speaker 3: By the bite of a tick. It's so weird, Aaron.
Speaker 2: Yeah, it is. It is very bizarre. It feels like
Speaker 2: something out of a sci fi novel that's like, you know,
Speaker 2: near future and the world is about to collapse because
Speaker 2: climate change is farming and whatever, and so then a
Speaker 2: rogue scientist introduces this thing into ticks that causes everyone
Speaker 2: to be vegetarian. Yeah, you get the you get the.
Speaker 3: Right, I got it. I liked it a lot. I
Speaker 3: would watch that movie, honestly.
Speaker 2: I would. Yeah, I would absolutely watch that movie and
Speaker 2: probably fall asleep halfway. But that's my that's my jam.
Speaker 3: Yeah, it's I'm really excited for it. It's gonna be
Speaker 3: a really fun episode. Yeah, I have so many it's
Speaker 3: so weird, it's so weird.
Speaker 2: Yeah, and we'll get we'll get into all of that
Speaker 2: weirdness business later on, but first we've got some other
Speaker 2: business to take care of.
Speaker 3: We do. It's quarantiney time as always. So what are
Speaker 3: we drinking this week? We're drinking gal Pal, you know,
Speaker 3: just Pal, gal Pal, you're out the gal Pal. It's
Speaker 3: a delicious beverage. Of course, it is made with none
Speaker 3: other than Beef Eater Gin Yeah sponsored.
Speaker 2: Not sponsored, but you know, we can't. We can't pass
Speaker 2: up that that name, that branding.
Speaker 3: As well as passion fruit and lemon lime soda. It's
Speaker 3: a really refreshing gin bev.
Speaker 2: Yeah, gal pales great. Yeah, and check it out because
Speaker 2: we'll be posting the recipe for gal Pal the Quarantini
Speaker 2: as well as Galpal the Place Barta on our website.
Speaker 2: This podcast will kill you dot Com and all over
Speaker 2: our social media channels. So if you're not following us there,
Speaker 2: you really should be, because we're coming out with some
Speaker 2: pretty stellar content if we do say so ourselves.
Speaker 3: And we do, we do say so ourselves pretty much
Speaker 3: every week we do. If you check out our website,
Speaker 3: you will also find a lot of other really great
Speaker 3: that we tell you about every single week, including transcripts
Speaker 3: from all of our episodes, which I believe you can
Speaker 3: now find as well on Apple podcasts. Speaking of Apple podcasts,
Speaker 3: are you subscribed? Because you should be to make sure
Speaker 3: that you're helping support the show. It really helps us
Speaker 3: to double check that you are subscribed and haven't accidentally
Speaker 3: been unsubscribed, which happened to me in fact from our
Speaker 3: own podcast. And anyways, back for our website, you can
Speaker 3: find transcripts, you can find merch. We have a whole
Speaker 3: bunch of merch. We have new merch, and we have
Speaker 3: a few items left from some of our old merch.
Speaker 3: So if you wanted to get your hands on things
Speaker 3: that you thought we were out of, double check because
Speaker 3: we might just have.
Speaker 2: It there limited stock.
Speaker 3: We've also got links to Bloodmobile, who does the music
Speaker 3: for all of our episodes. We've got a good Reads list,
Speaker 3: we've got a bookshop dot org affility account, we have
Speaker 3: the sources from all of our episodes. Oh my goodness,
Speaker 3: this podcast will kill you dot com check it out.
Speaker 2: I don't think we have any other business do no? Okay, well,
Speaker 2: then let's get started, because I feel like we have
Speaker 2: a lot of ground to cover when it comes to
Speaker 2: this bizarre thing called alphagal syndrome.
Speaker 3: We do, we do, we do. Let's get into it
Speaker 3: right after this break. Alpha gal syndrome is at its
Speaker 3: core a food allergy, and allergies are a hypersensitivity response
Speaker 3: to a very specific thing. Most allergies usually are a
Speaker 3: hyper sensitive response to a protein. So that right there
Speaker 3: is the first of so many places where the story
Speaker 3: of alphagal syndrome is so much weirder than just a
Speaker 3: food allergy, because in this case, it's an allergy to
Speaker 3: a specific sugar. Alpha gal an alpha gal of course,
Speaker 3: has a much more complicated chemical name. It's galactose alpha
Speaker 3: one three galactose.
Speaker 2: It's really hard to search for because I didn't want
Speaker 2: to have to put in the little alpha sign every
Speaker 2: time I searched.
Speaker 3: Actually, I never thought about if you just type alpha,
Speaker 3: does Google also recognize alpha as the word alpha?
Speaker 2: You know? Probably?
Speaker 3: I don't know it does, and I don't know enough
Speaker 3: about seo or whatever. Any Oh, gosh, no, In any case,
Speaker 3: galactose alpha one three galactose alpha GAL. So this is
Speaker 3: a short sugar, it's a aligosach ride. It's just a
Speaker 3: couple of sugar molecules linked together in a specific way.
Speaker 3: And alpha gal syndrome is when people develop an allergy
Speaker 3: to this particular sugar. And like we already mentioned, this
Speaker 3: food allergy is also different than most food allergies because
Speaker 3: it develops after an initial exposure not to a food,
Speaker 3: but to a tick. So I figured to understand the
Speaker 3: story of alpha gal. To understand this weird food allergy,
Speaker 3: we first have to kind of take a step back
Speaker 3: and understand allergies more generally, like how do allergies? Food
Speaker 3: allergies usually work. So, an allergy at its core, like
Speaker 3: I said, is a hypersensitivity reaction, which basically means it's
Speaker 3: your body overdoing it in response to some kind of exposure,
Speaker 3: and that exposure is usually a protein. So in the
Speaker 3: case of food allergies, it's proteins that we eat, and
Speaker 3: adverse reactions to foods can come in a lot of
Speaker 3: different types and flavors. We already covered this season seliac disease,
Speaker 3: which is an adverse food reaction to specific proteins in gluten.
Speaker 3: Some types of adverse reactions are classified as allergies, and
Speaker 3: these are usually what are called ig e mediated allergies
Speaker 3: and IgE mediated allergies are the types of allergies that
Speaker 3: you probably think of. If you think of a food allergy,
Speaker 3: you probably think of most classically peanuts m hm. So
Speaker 3: someone who's allergic to peanuts might develop hives and then
Speaker 3: throat swelling and then anaphylaxis difficulty breathing after exposure to peanuts.
Speaker 3: At its core, what's happening here is that our body
Speaker 3: is mistaking a food protein like a peanut protein, for
Speaker 3: a pathogen and then mounting an immune response to this
Speaker 3: perceived threat. But it's doing that in a weird way
Speaker 3: by making these antibodies called IgE antibodies. So to understand allergies,
Speaker 3: we then also have to understand what the heck is
Speaker 3: an IgE ant a body?
Speaker 2: Can I ask a question real quick?
Speaker 3: Please?
Speaker 2: Why proteins? Ooh, good question.
Speaker 3: I don't have an exact answer to that, except that
Speaker 3: proteins tend to be more iminogenic. Okay, So it's similar
Speaker 3: with like vaccines. A lot of times, if we try
Speaker 3: and develop a vaccine against just carbohydrates or sugars that
Speaker 3: we could also target on the outside of a pathogen
Speaker 3: that doesn't tend to last as long, so we usually
Speaker 3: then link it to a protein like, for example, tetnos toxoid,
Speaker 3: and then we'll link carbohydrates to that protein to generate
Speaker 3: a better immune response. But I don't know why proteins
Speaker 3: tend to be more iminogenic. Yeah, it's a good question.
Speaker 2: It's interesting. Okay, Yeah, and so I feel like maybe
Speaker 2: this is jumping ahead. Okay, you said when you are
Speaker 2: exposed to something that triggers this IgE response. The IgE
Speaker 2: response is because your body is thinking that this is
Speaker 2: a pathogen. But this response is kind of out of
Speaker 2: control and really bad. Yeah, and can be much worse
Speaker 2: for you than a pathogen than a potential pathogen could be.
Speaker 2: Totally Yeah, So I don't know what my question is
Speaker 2: why why would that happen? Like why why would that
Speaker 2: be an evolved response?
Speaker 3: Yeah, it's a great question, like why did allergies evolve?
Speaker 2: Is a bigger question than I can maybe not only
Speaker 2: something that we address in the R two parter, but.
Speaker 3: What what part of your question is getting at, is
Speaker 3: like why IgE? Like why is this response so weird?
Speaker 3: So let's talk about what IgE is and why the
Speaker 3: response with IgE antibodies can be so severe. So antibodies,
Speaker 3: I feel like we've talked a lot about on this
Speaker 3: podcast in various time points, But antibodies are one of
Speaker 3: our immune systems ways of having a very specific response.
Speaker 3: So antibodies are the things that we make, say, for example,
Speaker 3: but when we get a vaccine to then be able
Speaker 3: to specifically target and fight off one particular say virus
Speaker 3: or something, right, our antibodies can very precisely identify one
Speaker 3: particular protein, for example, or carbohydrate sugar on a particular virus.
Speaker 3: And then when we're exposed to that again, our antibodies
Speaker 3: bind to those antigens that they can identify, and they
Speaker 3: act like a flag. They alert our immune system, Hey,
Speaker 3: come over here, I found something that shouldn't be here, right,
Speaker 3: and then we do our immune response thing. Most of
Speaker 3: the time when we talk about antibodies, or at least
Speaker 3: on this podcast when we have, we haven't mentioned the
Speaker 3: different types. But in vaccines and those kinds of antibody responses,
Speaker 3: our body is usually making IgM and IgG antibodies. There's
Speaker 3: other ones that are like in the context of our
Speaker 3: guts and our mucosal membranes called IgA, and then there's
Speaker 3: IgE antibodies, and these are created in the same basic
Speaker 3: way as all of our other antibodies in response to
Speaker 3: one particular protein. They're very very specific, and it's our
Speaker 3: B cells, the same cells that are making these antibodies.
Speaker 3: It's thought that evolutionarily this antibody responds. IgE evolved mostly
Speaker 3: to respond to parasites and protozoan pathogens and maybe even
Speaker 3: venoms like snake venom. And what IgE does is it
Speaker 3: doesn't just serve as a flag the way that something
Speaker 3: like IgG does. IgE is an antibody that hangs out
Speaker 3: attached to some of our other immune cells, like called
Speaker 3: mass cells and our basofyls. That part's less important, but
Speaker 3: basically IgE is attached. It's not free floating. It's attached
Speaker 3: to these other white blood cells, and when they find
Speaker 3: the anigen that they're targeted for, they grab onto it.
Speaker 3: And what that does is it triggers these cells that
Speaker 3: they're attached to to kind of almost burst open and
Speaker 3: spew forth a ton of highly reactive, super inflammatory stuff
Speaker 3: really quick, all of a sudden. It's like a boom
Speaker 3: immune response rather than like a flag. Hey, guys, everyone
Speaker 3: come over and then that response takes some time.
Speaker 2: Right, It's kind of like scorched Earth policy exactly.
Speaker 3: Yes, it's like something's here, Wow, I just just destroy
Speaker 3: it all a.
Speaker 2: Little reactive maybe, like let's take a moment, let's breathe,
Speaker 2: let's just see do we need to do this? Are
Speaker 2: there less extreme responses that we can come up with?
Speaker 3: No?
Speaker 2: Apparently, not ig.
Speaker 3: Is like my toddler last night when I told me
Speaker 3: we needed to come out of the bath, Like yeah. So,
Speaker 3: in a food allergy, like a peanut allergy, our body
Speaker 3: is inappropriately recognizing a peanut protein and then it's mounting
Speaker 3: weirdly this IgE response to it. That process is called sensitization.
Speaker 3: That has to happen first. You have to be exposed
Speaker 3: to something. Your body does kind of a weird thing
Speaker 3: by deciding that it's going to make IgE antibodies against
Speaker 3: that protein, and our immune system doesn't ever forget things,
Speaker 3: so it holds on to those IgE antibodies just waiting
Speaker 3: in the wings. And then the next time that we
Speaker 3: eat a peanut, those antibodies are already there and they're
Speaker 3: like we prod the invader and they do their scorz
Speaker 3: ter thing. They bind to that peanut protein, all of
Speaker 3: those mass cells expel tons of inflammatory material and then
Speaker 3: you have the symptoms of that allergic reaction. And that
Speaker 3: is what we see in alphagau syndrome, except for a
Speaker 3: few pretty important details. M H. So again, alpha gal.
Speaker 3: It's a sugar, a carbohydrate, and already that's a little
Speaker 3: bit weird. We're mounting a massive immune response to an oligosaccharide.
Speaker 3: Why is this particular sugar so immunogenic. Well, it turns
Speaker 3: out that this particular sugar is found pretty universally attached
Speaker 3: to proteins and lipids on cell membranes of it seems
Speaker 3: like most all, many many different types of cells throughout
Speaker 3: the body of pretty much every mammal except for humans
Speaker 3: and apes and old old monkeys. Oh yeah, we'll get
Speaker 3: into it. I know, I cannot wait. I know, Aaron,
Speaker 3: that you're going to get into a lot more detail
Speaker 3: about alpha gal and the antibodies that we make against
Speaker 3: alpha gal from an evolutionary context. But just for some
Speaker 3: context on alphagel. So we do not make this sugar
Speaker 3: in our bodies. We happen to make from infancy and
Speaker 3: to bodies against this particular alphag sugar the same way
Speaker 3: that people who like me are blood group oh make
Speaker 3: antibodies against the A and B sugars that make blood
Speaker 3: groups A, B, and O that are attached to our
Speaker 3: red blood cells. So the antibodies that we make and
Speaker 3: have circulating around us are IgG antibodies. I like to
Speaker 3: think of them as like normal ones, even though they're
Speaker 3: all normal. That's a terrible descriptor, but you know what
Speaker 3: I mean, they're just like free floating. They're not doing
Speaker 3: much right. We can eat all the bacon that we
Speaker 3: want and it doesn't trigger any kind of immune response,
Speaker 3: even though we have these IgG anti bodies floating around. Now,
Speaker 3: we cannot take a pig heart and transplant it into
Speaker 3: a human body. It so happens that this particular sugar
Speaker 3: is one of the major barriers to transplantation of animal
Speaker 3: organs into humans. But we can eat bacon, be exposed
Speaker 3: to it through our guts, and do just fine unless
Speaker 3: we can't enter the tick.
Speaker 2: Oh gosh, yep, it's so weird.
Speaker 3: It it's so weird. So when I talked about how
Speaker 3: food allergies work, the first step that I went through
Speaker 3: was sensitization. Right there, has to be a period of
Speaker 3: sensitization where our body sees these antigens and goes, ooh,
Speaker 3: something's weird here. I'm going to make antibodies against it.
Speaker 3: And in alphagau syndrome, that's sensitization. To alpha gal it
Speaker 3: doesn't happen from food. It happens from a tick bite. Ticks,
Speaker 3: of course, are our little six to eight legged, depending
Speaker 3: on life stages, blood feeding friends. These are obligate blood
Speaker 3: feeders throughout their whole life cycle, and they have to
Speaker 3: stay attached for a pretty long time, like hours to days,
Speaker 3: in order to get a full blood meal. And while
Speaker 3: they do this, just like our friend the leech, they
Speaker 3: spit a whole bunch of their saliva into our bodies
Speaker 3: to help with things like anti coagulation and anesthetizing us
Speaker 3: so that we don't notice them and we're not bothered
Speaker 3: by them. It can hang out for a long time.
Speaker 2: Tick saliva is kind of a magical substance. Saliva is
Speaker 2: right exactly, and I feel like saliva. I know people
Speaker 2: are working on it, but I do feel like there
Speaker 2: are some amazing opportunities in tickspit.
Speaker 3: I agree. I was reading about like the sia loam.
Speaker 3: They call it the saliva microbiome. I love it.
Speaker 2: I love when there's a new word for microbiome for
Speaker 2: a different part of a different area, but different area.
Speaker 3: So what happens in alpha gau syndrome is that during
Speaker 3: blood feeding, some species of tick, somehow, some way introduce
Speaker 3: alpha gal into our bodies, directly into our bloodstream or
Speaker 3: our lymphatics while they're blood feeding, and for some people
Speaker 3: this triggers that sensitization, the development of those ig e
Speaker 3: anna bodies against that specific sugar alphagal. That is how
Speaker 3: sensitization happens. Often, but not always, when people develop alpha gal,
Speaker 3: they report like one specific tick bite that they had
Speaker 3: a more severe local reaction to, So they'll get like
Speaker 3: a large red welt that's super itchy, and this reaction
Speaker 3: will last like a lot longer or be a lot
Speaker 3: more extreme than other tick bites that they might have
Speaker 3: had in the past. And then what happens is that
Speaker 3: on re exposure to alpha gal, like the next time
Speaker 3: that somebody eats bacon, because alpha gal is all over
Speaker 3: any meat products that you're eating. Now their body has
Speaker 3: all of this IgE waiting and it goes whoa wha whoa,
Speaker 3: this is that highly varulent pathogen. I have to respond
Speaker 3: to it, binds to it. Those mast cells de granulate,
Speaker 3: they release all of their super inflammatory stuff, and you
Speaker 3: get this massive immune response aka allergy. That's that's how
Speaker 3: alpha that works.
Speaker 2: Well, Aaron, I have a few questions here.
Speaker 3: Well, Aaron, I thought that you might.
Speaker 2: Okay, we know that this is multiple tick species all
Speaker 2: over the world. The worst is happening yep, and so
Speaker 2: it's clearly not related to certain tick species or like
Speaker 2: tick phylogeny.
Speaker 3: Yeah, it's It was surprising to me how many different
Speaker 3: genera of ticks, like totally unrelated species of ticks across
Speaker 3: the whole globe can end up causing.
Speaker 2: This, right, which suggests like can any tick be a culprit?
Speaker 2: And this can can any tick induce this allergy? So
Speaker 2: where is like what is the trigger from the tick?
Speaker 3: Yeah, that's a great question. It's the trigger is alpha gal. Yeah,
Speaker 3: question is where is this alpha gal coming from? Right?
Speaker 2: Is it coming from a previous blood meal? Does that mean?
Speaker 2: But I also couldn't find I did a little bit
Speaker 2: of digging, and I couldn't find any relationship between life
Speaker 2: stage of the tick that bit someone and because you
Speaker 2: would think, Okay, now I'm just getting nitty gritty. But
Speaker 2: when when ticks are first born, or when ticks first
Speaker 2: hatch from their little eggs, they haven't eaten, they haven't
Speaker 2: taken any blood meals. So those larva, if they bite you,
Speaker 2: and they do bite you like the seed ticks, will
Speaker 2: that still induce alpha gal response? It can exactly, So
Speaker 2: like what the heck is going on?
Speaker 4: Right?
Speaker 3: So that's the question is what the heck is going on?
Speaker 3: Where is this alphagal coming from? For a long time,
Speaker 3: we really didn't know, like you said, was it coming
Speaker 3: from a previous blood meal that just was still there
Speaker 3: and so the ticks spit a little bit into us?
Speaker 3: Was it something that's in the tick? It seems like
Speaker 3: it is coming from the ticks themselves.
Speaker 2: There was a paper is coming from inside the house
Speaker 2: that doesn't really work in this context, but.
Speaker 4: Though we try.
Speaker 3: There was a paper from twenty nineteen in Frontiers and
Speaker 3: Immunology that found evidence of alpha gal in ticks, even
Speaker 3: ticks that had not fed on other mammals, like ticks
Speaker 3: that were fed on human blood. And they weren't able
Speaker 3: to find alpha gal in unfed ticks. So It was
Speaker 3: only after at least partial blood feeding that they were
Speaker 3: able to find alpha gal that was reactive to these
Speaker 3: anti alphagal antibodies, and they found this in multiple different
Speaker 3: ticks species, including the one that most commonly causes alphagal
Speaker 3: syndrome in the US Ambloma americanum. Now what's really weird
Speaker 3: is that we still don't know how the tick is
Speaker 3: making this alpha gal because ticks don't have the enzyme.
Speaker 3: Just like humans don't have the enzyme that other mammals
Speaker 3: use to make alpha GL, ticks don't have that enzyme.
Speaker 3: So what that means is that there has to be
Speaker 3: either some other chemical pathway that they're using to make
Speaker 3: alpha gl or is it one of their microbes? Is
Speaker 3: it something in the tick microbiome, like say a commensal
Speaker 3: or another pathogen like a ricketsia or something that is
Speaker 3: making alpha gal inside the tick and then it gets
Speaker 3: into the salary glands and then the tick is spinning
Speaker 3: it into us. That level, we don't know, so like
Speaker 3: we know it's coming from the tick, we know it's
Speaker 3: coming from tick saliva, but we don't know how the
Speaker 3: ticks are making it and why, Like why are ticks
Speaker 3: making this weird sugar? What why?
Speaker 2: Why does anyone make this weird sugar? Because so I
Speaker 2: spent a lot of.
Speaker 3: The time you would answer that questionarion.
Speaker 2: No, I mean the question that I am trying to
Speaker 2: answer is why don't we make it? But I never
Speaker 2: really considered why would we?
Speaker 3: Why would we? Yeah? Why do we? Don't know?
Speaker 2: I don't know.
Speaker 3: So it's very very weird. And like we mentioned, there's
Speaker 3: a lot of different tick species that can cause this.
Speaker 3: In the US, Amblioma americanum is the most common. In Australia,
Speaker 3: it's Exodees holocyclists, also called the paralysis tick. We have
Speaker 3: to do tick paralysis in we do, but also things
Speaker 3: like Exode's risinous rifycephalous Bursa hyaloma species, like so many
Speaker 3: different species across again the entire globe, North America, South America, Australia, Europe, Africa, everywhere.
Speaker 2: Yeah, you shall find, yes, resideolergy from tick bites yep.
Speaker 3: Including in some species like Exodi scapularis. People have found
Speaker 3: alpha gal in the saliva, but we have yet so
Speaker 3: far to see alphagau syndrome develop in people after Exodia
Speaker 3: scapularis bites as far we know astrisk, who knows what
Speaker 3: will happen, But what does actually alphagal syndrome look like.
Speaker 3: We haven't even talked about what the symptoms are aside
Speaker 3: from being like allergy, and it turns out that this
Speaker 3: also gets a little bit weirder than just your typical
Speaker 3: quote unquote food allergy. Of course, of course, so the
Speaker 3: symptoms of alphagal syndrome can of course vary, but they
Speaker 3: often start with GI symptoms that might include things like
Speaker 3: abdominal pain, nausea, or vomiting. They can also include skin
Speaker 3: symptoms like hives or what are called urticaria and hives.
Speaker 3: If anyone has never had them or never seen them,
Speaker 3: they're a very classic allergy association. They're these like red,
Speaker 3: irregularly shaped, slightly raised, kind of puffy looking weltz that
Speaker 3: you can get kind of anywhere across your whole body.
Speaker 3: They can be big, they can be little. There can
Speaker 3: be a combination of different sizes, and they're usually super
Speaker 3: super itchy hives are. And then you can also so
Speaker 3: get angioedema, which means swelling edema, swelling of the face,
Speaker 3: especially the lips and the mouth, and then the most
Speaker 3: severe reaction is anaphylaxis, and we think of anaphylaxis as
Speaker 3: that not being able to breathe right, airway constriction because
Speaker 3: of swelling an edema. But anaphylaxis is actually a widespread response.
Speaker 3: It's not local to just the respiratory system. So what's
Speaker 3: happening in anaphylaxis is widespread vasodilation of blood vessels and
Speaker 3: then constriction of your respiratory system of like your bronchioles,
Speaker 3: and that can lead to hypotension, so low blood pressure
Speaker 3: and eventually shock and death. Anaphylaxis is very, very scary
Speaker 3: and a serious emergency, and a pretty high proportion something
Speaker 3: like sixty percent or some studies site even more people
Speaker 3: report very severe reactions including anaphylaxis with AlphaGo syndrome.
Speaker 2: And so this those suite of symptoms there are found
Speaker 2: in other food allergies in alphagal is just delayed.
Speaker 3: Yeah. That's the other weird thing that's like alphagal apart
Speaker 3: from most other food allergies is that these symptoms usually
Speaker 3: develop hours three to six hours after exposure to the
Speaker 3: allergen in question, which is mammal meat, usually not minutes,
Speaker 3: and most other food allergies happen after a matter of
Speaker 3: minutes and peak even in like ten to twenty minutes
Speaker 3: after exposure. So I knew you were gonna ask. I asked,
Speaker 3: why the heck is there this delay? Yeah, unsurprisingly, we
Speaker 3: don't entirely know, but it's thought that it's not necessarily
Speaker 3: something like weird about alphagal or this allergy in specific,
Speaker 3: but it's just a delay in the circulation of this anigen.
Speaker 3: So the sugar itself alphagal it's not just like a
Speaker 3: free floating sugar. It's not like a carbohydrate that's like
Speaker 3: you know, what makes up your breads or something. These
Speaker 3: are sugars that are attached to proteins and lipids. They're
Speaker 3: glycoproteins and glycolipids, and so they enter the system. They
Speaker 3: enter your body a little bit more slowly, but we
Speaker 3: can see really quick on set reactions in someone with
Speaker 3: alphagou syndrome if they're exposed to alphagal via the bloodstream.
Speaker 3: And this we saw in the case of setuximab, which
Speaker 3: is an antibody, a monoclonal antibody. I think you'll probably
Speaker 3: talk about it erin uh huh, that happens to have
Speaker 3: some alphagl on it or in it in that medication,
Speaker 3: and people who were exposed to that, who they didn't
Speaker 3: know that they had alphagal but they did. Their response
Speaker 3: was much more rapid, on the order of minutes and
Speaker 3: peaked within twenty minutes, which is more like what we
Speaker 3: would expect with other food allergies. Okay, it's so weird, Aaron,
Speaker 3: So I want to like just like reframe it again
Speaker 3: as like, Okay, so what are we actually talking about?
Speaker 3: What is alphagau syndrome? Overall? Alphagal syndrome is just like
Speaker 3: a food allergy, except that it's a tick bite and
Speaker 3: not a food that causes that initial sensitization. It's a
Speaker 3: sugar and not a protein that you're reacting to. It's
Speaker 3: a delayed, like three to six hours later allergic response
Speaker 3: rather than an immediate one, and it often can develop
Speaker 3: later in life, but it can develop at any point
Speaker 3: in life. And most food allergies developed during childhood after
Speaker 3: just a few exposures, rather than like a lifetime of
Speaker 3: being able to tolerate it and now all of a
Speaker 3: sudden you can't. Oh and just so that I don't
Speaker 3: forget re exposure to ticks like getting more tick bites
Speaker 3: after you've already developed alphagal syndrome seems to heighten the
Speaker 3: sensitivity even more so that people have renewed worse reactions
Speaker 3: or are like never able to tolerate me to again.
Speaker 3: Whereas if people can not get any tick bites for
Speaker 3: a number of years, they might be then eventually able
Speaker 3: to tolerate meat again at some point in the future.
Speaker 2: Right, Okay, Okay, I have a few questions.
Speaker 3: Great, give them to me.
Speaker 2: Are there other carbohydrates that trigger food allergies in people?
Speaker 3: It's a great question. I try to find some more
Speaker 3: like specific details on this. Not really that I can see.
Speaker 3: There certainly can be carbohydrates that you have adverse reactions to,
Speaker 3: but an IgE mediated allergy response like this, No, this
Speaker 3: is pretty unique.
Speaker 2: Okay. And then another question is if every tick has
Speaker 2: the potential more or less I know, some more than others,
Speaker 2: has the potential to cause alphagal syndrome, does every person
Speaker 2: then have the capacity to develop alphagal syndrome?
Speaker 3: I love your question, Darren, such a good one. No idea,
Speaker 3: We have no idea what it is about one person
Speaker 3: versus another that predict why someone would develop alphagau syndrome
Speaker 3: after exposure to a tick and another person wouldn't. Like,
Speaker 3: same tick could bite two people, one could develop it
Speaker 3: and one could not. Why we don't know. And what's
Speaker 3: really weird too, is that a lot of times, like
Speaker 3: with allergies, food allergies and respiratory allergies, we often see
Speaker 3: this kind of like triad. It's called an atopic triad
Speaker 3: where you have like allergies asthma, eggzema. These are all
Speaker 3: kind of things that share similar immunologic pathways, and so
Speaker 3: you might expect that someone with one food allergy is
Speaker 3: more predisposed to have other food allergies because again it's
Speaker 3: this like hypersensitivity response. But a lot of times people
Speaker 3: with alphagau syndrome don't have any other allergies, They don't
Speaker 3: have any other food allergies, they don't have any other
Speaker 3: respiratory allergies. So it's like it we really don't know
Speaker 3: right now, Like why why?
Speaker 2: Yeah?
Speaker 4: Right?
Speaker 2: Who?
Speaker 3: We don't know.
Speaker 2: Ah, it's just it's so weird, Like what is it
Speaker 2: Just that it's this the alpha gal is coming into
Speaker 2: your body in a weird way.
Speaker 3: Like it's a weird way for sure, But like is
Speaker 3: every amblioma americanom tick bite doing that probably maybe we
Speaker 3: think it's probably a threshold thing, like maybe everyone develops
Speaker 3: some degree of these IgE antibodies, but not everyone is
Speaker 3: going to then have alphagal syndrome, like respond in this
Speaker 3: severe way to exposure to alpha gal in their meat,
Speaker 3: because there is also degrees, right, Alpha gal is a
Speaker 3: sugar on so many mammalian products, not just meat. It's
Speaker 3: also found in dairy at lower levels, but most people
Speaker 3: don't have reactions to dairy, and some people do. It's
Speaker 3: also found in things like gelatin, which means that it's
Speaker 3: in a lot of pharmaceuticals. And so for some people
Speaker 3: there's a really wide range of stuff that they now
Speaker 3: can't tolerate, and for other people they can tolerate all
Speaker 3: of those things just fine, and it's really only like
Speaker 3: bacon or like pork product or like red meat like beef,
Speaker 3: and so it's a really like wide variation. And so
Speaker 3: there's probably a lot that's like thresholds, like how much
Speaker 3: IgE do you have, how much did you make, how
Speaker 3: recent was it, you know, all of that kind of stuff.
Speaker 2: I remember talking with someone who had alpha gl syndrome
Speaker 2: and they could eat cured meats, but not like a hamburger.
Speaker 3: Interesting, Yeah, yeah, And is that just volume, Like when
Speaker 3: you eat a hamburger, do you just eat a lot
Speaker 3: more of it than you do with a cured meat?
Speaker 2: I don't know, or somehow the you get more degraded
Speaker 2: in cured meats, like exactly right, I do. I don't know.
Speaker 3: I don't know either. There's a lot. It's so, so,
Speaker 3: so so interesting. So yeah, Aaron, tell me m everything,
Speaker 3: like what I know you're going to talk about this sugar,
Speaker 3: Like where did it come from? Why do some mammals
Speaker 3: make it? Why do we not make it anymore? How
Speaker 3: did this come to be? And then also like how
Speaker 3: did we figure this out? Because yeah, you know what,
Speaker 3: I did not realize how recently we figured it out,
Speaker 3: because I feel like when we were in Panama, it
Speaker 3: was the thing. Everyone had it, everyone had it, Yeah,
Speaker 3: but it was like very new at the time.
Speaker 4: Yeah.
Speaker 2: Yeah, let's get into some of these questions and take
Speaker 2: a quick break and then we'll begin. Aaron, like you mentioned,
Speaker 2: we learned about this I think pretty recently.
Speaker 4: Yeah.
Speaker 2: The first time that I learned about the fact that
Speaker 2: you could become allergic to red meat following a tick bite.
Speaker 2: I was so confused, like I had no idea. I
Speaker 2: think it was thirteen and I had just started fieldwork
Speaker 2: in Panama for my PhD research on tics and climate change,
Speaker 2: and also for all of you listeners out there. Right now,
Speaker 2: I'm wearing my Smithsonian T shirt that has little larval
Speaker 2: ticks all over it. I love it so much. Actually,
Speaker 2: they have eight legs, so they must not be larvae.
Speaker 3: Even though they don't like the nymphs or adults. They're big.
Speaker 2: They're big, but they look I don't know. Some look
Speaker 2: like there's an adults. I think it's nymphs. Also, Okay, anyway,
Speaker 2: we don't need to get into it.
Speaker 3: She's wearing a tick shirt, guys the occasion.
Speaker 2: It's one of my favorite shirts. But yeah, So in
Speaker 2: twenty thirteen, a professor who was also in Panama reached
Speaker 2: out to me and was like, oh, I heard you're
Speaker 2: working on tics. Have you heard of a red meat
Speaker 2: allergy following a tick bite?
Speaker 4: I have it.
Speaker 2: A few other researchers who have spent a lot of
Speaker 2: time doing fieldwork in this area have also had it,
Speaker 2: and it could be a cool project. And I didn't
Speaker 2: end up pursuing it as a project because probably I
Speaker 2: was scared of like the immunology aspect of it, but
Speaker 2: over the I probably should have. But over the next
Speaker 2: few years that I worked there, every field season, people
Speaker 2: would come up to me and say, oh, I just
Speaker 2: got diagnosed with this red meat allergy. I ate a
Speaker 2: hamburger and nearly died yep, or hey, I think my
Speaker 2: allergy is getting better. I can eat salami now. Like
Speaker 2: there are so many people erin it definitely seems like
Speaker 2: Central Panama is a hotspot, but maybe it's just that
Speaker 2: everywhere is sort of a hot spot for red meat allergy.
Speaker 2: But it really was like a lot of.
Speaker 3: People that we hung out with, like got bit by
Speaker 3: a lot of ticks. Let's be we all did.
Speaker 2: Yeah exactly, Yeah, I mean yeah, thousands and thousands I
Speaker 2: would catch every day.
Speaker 3: Yeah.
Speaker 2: So anyway, but every time I learned if someone knew
Speaker 2: who had developed the allergy, I would do some like
Speaker 2: light google scholaring to try to answer the three main
Speaker 2: questions that I had, What the heck is going on
Speaker 2: in this allergy, how the heck did people discover the
Speaker 2: connection to tick bites, And why the heck does this happen. Yeah,
Speaker 2: and so Aarin, you just took us through the first question,
Speaker 2: and so I'm going to try to take on those
Speaker 2: other two, starting with the how, like, how was alpha
Speaker 2: gal syndrome first recognized? So the syndrome itself has no
Speaker 2: doubt been around for longer than people have recognized it.
Speaker 2: That professor that I mentioned had developed it, I believe
Speaker 2: in the early nineteen nineties. And there is apparently unpublished
Speaker 2: work from the State of Georgia in the late nineteen
Speaker 2: eighties that mention the potential of a red meat allergy
Speaker 2: in association with tick bites. But it took a series
Speaker 2: of kind of unusual events at opposite ends of the
Speaker 2: Earth for the connection to be made between tick bite
Speaker 2: and red meat allergy. On the one end of the
Speaker 2: earth was doctor Cheryl van Nonan, an immunologist who was
Speaker 2: working at an allergy clinic in Sydney, Australia. She noticed
Speaker 2: what seemed like an unusual number of people coming to
Speaker 2: the clinic complaining that they had recently developed an allergy
Speaker 2: to red meat, with a delayed onset of symptoms that
Speaker 2: involved things like tongue swelling, throat constriction, respiratory distress and
Speaker 2: all the other suite of symptoms that you mentioned, what's
Speaker 2: an unusual number you might ask, like, when did this
Speaker 2: start to stand out? So between two thousand and three
Speaker 2: and two thousand and seven, twenty five patients, seven men,
Speaker 2: eighteen women reported this allergy. And I'm sure that she
Speaker 2: and her collaborators ruled up many other potential causes, but
Speaker 2: ticks seemed like a strong possibility from the beginning, with
Speaker 2: twenty four of the twenty five patients reporting a history
Speaker 2: of having bad local reaction to tick bites, and the
Speaker 2: areas like the regions where these patients resided, were known
Speaker 2: to be quote unquote endemically infested with several tick species.
Speaker 2: In two thousand and seven, Van Noonan authored an abstract,
Speaker 2: the first academic publication linking the red meat allergy to
Speaker 2: a tick bite from the tick Exodes holocyclists. While Van
Speaker 2: Nounan was drawing her own conclusions down under, other researchers
Speaker 2: in the US were on a different trail, but one
Speaker 2: that would lead them to the same strange allergic reaction.
Speaker 2: In two thousand and four, trials were underway to test
Speaker 2: a cancer drug called Texa mab aaron texmab se tuxamab.
Speaker 2: No wonder, I didn't recognize it when you first said it,
Speaker 2: because I've only read it and I didn't try to
Speaker 2: say it in my head. But they were testing this
Speaker 2: cancer drug to see if it was safe for FDA approval,
Speaker 2: but researchers were noticing that in some patients this medication
Speaker 2: was causing a hypersensitivity reaction, particularly those patients residing in
Speaker 2: a handful of states in the southern US. The reactions
Speaker 2: could be quite severe, pretty quick, onset anaphylaxis that would
Speaker 2: have you on the floor and had even resulted in
Speaker 2: death for a few So the pressure was on to
Speaker 2: find out what was causing this. Researchers Christine Chung, Thomas Plats, Mills,
Speaker 2: Scott Commons, and others were tasked with solving the problem,
Speaker 2: and they quickly narrowed in on an IgE response to
Speaker 2: a carbohydrate antigen called alphagaw. So that answered one question
Speaker 2: they had, which was like what were people's immune systems
Speaker 2: reacting to with this drug? But it still left an
Speaker 2: important one unanswered, what was triggering this reaction, like why
Speaker 2: alpha gw Right. The first clue came from alpha gul itself.
Speaker 2: As you mentioned Aaron, This antigen is found in tissues
Speaker 2: of non primate mammals and some primate mammals with some
Speaker 2: notable exceptions like humans, apes and Old World monkeys. And
Speaker 2: so the researchers thought that maybe we should look for
Speaker 2: patients who have had allergic reactions to beef and then
Speaker 2: map where they live. And the story goes according to
Speaker 2: the Radio Lab episode on this that the researchers then
Speaker 2: took out their map of beef reactions and compared it
Speaker 2: to as many other maps that they could find, just
Speaker 2: like over laying other distribution maps, you know, other disease maps,
Speaker 2: like all sorts of environmental exposures, whatever, And one map
Speaker 2: in particular stuck out, which was the distribution of Rocky
Speaker 2: Mountain spotted fever cases. Could this allergy be triggered by
Speaker 2: a tick bite? They interviewed the patients with the beef
Speaker 2: allergy confirmed to be IgE antibodies to alpha gal and
Speaker 2: found that more than eighty percent of them had been
Speaker 2: bitten by a tick before experiencing symptoms. This finding, combined
Speaker 2: with the report from Australia, was more or less the
Speaker 2: solid proof that they needed to suggest that tick bites
Speaker 2: were triggering an allergy to red meat, specifically the alpha
Speaker 2: gal antigen, and fascinatingly it was different tick species and
Speaker 2: on opposite ends of the world and also just like
Speaker 2: found around the same time. I think that part is
Speaker 2: also amazing.
Speaker 3: It's so so so weird that it happened, especially like
Speaker 3: the tuxamap thing and then the figuring that out and
Speaker 3: the like Australia thing like to do it all. It's
Speaker 3: so weird, like the right serendipitous, I guess.
Speaker 2: Aaron, I feel like I need to throw in this
Speaker 2: well actually here so please, this is not for you,
Speaker 2: but the tick species that you mentioned that has thought
Speaker 2: to be primarily responsible for alpha gal syndrome here in
Speaker 2: the US is the lone star tick Ambloma americanum, which
Speaker 2: actually very very rarely transmits the causative agent of Rocky
Speaker 2: Mountain spotted fever. And so the fact that the maps
Speaker 2: line up for spotted fever and alpha gal it really
Speaker 2: just seems coincidental to some degree. It might just be
Speaker 2: overlapping distributions of the Rocky Mountain spotted fever ticks yeah
Speaker 2: or tick and yeah, but I was just like, wait,
Speaker 2: that doesn't.
Speaker 3: Like, in my understanding, distributions of all of those tick species.
Speaker 2: Yeah, but anyway, I had I am sorry, I had to.
Speaker 2: But once those reports came out, first Van Noonan in
Speaker 2: two thousand and seven, and then Commons and Plats Mills
Speaker 2: in two thousand and eight. Plots Mills, by the way,
Speaker 2: developed the red meat allergy during this research through a
Speaker 2: tick bite. But it seemed like following these reports the
Speaker 2: allergy was everywhere. All you had to do was look France, Spain, Germany, Switzerland, Sweden,
Speaker 2: South Korea, Japan, Central America, South Africa and more every
Speaker 2: year worldwide distribution.
Speaker 3: Yeah.
Speaker 2: The fact that this stranger than fiction allergy to red
Speaker 2: meat triggered by a tick bite was discovered on two
Speaker 2: different continents across the globe within a few years of
Speaker 2: each other is pretty incredible. Is it coincidence? Maybe? But
Speaker 2: is it serendipitous Maybe. But some of the researchers have
Speaker 2: also hypothesized that exposure to ticks has been steadily on
Speaker 2: the rise over the past few decades in some regions
Speaker 2: where the allergy is common, as a result of increasing
Speaker 2: numbers of mammalian hosts like bandicoots in affected regions of
Speaker 2: Australia and white tailed deer in the southeastern us in
Speaker 2: addition to habitat encroachment. So we're basically just like more,
Speaker 2: we're encountering ticks more readily, classic and more tis ticks
Speaker 2: are there to encounter exactly.
Speaker 3: Yeah.
Speaker 2: And as for what the future may hold, I'll leave
Speaker 2: that to you Arin, except to say that as the
Speaker 2: climate continues to change, impacting the range of ticks species,
Speaker 2: as we continue to encroach into these habitats, I'm sure
Speaker 2: we'll just see more and more of this allergy develop.
Speaker 3: The ticks are just trying to save us all from
Speaker 3: eating too much meat.
Speaker 2: Yeah, thank you, ticks, We appreciate you.
Speaker 3: Yeah.
Speaker 2: But for now, let's turn back in time to get
Speaker 2: at the second question that I mentioned at the top
Speaker 2: of this, like, why the heck does this happen evolutionarily? So,
Speaker 2: like you mentioned, Aaron, humans react to alpha gal because
Speaker 2: we don't produce it ourselves, and so we recognize it
Speaker 2: as non self and we attack it. Pretty standard issue
Speaker 2: immune stuff, right, Yeah, And that inability to produce alpha
Speaker 2: gl makes us outliers among mammals. Of all mammal species, catarines,
Speaker 2: which includes old World monkeys and apes including humans, are
Speaker 2: the only ones who can't make alpha gal, who don't
Speaker 2: make alpha gl. That means that other primates like New
Speaker 2: World monkeys, lemurs, lorises, and tarsiars, not to mention cows, pigs, dogs, mice, etc.
Speaker 2: All produce alpha gal. We also continuously circulate antibodies against it.
Speaker 2: Alpha gal is, in fact, the most abundant natural antibody
Speaker 2: in humans, making up about one percent of immunoglobulence.
Speaker 3: That's so bizarre.
Speaker 2: It's so bizarre, and so it seems like this kind
Speaker 2: of a big deal. So what makes us different? Like
Speaker 2: why why us? Or why not us? Rather? And that's
Speaker 2: the question that researchers have been trying to figure out
Speaker 2: for decades now, looking at which species make alphagal and
Speaker 2: which species don't. Two things stand out. Number one, since
Speaker 2: the ability to produce this is so widespread among mammals,
Speaker 2: including both placental and marsupial mammals, it's clear that catarines
Speaker 2: once produced alpha gal like all other mammals, and lost
Speaker 2: the ability at some point.
Speaker 3: Okay, And number.
Speaker 2: Two, that point was around twenty eight million years ago,
Speaker 2: before the Old World monkeys and apes diverged.
Speaker 3: Okay, that makes sense.
Speaker 2: What happened twenty eight million years ago to cause such
Speaker 2: a big shift, resulting in both the loss of the
Speaker 2: ability to make alpha gal and the production of antibodies
Speaker 2: against it.
Speaker 3: Right, and like, did that did that happen like all
Speaker 3: of a set in or was it?
Speaker 1: Yeah?
Speaker 3: Because all using all catarines make antibodies against alpha gl.
Speaker 2: Yes, okay, right, so what happened?
Speaker 3: Yeah?
Speaker 2: How does a deadly disease sound?
Speaker 3: Oh? It sounds like sounds like right up our alleys.
Speaker 2: Right up our alley. This carbohydrate will kill you. Some researchers,
Speaker 2: namely Uri Galilee, who has done a tremendous amount of
Speaker 2: work on alpha gal, have proposed that around twenty eight
Speaker 2: million years or so ago, a highly virulent pathogen or
Speaker 2: pathogens I've seen airborne envelope viruses suggested, and also sepsis
Speaker 2: causing bacteria suggested. Some pathogen swept through Old World primates
Speaker 2: on the Eurasia Africa land mass, killing those who produced
Speaker 2: alpha gal and sparing the very few who didn't, who
Speaker 2: would over the next generations increase in number. And there
Speaker 2: seems to be some debate as to the cause or causes,
Speaker 2: like was it a pathogen, was it climate? Was it
Speaker 2: a mix of both? But there does seem to be
Speaker 2: a sharp decline in Old World primate populations during this time,
Speaker 2: almost leading to extinction like overall, but I think also
Speaker 2: extinction of certain species. But why would not producing ALPHAGL
Speaker 2: help protect you from severe infection or death? That's where
Speaker 2: things get super interesting, Okay, because it turns out that
Speaker 2: mammals aren't the only species to produce ALPHAGL. In fact,
Speaker 2: some viruses, bacteria, and parasites do, or they bind to
Speaker 2: host produced ALPHAGL to gain entry into their host cells.
Speaker 2: Ecoli species of Clebsiella, Plasmodium species, some of which cause
Speaker 2: malaria and humans, Micolplasma causative agent of tuberculosis, Salmonella, trepanosoma,
Speaker 2: leish Mania, sea diff mosquito borne viruses. I mean, a
Speaker 2: lot of pathogens either produce or use ALPHAGL in some capacity,
Speaker 2: and also microbes that aren't pathogenic to us. For instance,
Speaker 2: some members of our gut microbiome may produce alphagal, which
Speaker 2: triggers this constantly elevated anti body response, which could then
Speaker 2: protect us from things like malaria. And some people are
Speaker 2: looking at this in terms of an actual mechanism for
Speaker 2: how we can shape our gut microbiome to boost our
Speaker 2: immune system like adding in more bacteria that produce alpha
Speaker 2: gal as a way to raise those antibody levels and
Speaker 2: neutralize any invading malaria parasites. Why it's so cool because
Speaker 2: there does seem to be this association between gut microbiome,
Speaker 2: alpha gall production, anti gal antibodies, and then malaria susceptibility.
Speaker 2: And so I love it because I'm like, oh, is
Speaker 2: this the first time that I've actually seen the microbiome
Speaker 2: like a mechanism. Yeah, for the microbiome kind of just sational.
Speaker 3: Right, It's not just like what are these bacteria? It's like,
Speaker 3: what is the function of this and how is that
Speaker 3: interacting with our.
Speaker 2: It's direct links instead of there's an association, which is
Speaker 2: also really important. But at the same time it's exciting
Speaker 2: to see like this sort of concrete pathway of logic. Yes,
Speaker 2: love it. Alpha gal can also provide some insight into
Speaker 2: blood types and disease. People who have type B or
Speaker 2: type A B blood seem to be less susceptible to
Speaker 2: alpha gl syndrome because the b like me, because that
Speaker 2: B antigen that they produce is very similar apparently structurally
Speaker 2: to alpha gal, and so their bodies see it as
Speaker 2: more like self and so they're not as liable to
Speaker 2: attack it.
Speaker 3: Yeah. I've heard too that that you have more specific
Speaker 3: anti gal proteins anti alphagal proteins, whereas people who are
Speaker 3: O or A have like less specific ones that bind
Speaker 3: into maybe B and alpha gown like are just a
Speaker 3: little bit messier.
Speaker 2: It's massy. It's just a little more efficient.
Speaker 3: Yeah, there you go.
Speaker 2: Yeah, painting with the broadbrush. But researchers have also genetically
Speaker 2: engineered mice to knock out the alpha gal producing gene
Speaker 2: and found some fascinating results, with knockout mice being more
Speaker 2: protected against some pathogens like sinv virus or syndibis virus
Speaker 2: and less protected against others like herpie simplex type two.
Speaker 3: Huh.
Speaker 2: Yeah.
Speaker 3: Interesting.
Speaker 2: And then there's the genetic engineering of pigs to not
Speaker 2: produce alpha gal, so called gal safe pigs, which I
Speaker 2: love because it makes them not only safe to consume
Speaker 2: for people with alpha gal syndrome, but also it opens
Speaker 2: the doors for zeno transplantation, transplanting pig organs into humans, which,
Speaker 2: as you mentioned aarin previously could not be done in
Speaker 2: part because or in major part because of this alpha
Speaker 2: gala carbohydrate.
Speaker 3: Ye it's wild that this particular carbohydrate, like this little
Speaker 3: sugar is that important, I know, right, Like it was
Speaker 3: one of the major I mean, it still is one
Speaker 3: of the major barriers to animal organ like transplant into humans.
Speaker 3: And so now with the development of these pigs like
Speaker 3: it's it's so it's so fascinating, Aran.
Speaker 2: I think the thing that surprised me the most about
Speaker 2: doing this episode is that I had never heard of
Speaker 2: alpha gal before twenty thirteen, and I since then have
Speaker 2: never heard about it outside of the context of alphagal syndrome. Same,
Speaker 2: but this is one of the most important components of
Speaker 2: our life, of our immune system in terms of anti gall,
Speaker 2: in terms of other animals, and it just plays so
Speaker 2: many more roles than preventing you from eating meat.
Speaker 3: Right than just alphagal syndrome, which is also very like
Speaker 3: interesting and important and cool.
Speaker 2: Yeah, it's wild. The other big takeaway from this, I think,
Speaker 2: and that is very obvious, is that the story of
Speaker 2: alpha gal is still very much unfolding, and the tickboarn
Speaker 2: allergy is really just a part of it. Yeah, I mean,
Speaker 2: I was going down so many rabbit holes in terms
Speaker 2: of autoimmune diseases and alpha gal. Whether there are people
Speaker 2: who do produce alpha gal and how they respond to
Speaker 2: different pathogens, because it really is just like a simple
Speaker 2: frame shift mutation. We still have the gene. It's just
Speaker 2: like is non It's just should work right, and then
Speaker 2: blood types and association with different diseases. Let's do an
Speaker 2: episode on that. I mean, but every answer that I found,
Speaker 2: or every partial answer that I found, just led to
Speaker 2: a million more questions. And so now I'll end this
Speaker 2: with a question for you, Aaron, which is where are
Speaker 2: we today with alpha gal syndrome?
Speaker 3: Oh? I can't wait to tell you all about it
Speaker 3: right after this break. According to the CDC in the US,
Speaker 3: there were over one hundred and ten thousand cases of
Speaker 3: alpha gau reported between twenty ten and twenty twenty two,
Speaker 3: and most of those are the latter half of that
Speaker 3: twelve years, Okay, which is somehow both way more than
Speaker 3: I expected, but also likely a gross underestimate because alpha
Speaker 3: gaul syndrome is not a notifiable disease, and the estimates
Speaker 3: of prevalence globally really really range and I think will
Speaker 3: likely change drastically over time, and not just because numbers
Speaker 3: are actually changing, but the estimates that I saw right
Speaker 3: now in places where we have prevalence estimates range between
Speaker 3: in Germany four cases per one hundred thousand people to
Speaker 3: thirteen cases per one hundred thousand people in Virginia, which
Speaker 3: is a part of the US that has a higher
Speaker 3: number of cases than a lot of parts of the US,
Speaker 3: and one hundred and thirteen per one hundred thousand people
Speaker 3: in the Sydney Basin in Australia. Wow. Okay, Right, so
Speaker 3: like really big variation, and a lot of that has
Speaker 3: to do with both tick species and where those ticks exist,
Speaker 3: how much people are interacting with ticks, right, Like, if
Speaker 3: you're in a big city, you're not probably going to
Speaker 3: be interacting with ticks as much as if you're in
Speaker 3: a more rural area, et cetera. But also where are
Speaker 3: we looking, Like, where are we looking for this? Because
Speaker 3: like we said, if you're looking for it, you'll find it.
Speaker 3: And cases are on the rise without a doubt. For example,
Speaker 3: in the US in twenty seventeen, there were just over
Speaker 3: thirteen thousand new cases diagnosed. There were nearly nineteen thousand
Speaker 3: cases diagnosed in twenty twenty one.
Speaker 4: Wow.
Speaker 3: Yeah, And what's really mind blowing is that in studies
Speaker 3: where they have looked at like larger populations, just like
Speaker 3: checking for people who might have IgE those allergy associate
Speaker 3: antibodies against alpha gal. In some populations, they found up
Speaker 3: to twenty percent of people who had IgE antibodies against
Speaker 3: alpha GL. But by no means does that mean that
Speaker 3: all of those people have alphagal syndrome. So there's still
Speaker 3: a really big open question of like what is that threshold,
Speaker 3: Like how much IgE do you have to have? And
Speaker 3: why are some people reacting and developing alphagal syndrome and
Speaker 3: some people aren't.
Speaker 2: Do levels of IgE correspond directly with that allergic response
Speaker 2: or can some people have like two people have the
Speaker 2: same levels of IgE and one person has anaphylaxis and
Speaker 2: the other person does not react whatsoever.
Speaker 3: Yeah, it's a great question. It does seem to be
Speaker 3: that the levels do matter in terms of what your
Speaker 3: response is. Okay, there still isn't a very clear, like
Speaker 3: for example, diagnostic threshold of like okay, this is the
Speaker 3: value which you have alphagal syndrome versus this is the
Speaker 3: value where you don't. That is still a little bit
Speaker 3: like up for debate. It seems like okay, yeah, but
Speaker 3: it does seem to correspond where higher levels more response
Speaker 3: and like repeat tick bite, those levels go up. And
Speaker 3: like you mentioned Aaron, as with all I think ever
Speaker 3: of our vector born disease episodes, there's a lot that
Speaker 3: is probably contributing to this rise in incidents and prevalence.
Speaker 3: This includes things like changes in the distribution of ticks
Speaker 3: in the US, especially increases in things like deer populations
Speaker 3: and other mammal populations and other parts of the globe
Speaker 3: that are really great hosts for ticks, but also our
Speaker 3: exposures to ticks, things like land use change, deforestation blah
Speaker 3: blah blah, climate change, everything that changes the way that
Speaker 3: we interact with ticks and other tick hosts is going
Speaker 3: to affect any kind of tick born disease, including alpha glah,
Speaker 3: but also things like getting better at recognizing and diagnosing
Speaker 3: this because one of the things that we I always
Speaker 3: try and talk about, like well, where's the current research
Speaker 3: or where's the research going, and for a disease like
Speaker 3: alpha gal that is still so brand new in the
Speaker 3: scheme of what medicine understands about this disease to begin with,
Speaker 3: Like we just figured out this existed a couple decades ago,
Speaker 3: not even like twenty years ago, so we're still very
Speaker 3: much writing that story of like where do we go
Speaker 3: with alphagau syndrome from here? And right now we need
Speaker 3: people to know that it exists because a recent survey
Speaker 3: by the CDC from twenty twenty two found that forty
Speaker 3: two percent of healthcare providers in their particular study hadn't
Speaker 3: heard of alphagau syndrome. They didn't know about it.
Speaker 4: Wow.
Speaker 3: And I will say that that was just a survey
Speaker 3: of primary care providers, so it was like pediatricians, internists,
Speaker 3: and family practice physicians and then nps and pas, and
Speaker 3: rates of knowledge are probably much higher among say allergists
Speaker 3: or even GI specialists that people might get referred to
Speaker 3: for their GI symptoms, but that is still a pretty
Speaker 3: important knowledge gap to kind of highlight. Absolutely, We've talked
Speaker 3: a lot on this podcast about like delays in diagnosis
Speaker 3: and things like that, and these are very severe reactions,
Speaker 3: so this is like pretty significant. Yeah, yeah, So I
Speaker 3: think that's one of the biggest areas of like how
Speaker 3: to make everyone know about it, Maybe make a podcast.
Speaker 2: Maybe you can help a solution.
Speaker 3: And in truth, there is there is so much that
Speaker 3: is still unknown in terms of what is the next
Speaker 3: big research area. It's everything like why do some people
Speaker 3: mount this response and others don't? What really is that
Speaker 3: IgE threshold? And what's causing it in some people? What
Speaker 3: other treatment options might exist besides just never eating any
Speaker 3: kind of mammalian meat again, how can we desensitize people
Speaker 3: like we might do for other food allergies? Can we
Speaker 3: do that? Is it just avoidance of tick bites or
Speaker 3: is there anything else? What are all the different tick
Speaker 3: species that can cause this? How many have we not
Speaker 3: yet discovered? How is it going to change with things
Speaker 3: like climate change? How are these ticks making alpha gal
Speaker 3: to begin with?
Speaker 2: Right?
Speaker 3: Right?
Speaker 2: There are so many different questions and different opportunities for
Speaker 2: research into this from so many perspectives to make it
Speaker 2: super integrative research. Like it's a really incredibly open field
Speaker 2: with a lot of opportunity to understand too, Like something
Speaker 2: that is so universal in across mammals except for a handful.
Speaker 3: Except for us and a handful of our cousins. H.
Speaker 3: It's yeah, it is really really an interesting disease and
Speaker 3: such a weird and wacky mechanism. I also am dying
Speaker 3: to know everyone who's listening, had you heard of alpha
Speaker 3: GAO syndrome, because I never know with things like this,
Speaker 3: if it's like everyone knows about it at least a
Speaker 3: little bit, or if we really are just that weird,
Speaker 3: where like we've been talking about it since like twenty
Speaker 3: thirteen because so many people in Panama had it right,
Speaker 3: and like it's not that normal and there was that
Speaker 3: radio lab episode so many years ago, But like, how
Speaker 3: had you heard of this? How much did you know
Speaker 3: about this? Right? I really want to know.
Speaker 2: Do you have this?
Speaker 3: Do you have this?
Speaker 2: Because we have had a lot of people reach out
Speaker 2: to say I am allergic to red meat thanks to
Speaker 2: a tick bite. What's going on here?
Speaker 3: And how long did it take to get diagnosed because
Speaker 3: it seems like there's a pretty big gap in diagnosis.
Speaker 3: But yeah, I have so many more questions arin.
Speaker 2: I think that we all do, And so let's direct
Speaker 2: people to the best source of where they can try
Speaker 2: to answer those questions, which they can answer our questions
Speaker 2: for us a million sources. I truly do have like
Speaker 2: million sources here. I want to shout out just a few.
Speaker 2: So there's one by Commons and Plats Mills from two
Speaker 2: thousand and nine that goes into sort of anaphylaxis syndromes
Speaker 2: relating to alpha gal. Then there are a couple of
Speaker 2: interesting papers about sort of the evolutionary significance of alpha
Speaker 2: GL one by Gillilee from twenty nineteen, as well as
Speaker 2: a handful of many more. Actually, and this paper goes
Speaker 2: into how viruses may have led to the loss of
Speaker 2: alpha gl production and the rise in alpha gal antibodies.
Speaker 2: And then there's a paper by Rodriguez and Welsh from
Speaker 2: twenty thirteen no relation as far as I'm aware, titled
Speaker 2: possible role of a cell surface carbohydrate and evolution of
Speaker 2: resistance to viral infections in Old World primates. And there's
Speaker 2: so many more, including the paper on this pig that's
Speaker 2: been on the pigs that have been engineered to not
Speaker 2: produce alpha gl amazing, and a paper about how dogs
Speaker 2: can actually develop alphagal syndrome possibly.
Speaker 3: What even though they make alpha gal.
Speaker 2: Yeah, I found a paper from twenty nineteen about how
Speaker 2: tick bites can induce anti alpha gal antibodies in dogs. Woow,
Speaker 2: really strange.
Speaker 3: It is really wild. I also had quite a lot
Speaker 3: of papers for this episode, probably some of the same
Speaker 3: ones Aaron that you read and mentioned. Some of the
Speaker 3: early reports from like two thousand and nine from Van
Speaker 3: Noonan as well as an early one from commons at
Speaker 3: all from two thousand and nine in Journal of Allergy
Speaker 3: and Clinical Immunology. The one from Van Nounin was in
Speaker 3: the Medical Journal of Australia. I also had update ones
Speaker 3: from both of those authors. There's like so many. The
Speaker 3: really interesting paper from twenty nineteen was by Chris Bell
Speaker 3: at all in Frontiers and Immunology. That was discovery of
Speaker 3: alpha gal containing antigens in North American tick species believed
Speaker 3: to induce red meat allergy. That one was super interesting.
Speaker 3: And then I had a bunch as well about allergies
Speaker 3: and allergic responses in general if you want more details
Speaker 3: on like how food allergies work and IgE and all
Speaker 3: of that kind of stuff. As always, we'll post the
Speaker 3: list of our sources from this episode and every one
Speaker 3: of our episodes on our website, This Podcast will Kill
Speaker 3: You dot com ran under the episodes tab. You can
Speaker 3: find it there.
Speaker 2: Thank you again so much, Winnie for sharing your story
Speaker 2: with us. We appreciate it so so much, we.
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Speaker 3: for providing the music for this episode and all of
Speaker 3: our episodes.
Speaker 2: Thank you to Tom Brifogel and Leanna Squalacci for our
Speaker 2: amazing audio mixing.
Speaker 3: Thank you to Exactly Right Network and everybody there.
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Speaker 3: You filthy animals.