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

One day, you’re enjoying a beautiful hike through the tall grass. A few months later, you find yourself in anaphylaxis from a post-hike hamburger. The culprit: a tick bite. In this much-requested episode, we take on alpha-gal syndrome, the red meat allergy triggered by the bite of a tick. Sometimes science is stranger than fiction. How exactly does an encounter with a tiny arachnid cause your throat to swell up and your skin break out into hives hours after eating red meat? Is it all red meat? Is it all ticks? How on earth did anyone even make this connection in the first place? Those are just a few of the questions we answer in this action-packed episode that has us venturing into surprising topics, like primate evolution, ancient epidemics, and cancer treatments. Tune in for all this and more.

Support this podcast by shopping our latest sponsor deals and promotions at this link: https://bit.ly/3WwtIAu

See omnystudio.com/listener for privacy information.

Episode Transcript

Speaker 1 (00:00):
Hi. My name is Winnie and I'm an ecologist. In
the summer of twenty eighteen, 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.
We had about a mile left in the hike when
we heard rustling in the brush beneath some big oak trees.

(00:22):
It turned out to be a red tailed hawk with
a broken wing. In order to bring the bird to
the nearest wildlife veterinarian located in Columbia, Missouri, we needed
to get the bird to our car, so my husband
gave me his overshirt while he distracted the hawk. I
tossed the shirt over the bird's head to calmb it down,

(00:42):
and we safely carried the bird back to our car.
It was like a ninety minute drive to Missoo 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, so that's when I pulled down
my sock and I saw what looked like thousands of

(01:04):
tiny grains of sand moving across my ankles. At the time,
I was convinced that these were chiggers. 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.

(01:25):
After that day. In twenty eighteen, my husband and I
avoided areas that were chigger prone, particularly between April and
September when they're the worst. We also used repellent sprays,
and we treated our clothes and shoes with permethrin to
deter chiggers. It's worth noting that we had also been
warned about lone star ticks. These are really common in Missouri,

(01:49):
and they're common even in urban and suburban areas, and
they're also really aggressive feeders. So we were really careful
not to get any ticks. And it turns out that
chigger treatment and tick treatment for clothes and repellents, they're
the same thing. One evening in October of twenty twenty two,
we made a meal with hamburger. It was noteworthy because

(02:12):
we didn't eat much meat and it was a special
treat for us. Later that night, I woke up violently ill,
and I was certain that I had gotten food poisoning.
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. I was struggling to breathe,

(02:36):
and I remember feeling that numb feeling in my entire body,
you know, the feeling when you get novacine. At the
dentist it was like that, but everywhere. I wasn't thinking
entirely clearly, but I do remember taking to benadryl, waiting
about five minutes panicking, and then taking two more benadryl

(02:56):
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. He sent off a bunch of blood tests
and one of them came back positive. It was for
Alpha gal. As an ecologist, I knew about Alpha Gal.
I had friends with Alpha Gal, I have coworkers with

(03:18):
Alpha gal. It's something that we're aware of in the
ecology world, at least in Missouri. 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 twenty eighteen. But
then I remembered. I remembered those chiggers, and in hindsight,

(03:39):
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. 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. You see,
Sometimes I had I'd noticed that my ankles in my

(04:01):
arms would get really itchy for no apparent reason. In hindsight,
it was usually after I had like jello or soup
that was made with beef broth. Fast forward to the present.
In twenty twenty three, we moved to Minnesota. As an ecologist,
i'd like to keep an eye out for all sorts
of different organisms, and I note how their ranges are changing.

(04:22):
Just last month, I found a lone star tick on
my dog. 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.

Speaker 2 (04:34):
North, Winnie, thank you so much for sharing your story

(05:23):
with us. We really appreciate it, and like, my gosh,
what a strange yeah thing this is.

Speaker 3 (05:31):
I know, thank you so much for being willing to
go through all of that with us and with all
of our listeners. We really appreciate it. Yeah. Hi, I'm
Aaron Welsh and I'm Erin Allman Updike.

Speaker 2 (05:42):
And this is this podcast will kill you.

Speaker 3 (05:44):
And today we're getting real weird, really weird, because we're
talking about alpha gal syndrome aka red meat.

Speaker 2 (05:53):
Allergy, as given to you by the bite of a tick.

Speaker 3 (05:57):
By the bite of a tick. It's so weird, Aaron.

Speaker 2 (06:00):
Yeah, it is. It is very bizarre. It feels like
something out of a sci fi novel that's like, you know,
near future and the world is about to collapse because
climate change is farming and whatever, and so then a
rogue scientist introduces this thing into ticks that causes everyone

(06:21):
to be vegetarian. Yeah, you get the you get the.

Speaker 3 (06:23):
Right, I got it. I liked it a lot. I
would watch that movie, honestly.

Speaker 2 (06:27):
I would. Yeah, I would absolutely watch that movie and
probably fall asleep halfway. But that's my that's my jam.

Speaker 3 (06:35):
Yeah, it's I'm really excited for it. It's gonna be
a really fun episode. Yeah, I have so many it's
so weird, it's so weird.

Speaker 2 (06:43):
Yeah, and we'll get we'll get into all of that
weirdness business later on, but first we've got some other
business to take care of.

Speaker 3 (06:51):
We do. It's quarantiney time as always. So what are
we drinking this week? We're drinking gal Pal, you know,
just Pal, gal Pal, you're out the gal Pal. It's
a delicious beverage. Of course, it is made with none
other than Beef Eater Gin Yeah sponsored.

Speaker 2 (07:13):
Not sponsored, but you know, we can't. We can't pass
up that that name, that branding.

Speaker 3 (07:20):
As well as passion fruit and lemon lime soda. It's
a really refreshing gin bev.

Speaker 2 (07:26):
Yeah, gal pales great. Yeah, and check it out because
we'll be posting the recipe for gal Pal the Quarantini
as well as Galpal the Place Barta on our website.
This podcast will kill you dot Com and all over
our social media channels. 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 3 (07:49):
And we do, we do say so ourselves pretty much
every week we do. If you check out our website,
you will also find a lot of other really great
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. Speaking of Apple podcasts,
are you subscribed? Because you should be to make sure

(08:13):
that you're helping support the show. 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. And anyways, back for our website, you can
find transcripts, you can find merch. We have a whole

(08:33):
bunch of merch. We have new merch, and we have
a few items left from some of our old merch.
So if you wanted to get your hands on things
that you thought we were out of, double check because
we might just have.

Speaker 2 (08:42):
It there limited stock.

Speaker 3 (08:45):
We've also got links to Bloodmobile, who does the music
for all of our episodes. We've got a good Reads list,
we've got a bookshop dot org affility account, we have
the sources from all of our episodes. Oh my goodness,
this podcast will kill you dot com check it out.

Speaker 2 (08:58):
I don't think we have any other business do no? 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 alphagal syndrome.

Speaker 3 (09:12):
We do, we do, we do. Let's get into it
right after this break. Alpha gal syndrome is at its

(09:33):
core a food allergy, and allergies are a hypersensitivity response
to a very specific thing. Most allergies usually are a
hyper sensitive response to a protein. So that right there
is the first of so many places where the story

(09:55):
of alphagal syndrome is so much weirder than just a
food allergy, because in this case, it's an allergy to
a specific sugar. Alpha gal an alpha gal of course,
has a much more complicated chemical name. It's galactose alpha
one three galactose.

Speaker 2 (10:12):
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 3 (10:20):
Actually, I never thought about if you just type alpha,
does Google also recognize alpha as the word alpha?

Speaker 2 (10:27):
You know? Probably?

Speaker 3 (10:29):
I don't know it does, and I don't know enough
about seo or whatever. Any Oh, gosh, no, In any case,
galactose alpha one three galactose alpha GAL. So this is
a short sugar, it's a aligosach ride. It's just a
couple of sugar molecules linked together in a specific way.
And alpha gal syndrome is when people develop an allergy

(10:50):
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. So I figured to understand the
story of alpha gal. To understand this weird food allergy,
we first have to kind of take a step back

(11:12):
and understand allergies more generally, like how do allergies? Food
allergies usually work. 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. So in the

(11:35):
case of food allergies, it's proteins that we eat, and
adverse reactions to foods can come in a lot of
different types and flavors. We already covered this season seliac disease,
which is an adverse food reaction to specific proteins in gluten.
Some types of adverse reactions are classified as allergies, and

(11:57):
these are usually what are called ig e mediated allergies
and IgE mediated allergies are the types of allergies that
you probably think of. If you think of a food allergy,
you probably think of most classically peanuts m hm. So
someone who's allergic to peanuts might develop hives and then

(12:18):
throat swelling and then anaphylaxis difficulty breathing after exposure to peanuts.
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. But it's doing that in a weird way

(12:40):
by making these antibodies called IgE antibodies. So to understand allergies,
we then also have to understand what the heck is
an IgE ant a body?

Speaker 2 (12:53):
Can I ask a question real quick?

Speaker 3 (12:56):
Please?

Speaker 2 (12:57):
Why proteins? Ooh, good question.

Speaker 3 (13:02):
I don't have an exact answer to that, except that
proteins tend to be more iminogenic. Okay, So it's similar
with like vaccines. 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, so we usually

(13:25):
then link it to a protein like, for example, tetnos toxoid,
and then we'll link carbohydrates to that protein to generate
a better immune response. But I don't know why proteins
tend to be more iminogenic. Yeah, it's a good question.

Speaker 2 (13:40):
It's interesting. Okay, Yeah, and so I feel like maybe
this is jumping ahead. Okay, you said when you are
exposed to something that triggers this IgE response. The IgE
response is because your body is thinking that this is
a pathogen. But this response is kind of out of

(14:01):
control and really bad. Yeah, and can be much worse
for you than a pathogen than a potential pathogen could be.
Totally Yeah, So I don't know what my question is
why why would that happen? Like why why would that
be an evolved response?

Speaker 3 (14:22):
Yeah, it's a great question, like why did allergies evolve?

Speaker 2 (14:26):
Is a bigger question than I can maybe not only
something that we address in the R two parter, but.

Speaker 3 (14:33):
What what part of your question is getting at, is
like why IgE? Like why is this response so weird?
So let's talk about what IgE is and why the
response with IgE antibodies can be so severe. 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.

(14:56):
So antibodies are the things that we make, say, for example,
but when we get a vaccine to then be able
to specifically target and fight off one particular say virus
or something, right, our antibodies can very precisely identify one
particular protein, for example, or carbohydrate sugar on a particular virus.

(15:19):
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. They alert our immune system, Hey,
come over here, I found something that shouldn't be here, right,
and then we do our immune response thing. Most of
the time when we talk about antibodies, or at least

(15:39):
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. There's
other ones that are like in the context of our
guts and our mucosal membranes called IgA, and then there's

(16:00):
IgE antibodies, and these are created in the same basic
way as all of our other antibodies in response to
one particular protein. They're very very specific, and it's our
B cells, the same cells that are making these antibodies.
It's thought that evolutionarily this antibody responds. IgE evolved mostly

(16:22):
to respond to parasites and protozoan pathogens and maybe even
venoms like snake venom. And what IgE does is it
doesn't just serve as a flag the way that something
like IgG does. IgE is an antibody that hangs out
attached to some of our other immune cells, like called
mass cells and our basofyls. That part's less important, but

(16:44):
basically IgE is attached. It's not free floating. It's attached
to these other white blood cells, and when they find
the anigen that they're targeted for, they grab onto it.
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

(17:11):
really quick, all of a sudden. It's like a boom
immune response rather than like a flag. Hey, guys, everyone
come over and then that response takes some time.

Speaker 2 (17:20):
Right, It's kind of like scorched Earth policy exactly.

Speaker 3 (17:24):
Yes, it's like something's here, Wow, I just just destroy
it all a.

Speaker 2 (17:29):
Little reactive maybe, 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?

Speaker 3 (17:38):
No?

Speaker 2 (17:38):
Apparently, not ig.

Speaker 3 (17:40):
Is like my toddler last night when I told me
we needed to come out of the bath, Like yeah. 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. That process is called sensitization.

(18:04):
That has to happen first. You have to be exposed
to something. Your body does kind of a weird thing
by deciding that it's going to make IgE antibodies against
that protein, and our immune system doesn't ever forget things,
so it holds on to those IgE antibodies just waiting
in the wings. And then the next time that we
eat a peanut, those antibodies are already there and they're

(18:26):
like we prod the invader and they do their scorz
ter thing. They bind to that peanut protein, all of
those mass cells expel tons of inflammatory material and then
you have the symptoms of that allergic reaction. And that
is what we see in alphagau syndrome, except for a
few pretty important details. M H. So again, alpha gal.

(18:50):
It's a sugar, a carbohydrate, and already that's a little
bit weird. We're mounting a massive immune response to an oligosaccharide.
Why is this particular sugar so immunogenic. Well, it turns
out that this particular sugar is found pretty universally attached

(19:11):
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 old monkeys. Oh yeah, we'll get
into it. I know, I cannot wait. I know, Aaron,

(19:33):
that you're going to get into a lot more detail
about alpha gal and the antibodies that we make against
alpha gal from an evolutionary context. But just for some
context on alphagel. So we do not make this sugar
in our bodies. We happen to make from infancy and
to bodies against this particular alphag sugar the same way

(19:56):
that people who like me are blood group oh make
antibodies against the A and B sugars that make blood
groups A, B, and O that are attached to our
red blood cells. So the antibodies that we make and
have circulating around us are IgG antibodies. I like to

(20:18):
think of them as like normal ones, even though they're
all normal. That's a terrible descriptor, but you know what
I mean, they're just like free floating. They're not doing
much right. 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 anti bodies floating around. Now,
we cannot take a pig heart and transplant it into

(20:39):
a human body. It so happens that this particular sugar
is one of the major barriers to transplantation of animal
organs into humans. But we can eat bacon, be exposed
to it through our guts, and do just fine unless
we can't enter the tick.

Speaker 2 (20:59):
Oh gosh, yep, it's so weird.

Speaker 3 (21:02):
It it's so weird. So when I talked about how
food allergies work, the first step that I went through
was sensitization. Right there, has to be a period of
sensitization where our body sees these antigens and goes, ooh,
something's weird here. I'm going to make antibodies against it.
And in alphagau syndrome, that's sensitization. To alpha gal it

(21:26):
doesn't happen from food. It happens from a tick bite. Ticks,
of course, are our little six to eight legged, depending
on life stages, blood feeding friends. 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,

(21:50):
in order to get a full blood meal. 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 anti coagulation and anesthetizing us
so that we don't notice them and we're not bothered
by them. It can hang out for a long time.

Speaker 2 (22:08):
Tick saliva is kind of a magical substance. Saliva is
right exactly, and I feel like saliva. I know people
are working on it, but I do feel like there
are some amazing opportunities in tickspit.

Speaker 3 (22:22):
I agree. I was reading about like the sia loam.
They call it the saliva microbiome. I love it.

Speaker 2 (22:29):
I love when there's a new word for microbiome for
a different part of a different area, but different area.

Speaker 3 (22:38):
So what happens in alpha gau 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, and for some people
this triggers that sensitization, the development of those ig e

(23:00):
anna bodies against that specific sugar alphagal. That is how
sensitization happens. 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, So they'll get like
a large red welt that's super itchy, and this reaction

(23:23):
will last like a lot longer or be a lot
more extreme than other tick bites that they might have
had in the past. 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 wha whoa,

(23:46):
this is that highly varulent pathogen. I have to respond
to it, binds to it. Those mast cells de granulate,
they release all of their super inflammatory stuff, and you
get this massive immune response aka allergy. That's that's how
alpha that works.

Speaker 2 (24:06):
Well, Aaron, I have a few questions here.

Speaker 3 (24:10):
Well, Aaron, I thought that you might.

Speaker 2 (24:13):
Okay, we know that this is multiple tick species all
over the world. The worst is happening yep, and so
it's clearly not related to certain tick species or like
tick phylogeny.

Speaker 3 (24:26):
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.

Speaker 2 (24:36):
This, right, which suggests like can any tick be a culprit?
And this can can any tick induce this allergy? So
where is like what is the trigger from the tick?

Speaker 3 (24:50):
Yeah, that's a great question. It's the trigger is alpha gal. Yeah,
question is where is this alpha gal coming from? Right?

Speaker 2 (24:57):
Is it coming from a previous blood meal? 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
when when ticks are first born, or when ticks first
hatch from their little eggs, they haven't eaten, they haven't

(25:18):
taken any blood meals. So those larva, if they bite you,
and they do bite you like the seed ticks, will
that still induce alpha gal response? It can exactly, So
like what the heck is going on?

Speaker 4 (25:30):
Right?

Speaker 3 (25:31):
So that's the question is what the heck is going on?
Where is this alphagal coming from? For a long time,
we really didn't know, like you said, was it coming
from a previous blood meal that just was still there
and so the ticks spit a little bit into us?
Was it something that's in the tick? It seems like
it is coming from the ticks themselves.

Speaker 2 (25:51):
There was a paper is coming from inside the house
that doesn't really work in this context, but.

Speaker 4 (26:00):
Though we try.

Speaker 3 (26:14):
There was a paper from twenty nineteen in Frontiers and
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. And they weren't able
to find alpha gal in unfed ticks. So It was
only after at least partial blood feeding that they were

(26:37):
able to find alpha gal that was reactive to these
anti alphagal antibodies, and they found this in multiple different
ticks species, including the one that most commonly causes alphagal
syndrome in the US Ambloma americanum. 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.

(27:01):
Just like humans don't have the enzyme that other mammals
use to make alpha GL, ticks don't have that enzyme.
So what that means is that there has to be
either some other chemical pathway that they're using to make
alpha gl or is it one of their microbes? Is
it something in the tick microbiome, like say a commensal

(27:24):
or another pathogen like a ricketsia or something that is
making alpha gal inside the tick and then it gets
into the salary glands and then the tick is spinning
it into us. That level, we don't know, so like
we know it's coming from the tick, we know it's
coming from tick saliva, but we don't know how the
ticks are making it and why, Like why are ticks

(27:44):
making this weird sugar? What why?

Speaker 2 (27:48):
Why does anyone make this weird sugar? Because so I
spent a lot of.

Speaker 3 (27:51):
The time you would answer that questionarion.

Speaker 2 (27:53):
No, I mean the question that I am trying to
answer is why don't we make it? But I never
really considered why would we?

Speaker 3 (28:02):
Why would we? Yeah? Why do we? Don't know?

Speaker 2 (28:04):
I don't know.

Speaker 3 (28:06):
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, Amblioma americanum is the most common. In Australia,
it's Exodees holocyclists, also called the paralysis tick. We have
to do tick paralysis in we do, but also things

(28:27):
like Exode's risinous rifycephalous Bursa hyaloma species, like so many
different species across again the entire globe, North America, South America, Australia, Europe, Africa, everywhere.

Speaker 2 (28:41):
Yeah, you shall find, yes, resideolergy from tick bites yep.

Speaker 3 (28:47):
Including in some species like Exodi scapularis. People have found
alpha gal in the saliva, but we have yet so
far to see alphagau syndrome develop in people after Exodia
scapularis bites as far we know astrisk, who knows what
will happen, But what does actually alphagal syndrome look like.
We haven't even talked about what the symptoms are aside

(29:09):
from being like allergy, and it turns out that this
also gets a little bit weirder than just your typical
quote unquote food allergy. Of course, of course, so the
symptoms of alphagal syndrome can of course vary, but they
often start with GI symptoms that might include things like
abdominal pain, nausea, or vomiting. They can also include skin

(29:32):
symptoms like hives or what are called urticaria and hives.
If anyone has never had them or never seen them,
they're a very classic allergy association. They're these like red,
irregularly shaped, slightly raised, kind of puffy looking weltz that
you can get kind of anywhere across your whole body.
They can be big, they can be little. There can

(29:53):
be a combination of different sizes, and they're usually super
super itchy hives are. And then you can also so
get angioedema, which means swelling edema, swelling of the face,
especially the lips and the mouth, and then the most
severe reaction is anaphylaxis, and we think of anaphylaxis as
that not being able to breathe right, airway constriction because

(30:16):
of swelling an edema. But anaphylaxis is actually a widespread response.
It's not local to just the respiratory system. So what's
happening in anaphylaxis is widespread vasodilation of blood vessels and
then constriction of your respiratory system of like your bronchioles,

(30:38):
and that can lead to hypotension, so low blood pressure
and eventually shock and death. Anaphylaxis is very, very scary
and a serious emergency, and a pretty high proportion something
like sixty percent or some studies site even more people
report very severe reactions including anaphylaxis with AlphaGo syndrome.

Speaker 2 (31:00):
And so this those suite of symptoms there are found
in other food allergies in alphagal is just delayed.

Speaker 3 (31:09):
Yeah. That's the other weird thing that's like 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 not minutes,
and most other food allergies happen after a matter of

(31:29):
minutes and peak even in like ten to twenty minutes
after exposure. So I knew you were gonna ask. I asked,
why the heck is there this delay? Yeah, unsurprisingly, we
don't entirely know, but it's thought that it's not necessarily
something like weird about alphagal or this allergy in specific,

(31:50):
but it's just a delay in the circulation of this anigen.
So the sugar itself alphagal it's not just like a
free floating sugar. It's not like a carbohydrate that's like
you know, what makes up your breads or something. These
are sugars that are attached to proteins and lipids. They're
glycoproteins and glycolipids, and so they enter the system. They

(32:11):
enter your body a little bit more slowly, but we
can see really quick on set reactions in someone with
alphagou syndrome if they're exposed to alphagal via the bloodstream.
And this we saw in the case of setuximab, which
is an antibody, a monoclonal antibody. I think you'll probably
talk about it erin uh huh, that happens to have

(32:33):
some alphagl on it or in it in that medication,
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 twenty minutes, which is more like what we
would expect with other food allergies. Okay, it's so weird, Aaron,

(32:53):
So I want to like just like reframe it again
as like, Okay, so what are we actually talking about?
What is alphagau syndrome? Overall? Alphagal syndrome is just like
a food allergy, except that it's a tick bite and
not a food that causes that initial sensitization. It's a

(33:14):
sugar and not a protein that you're reacting to. It's
a delayed, like three to six hours later allergic response
rather than an immediate one, and it often can develop
later in life, but it can develop at any point
in life. And most food allergies developed during childhood after

(33:34):
just a few exposures, rather than like a lifetime of
being able to tolerate it and now all of a
sudden you can't. Oh and just so that I don't
forget re exposure to ticks like getting more tick bites
after you've already developed alphagal syndrome seems to heighten the
sensitivity even more so that people have renewed worse reactions

(33:57):
or are like never able to tolerate me to again.
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 2 (34:10):
Right, Okay, Okay, I have a few questions.

Speaker 3 (34:13):
Great, give them to me.

Speaker 2 (34:15):
Are there other carbohydrates that trigger food allergies in people?

Speaker 3 (34:19):
It's a great question. I try to find some more
like specific details on this. Not really that I can see.
There certainly can be carbohydrates that you have adverse reactions to,
but an IgE mediated allergy response like this, No, this
is pretty unique.

Speaker 2 (34:34):
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 alphagal syndrome, does every person
then have the capacity to develop alphagal syndrome?

Speaker 3 (34:51):
I love your question, Darren, such a good one. No idea,
We have no idea what it is about one person
versus another that predict why someone would develop alphagau syndrome
after exposure to a tick and another person wouldn't. Like,
same tick could bite two people, one could develop it
and one could not. Why we don't know. And what's

(35:12):
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. It's called an atopic triad
where you have like allergies asthma, eggzema. These are all
kind of things that share similar immunologic pathways, and so
you might expect that someone with one food allergy is

(35:33):
more predisposed to have other food allergies because again it's
this like hypersensitivity response. But a lot of times people
with alphagau syndrome don't have any other allergies, They don't
have any other food allergies, they don't have any other
respiratory allergies. So it's like it we really don't know
right now, Like why why?

Speaker 2 (35:51):
Yeah?

Speaker 4 (35:51):
Right?

Speaker 2 (35:52):
Who?

Speaker 3 (35:53):
We don't know.

Speaker 2 (35:54):
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 3 (36:02):
Like it's a weird way for sure, But like is
every amblioma americanom tick bite doing that probably maybe we
think it's probably a threshold thing, 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 alpha gal in their meat,

(36:27):
because there is also degrees, right, Alpha gal is a
sugar on so many mammalian products, not just meat. It's
also found in dairy at lower levels, but most people
don't have reactions to dairy, and some people do. It's
also found in things like gelatin, which means that it's
in a lot of pharmaceuticals. And so for some people

(36:48):
there's a really wide range of stuff that they now
can't tolerate, and for other people they can tolerate all
of those things just fine, and it's really only like
bacon or like pork product or like red meat like beef,
and so it's a really like wide variation. And so
there's probably a lot that's like thresholds, like how much
IgE do you have, how much did you make, how

(37:09):
recent was it, you know, all of that kind of stuff.

Speaker 2 (37:13):
I remember talking with someone who had alpha gl syndrome
and they could eat cured meats, but not like a hamburger.

Speaker 3 (37:19):
Interesting, Yeah, yeah, And is that just volume, Like when
you eat a hamburger, do you just eat a lot
more of it than you do with a cured meat?

Speaker 2 (37:25):
I don't know, or somehow the you get more degraded
in cured meats, like exactly right, I do. I don't know.

Speaker 3 (37:32):
I don't know either. There's a lot. It's so, so,
so so interesting. So yeah, Aaron, tell me m everything,
like what I know you're going to talk about this sugar,
Like where did it come from? Why do some mammals
make it? Why do we not make it anymore? How
did this come to be? And then also like how

(37:54):
did we figure this out? Because yeah, you know what,
I did not realize how recently we figured it out,
because I feel like when we were in Panama, it
was the thing. Everyone had it, everyone had it, Yeah,
but it was like very new at the time.

Speaker 4 (38:11):
Yeah.

Speaker 2 (38:12):
Yeah, let's get into some of these questions and take
a quick break and then we'll begin. Aaron, like you mentioned,

(38:46):
we learned about this I think pretty recently.

Speaker 4 (38:49):
Yeah.

Speaker 2 (38:49):
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. I
think it was thirteen and I had just started fieldwork
in Panama for my PhD research on tics and climate change,
and also for all of you listeners out there. Right now,
I'm wearing my Smithsonian T shirt that has little larval

(39:12):
ticks all over it. I love it so much. Actually,
they have eight legs, so they must not be larvae.

Speaker 3 (39:16):
Even though they don't like the nymphs or adults. They're big.

Speaker 2 (39:19):
They're big, but they look I don't know. Some look
like there's an adults. I think it's nymphs. Also, Okay, anyway,
we don't need to get into it.

Speaker 3 (39:28):
She's wearing a tick shirt, guys the occasion.

Speaker 2 (39:32):
It's one of my favorite shirts. But yeah, So in
twenty thirteen, a professor who was also in Panama reached
out to me and was like, oh, I heard you're
working on tics. Have you heard of a red meat
allergy following a tick bite?

Speaker 4 (39:45):
I have it.

Speaker 2 (39:46):
A few other researchers who have spent a lot of
time doing fieldwork in this area have also had it,
and it could be a cool project. And I didn't
end up pursuing it as a project because probably I
was scared of like the immunology aspect of it, but
over the I probably should have. But over the next
few years that I worked there, every field season, people

(40:07):
would come up to me and say, oh, I just
got diagnosed with this red meat allergy. 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 erin it definitely seems like
Central Panama is a hotspot, but maybe it's just that
everywhere is sort of a hot spot for red meat allergy.
But it really was like a lot of.

Speaker 3 (40:28):
People that we hung out with, like got bit by
a lot of ticks. Let's be we all did.

Speaker 2 (40:32):
Yeah exactly, Yeah, I mean yeah, thousands and thousands I
would catch every day.

Speaker 3 (40:37):
Yeah.

Speaker 2 (40:38):
So anyway, but every time I learned if someone knew
who had developed the allergy, I would do some like
light google scholaring to try to answer the three main
questions that I had, 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,
and so Aarin, you just took us through the first question,

(41:00):
and so I'm going to try to take on those
other two, starting with the how, like, how was alpha
gal syndrome first recognized? So the syndrome itself has no
doubt been around for longer than people have recognized it.
That professor that I mentioned had developed it, I believe
in the early nineteen nineties. And there is apparently unpublished

(41:22):
work from the State of Georgia in the late nineteen
eighties 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. On the one end of the
earth was doctor Cheryl van Nonan, an immunologist who was

(41:44):
working at an allergy clinic in Sydney, Australia. 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 suite of symptoms that you mentioned, what's

(42:08):
an unusual number you might ask, like, when did this
start to stand out? So between two thousand and three
and two thousand and seven, twenty five patients, seven men,
eighteen women reported this allergy. And I'm sure that she
and her collaborators ruled up many other potential causes, but
ticks seemed like a strong possibility from the beginning, with

(42:29):
twenty four of the twenty five patients reporting a history
of having bad local reaction to tick bites, and the
areas like the regions where these patients resided, were known
to be quote unquote endemically infested with several tick species.
In two thousand and seven, Van Noonan authored an abstract,

(42:50):
the first academic publication linking the red meat allergy to
a tick bite from the tick Exodes holocyclists. While Van
Nounan was drawing her own conclusions down under, other researchers
in the US were on a different trail, but one
that would lead them to the same strange allergic reaction.
In two thousand and four, trials were underway to test

(43:12):
a cancer drug called Texa mab aaron texmab se tuxamab.
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. But they were testing this
cancer drug to see if it was safe for FDA approval,
but researchers were noticing that in some patients this medication

(43:35):
was causing a hypersensitivity reaction, particularly those patients residing in
a handful of states in the southern US. 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 So the pressure was on to

(43:55):
find out what was causing this. Researchers Christine Chung, Thomas Plats, 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 alphagaw. So that answered one question
they had, which was like what were people's immune systems

(44:16):
reacting to with this drug? But it still left an
important one unanswered, what was triggering this reaction, like why
alpha gw Right. The first clue came from alpha gul itself.
As you mentioned Aaron, This antigen is found in tissues
of non primate mammals and some primate mammals with some

(44:37):
notable exceptions like humans, apes and Old World monkeys. 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. And the story goes according to
the Radio Lab 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

(44:59):
like over laying other distribution maps, you know, other disease maps,
like all sorts of environmental exposures, whatever, 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? They interviewed the patients with the beef

(45:19):
allergy confirmed to be IgE antibodies to alpha gal and
found that more than eighty percent of them had been
bitten by a tick before experiencing symptoms. This finding, combined
with the report from Australia, was more or less the
solid proof that they needed to suggest that tick bites

(45:40):
were triggering an allergy to red meat, specifically the alpha
gal antigen, 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 3 (45:55):
It's so so so weird that it happened, especially like
the tuxamap thing and then the figuring that out and
the like Australia thing like to do it all. It's
so weird, like the right serendipitous, I guess.

Speaker 2 (46:07):
Aaron, I feel like I need to throw in this
well actually here so please, this is not for you,
but the tick species that you mentioned that has thought
to be primarily responsible for alpha gal syndrome here in
the US is the lone star tick Ambloma americanum, which
actually very very rarely transmits the causative agent of Rocky

(46:29):
Mountain spotted fever. And so the fact that the maps
line up for spotted fever and alpha gal it really
just seems coincidental to some degree. It might just be
overlapping distributions of the Rocky Mountain spotted fever ticks yeah
or tick and yeah, but I was just like, wait,
that doesn't.

Speaker 3 (46:49):
Like, in my understanding, distributions of all of those tick species.

Speaker 2 (46:53):
Yeah, but anyway, I had I am sorry, I had to.
But once those reports came out, first Van Noonan in
two thousand and seven, and then Commons and Plats Mills
in two thousand and eight. Plots Mills, by the way,
developed the red meat allergy during this research through a
tick bite. But it seemed like following these reports the
allergy was everywhere. All you had to do was look France, Spain, Germany, Switzerland, Sweden,

(47:18):
South Korea, Japan, Central America, South Africa and more every
year worldwide distribution.

Speaker 3 (47:24):
Yeah.

Speaker 2 (47:25):
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. Is it coincidence? Maybe? But
is it serendipitous Maybe. But some of the researchers have
also hypothesized that exposure to ticks has been steadily on

(47:49):
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 us in
addition to habitat encroachment. So we're basically just like more,
we're encountering ticks more readily, classic and more tis ticks

(48:12):
are there to encounter exactly.

Speaker 3 (48:13):
Yeah.

Speaker 2 (48:15):
And as for what the future may hold, I'll leave
that to you Arin, except to say that as the
climate continues to change, impacting the range of ticks species,
as we continue to encroach into these habitats, I'm sure
we'll just see more and more of this allergy develop.

Speaker 3 (48:32):
The ticks are just trying to save us all from
eating too much meat.

Speaker 2 (48:35):
Yeah, thank you, ticks, We appreciate you.

Speaker 3 (48:40):
Yeah.

Speaker 2 (48:41):
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? 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, Yeah, And that inability to produce alpha

(49:06):
gl makes us outliers among mammals. 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 gl. That means that other primates like New
World monkeys, lemurs, lorises, and tarsiars, not to mention cows, pigs, dogs, mice, etc.

(49:28):
All produce alpha gal. We also continuously circulate antibodies against it.
Alpha gal is, in fact, the most abundant natural antibody
in humans, making up about one percent of immunoglobulence.

Speaker 3 (49:45):
That's so bizarre.

Speaker 2 (49:47):
It's so bizarre, and so it seems like this kind
of a big deal. So what makes us different? Like
why why us? Or why not us? Rather? And that's
the question that researchers have been trying to figure out
for decades now, looking at which species make alphagal and
which species don't. Two things stand out. Number one, since

(50:09):
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 3 (50:24):
Okay, And number.

Speaker 2 (50:25):
Two, that point was around twenty eight million years ago,
before the Old World monkeys and apes diverged.

Speaker 3 (50:32):
Okay, that makes sense.

Speaker 2 (50:33):
What happened twenty eight 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 3 (50:43):
Right, and like, did that did that happen like all
of a set in or was it?

Speaker 1 (50:48):
Yeah?

Speaker 3 (50:48):
Because all using all catarines make antibodies against alpha gl.

Speaker 2 (50:52):
Yes, okay, right, so what happened?

Speaker 3 (50:57):
Yeah?

Speaker 2 (50:58):
How does a deadly disease sound?

Speaker 3 (51:00):
Oh? It sounds like sounds like right up our alleys.

Speaker 2 (51:03):
Right up our alley. This carbohydrate will kill you. Some researchers,
namely Uri Galilee, who has done a tremendous amount of
work on alpha gal, have proposed that around twenty eight
million years or so ago, a highly virulent pathogen or
pathogens I've seen airborne envelope viruses suggested, and also sepsis

(51:27):
causing bacteria suggested. Some pathogen swept through Old World primates
on the Eurasia Africa land mass, killing those who produced
alpha gal and sparing the very few who didn't, who
would over the next generations increase in number. And there
seems to be some debate as to the cause or causes,

(51:47):
like was it a pathogen, was it climate? Was it
a mix of both? 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. But why would not producing ALPHAGL
help protect you from severe infection or death? That's where

(52:10):
things get super interesting, Okay, because it turns out that
mammals aren't the only species to produce ALPHAGL. In fact,
some viruses, bacteria, and parasites do, or they bind to
host produced ALPHAGL to gain entry into their host cells.
Ecoli species of Clebsiella, Plasmodium species, some of which cause

(52:32):
malaria and humans, Micolplasma causative agent of tuberculosis, Salmonella, trepanosoma,
leish Mania, sea diff mosquito borne viruses. I mean, a
lot of pathogens either produce or use ALPHAGL in some capacity,
and also microbes that aren't pathogenic to us. For instance,
some members of our gut microbiome may produce alphagal, which

(52:57):
triggers this constantly elevated anti body response, which could then
protect us from things like malaria. 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. Why it's so cool because

(53:22):
there does seem to be this association between gut microbiome,
alpha gall production, anti gal antibodies, and then malaria susceptibility.
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 kind of just sational.

Speaker 3 (53:40):
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 2 (53:46):
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. Alpha gal can also provide some insight into
blood types and disease. People who have type B or

(54:06):
type A B blood seem to be less susceptible to
alpha gl syndrome because the b like me, 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 3 (54:25):
Yeah. I've heard too that that you have more specific
anti gal proteins anti alphagal proteins, whereas people who are
O or A have like less specific ones that bind
into maybe B and alpha gown like are just a
little bit messier.

Speaker 2 (54:40):
It's massy. It's just a little more efficient.

Speaker 3 (54:45):
Yeah, there you go.

Speaker 2 (54:46):
Yeah, painting with the broadbrush. But 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 sinv virus or syndibis virus
and less protected against others like herpie simplex type two.

Speaker 3 (55:10):
Huh.

Speaker 2 (55:11):
Yeah.

Speaker 3 (55:11):
Interesting.

Speaker 2 (55:13):
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 zeno transplantation, transplanting pig organs into humans, which,

(55:33):
as you mentioned aarin previously could not be done in
part because or in major part because of this alpha
gala carbohydrate.

Speaker 3 (55:41):
Ye it's wild that this particular carbohydrate, like this little
sugar is that important, I know, right, Like it was
one of the major I mean, it still is one
of the major barriers to animal organ like transplant into humans.
And so now with the development of these pigs like

(56:02):
it's it's so it's so fascinating, Aran.

Speaker 2 (56:06):
I think the thing that surprised me the most about
doing this episode is that I had never heard of
alpha gal before twenty thirteen, and I since then have
never heard about it outside of the context of alphagal syndrome. Same,
but this is one of the most important components of
our life, of our immune system in terms of anti gall,

(56:26):
in terms of other animals, and it just plays so
many more roles than preventing you from eating meat.

Speaker 3 (56:32):
Right than just alphagal syndrome, which is also very like
interesting and important and cool.

Speaker 2 (56:38):
Yeah, it's wild. The other big takeaway from this, I think,
and that is very obvious, is that the story of
alpha gal is still very much unfolding, and the tickboarn
allergy is really just a part of it. Yeah, I mean,
I was going down so many rabbit holes in terms
of autoimmune diseases and alpha gal. Whether there are people

(57:00):
who do produce alpha gal and how they respond to
different pathogens, because it really is just like a simple
frame shift mutation. We still have the gene. It's just
like is non It's just should work right, and then
blood types and association with different diseases. Let's do an
episode on that. I mean, but every answer that I found,

(57:20):
or every partial answer that I found, just led to
a million more questions. And so now I'll end this
with a question for you, Aaron, which is where are
we today with alpha gal syndrome?

Speaker 3 (57:32):
Oh? I can't wait to tell you all about it
right after this break. According to the CDC in the US,

(58:05):
there were over one hundred and ten thousand cases of
alpha gau reported between twenty ten and twenty twenty two,
and most of those are the latter half of that
twelve years, Okay, which is somehow both way more than
I expected, but also likely a gross underestimate because alpha

(58:26):
gaul syndrome is not a notifiable disease, and the estimates
of prevalence globally really really range and I think will
likely change drastically over time, and not just because numbers
are actually changing, but the estimates that I saw right
now in places where we have prevalence estimates range between

(58:47):
in Germany four cases per one hundred thousand people to
thirteen cases per one hundred thousand people in Virginia, which
is a part of the US that has a higher
number of cases than a lot of parts of the US,
and one hundred and thirteen per one hundred thousand people
in the Sydney Basin in Australia. Wow. Okay, Right, so

(59:08):
like really big variation, 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, 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. But also where are
we looking, Like, where are we looking for this? Because

(59:30):
like we said, if you're looking for it, you'll find it.
And cases are on the rise without a doubt. For example,
in the US in twenty seventeen, there were just over
thirteen thousand new cases diagnosed. There were nearly nineteen thousand
cases diagnosed in twenty twenty one.

Speaker 4 (59:47):
Wow.

Speaker 3 (59:48):
Yeah, 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 associate
antibodies against alpha gal. In some populations, they found up
to twenty percent of people who had IgE antibodies against

(01:00:08):
alpha GL. But by no means does that mean that
all of those people have alphagal syndrome. So there's still
a really big open question of like what is that threshold,
Like how much IgE do you have to have? And
why are some people reacting and developing alphagal syndrome and
some people aren't.

Speaker 2 (01:00:28):
Do levels of IgE correspond directly with that allergic response
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 3 (01:00:41):
Yeah, it's a great question. It does seem to be
that the levels do matter in terms of what your
response is. Okay, there still isn't a very clear, like
for example, diagnostic threshold of like okay, this is the
value which you have alphagal syndrome versus this is the
value where you don't. That is still a little bit
like up for debate. It seems like okay, yeah, but

(01:01:02):
it does seem to correspond where higher levels more response
and like repeat tick bite, those levels go up. And
like you mentioned Aaron, as with all I think ever
of our vector born disease episodes, there's a lot that
is probably contributing to this rise in incidents and prevalence.

(01:01:23):
This includes things like changes in the distribution of ticks
in the US, especially increases in things like deer populations
and other mammal populations and 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

(01:01:44):
we interact with ticks and other tick hosts is going
to affect any kind of tick born disease, including alpha glah,
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, and for a disease like
alpha gal that is still so brand new in the

(01:02:08):
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 twenty years ago, so we're still very
much writing that story of like where do we go
with alphagau syndrome from here? And right now we need

(01:02:30):
people to know that it exists because a recent survey
by the CDC from twenty twenty two found that forty
two percent of healthcare providers in their particular study hadn't
heard of alphagau syndrome. They didn't know about it.

Speaker 4 (01:02:46):
Wow.

Speaker 3 (01:02:47):
And I will say that that was just a survey
of primary care providers, so it was like pediatricians, internists,
and family practice physicians and then nps and pas, 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, but that is still a pretty
important knowledge gap to kind of highlight. Absolutely, We've talked

(01:03:10):
a lot on this podcast about like delays in diagnosis
and things like that, and these are very severe reactions,
so this is like pretty significant. Yeah, yeah, So I
think that's one of the biggest areas of like how
to make everyone know about it, Maybe make a podcast.

Speaker 2 (01:03:31):
Maybe you can help a solution.

Speaker 3 (01:03:34):
And in truth, there is there is so much that
is still unknown in terms of what is the next
big research area. It's everything like why do some people
mount this response and others don't? What really is that
IgE threshold? And what's causing it in some people? What
other treatment options might exist besides just never eating any
kind of mammalian meat again, how can we desensitize people

(01:03:59):
like we might do for other food allergies? Can we
do that? Is it just avoidance of tick bites or
is there anything else? What are all the different tick
species that can cause this? How many have we not
yet discovered? How is it going to change with things
like climate change? How are these ticks making alpha gal
to begin with?

Speaker 2 (01:04:16):
Right?

Speaker 3 (01:04:17):
Right?

Speaker 2 (01:04:18):
There are so many different questions and different opportunities for
research into this from so many perspectives to make it
super integrative research. Like it's a really incredibly open field
with a lot of opportunity to understand too, Like something
that is so universal in across mammals except for a handful.

Speaker 3 (01:04:43):
Except for us and a handful of our cousins. H.
It's yeah, it is really really an interesting disease and
such a weird and wacky mechanism. I also am dying
to know everyone who's listening, had you heard of alpha
GAO syndrome, because I never know with things like this,

(01:05:06):
if it's like 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 twenty
thirteen because so many people in Panama had it right,
and like it's not that normal and there was that
radio lab episode so many years ago, But like, how
had you heard of this? How much did you know
about this? Right? I really want to know.

Speaker 2 (01:05:29):
Do you have this?

Speaker 3 (01:05:31):
Do you have this?

Speaker 2 (01:05:31):
Because we have had a lot of people reach out
to say I am allergic to red meat thanks to
a tick bite. What's going on here?

Speaker 3 (01:05:37):
And how long did it take to get diagnosed because
it seems like there's a pretty big gap in diagnosis.
But yeah, I have so many more questions arin.

Speaker 2 (01:05:45):
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 they can answer our questions
for us a million sources. I truly do have like
million sources here. I want to shout out just a few.
So there's one by Commons and Plats Mills from two

(01:06:06):
thousand and nine that goes into sort of anaphylaxis syndromes
relating to alpha gal. Then there are a couple of
interesting papers about sort of the evolutionary significance of alpha
GL one by Gillilee from twenty nineteen, as well as
a handful of many more. Actually, and this paper goes
into how viruses may have led to the loss of

(01:06:26):
alpha gl production and the rise in alpha gal antibodies.
And then there's a paper by Rodriguez and Welsh from
twenty thirteen no relation as far as I'm aware, titled
possible role of a cell surface carbohydrate and evolution of
resistance to viral infections in Old World primates. And there's
so many more, including the paper on this pig that's

(01:06:48):
been on the pigs that have been engineered to not
produce alpha gl amazing, and a paper about how dogs
can actually develop alphagal syndrome possibly.

Speaker 3 (01:06:56):
What even though they make alpha gal.

Speaker 2 (01:06:59):
Yeah, I found a paper from twenty nineteen about how
tick bites can induce anti alpha gal antibodies in dogs. Woow,
really strange.

Speaker 3 (01:07:11):
It is really wild. I also had quite a lot
of papers for this episode, probably some of the same
ones Aaron that you read and mentioned. Some of the
early reports from like two thousand and nine from Van
Noonan as well as an early one from commons at
all from two thousand and nine in Journal of Allergy

(01:07:31):
and Clinical Immunology. The one from Van Nounin was in
the Medical Journal of Australia. I also had update ones
from both of those authors. There's like so many. The
really interesting paper from twenty nineteen was by Chris Bell
at all in Frontiers and Immunology. That was discovery of
alpha gal containing antigens in North American tick species believed
to induce red meat allergy. That one was super interesting.

(01:07:53):
And then I had a bunch as well about allergies
and allergic responses in general if you want more details
on like how food allergies work and IgE and all
of that kind of stuff. As always, we'll post the
list of our sources from this episode and every one
of our episodes on our website, This Podcast will Kill
You dot com ran under the episodes tab. You can
find it there.

Speaker 2 (01:08:13):
Thank you again so much, Winnie for sharing your story
with us. We appreciate it so so much, we.

Speaker 3 (01:08:21):
Really really do. Thank you. Thank you also to Bloodmobile
for providing the music for this episode and all of
our episodes.

Speaker 2 (01:08:28):
Thank you to Tom Brifogel and Leanna Squalacci for our
amazing audio mixing.

Speaker 3 (01:08:33):
Thank you to Exactly Right Network and everybody there.

Speaker 2 (01:08:36):
And thank you to you listeners. We hope that you
enjoyed this and are like wait what wait, Well you
have questions? I'm sure you do. Send them our way.
We can ponder them together.

Speaker 3 (01:08:46):
Yeah, we have them too, Yeah we do. And as always,
a special shout out to our patrons, Thank you so
so much for your support. It means the world to us.
If you would like to support the show in other ways,
there are a lot of ways that you too can
support the show. Just listening this far is a great
way to show support, so thank you again for doing that.

(01:09:08):
You can also tell a friend if you haven't told
all of your friends about us, help spread the word.
We love to have new listeners. 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. There's lots that you can do,
and we really appreciate all your support.

Speaker 2 (01:09:25):
Yeah we do. Well. Until next time, wash your hands

Speaker 3 (01:09:30):
You filthy animals.