November 11, 2025 • 47 mins
Daniel and Kelly chat with Dr. John Hawdon about how parasites like hookworm, malaria, and schistosomes hide from our immune system.
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Speaker 1 (00:00):
Howdy friends, Just a heads up that we're talking about
parasites again, and as you're probably aware of by now.
Speaker 2 (00:06):
That can get pretty gross.
Speaker 1 (00:08):
Also, it's kind of upsetting to hear about parasite life
cycles and the effects of parasites on our health. I
get that today we're going to be talking about malarias
just a semiasis and hookworm, So decide if those are
topics you are prepared.
Speaker 2 (00:19):
To hear about. All Right, here we go.
Speaker 1 (00:29):
According to the World Health Organization, in twenty twenty three,
about two hundred and sixty three million people were infected
by malaria, of which five hundred and ninety seven thousand
passed away from this disease. Most of these deaths happened
in Africa, in seventy six percent of the deaths or
children under five. You might remember from a past episode
(00:49):
that we were able to create a vaccine for smallpox,
and that that vaccine was used to wipe smallpox off
the face of the planet, saving humanity from this ancient scourge.
And yeah, thanks to all who wrote in. I pronounce
the word correctly. Now we also have vaccines for other
bacterial and viral infections like polio, chicken pox, human papilloma virus, COVID, nineteen, measles, mumps,
(01:11):
et cetera. With the exception of some tricky viruses like
HIV which hide in our immune cells, We've had a
lot of success making vaccines for viral and bacterial infections,
and we know that our immune systems attack big stuff
as well as the little stuff like bacteria and viruses.
In a past episode, we talked about how our immune
systems will attack entire organs following a transplant. So why
(01:37):
do our immune systems seem to do such a crummy
job of attacking parasites in our bodies, things like nematodes,
And why is it so hard to make vaccines to
give our immune system a leg up on these invaders.
We've been working on malaria vaccines for a really long time,
but only recently have two malaria vaccines become widely available
in areas in Africa where malaria is prevalent. That's good,
(02:00):
but why did it take so long? And why don't
we have a vaccine for hookworms yet? Remember hookworms, those
dirt worms we talked about a few months back.
Speaker 2 (02:07):
Yeah, those guys.
Speaker 1 (02:09):
There are many parasitic diseases that have proven stubbornly difficult
to control with vaccines, and so today we're going to
talk to doctor John Hawden, a molecular biologist and parasitologist
who's going to help us understand why it's so darn
hard to make vaccines against parasites. Welcome to Daniel and
Kelly's Extraordinary Universe.
Speaker 3 (02:42):
Hi. I'm Daniel. I'm a particle physicist, and I'm excited
to be talking about all sorts of ikey invaders today.
Speaker 2 (02:49):
Hello.
Speaker 1 (02:49):
I'm Kelly wieder Smith, and I always love talking about
ikey invaders, although with all the required sensitivity for the
pain and suffering that these parasites cause. But anyway, I
study parasites and space, and today we're talking about my
first love, parasitology, your first love.
Speaker 3 (03:04):
Something I love about science is how excited people get
about their finy, little, tiny little niche. You know, you're
going to meet somebody who's like amazed at the hairs
on spider's legs, or somebody else who like can't stop
thinking about how, you know, the mantle flows and how
rocks form, and like, these nerds get so excited about
(03:26):
their little niche. It's wonderful, right, that's why we know
so much about the universe and spider legs and rocks
and parasites because people get weirdly excited about stuff.
Speaker 1 (03:36):
My friend Ashley Smythe refers to this as a limitless
human curiosity. Yes, because I was asking her about like, oh,
why do parasitologists sometimes infect themselves with the parasites that
they study? Isn't it weird that we do that? And
she was like, Kelly, that's our limitless human curiosity.
Speaker 3 (03:52):
And I was like, Okay, I totally love that about humanity.
I mean, curiosity is something deep about being human. Actually,
I wonder if it is just about being human, or
if you know, aliens are curious about the universe also,
if that's something that really is universal. But today, unfortunately,
we're not talking about aliens. We're talking about critters so
gross that invade you that it almost feels like they
(04:14):
are alien.
Speaker 1 (04:15):
And today we invited on the show my friend John.
He's going to be talking about three different kinds of parasites.
And specifically we invited John on the show because we
had two listener questions that felt somewhat out of my expertise,
even though I'm a parasite person and so I knew
the guy to invite on the show. So let's go
ahead and listen to the two questions from listeners before
(04:35):
we bring John on.
Speaker 4 (04:37):
Hi, Daniel and Kelly. This is David from the San
Francisco Bay area, and this question is for Kelly. What
makes developing a vaccine for parasitic infections so difficult? It
seems like progress has been only recent and incremental with
some experimental vaccines for hookworm, and the one approved laria
vaccine is not very efficacious. So what gives? And this
topic is at least tangentially related to what I do
(04:57):
for a living, which is working on a new platform
produce rnaate therapeutics, So I'm especially interested in what you
have to say. Anyway, keep up the great work, both
of you and Daniel, I forgive you for your chemistry phobia. Cheers.
Speaker 5 (05:10):
I got my master's degree in the late seventies. At
that time there are three theories on how sysystems evade
immune system an advisor's theory was called molecular mimicry. Although
it was over fourty years ago, I remember it well
because for the final exam we had eight hours to
answer two questions. One of which was your name, the
three current theories of how the treatment HOS evased immune
(05:31):
system and which one do you agree with and why?
Of course I chose my advisor's theory, but after receiving
my master's degree, I lost track of the issue. Since
I got my doctorate in different but related subjects. My
question is what advances have been made and have any
conclusions been made pertaining to their evasion of the host
immune system, and if so, will lead to a practical
(05:52):
subject such as tissue transplantation.
Speaker 3 (05:54):
All right, these are awesome questions, and thank you to
everybody who writes to us with your questions. We really
do love to hear from you. If you have questions
about comments, or about malaria, or about parasites, or about
whatever you have limitless curiosity about, please do send them
to us. We'd love to hear from you questions at
Danielankelly dot org.
Speaker 1 (06:15):
All right, and without any further ado, let's bring my
friend John on the show to answer these listener questions.
Doctor John Hawden is a parasitologist and molecular biologist at
the George Washington School of Medicine and Health Sciences. He
was previously the president of both the American Society of
Parasitologists and the Helmethological Society of Washington. He's done some
really fantastic work on hookworms, which you'll remember are one
(06:38):
of the dirt worms or geohelmans that we talked about
in a prior episode, and we're very lucky to have
him come on the show to talk to us about
parasites and vaccines.
Speaker 2 (06:47):
Welcome to the show, John, Thank you, my pleasure. We're
excited you're here.
Speaker 6 (06:50):
I'm excited to be here.
Speaker 1 (06:52):
You sound really excited, John. Okay, so let's start with hookworms.
So we did have a whole episode on the soil geohelmets,
which we call dirt worms, but just to remind everybody,
can you talk about the life cycle of hookworms?
Speaker 6 (07:07):
Sure? So hookworms live as male and female worms in
the intestinal track of various mammalan hosts, and they get
together and have their little party and the female legs
that are been fertilized and they pass out in the pieces.
They spend a period in the ground where they hatch
and they develop through two molts to a third stage
(07:29):
larvae or L three that's infective for the next toast
and then the next host gets infected by either coming
into skin contact with the infective larvae or, in some cases,
like in dolog hookworms, for instance, by ingestion of the larvae.
Speaker 3 (07:46):
We're talking about eating poop.
Speaker 6 (07:47):
Well, yeah, as I tell my students, you know, when
you get one of these fecal oral diseases, it means
you ate a tiny little bit of.
Speaker 2 (07:55):
Poop, yeah, poop to mouth.
Speaker 6 (07:57):
So once they get into this into your the host body,
if they go through the skin, they undergo a migration
that takes them into the circulatory system to the lungs
where they break out in the bronchioles and they crawl
up your bronchile tree to the trachea to your mouth
where they're swallowed and they are carried to the small
(08:19):
intestine where they will resume the development and to the
adult stage. If they enter orally, they don't need to
leave the intestine and they can develop directly to the
adult stage.
Speaker 3 (08:31):
And they're called hookworms because they bite onto the wall
of your intestine and hook in.
Speaker 6 (08:36):
That's a common misconception, all right, it's actually it's actually
because of the way the worms appear. They can't see me.
I'm doing this for the camera, but do a little bend.
But yeah, so there's a little bend in them that
makes it look like a hook Like if you have
gotten some from inside an animal and you put them
(08:57):
in a dish, or even if you're looking at the
surface of an infected small intestine, they will be appear
to be.
Speaker 3 (09:03):
Bent, you said, if you're looking at a dish of them,
like you mean, you at a restaurant and somebody serves
you like a hookworm salad or something.
Speaker 1 (09:16):
Sorry, we love body humor us parasitologists, all right. I
don't want to get us too far off track, but
I have to ask, when the worms crawl up your
trachea into your mouth, do people feel that?
Speaker 2 (09:29):
I think?
Speaker 1 (09:29):
I asked our mutual friend Jimmy, who got infected with
hookworms as part of an experiment, and he said he
did not at any point feel the hookworms crawling in
his mouth.
Speaker 6 (09:37):
What's the deal there, John, Well, he's the expert on that.
I have never been infected, but my understanding is you
don't notice it, okay, right, So you'll swallow them with
food or with slave or whatever.
Speaker 2 (09:47):
Gross and amazing, Oh.
Speaker 6 (09:49):
My god, Well, they're clean by the time they run
through your body. So sure, all right.
Speaker 1 (09:57):
So with a lot of infections like chicken pox, you
get it once and then you have lifelong immunity. So
why doesn't that happen with hookworms? Like, why can't you
give everybody one hookworm and then for the rest of
their life they never have to worry about getting hookworm.
Speaker 6 (10:10):
Boy, life would be a lot easier if you could
do that.
Speaker 2 (10:13):
Yeah.
Speaker 6 (10:13):
Hookworms are, like most parasites, are very good at evading
the immune system, and they can do this actively or passively.
Primarily actively, they release molecules, most of which are unknown,
that alter the immune response to be a favorable environment
for them to survive. The human hookworms, notably, you never
(10:35):
really get a sterile immunity to them. You can be
reinfected over your entire lifetime. Dog hookworm, for instance, the
second infection never takes as well as the first, and
the older the dog gets, the less likely it is
to get a heavy infection of worms.
Speaker 1 (10:50):
So okay, So wait, dogs mountain immune response better than humans.
Speaker 2 (10:54):
What do we understand why that's different?
Speaker 3 (10:56):
Uh?
Speaker 6 (10:56):
No, okay, but there's a independently there's an age associated
resistance in dog hookworm, so that the older the dog
gets the less likely it is to get a heavy infection.
You don't see this in any of the human species.
It's our knowledge. I mean, you can get infected as
a kid, and you can infect it as an elderly
person with Nicator americanas, for instance, and you're gonna you'll
(11:21):
still be infected.
Speaker 1 (11:22):
Got it, And just a quick reminder for folks that
Nicator americanas is a species of hookworm.
Speaker 3 (11:27):
But microscopically, like, what's the issue? The hookworm has got
to be a foreign body. Doesn't the immune system identify
it as foreign and attack it the way it does
if you like get a splinter or get an organ donation.
What's the obstacle for the immune system? Have these hookworms
evolved to like look like human flesh.
Speaker 6 (11:44):
There's a couple problems. First of all, there's no good
way to get rid of a large organism like a hookworm.
It's also in the gut, which is a little bit
harder to deal with too, So you get what's called
a weep sweep reaction where you get a lot of
secretion of liquid of water and things into the gut
(12:07):
that cause it to be flushed out. And you don't
see that in hookworm, then it's probably due to them
suppressing that and turning the immune reaction into one that
they can tolerate. And it basically it becomes a trade
off because if the host puts enough evolutionary effort into
getting rid of worms, they could do it, but it
(12:29):
would be costly for them to do it. So in
general you come to this equilibrium where the number of
worms is not really a big has a large effect
on the host. Now there's exceptions to that. Some people
get really high level infections that are dangerous, but for
the most part, the host and the worm seem to
(12:51):
come to an agreement where they kind of limit the damage, right,
And it's just negotiation down on a molecular level really
between immunes them and the molecules that the worm produces.
Speaker 1 (13:02):
If the hookworms and our immune system have essentially like
come to a stand still, a standoff, why do we
need a vaccine for hookworms? If our immune system has
decided this isn't worth fighting off?
Speaker 6 (13:15):
Did I say we needed one?
Speaker 1 (13:16):
Okay, okay, all right, So put yourself in the shoes
of one of the people who are working on a
vaccine for hookworms.
Speaker 2 (13:24):
What would they say for why we need a hookworm vaccine.
Speaker 3 (13:27):
I mean, I want a vaccine. I don't want to
get hookworm. This sounds gross. Please give me a vaccine.
Speaker 6 (13:32):
You know, there used to be hookworm in the United States,
and the reason you don't get hookworm here is because toilets. Right.
Once you separated people from their waist, you break the
life cycle and you don't have transmission anymore. In places
where it's too poor to have sewers and sanitation like this,
there's some need or desire to vaccinate, especially kids, so
(13:57):
that they can minimize the effects of the infection. So
it's thought that if you periodically deworm, or if you vaccinated,
you would improve growth and development, you would improve school
performance and all these other economic indicators later in life,
that people would make more money in this sort of thing,
(14:19):
And there are some evidence for that, but there's also
contradictory evidence that that would really happen. Again. In the
most cases, even children aren't infected with dangerous levels of hookworm, right.
But there is a small population, a group of the
population that is highly susceptible to worms, called wormy people basically,
(14:42):
and for it's either genetics or sometimes it exposure. You know,
behavioral things like that that increase exposure.
Speaker 3 (14:49):
I can't tell because of your deadpan delivery if you're joking,
or if scientists really call them warmy people.
Speaker 6 (14:55):
Oh, no, they do. They do. There's an article about this,
a famous article by a and named Stole. I believe
is said, this wormy world. So and if people are
called wormy because they tend to get more worms, and
it's that small that group there that's going to have
the pathology and everything. And I guess the question of
skeptics of vaccines is is it worth the investment to
(15:17):
get to this small population with a vaccine, to target
that small population with a vaccine, or would the money
be better spent either targeted treatment of this group of people,
identifying them and then treating them, which is also expensive
but probably not as expensive as a vaccine, or just
improving sanitation in general in these places and essentially the
(15:41):
only places that ever really controlled these dirt worms were
places that economically grew out of it. For instance, Japan,
South Korea, the United States, Europe. All these places basically
built toilets and economically developed their way out of these
parasites these infections.
Speaker 3 (16:00):
Can I ask a question about that I have a
toilet related question. Sure, you're saying that the presence of
toilets basically separates people from their waist and that breaks
the cycle. And that makes sense to me, except that
I live with a microbiologist and she refers to toilets
as fecal tornadoes because when you flush, there's like a
spray of microscopic poop basically, And she does all these
(16:22):
studies that show that if you live with people long enough,
your microbiomes all sync because you're basically breathing and eating
each other's poop particles in the air. It's very romantic.
Let me tell you to be married to a microbiologist.
And so how do I understand that at the same
time as understanding that we've broken the hookworm life cycle?
Are these hookworm larva too small to take a ride
(16:42):
on the fecal tornadoes? Is that the issue?
Speaker 6 (16:46):
I don't know, But your fecal tornado is only going
to have the eggs, which are non infectious. It takes
three or four days at a tropical temperature in order
to develop to that effective stage. So unless you're leaving
your poost it in the toilet for a few days
and then I'm not even sure they would develop in
and then you did your fecal tornado. But you know,
(17:09):
I mean, why do we have an immune system for
things like fecal tornadoes? Right, It's probably good for you
to stimulate your immune system.
Speaker 3 (17:17):
A lot of life lessons here too.
Speaker 6 (17:19):
I try to hilt the humans. Yeah, worm me or not?
Speaker 2 (17:22):
Yeah?
Speaker 1 (17:23):
All right, So you said that hook worms release chemicals
that sort of trick the immune system into not responding
to it. So how do we have any hope of
creating a vaccine against it? What have people tried so far?
Speaker 2 (17:34):
Well?
Speaker 6 (17:35):
No, I don't know how much of this I should say,
but there is some promising results with vaccines now, and
they seem to target anigens that aren't normally seen by
the body and are involved in feeding, for instance, like
gut proteins in the worm that will block feeding. Whether
these pan out eventually to be vaccines is not clear,
(17:57):
but in some early studies they to be promising.
Speaker 3 (18:02):
Is an antigen something your immune system produces? No, that's
an antibody. So then what's an antigen?
Speaker 6 (18:09):
Well, it's what your immune system recognizes to react to
produce an antibody or to.
Speaker 3 (18:15):
It's a thing that triggers the immune response exactly. Okay,
to be honest, I thought, Man, this isn't gonna work.
And sometimes I think it even surprised the people who
do the experiments that work, because you know, these are
hard organisms to kill, they're big, and they have all
these chemical defenses. The more we learn about them, the
more there are there are multiple overlying mechanisms to subvert
(18:39):
the immune system. So yeah, it is a daunting prospect.
And one argument I've always had is that we jumped
into making vaccines before we knew enough about the worm
that a lot of the money that went into early
investment into the vaccines would have been much better learning
some basic biology about the worms. And we're starting to
(19:00):
know more about what they release, but we still don't
know how they affect the immune system. So maybe had
we waited a little longer, we would have had better
antigens to use for the vaccine. But again, that money
could also been spent to build sustainable toilets in developing countries,
which is something I had advocated for in earlier in
(19:22):
my career. Well, it sounds like you have fundamental criticisms
of this whole program, and yet you're the president of
the American Society of Parasitologists. Why don't you have more influence?
Why aren't they listening to you? John former President? Because well,
there are people with bigger voices than me involved in this,
(19:45):
the Who and various people there. There's a lot of
money in trying to develop this. I don't want to
be a cynic and say, well, this is how they
make their money or whatever. This is what they truly believe,
and they're advocates for it, right, and they have a
larger voice, and I doing this. I don't think it's
you know, the money spent on the vaccine. You know,
(20:06):
we did learn some things from that, so it's not
money wasted in that case. And if they get a vaccine,
I think it made it useful in certain situations. But
then you get into the question, you know, do you
want to kill all the worms?
Speaker 6 (20:19):
Right? I mean, there's a whole group of people in
this in this country and around the world who think
having a few worms is actually beneficial for your immune system.
And there's a lot of there's an absence, let's say,
or a dearth of information about how parasites and their
hosts have co evolved, and you know, does this effect
(20:43):
on the immune system that allows the hookworm to live,
how does that affect other parasites and other diseases. And
if you take that component away, what are you going
to do to these other diseases. Some people think that
that's why the West has this large number of autoimmune diseases,
like you know, loopus and MS and all kinds of things,
(21:03):
because they've taken away some of the regulatory we're getting
out into the hygiene hypothesis, but you know, they've taken
away the early exposure to things our old friends, like parasites,
that have trained our immune system to not react to
the little things and to only react to the big
things that are dangerous. And you take that away, and
(21:24):
now you've got an entire arm of your immune system,
which is designed to fight worms, is now looking for
something to do, and it picks on you know, it
starts going after self enagines and things like that. So
these are all questions that we don't really know enough about.
So jumping into deworming and vaccinating the entire world may
(21:44):
lead us to places we don't necessarily want to go.
Speaker 3 (21:47):
We could end up nostalgic for the time when we
had worms.
Speaker 6 (21:50):
They could some of us are.
Speaker 4 (21:54):
All right.
Speaker 1 (21:55):
Well, in a future episode, I think we'll do a
whole hour on the hygiene hypothesis because I find this
topic absolutely fascinating. So wait for that in the future, folks.
And in the meantime, let's take a break, and when
we get back, we'll talk about parasite number two, the schistosomes.
(22:30):
All right, and we're back, and now we are talking.
Speaker 2 (22:32):
About the schistosomes.
Speaker 1 (22:34):
They cause a disease called schistosomiasis, and they're quite nasty parasites.
Speaker 2 (22:38):
And Daniel's laughing at me. Why are you laughing?
Speaker 3 (22:41):
I'm laughing because we just went from the ones you
get if you eat poop to ones called shisto which
you know has some sort of resonance with other words
we shouldn't say on the podcast. So tell me, is
this another poop related parasite?
Speaker 2 (22:55):
John?
Speaker 6 (22:56):
Indirectly? Indirectly, it's life cycle is a little bit different
for a couple of reasons. The adults live in the
bloodstream and the eggs come out in the feces. But
let's just start with the feces. And the eggs come out,
they have to get into water, and when they get
into water, they hatch and they get a small larval
(23:18):
stage that now is on the hunt for a snail.
And in the case of justtosomes, the snail is very particular.
It has to be a particular species. They find it,
they penetrate into it, and then they do several generations
of asexual reproduction. And what this does is it builds
up the number of the next stage, which is called
(23:40):
a circarrea, and this is the stage it's going to
infect people. So in order to get schistosome, you have
to have contact with water that has had both feces
and the right species of snail. And if you do
Thisstosomali swim and it will penetrate into your skin and
then it will undergo a migration that goes up much
hits all the highlights in the body. It goes to
(24:02):
the liver, it goes to the lungs, and eventually they
come back to the liver and they pair up as
a male and a female and they move up into
the vessels. And depending on a species, it's either the
vessels of the large intestine, small intestine, or the bladder,
and here the male and the female live in what's
(24:23):
called incopulo forever. The male has a body that's split,
hence the name shisto soma split body, and the female
nestles in there and is mating essentially all the time
with the male, and then they release their eggs into
the bloodstream that then undergo a remarkable journey to get
(24:45):
out of the bloodstream.
Speaker 3 (24:46):
This is ridiculous, I mean, it just seems so implausible,
like step after step after step, and then you got
a snail and it's got to do this and you've
got to go swimming. But my specific question is when
you're swimming and the thing crawls through your skin, how
big is this thing? Is this something you notice or
just like are you in twimming? You have no idea
and now it's inside you?
Speaker 6 (25:06):
Yeah, I don't think you notice it. It's pretty tiny.
Speaker 3 (25:09):
And why do they have to be snailo sexuals, Like,
why do they have to do this thing inside the snail?
Why can't they just do it themselves in the water.
Speaker 6 (25:16):
Well, they first of all will need something to feed on,
where they basically will feed on the snail. Then it
absorbs nutrients from the snail and makes all these new
stages the circarria. The purpose of this is that this
allows them to go from a single mirror citium it's
called that infects the snail into thousands of these circarria
(25:38):
that's going to affect the next toast. And what that
does is it increases the odds of infection by putting
more of these infective stages into the environment. If the
mirror citium just tried to infect the host directly, even
if it developed to the effective stage, the odds of
that happening are pretty low. But the more of these
infective stages you can put into the environment, the high
(26:00):
or the odds are that one or more of them
is going to get into the next toast. And in
the case it's just the sums, you need a male
and a female sir carrier to get in.
Speaker 3 (26:08):
So the snail is like a schisto amplifier or something.
Speaker 6 (26:11):
It's just like exactly, that's exactly what it is.
Speaker 2 (26:13):
Crazy, it's kind of ingenious.
Speaker 4 (26:15):
You know.
Speaker 1 (26:15):
The snail goes around grazing and collecting more food, and
that energy goes towards making more parasites, and so the
parasites are getting like a buffet for doing nothing.
Speaker 2 (26:23):
Once they establish in the snail.
Speaker 6 (26:26):
This is a pretty gruesome parasite in the host, though.
It causes a lot of problems. And it's not because
of the worm, which is relatively tiny and living in
the blood vessels. It's because of the eggs. So this
mechanism that gets the eggs out is really elegant, but
it's very inefficient, so a vast majority of the eggs
don't get out. They end up in the liver and
(26:47):
they form what are called granulomas when the host reacts
to them, and that's where the damage comes from. Are
these granulomas in the liver and other organs as well?
Speaker 3 (26:56):
Well, that was gonna be my question. The hookworm we
were talking about was most in the gut, and there's
some sort of negotiation. You can hang out there because
it's difficult for us to attack you anyway. But these
guys are all over I hear them being in the blood,
they're in the bladder, they're in the liver. So the
immune sism does respond to them. It forms these glass ulummas, granulomas, granulomas, yes,
(27:17):
thank you, yes, Why doesn't it get rid of them?
Speaker 6 (27:20):
Well, the worms in the blood are pretty much untouched
and they have a bunch of immunovasive mechanisms as well.
It sort of similar to the whole worm, but different mechanisms.
The eggs, on the other hand, they alter the immune
system to make what's called a THH two response, which
is when you get a whole bunch of cells will
come in and they'll surround the egg and form this granuloma,
(27:41):
and then it will slowly move it through the tissue
right and eventually they'll come to the bladder wall or
the intestinal wall and they will just basically dump the
egg out, but they often get stuck, so you'll have
these eggs stuck in the bladder wall. All this depends
on the species where is is it in a bladder,
is it in a large or small intestine, But in
(28:03):
any case, you'll get them stuck in those in the
wall of those organs, as well as in the liver,
and then they're constantly releasing anigens that are pulling more
cells in, and these gran omans can get very big
and then start impacting the function of the tissue that
they're in, and you get fibrosis in the liver and
(28:24):
just the surmises can be really nasty disease. It's probably
the most pathogenic of the worms that in fact humans.
Speaker 1 (28:31):
I thought I heard, and remind me if I'm wrong.
I thought there were some areas where the kind of
schistosome that they have is near the bladder, and the
granulomas build up in the bladder, and every once in
a while, like the males will get it so much
that they will start to bleed along with the you know,
with the females of a certain age, and it's almost
like a rite of passage. So many kids get this.
(28:52):
That blood in your urine is just something you expect
for both sexes. Is that Wow? Is that still the case?
Speaker 2 (28:58):
John?
Speaker 6 (28:58):
Yeah, that's the called just the soma heematobium. It's found
exclusively in Africa. And yeah, it will cause it because
these granny loanans move it to the bladder wall. They
cause it to erode and then you will get blood
in the urine. And there's some evidence that I think
they're pretty convinced now that schistosome as well, some of
(29:20):
these other trematodes can cause cancer as well, including bladder
cancer in that case, because of over years and years
of this erosion occurring and the body responding to it
in the eggs releasing these these antigens that it could
result in cancer.
Speaker 3 (29:37):
Well, that sounds like something we should vaccinate against.
Speaker 6 (29:40):
Yes, I would be in favor of that. I think
I think schistosimiasis is one that we can do without.
It's going to be just as hard to go to
make a vaccine. Again, they have some promising candidates, but
we're still a long way away from the actually using
a vaccine. Again, it's a sanitar thing, right in this case,
(30:02):
if you keep your feces away from water, you're not
going to have a problem. Snail control is possible, but
it's difficult, it's expensive. We see some promise with introducing
predators that actually eat the snails. In some areas in
West Africa they've done this and they've seen you know,
you can combine it with chemotherapy and snail control and
(30:25):
you could see a huge decrease in the prevalence and
just to some infections. But step one you said was
keep your feces away from water. But in the previous
segment we were talking about toilets, and that's like the
basic operating principles like turn your poop into sewage, right, right,
how do you do both at once? Well? As long
as you don't have snails in your sewage, you're gonna
(30:45):
be okay. And plus people generally, I mean, if you're
talking about Western sewage systems, you've kept away from the
sewage the entire time. The water, you know, goes through
a sewage treatment plant and gets treated and converted back
into usable water. So you know you're still breaking the
transmission in that case, right, Remember you need water and snails.
Speaker 1 (31:08):
This sounds like a particularly tricky problem because you've got
like the adults that hide from the immune system, and
then you've got the eggs that as they pass through
the body definitely do not seem to be good at
hiding from the immune system, and the immune system responds
and that's what causes the problem for people. So it
seems to me that if you made a vaccine, you'd
need to be careful to not make the problem with
(31:29):
the eggs worse because now your immune system is over responding.
Speaker 6 (31:33):
Yeah, I think you would have to stop it before
they got to the egg producing adults, and you would
have to make your vaccine against the stages that are
penetrating into the host.
Speaker 2 (31:43):
Do we understand how the adults are hiding from the
immune system.
Speaker 6 (31:46):
Right, so they do several things. First of all, they
will actually take host molecules and bind them to their
cuticle so that then the host immune system doesn't see
it as foreign. I mean, yes, we can.
Speaker 1 (32:01):
We just sit on that for a second. That's like
taking like you know, taking the skin off of a
human and putting it on themselves or something like that.
That's amazing. They hide with our own material to.
Speaker 3 (32:11):
Wolf in sheep's clothing.
Speaker 6 (32:12):
Yeah, but that's not all go on. They also make
what's molecular mimicry. They will make molecules that are very
similar to molecules in the host, like a hormone for instance.
They will then get processed by the host enzymes and
act as a suppressor of the immune response.
Speaker 3 (32:30):
Do we know how all of this elaborate machinery evolved?
We have any idea of the history here? Is that, like,
do you need all these pieces together to survive? Can
you like do it one step at a time and
refine it? How does it work? How does it evolve incrementally?
And ones that add more and more mechanisms probably are
better at survival. So it might have one of these
things initially and at lets more of them survive, and
(32:53):
then you will get the mutations for the other things
that occur, and they get just pile up to have
a whole suite of thing that is really efficient at
inhimbiting the immune system. So each of these tricks is helpful.
None of them are absolutely necessary, and so as you evolve,
you developed more and more tricks to sort of optimize
survival in the host.
Speaker 6 (33:12):
Right.
Speaker 3 (33:13):
Wow, impressive.
Speaker 1 (33:14):
I know this episode isn't about the history of Kelly,
but when I read about this in Curl Zimmer's book
Parasite Rex, this was like literally a turning point in
my life. I had gone from being like parasites, Oh,
they're just kind of gross, to being like, holy cow,
it's like amazing the way they've managed to hide inside
of our bodies, and like it totally changed the way
I looked at parasites and like literally altered the course
(33:36):
of my life. So anyway it infected your mind, it
infected my mind, and now we got to share it
with everybody, and so I'm very excited.
Speaker 3 (33:44):
Wait, no, this is the like intellectual version of the
snail amplification that goes into Kelly's brain just states for
a while, she gets a podcast and then she spreads
it to the whole community through John.
Speaker 1 (33:55):
John is my snail and I am the parasite and
this is gone. This has gone too okay, So let's well,
I can I play on the word shisto, like take
a break?
Speaker 2 (34:06):
Can we split for a second? Nope? Not clever enough.
All right, Daniel, do you have something in.
Speaker 3 (34:13):
Case anybody needs to take a break and have a shift.
Go ahead and we'll be back in a minute to
talk about another parasite poop related jokes.
Speaker 1 (34:22):
Love it, and we're back, and we are going to
(34:44):
start with John's snail related joke that he queued up
during the break for us.
Speaker 2 (34:49):
Oh wait, did you just say that this might not
be appropriate for the show?
Speaker 6 (34:52):
This one's fine. Okay, this one's fine. So I tell
this in my class. So this guy goes to a
Halloween park a costume party and he's got this girl
draped over his shoulders and he goes in and the
host says, hey, how you doing great, and everything says
are you a costume? He goes, yeah, this is my costume.
(35:13):
Well what's with the girl? And I said, well that's Michelle,
Oh my Shelle.
Speaker 2 (35:20):
He's a snail.
Speaker 6 (35:22):
I think I left out the snail part.
Speaker 2 (35:28):
We got there though as a team, as a team, so.
Speaker 6 (35:33):
Yeah, sorry, I blew the d.
Speaker 1 (35:36):
So malaria has some tricky ways of evading the immune system.
But we're going to start with the malarial life cycle
and get to the immune system stuff in a second.
And I've always found the malarial life cycle to be
super confusing. It has a bunch of stages. All the
stages have similar and kind of heart to remember names.
So I'm going to give a super simplified version of
(35:57):
the life cycle that I think will be sufficient for
the discussion we're about to have. All right, So, when
a mosquito bites a person who's already infected by malaria,
the parasite goes to the mosquito's gut and it starts
to replicate. So after that it moves to the mosquito's
salivary glands. And that's right, mosquitoes have salivary glands. I
(36:17):
don't know why that's surprising to me, but anyway, when
a mosquito bites a person, the parasites are injected by
the mosquito into the human body. The stage of the
parasite that gets released into a person is called a sporozoite.
This is the only stage we're going to name, so
just remember the sporozoite is the early stage in humans.
(36:38):
From there, the parasite moves onto the liver and does
some replicating. After that, it moves on to our red
blood cells. When a parasite gets into the red blood cell,
it's able to sneak proteins through the surface of the
red blood cell, and those proteins stick onto the surface
of the red blood cell. This helps the parasite hide
(36:58):
from the immune system. And I'm sure John's going to
tell us more about this later, all right, So, the
parasite is living in the red blood cell and it's
eating the hemoglobin.
Speaker 2 (37:07):
In the cell.
Speaker 1 (37:08):
And as you might remember from our past conversation about
synthetic blood, hemoglobin is the protein in your red blood
cell that helps your cells carry oxygen to different parts
of the body. So the parasite is hiding in the
red blood cell and shower down on the hemoglobin. It's
replicating while it's in the red blood cell, And every
like twenty four to forty eight hours, the red blood
(37:30):
cell will burst open and these newly released stages will
go off to search for new red blood cells to
infect so that like red blood cell cycle will start
again over time. A lot of the red blood cells
get infected this way, so you're regularly losing your red
blood cells, which can result in anemia. And your body
gets poisoned when these red blood cells burst open, and
(37:53):
all of the stuff that used to be in the
red blood cells is now like in circulation, and that's
not good. Plus when the red blood cells burst, there's
suddenly loads of new parasites in the circulation and the
immune system goes nuts. You get chills, you get fevers,
et cetera. And the parasite is bad for a lot
of other reasons, some of which I'm sure John is
(38:13):
going to tell us about in a few moments here.
And all of this on note is particularly dangerous for
children or for adults who have never been exposed to
malaria before, like travelers for example.
Speaker 3 (38:23):
And does it use the mosquito just as a way
to get from one body to another or is this
something that happens inside the mosquito like snail amplification.
Speaker 6 (38:31):
Oh yeah, very important part of life cycle happens in
the snail. So there is an amplification in number. Plus
there's also sex or recombination occurring in the mosquito.
Speaker 3 (38:40):
So we can definitely blame the mosquito for part of this.
Speaker 6 (38:43):
Absolutely absolutely good. And you know it, blame the female
mosquitoes because they're the only ones that take a blood male.
Speaker 2 (38:51):
I don't like where this is going.
Speaker 3 (38:55):
So I'm broadly into mosquito female male. I don't care.
I'm not sexist about it.
Speaker 6 (38:59):
You know, it doesn't work without the male, So they're
partially involved, but they're not the ones that are lighting you.
Speaker 3 (39:04):
Yeah, exactly blame them all.
Speaker 1 (39:06):
I'm broadly antidipterine, so dipterines are flies and mosquitoes.
Speaker 2 (39:11):
I'm not a big fan of any of them.
Speaker 1 (39:12):
But anyway, so inside the body of us, we get
these cycles where they live in our red blood cells.
They replicate and then they burst out of our red
blood cells, and then they go back into red blood cells.
So it seems like when they're in red blood cells,
I can imagine it would be harder for our immune
system to find them because they're like hiding in our cells.
Speaker 6 (39:31):
They have evolved ways to transport things across their membrane,
across the vacual membrane to be displayed on the red
cell membrane, and one of the things that they display
is a molecule called, in the case of plasmonium fell siperum,
which is the most dangerous one erythrocytic membrane protein one,
(39:53):
or as I call it, PfEMP one, and p FMP
one then is expressed on the surface of the cell,
so there is an immune reaction that develops against this
PFMP one molecular. And the PFMP is interesting because it
is able to bind to receptors in the blood vessels,
(40:16):
the veins of the host, and it basically takes those
out of circulation, right, so they're bound to the inner
vessels right of your larger veins in everything, and they
just sit there so they're not being circulated through the spleen,
which would recognize the red cells as being deformed and
would take them out of circulation. So that's one way
(40:38):
they avoid the physical destruction associated with the spleen, and
they'll sit there and they'll do their you know, their
replication bound to these vessels. And that's also a major
cause of the pathology because when they bind to the
small vessels like in the brain or in the placenta,
in the kidney. This is where you get this micro
(40:58):
occlusion of the the capitilarias, and you get decreased oxygenation,
and then you get the metabolic acidosis. And these are
the kind of things that cause the big problems with malarium.
Speaker 1 (41:10):
Not one hundred percent sure I understand. Let me see
if I can explain it back and if if I'm right. So,
I think what you're saying is that the red blood cells,
they end up with the stuff that sticks out of
the cell. It connects them to like the veins or
arteries so that they don't go to the spleen, whose
job is to remove infected or disfigured cells and get
(41:30):
rid of them. So they essentially keep themselves from going
to the police station by hanging on in one spot.
And if that happens, like in your brain or in
a placenta, it causes clogs that are bad.
Speaker 6 (41:42):
Right, and it seems to be particular bad, like it's
one of the major causes of the cerebral malarium, which
is the big killer.
Speaker 3 (41:49):
So then what are the possibilities here for a vaccine?
Since this sounds pretty bad and we all hate mosquitoes
and nobody wants the stuff in your brain.
Speaker 6 (41:58):
Yeah, that's a good question. So I think most of
the success for the vaccines has been against the sporsoa.
If you have an immune response to sporizoi when it
gets into the skin, that can stop the infection right there.
And I there are some promising vaccines, some that have
actually been used are in use that maybe give you
(42:21):
sixty percent protection or so, I'll ticket. Yeah, it's you know,
it's kind of what a flu vaccine does too, you know. Yeah,
So there are some promising ones in there, maybe more
in the future because it put a lot of a
lot of effort into this vaccine development from malaria, and
definitely would be a good thing. You just need to
(42:41):
prevent people from dying because as they live there, they're
going to build up this natural immunity that occurs over
time and then it won't be an issue anymore. But
it'd be important for kids and also for travelers, like
if you're going into Africa and you've never had malaria,
then that would be very useful to have a vaccine,
or for the military or something like that. So there's
(43:04):
definitely a need for vaccine here. We're getting closer. I
think there are, Like I said, several have been deployed,
so it's promising, I think, more so, I think than
with the worms at this point.
Speaker 1 (43:16):
Oh yeah, we never said what kind of an organism
malaria is. So the first example we talked about was
a nematode, the second one was a trematode, and malaria
is a protozoan protist.
Speaker 3 (43:25):
Yeah.
Speaker 1 (43:26):
Why is it so much harder to make vaccines for
parasites than for bacteria and viruses? And so my first
question is that actually true? I feel like the answer
is yes. And then is there a big picture reason
for why?
Speaker 5 (43:41):
Uh?
Speaker 6 (43:41):
Well, okay, it's generally it's true. But think about HIV.
I haven't had a vaccine against that yet, right, Yeah,
so it's not always easy to do, but I think
it's because the immune system seems to be much better
able to handle small things. Right. You can make an
antibody response, it'll bind to the bacterium or to the
(44:04):
viral particle, and then you can get your complement system
involved to destroy it. But you know the pathogens have
ways to get around the immune system as well, right,
So your bacteria and your viruses could subvert the immune
system too.
Speaker 3 (44:19):
Wait, I didn't understand that first thing you said, and
it reminds me of a big puzzle in physics, you know,
you said, essentially, the immune system is better at attacking
small things, but big things are all made out of
small things. So why can't you just attack all the
small things that a big thing is made out of.
It's like the puzzle of like every classical object is
made of quantum particles. Why can't we understand it? I'm
(44:39):
not suggesting this quantum mechanical magic happening here, but what
keeps the immune system from attacking each individual cell inside
one of these bigger objects.
Speaker 6 (44:49):
In case of the worms, they all have a cuticle
that protects the inner cells from damage. Right In the
case of like the hookworms, the immune system's able to
go after the small part of the worm, which is
the gut right that is exposed. It also takes a
lot of cells to kill, you know, a bigger worm.
It's just harder to do, I think. And like I said,
(45:12):
a lot of the mechanisms get where the worms involve
things like, well, we're just gonna flush them out, right,
We're not going to try to kill them. We're just
to try to flush them out. Whereas we have cells
that will actually ingest viruses and opsonize viruses at least
and bacteria, right, they recognize the antibody and they bind
to it and then ingest it and destroy it. Right.
(45:35):
So it's a lot easier to do that than it
is to try to kill a big worm that's got
this protective armor around it and is living in the gut,
for instance.
Speaker 1 (45:45):
Yeah, So as a biologist, one of the things I
think is super interesting about this conversation is not just
how do the parasites evaide the immune system, but it's
also just that they have such complicated life cycles. There's
so many different places where you could choose to try
to protect against parasites. So you know, for mosquitos, you
can pay for bed nets because the mosquitos are most
active at night, and maybe you just keep the mosquitos
from biting, and maybe that's even you know, better than
(46:07):
some of the medicines. Just you know, if you don't
encounter with them in the first place, that's hopeful. But
you know, all of these systems are evolving, so if you,
for example, go after the mosquitoes with pesticides, they evolve
resistance and anyway, it's a very complicated problem, and all
of those complications is sort of what got me interested
in parasitology in the first place. Anyway, back to Kelly's
(46:27):
origin story, but this has been a fascinating, fascinating chat.
Thanks so much, John for coming on the show to
tell us all about the parasites you study and the
parasites you don't study that I put you on the
spot to talk about.
Speaker 2 (46:39):
Anyway.
Speaker 6 (46:39):
Ah, well, you know, all these years of teaching, I've
learned something.
Speaker 2 (46:43):
So that's excellent.
Speaker 3 (46:45):
You've learned how to nail a snail joke or snail
it I guess.
Speaker 2 (46:48):
Yeah, well, John, let's save those for another episode. We
don't want to overwhelm the audience.
Speaker 6 (46:52):
Thank you was fun.
Speaker 1 (47:01):
Daniel and Kelly's Extraordinary Universe is produced by iHeartRadio.
Speaker 2 (47:05):
We would love to hear from you, We really would.
Speaker 3 (47:08):
We want to know what questions you have about this
Extraordinary Universe.
Speaker 1 (47:12):
We want to know your thoughts on recent shows, suggestions
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Speaker 2 (47:16):
If you contact us, we will get back to you.
Speaker 3 (47:19):
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Speaker 1 (47:25):
Dot org, or you can find us on social media.
We have accounts on x Instagram, Blue Sky, and on
all of those platforms.
Speaker 2 (47:32):
You can find us at D and K Universe.
Speaker 3 (47:35):
Don't be shy, write to us,
Howdy friends, Just a heads up that we're talking about
parasites again, and as you're probably aware of by now.
Speaker 2 (00:06):
That can get pretty gross.
Speaker 1 (00:08):
Also, it's kind of upsetting to hear about parasite life
cycles and the effects of parasites on our health. I
get that today we're going to be talking about malarias
just a semiasis and hookworm, So decide if those are
topics you are prepared.
Speaker 2 (00:19):
To hear about. All Right, here we go.
Speaker 1 (00:29):
According to the World Health Organization, in twenty twenty three,
about two hundred and sixty three million people were infected
by malaria, of which five hundred and ninety seven thousand
passed away from this disease. Most of these deaths happened
in Africa, in seventy six percent of the deaths or
children under five. You might remember from a past episode
(00:49):
that we were able to create a vaccine for smallpox,
and that that vaccine was used to wipe smallpox off
the face of the planet, saving humanity from this ancient scourge.
And yeah, thanks to all who wrote in. I pronounce
the word correctly. Now we also have vaccines for other
bacterial and viral infections like polio, chicken pox, human papilloma virus, COVID, nineteen, measles, mumps,
(01:11):
et cetera. With the exception of some tricky viruses like
HIV which hide in our immune cells, We've had a
lot of success making vaccines for viral and bacterial infections,
and we know that our immune systems attack big stuff
as well as the little stuff like bacteria and viruses.
In a past episode, we talked about how our immune
systems will attack entire organs following a transplant. So why
(01:37):
do our immune systems seem to do such a crummy
job of attacking parasites in our bodies, things like nematodes,
And why is it so hard to make vaccines to
give our immune system a leg up on these invaders.
We've been working on malaria vaccines for a really long time,
but only recently have two malaria vaccines become widely available
in areas in Africa where malaria is prevalent. That's good,
(02:00):
but why did it take so long? And why don't
we have a vaccine for hookworms yet? Remember hookworms, those
dirt worms we talked about a few months back.
Speaker 2 (02:07):
Yeah, those guys.
Speaker 1 (02:09):
There are many parasitic diseases that have proven stubbornly difficult
to control with vaccines, and so today we're going to
talk to doctor John Hawden, a molecular biologist and parasitologist
who's going to help us understand why it's so darn
hard to make vaccines against parasites. Welcome to Daniel and
Kelly's Extraordinary Universe.
Speaker 3 (02:42):
Hi. I'm Daniel. I'm a particle physicist, and I'm excited
to be talking about all sorts of ikey invaders today.
Speaker 2 (02:49):
Hello.
Speaker 1 (02:49):
I'm Kelly wieder Smith, and I always love talking about
ikey invaders, although with all the required sensitivity for the
pain and suffering that these parasites cause. But anyway, I
study parasites and space, and today we're talking about my
first love, parasitology, your first love.
Speaker 3 (03:04):
Something I love about science is how excited people get
about their finy, little, tiny little niche. You know, you're
going to meet somebody who's like amazed at the hairs
on spider's legs, or somebody else who like can't stop
thinking about how, you know, the mantle flows and how
rocks form, and like, these nerds get so excited about
(03:26):
their little niche. It's wonderful, right, that's why we know
so much about the universe and spider legs and rocks
and parasites because people get weirdly excited about stuff.
Speaker 1 (03:36):
My friend Ashley Smythe refers to this as a limitless
human curiosity. Yes, because I was asking her about like, oh,
why do parasitologists sometimes infect themselves with the parasites that
they study? Isn't it weird that we do that? And
she was like, Kelly, that's our limitless human curiosity.
Speaker 3 (03:52):
And I was like, Okay, I totally love that about humanity.
I mean, curiosity is something deep about being human. Actually,
I wonder if it is just about being human, or
if you know, aliens are curious about the universe also,
if that's something that really is universal. But today, unfortunately,
we're not talking about aliens. We're talking about critters so
gross that invade you that it almost feels like they
(04:14):
are alien.
Speaker 1 (04:15):
And today we invited on the show my friend John.
He's going to be talking about three different kinds of parasites.
And specifically we invited John on the show because we
had two listener questions that felt somewhat out of my expertise,
even though I'm a parasite person and so I knew
the guy to invite on the show. So let's go
ahead and listen to the two questions from listeners before
(04:35):
we bring John on.
Speaker 4 (04:37):
Hi, Daniel and Kelly. This is David from the San
Francisco Bay area, and this question is for Kelly. What
makes developing a vaccine for parasitic infections so difficult? It
seems like progress has been only recent and incremental with
some experimental vaccines for hookworm, and the one approved laria
vaccine is not very efficacious. So what gives? And this
topic is at least tangentially related to what I do
(04:57):
for a living, which is working on a new platform
produce rnaate therapeutics, So I'm especially interested in what you
have to say. Anyway, keep up the great work, both
of you and Daniel, I forgive you for your chemistry phobia. Cheers.
Speaker 5 (05:10):
I got my master's degree in the late seventies. At
that time there are three theories on how sysystems evade
immune system an advisor's theory was called molecular mimicry. Although
it was over fourty years ago, I remember it well
because for the final exam we had eight hours to
answer two questions. One of which was your name, the
three current theories of how the treatment HOS evased immune
(05:31):
system and which one do you agree with and why?
Of course I chose my advisor's theory, but after receiving
my master's degree, I lost track of the issue. Since
I got my doctorate in different but related subjects. My
question is what advances have been made and have any
conclusions been made pertaining to their evasion of the host
immune system, and if so, will lead to a practical
(05:52):
subject such as tissue transplantation.
Speaker 3 (05:54):
All right, these are awesome questions, and thank you to
everybody who writes to us with your questions. We really
do love to hear from you. If you have questions
about comments, or about malaria, or about parasites, or about
whatever you have limitless curiosity about, please do send them
to us. We'd love to hear from you questions at
Danielankelly dot org.
Speaker 1 (06:15):
All right, and without any further ado, let's bring my
friend John on the show to answer these listener questions.
Doctor John Hawden is a parasitologist and molecular biologist at
the George Washington School of Medicine and Health Sciences. He
was previously the president of both the American Society of
Parasitologists and the Helmethological Society of Washington. He's done some
really fantastic work on hookworms, which you'll remember are one
(06:38):
of the dirt worms or geohelmans that we talked about
in a prior episode, and we're very lucky to have
him come on the show to talk to us about
parasites and vaccines.
Speaker 2 (06:47):
Welcome to the show, John, Thank you, my pleasure. We're
excited you're here.
Speaker 6 (06:50):
I'm excited to be here.
Speaker 1 (06:52):
You sound really excited, John. Okay, so let's start with hookworms.
So we did have a whole episode on the soil geohelmets,
which we call dirt worms, but just to remind everybody,
can you talk about the life cycle of hookworms?
Speaker 6 (07:07):
Sure? So hookworms live as male and female worms in
the intestinal track of various mammalan hosts, and they get
together and have their little party and the female legs
that are been fertilized and they pass out in the pieces.
They spend a period in the ground where they hatch
and they develop through two molts to a third stage
(07:29):
larvae or L three that's infective for the next toast
and then the next host gets infected by either coming
into skin contact with the infective larvae or, in some cases,
like in dolog hookworms, for instance, by ingestion of the larvae.
Speaker 3 (07:46):
We're talking about eating poop.
Speaker 6 (07:47):
Well, yeah, as I tell my students, you know, when
you get one of these fecal oral diseases, it means
you ate a tiny little bit of.
Speaker 2 (07:55):
Poop, yeah, poop to mouth.
Speaker 6 (07:57):
So once they get into this into your the host body,
if they go through the skin, they undergo a migration
that takes them into the circulatory system to the lungs
where they break out in the bronchioles and they crawl
up your bronchile tree to the trachea to your mouth
where they're swallowed and they are carried to the small
(08:19):
intestine where they will resume the development and to the
adult stage. If they enter orally, they don't need to
leave the intestine and they can develop directly to the
adult stage.
Speaker 3 (08:31):
And they're called hookworms because they bite onto the wall
of your intestine and hook in.
Speaker 6 (08:36):
That's a common misconception, all right, it's actually it's actually
because of the way the worms appear. They can't see me.
I'm doing this for the camera, but do a little bend.
But yeah, so there's a little bend in them that
makes it look like a hook Like if you have
gotten some from inside an animal and you put them
(08:57):
in a dish, or even if you're looking at the
surface of an infected small intestine, they will be appear
to be.
Speaker 3 (09:03):
Bent, you said, if you're looking at a dish of them,
like you mean, you at a restaurant and somebody serves
you like a hookworm salad or something.
Speaker 1 (09:16):
Sorry, we love body humor us parasitologists, all right. I
don't want to get us too far off track, but
I have to ask, when the worms crawl up your
trachea into your mouth, do people feel that?
Speaker 2 (09:29):
I think?
Speaker 1 (09:29):
I asked our mutual friend Jimmy, who got infected with
hookworms as part of an experiment, and he said he
did not at any point feel the hookworms crawling in
his mouth.
Speaker 6 (09:37):
What's the deal there, John, Well, he's the expert on that.
I have never been infected, but my understanding is you
don't notice it, okay, right, So you'll swallow them with
food or with slave or whatever.
Speaker 2 (09:47):
Gross and amazing, Oh.
Speaker 6 (09:49):
My god, Well, they're clean by the time they run
through your body. So sure, all right.
Speaker 1 (09:57):
So with a lot of infections like chicken pox, you
get it once and then you have lifelong immunity. So
why doesn't that happen with hookworms? Like, why can't you
give everybody one hookworm and then for the rest of
their life they never have to worry about getting hookworm.
Speaker 6 (10:10):
Boy, life would be a lot easier if you could
do that.
Speaker 2 (10:13):
Yeah.
Speaker 6 (10:13):
Hookworms are, like most parasites, are very good at evading
the immune system, and they can do this actively or passively.
Primarily actively, they release molecules, most of which are unknown,
that alter the immune response to be a favorable environment
for them to survive. The human hookworms, notably, you never
(10:35):
really get a sterile immunity to them. You can be
reinfected over your entire lifetime. Dog hookworm, for instance, the
second infection never takes as well as the first, and
the older the dog gets, the less likely it is
to get a heavy infection of worms.
Speaker 1 (10:50):
So okay, So wait, dogs mountain immune response better than humans.
Speaker 2 (10:54):
What do we understand why that's different?
Speaker 3 (10:56):
Uh?
Speaker 6 (10:56):
No, okay, but there's a independently there's an age associated
resistance in dog hookworm, so that the older the dog
gets the less likely it is to get a heavy infection.
You don't see this in any of the human species.
It's our knowledge. I mean, you can get infected as
a kid, and you can infect it as an elderly
person with Nicator americanas, for instance, and you're gonna you'll
(11:21):
still be infected.
Speaker 1 (11:22):
Got it, And just a quick reminder for folks that
Nicator americanas is a species of hookworm.
Speaker 3 (11:27):
But microscopically, like, what's the issue? The hookworm has got
to be a foreign body. Doesn't the immune system identify
it as foreign and attack it the way it does
if you like get a splinter or get an organ donation.
What's the obstacle for the immune system? Have these hookworms
evolved to like look like human flesh.
Speaker 6 (11:44):
There's a couple problems. First of all, there's no good
way to get rid of a large organism like a hookworm.
It's also in the gut, which is a little bit
harder to deal with too, So you get what's called
a weep sweep reaction where you get a lot of
secretion of liquid of water and things into the gut
(12:07):
that cause it to be flushed out. And you don't
see that in hookworm, then it's probably due to them
suppressing that and turning the immune reaction into one that
they can tolerate. And it basically it becomes a trade
off because if the host puts enough evolutionary effort into
getting rid of worms, they could do it, but it
(12:29):
would be costly for them to do it. So in
general you come to this equilibrium where the number of
worms is not really a big has a large effect
on the host. Now there's exceptions to that. Some people
get really high level infections that are dangerous, but for
the most part, the host and the worm seem to
(12:51):
come to an agreement where they kind of limit the damage, right,
And it's just negotiation down on a molecular level really
between immunes them and the molecules that the worm produces.
Speaker 1 (13:02):
If the hookworms and our immune system have essentially like
come to a stand still, a standoff, why do we
need a vaccine for hookworms? If our immune system has
decided this isn't worth fighting off?
Speaker 6 (13:15):
Did I say we needed one?
Speaker 1 (13:16):
Okay, okay, all right, So put yourself in the shoes
of one of the people who are working on a
vaccine for hookworms.
Speaker 2 (13:24):
What would they say for why we need a hookworm vaccine.
Speaker 3 (13:27):
I mean, I want a vaccine. I don't want to
get hookworm. This sounds gross. Please give me a vaccine.
Speaker 6 (13:32):
You know, there used to be hookworm in the United States,
and the reason you don't get hookworm here is because toilets. Right.
Once you separated people from their waist, you break the
life cycle and you don't have transmission anymore. In places
where it's too poor to have sewers and sanitation like this,
there's some need or desire to vaccinate, especially kids, so
(13:57):
that they can minimize the effects of the infection. So
it's thought that if you periodically deworm, or if you vaccinated,
you would improve growth and development, you would improve school
performance and all these other economic indicators later in life,
that people would make more money in this sort of thing,
(14:19):
And there are some evidence for that, but there's also
contradictory evidence that that would really happen. Again. In the
most cases, even children aren't infected with dangerous levels of hookworm, right.
But there is a small population, a group of the
population that is highly susceptible to worms, called wormy people basically,
(14:42):
and for it's either genetics or sometimes it exposure. You know,
behavioral things like that that increase exposure.
Speaker 3 (14:49):
I can't tell because of your deadpan delivery if you're joking,
or if scientists really call them warmy people.
Speaker 6 (14:55):
Oh, no, they do. They do. There's an article about this,
a famous article by a and named Stole. I believe
is said, this wormy world. So and if people are
called wormy because they tend to get more worms, and
it's that small that group there that's going to have
the pathology and everything. And I guess the question of
skeptics of vaccines is is it worth the investment to
(15:17):
get to this small population with a vaccine, to target
that small population with a vaccine, or would the money
be better spent either targeted treatment of this group of people,
identifying them and then treating them, which is also expensive
but probably not as expensive as a vaccine, or just
improving sanitation in general in these places and essentially the
(15:41):
only places that ever really controlled these dirt worms were
places that economically grew out of it. For instance, Japan,
South Korea, the United States, Europe. All these places basically
built toilets and economically developed their way out of these
parasites these infections.
Speaker 3 (16:00):
Can I ask a question about that I have a
toilet related question. Sure, you're saying that the presence of
toilets basically separates people from their waist and that breaks
the cycle. And that makes sense to me, except that
I live with a microbiologist and she refers to toilets
as fecal tornadoes because when you flush, there's like a
spray of microscopic poop basically, And she does all these
(16:22):
studies that show that if you live with people long enough,
your microbiomes all sync because you're basically breathing and eating
each other's poop particles in the air. It's very romantic.
Let me tell you to be married to a microbiologist.
And so how do I understand that at the same
time as understanding that we've broken the hookworm life cycle?
Are these hookworm larva too small to take a ride
(16:42):
on the fecal tornadoes? Is that the issue?
Speaker 6 (16:46):
I don't know, But your fecal tornado is only going
to have the eggs, which are non infectious. It takes
three or four days at a tropical temperature in order
to develop to that effective stage. So unless you're leaving
your poost it in the toilet for a few days
and then I'm not even sure they would develop in
and then you did your fecal tornado. But you know,
(17:09):
I mean, why do we have an immune system for
things like fecal tornadoes? Right, It's probably good for you
to stimulate your immune system.
Speaker 3 (17:17):
A lot of life lessons here too.
Speaker 6 (17:19):
I try to hilt the humans. Yeah, worm me or not?
Speaker 2 (17:22):
Yeah?
Speaker 1 (17:23):
All right, So you said that hook worms release chemicals
that sort of trick the immune system into not responding
to it. So how do we have any hope of
creating a vaccine against it? What have people tried so far?
Speaker 2 (17:34):
Well?
Speaker 6 (17:35):
No, I don't know how much of this I should say,
but there is some promising results with vaccines now, and
they seem to target anigens that aren't normally seen by
the body and are involved in feeding, for instance, like
gut proteins in the worm that will block feeding. Whether
these pan out eventually to be vaccines is not clear,
(17:57):
but in some early studies they to be promising.
Speaker 3 (18:02):
Is an antigen something your immune system produces? No, that's
an antibody. So then what's an antigen?
Speaker 6 (18:09):
Well, it's what your immune system recognizes to react to
produce an antibody or to.
Speaker 3 (18:15):
It's a thing that triggers the immune response exactly. Okay,
to be honest, I thought, Man, this isn't gonna work.
And sometimes I think it even surprised the people who
do the experiments that work, because you know, these are
hard organisms to kill, they're big, and they have all
these chemical defenses. The more we learn about them, the
more there are there are multiple overlying mechanisms to subvert
(18:39):
the immune system. So yeah, it is a daunting prospect.
And one argument I've always had is that we jumped
into making vaccines before we knew enough about the worm
that a lot of the money that went into early
investment into the vaccines would have been much better learning
some basic biology about the worms. And we're starting to
(19:00):
know more about what they release, but we still don't
know how they affect the immune system. So maybe had
we waited a little longer, we would have had better
antigens to use for the vaccine. But again, that money
could also been spent to build sustainable toilets in developing countries,
which is something I had advocated for in earlier in
(19:22):
my career. Well, it sounds like you have fundamental criticisms
of this whole program, and yet you're the president of
the American Society of Parasitologists. Why don't you have more influence?
Why aren't they listening to you? John former President? Because well,
there are people with bigger voices than me involved in this,
(19:45):
the Who and various people there. There's a lot of
money in trying to develop this. I don't want to
be a cynic and say, well, this is how they
make their money or whatever. This is what they truly believe,
and they're advocates for it, right, and they have a
larger voice, and I doing this. I don't think it's
you know, the money spent on the vaccine. You know,
(20:06):
we did learn some things from that, so it's not
money wasted in that case. And if they get a vaccine,
I think it made it useful in certain situations. But
then you get into the question, you know, do you
want to kill all the worms?
Speaker 6 (20:19):
Right? I mean, there's a whole group of people in
this in this country and around the world who think
having a few worms is actually beneficial for your immune system.
And there's a lot of there's an absence, let's say,
or a dearth of information about how parasites and their
hosts have co evolved, and you know, does this effect
(20:43):
on the immune system that allows the hookworm to live,
how does that affect other parasites and other diseases. And
if you take that component away, what are you going
to do to these other diseases. Some people think that
that's why the West has this large number of autoimmune diseases,
like you know, loopus and MS and all kinds of things,
(21:03):
because they've taken away some of the regulatory we're getting
out into the hygiene hypothesis, but you know, they've taken
away the early exposure to things our old friends, like parasites,
that have trained our immune system to not react to
the little things and to only react to the big
things that are dangerous. And you take that away, and
(21:24):
now you've got an entire arm of your immune system,
which is designed to fight worms, is now looking for
something to do, and it picks on you know, it
starts going after self enagines and things like that. So
these are all questions that we don't really know enough about.
So jumping into deworming and vaccinating the entire world may
(21:44):
lead us to places we don't necessarily want to go.
Speaker 3 (21:47):
We could end up nostalgic for the time when we
had worms.
Speaker 6 (21:50):
They could some of us are.
Speaker 4 (21:54):
All right.
Speaker 1 (21:55):
Well, in a future episode, I think we'll do a
whole hour on the hygiene hypothesis because I find this
topic absolutely fascinating. So wait for that in the future, folks.
And in the meantime, let's take a break, and when
we get back, we'll talk about parasite number two, the schistosomes.
(22:30):
All right, and we're back, and now we are talking.
Speaker 2 (22:32):
About the schistosomes.
Speaker 1 (22:34):
They cause a disease called schistosomiasis, and they're quite nasty parasites.
Speaker 2 (22:38):
And Daniel's laughing at me. Why are you laughing?
Speaker 3 (22:41):
I'm laughing because we just went from the ones you
get if you eat poop to ones called shisto which
you know has some sort of resonance with other words
we shouldn't say on the podcast. So tell me, is
this another poop related parasite?
Speaker 2 (22:55):
John?
Speaker 6 (22:56):
Indirectly? Indirectly, it's life cycle is a little bit different
for a couple of reasons. The adults live in the
bloodstream and the eggs come out in the feces. But
let's just start with the feces. And the eggs come out,
they have to get into water, and when they get
into water, they hatch and they get a small larval
(23:18):
stage that now is on the hunt for a snail.
And in the case of justtosomes, the snail is very particular.
It has to be a particular species. They find it,
they penetrate into it, and then they do several generations
of asexual reproduction. And what this does is it builds
up the number of the next stage, which is called
(23:40):
a circarrea, and this is the stage it's going to
infect people. So in order to get schistosome, you have
to have contact with water that has had both feces
and the right species of snail. And if you do
Thisstosomali swim and it will penetrate into your skin and
then it will undergo a migration that goes up much
hits all the highlights in the body. It goes to
(24:02):
the liver, it goes to the lungs, and eventually they
come back to the liver and they pair up as
a male and a female and they move up into
the vessels. And depending on a species, it's either the
vessels of the large intestine, small intestine, or the bladder,
and here the male and the female live in what's
(24:23):
called incopulo forever. The male has a body that's split,
hence the name shisto soma split body, and the female
nestles in there and is mating essentially all the time
with the male, and then they release their eggs into
the bloodstream that then undergo a remarkable journey to get
(24:45):
out of the bloodstream.
Speaker 3 (24:46):
This is ridiculous, I mean, it just seems so implausible,
like step after step after step, and then you got
a snail and it's got to do this and you've
got to go swimming. But my specific question is when
you're swimming and the thing crawls through your skin, how
big is this thing? Is this something you notice or
just like are you in twimming? You have no idea
and now it's inside you?
Speaker 6 (25:06):
Yeah, I don't think you notice it. It's pretty tiny.
Speaker 3 (25:09):
And why do they have to be snailo sexuals, Like,
why do they have to do this thing inside the snail?
Why can't they just do it themselves in the water.
Speaker 6 (25:16):
Well, they first of all will need something to feed on,
where they basically will feed on the snail. Then it
absorbs nutrients from the snail and makes all these new
stages the circarria. The purpose of this is that this
allows them to go from a single mirror citium it's
called that infects the snail into thousands of these circarria
(25:38):
that's going to affect the next toast. And what that
does is it increases the odds of infection by putting
more of these infective stages into the environment. If the
mirror citium just tried to infect the host directly, even
if it developed to the effective stage, the odds of
that happening are pretty low. But the more of these
infective stages you can put into the environment, the high
(26:00):
or the odds are that one or more of them
is going to get into the next toast. And in
the case it's just the sums, you need a male
and a female sir carrier to get in.
Speaker 3 (26:08):
So the snail is like a schisto amplifier or something.
Speaker 6 (26:11):
It's just like exactly, that's exactly what it is.
Speaker 2 (26:13):
Crazy, it's kind of ingenious.
Speaker 4 (26:15):
You know.
Speaker 1 (26:15):
The snail goes around grazing and collecting more food, and
that energy goes towards making more parasites, and so the
parasites are getting like a buffet for doing nothing.
Speaker 2 (26:23):
Once they establish in the snail.
Speaker 6 (26:26):
This is a pretty gruesome parasite in the host, though.
It causes a lot of problems. And it's not because
of the worm, which is relatively tiny and living in
the blood vessels. It's because of the eggs. So this
mechanism that gets the eggs out is really elegant, but
it's very inefficient, so a vast majority of the eggs
don't get out. They end up in the liver and
(26:47):
they form what are called granulomas when the host reacts
to them, and that's where the damage comes from. Are
these granulomas in the liver and other organs as well?
Speaker 3 (26:56):
Well, that was gonna be my question. The hookworm we
were talking about was most in the gut, and there's
some sort of negotiation. You can hang out there because
it's difficult for us to attack you anyway. But these
guys are all over I hear them being in the blood,
they're in the bladder, they're in the liver. So the
immune sism does respond to them. It forms these glass ulummas, granulomas, granulomas, yes,
(27:17):
thank you, yes, Why doesn't it get rid of them?
Speaker 6 (27:20):
Well, the worms in the blood are pretty much untouched
and they have a bunch of immunovasive mechanisms as well.
It sort of similar to the whole worm, but different mechanisms.
The eggs, on the other hand, they alter the immune
system to make what's called a THH two response, which
is when you get a whole bunch of cells will
come in and they'll surround the egg and form this granuloma,
(27:41):
and then it will slowly move it through the tissue
right and eventually they'll come to the bladder wall or
the intestinal wall and they will just basically dump the
egg out, but they often get stuck, so you'll have
these eggs stuck in the bladder wall. All this depends
on the species where is is it in a bladder,
is it in a large or small intestine, But in
(28:03):
any case, you'll get them stuck in those in the
wall of those organs, as well as in the liver,
and then they're constantly releasing anigens that are pulling more
cells in, and these gran omans can get very big
and then start impacting the function of the tissue that
they're in, and you get fibrosis in the liver and
(28:24):
just the surmises can be really nasty disease. It's probably
the most pathogenic of the worms that in fact humans.
Speaker 1 (28:31):
I thought I heard, and remind me if I'm wrong.
I thought there were some areas where the kind of
schistosome that they have is near the bladder, and the
granulomas build up in the bladder, and every once in
a while, like the males will get it so much
that they will start to bleed along with the you know,
with the females of a certain age, and it's almost
like a rite of passage. So many kids get this.
(28:52):
That blood in your urine is just something you expect
for both sexes. Is that Wow? Is that still the case?
Speaker 2 (28:58):
John?
Speaker 6 (28:58):
Yeah, that's the called just the soma heematobium. It's found
exclusively in Africa. And yeah, it will cause it because
these granny loanans move it to the bladder wall. They
cause it to erode and then you will get blood
in the urine. And there's some evidence that I think
they're pretty convinced now that schistosome as well, some of
(29:20):
these other trematodes can cause cancer as well, including bladder
cancer in that case, because of over years and years
of this erosion occurring and the body responding to it
in the eggs releasing these these antigens that it could
result in cancer.
Speaker 3 (29:37):
Well, that sounds like something we should vaccinate against.
Speaker 6 (29:40):
Yes, I would be in favor of that. I think
I think schistosimiasis is one that we can do without.
It's going to be just as hard to go to
make a vaccine. Again, they have some promising candidates, but
we're still a long way away from the actually using
a vaccine. Again, it's a sanitar thing, right in this case,
(30:02):
if you keep your feces away from water, you're not
going to have a problem. Snail control is possible, but
it's difficult, it's expensive. We see some promise with introducing
predators that actually eat the snails. In some areas in
West Africa they've done this and they've seen you know,
you can combine it with chemotherapy and snail control and
(30:25):
you could see a huge decrease in the prevalence and
just to some infections. But step one you said was
keep your feces away from water. But in the previous
segment we were talking about toilets, and that's like the
basic operating principles like turn your poop into sewage, right, right,
how do you do both at once? Well? As long
as you don't have snails in your sewage, you're gonna
(30:45):
be okay. And plus people generally, I mean, if you're
talking about Western sewage systems, you've kept away from the
sewage the entire time. The water, you know, goes through
a sewage treatment plant and gets treated and converted back
into usable water. So you know you're still breaking the
transmission in that case, right, Remember you need water and snails.
Speaker 1 (31:08):
This sounds like a particularly tricky problem because you've got
like the adults that hide from the immune system, and
then you've got the eggs that as they pass through
the body definitely do not seem to be good at
hiding from the immune system, and the immune system responds
and that's what causes the problem for people. So it
seems to me that if you made a vaccine, you'd
need to be careful to not make the problem with
(31:29):
the eggs worse because now your immune system is over responding.
Speaker 6 (31:33):
Yeah, I think you would have to stop it before
they got to the egg producing adults, and you would
have to make your vaccine against the stages that are
penetrating into the host.
Speaker 2 (31:43):
Do we understand how the adults are hiding from the
immune system.
Speaker 6 (31:46):
Right, so they do several things. First of all, they
will actually take host molecules and bind them to their
cuticle so that then the host immune system doesn't see
it as foreign. I mean, yes, we can.
Speaker 1 (32:01):
We just sit on that for a second. That's like
taking like you know, taking the skin off of a
human and putting it on themselves or something like that.
That's amazing. They hide with our own material to.
Speaker 3 (32:11):
Wolf in sheep's clothing.
Speaker 6 (32:12):
Yeah, but that's not all go on. They also make
what's molecular mimicry. They will make molecules that are very
similar to molecules in the host, like a hormone for instance.
They will then get processed by the host enzymes and
act as a suppressor of the immune response.
Speaker 3 (32:30):
Do we know how all of this elaborate machinery evolved?
We have any idea of the history here? Is that, like,
do you need all these pieces together to survive? Can
you like do it one step at a time and
refine it? How does it work? How does it evolve incrementally?
And ones that add more and more mechanisms probably are
better at survival. So it might have one of these
things initially and at lets more of them survive, and
(32:53):
then you will get the mutations for the other things
that occur, and they get just pile up to have
a whole suite of thing that is really efficient at
inhimbiting the immune system. So each of these tricks is helpful.
None of them are absolutely necessary, and so as you evolve,
you developed more and more tricks to sort of optimize
survival in the host.
Speaker 6 (33:12):
Right.
Speaker 3 (33:13):
Wow, impressive.
Speaker 1 (33:14):
I know this episode isn't about the history of Kelly,
but when I read about this in Curl Zimmer's book
Parasite Rex, this was like literally a turning point in
my life. I had gone from being like parasites, Oh,
they're just kind of gross, to being like, holy cow,
it's like amazing the way they've managed to hide inside
of our bodies, and like it totally changed the way
I looked at parasites and like literally altered the course
(33:36):
of my life. So anyway it infected your mind, it
infected my mind, and now we got to share it
with everybody, and so I'm very excited.
Speaker 3 (33:44):
Wait, no, this is the like intellectual version of the
snail amplification that goes into Kelly's brain just states for
a while, she gets a podcast and then she spreads
it to the whole community through John.
Speaker 1 (33:55):
John is my snail and I am the parasite and
this is gone. This has gone too okay, So let's well,
I can I play on the word shisto, like take
a break?
Speaker 2 (34:06):
Can we split for a second? Nope? Not clever enough.
All right, Daniel, do you have something in.
Speaker 3 (34:13):
Case anybody needs to take a break and have a shift.
Go ahead and we'll be back in a minute to
talk about another parasite poop related jokes.
Speaker 1 (34:22):
Love it, and we're back, and we are going to
(34:44):
start with John's snail related joke that he queued up
during the break for us.
Speaker 2 (34:49):
Oh wait, did you just say that this might not
be appropriate for the show?
Speaker 6 (34:52):
This one's fine. Okay, this one's fine. So I tell
this in my class. So this guy goes to a
Halloween park a costume party and he's got this girl
draped over his shoulders and he goes in and the
host says, hey, how you doing great, and everything says
are you a costume? He goes, yeah, this is my costume.
(35:13):
Well what's with the girl? And I said, well that's Michelle,
Oh my Shelle.
Speaker 2 (35:20):
He's a snail.
Speaker 6 (35:22):
I think I left out the snail part.
Speaker 2 (35:28):
We got there though as a team, as a team, so.
Speaker 6 (35:33):
Yeah, sorry, I blew the d.
Speaker 1 (35:36):
So malaria has some tricky ways of evading the immune system.
But we're going to start with the malarial life cycle
and get to the immune system stuff in a second.
And I've always found the malarial life cycle to be
super confusing. It has a bunch of stages. All the
stages have similar and kind of heart to remember names.
So I'm going to give a super simplified version of
(35:57):
the life cycle that I think will be sufficient for
the discussion we're about to have. All right, So, when
a mosquito bites a person who's already infected by malaria,
the parasite goes to the mosquito's gut and it starts
to replicate. So after that it moves to the mosquito's
salivary glands. And that's right, mosquitoes have salivary glands. I
(36:17):
don't know why that's surprising to me, but anyway, when
a mosquito bites a person, the parasites are injected by
the mosquito into the human body. The stage of the
parasite that gets released into a person is called a sporozoite.
This is the only stage we're going to name, so
just remember the sporozoite is the early stage in humans.
(36:38):
From there, the parasite moves onto the liver and does
some replicating. After that, it moves on to our red
blood cells. When a parasite gets into the red blood cell,
it's able to sneak proteins through the surface of the
red blood cell, and those proteins stick onto the surface
of the red blood cell. This helps the parasite hide
(36:58):
from the immune system. And I'm sure John's going to
tell us more about this later, all right, So, the
parasite is living in the red blood cell and it's
eating the hemoglobin.
Speaker 2 (37:07):
In the cell.
Speaker 1 (37:08):
And as you might remember from our past conversation about
synthetic blood, hemoglobin is the protein in your red blood
cell that helps your cells carry oxygen to different parts
of the body. So the parasite is hiding in the
red blood cell and shower down on the hemoglobin. It's
replicating while it's in the red blood cell, And every
like twenty four to forty eight hours, the red blood
(37:30):
cell will burst open and these newly released stages will
go off to search for new red blood cells to
infect so that like red blood cell cycle will start
again over time. A lot of the red blood cells
get infected this way, so you're regularly losing your red
blood cells, which can result in anemia. And your body
gets poisoned when these red blood cells burst open, and
(37:53):
all of the stuff that used to be in the
red blood cells is now like in circulation, and that's
not good. Plus when the red blood cells burst, there's
suddenly loads of new parasites in the circulation and the
immune system goes nuts. You get chills, you get fevers,
et cetera. And the parasite is bad for a lot
of other reasons, some of which I'm sure John is
(38:13):
going to tell us about in a few moments here.
And all of this on note is particularly dangerous for
children or for adults who have never been exposed to
malaria before, like travelers for example.
Speaker 3 (38:23):
And does it use the mosquito just as a way
to get from one body to another or is this
something that happens inside the mosquito like snail amplification.
Speaker 6 (38:31):
Oh yeah, very important part of life cycle happens in
the snail. So there is an amplification in number. Plus
there's also sex or recombination occurring in the mosquito.
Speaker 3 (38:40):
So we can definitely blame the mosquito for part of this.
Speaker 6 (38:43):
Absolutely absolutely good. And you know it, blame the female
mosquitoes because they're the only ones that take a blood male.
Speaker 2 (38:51):
I don't like where this is going.
Speaker 3 (38:55):
So I'm broadly into mosquito female male. I don't care.
I'm not sexist about it.
Speaker 6 (38:59):
You know, it doesn't work without the male, So they're
partially involved, but they're not the ones that are lighting you.
Speaker 3 (39:04):
Yeah, exactly blame them all.
Speaker 1 (39:06):
I'm broadly antidipterine, so dipterines are flies and mosquitoes.
Speaker 2 (39:11):
I'm not a big fan of any of them.
Speaker 1 (39:12):
But anyway, so inside the body of us, we get
these cycles where they live in our red blood cells.
They replicate and then they burst out of our red
blood cells, and then they go back into red blood cells.
So it seems like when they're in red blood cells,
I can imagine it would be harder for our immune
system to find them because they're like hiding in our cells.
Speaker 6 (39:31):
They have evolved ways to transport things across their membrane,
across the vacual membrane to be displayed on the red
cell membrane, and one of the things that they display
is a molecule called, in the case of plasmonium fell siperum,
which is the most dangerous one erythrocytic membrane protein one,
(39:53):
or as I call it, PfEMP one, and p FMP
one then is expressed on the surface of the cell,
so there is an immune reaction that develops against this
PFMP one molecular. And the PFMP is interesting because it
is able to bind to receptors in the blood vessels,
(40:16):
the veins of the host, and it basically takes those
out of circulation, right, so they're bound to the inner
vessels right of your larger veins in everything, and they
just sit there so they're not being circulated through the spleen,
which would recognize the red cells as being deformed and
would take them out of circulation. So that's one way
(40:38):
they avoid the physical destruction associated with the spleen, and
they'll sit there and they'll do their you know, their
replication bound to these vessels. And that's also a major
cause of the pathology because when they bind to the
small vessels like in the brain or in the placenta,
in the kidney. This is where you get this micro
(40:58):
occlusion of the the capitilarias, and you get decreased oxygenation,
and then you get the metabolic acidosis. And these are
the kind of things that cause the big problems with malarium.
Speaker 1 (41:10):
Not one hundred percent sure I understand. Let me see
if I can explain it back and if if I'm right. So,
I think what you're saying is that the red blood cells,
they end up with the stuff that sticks out of
the cell. It connects them to like the veins or
arteries so that they don't go to the spleen, whose
job is to remove infected or disfigured cells and get
(41:30):
rid of them. So they essentially keep themselves from going
to the police station by hanging on in one spot.
And if that happens, like in your brain or in
a placenta, it causes clogs that are bad.
Speaker 6 (41:42):
Right, and it seems to be particular bad, like it's
one of the major causes of the cerebral malarium, which
is the big killer.
Speaker 3 (41:49):
So then what are the possibilities here for a vaccine?
Since this sounds pretty bad and we all hate mosquitoes
and nobody wants the stuff in your brain.
Speaker 6 (41:58):
Yeah, that's a good question. So I think most of
the success for the vaccines has been against the sporsoa.
If you have an immune response to sporizoi when it
gets into the skin, that can stop the infection right there.
And I there are some promising vaccines, some that have
actually been used are in use that maybe give you
(42:21):
sixty percent protection or so, I'll ticket. Yeah, it's you know,
it's kind of what a flu vaccine does too, you know. Yeah,
So there are some promising ones in there, maybe more
in the future because it put a lot of a
lot of effort into this vaccine development from malaria, and
definitely would be a good thing. You just need to
(42:41):
prevent people from dying because as they live there, they're
going to build up this natural immunity that occurs over
time and then it won't be an issue anymore. But
it'd be important for kids and also for travelers, like
if you're going into Africa and you've never had malaria,
then that would be very useful to have a vaccine,
or for the military or something like that. So there's
(43:04):
definitely a need for vaccine here. We're getting closer. I
think there are, Like I said, several have been deployed,
so it's promising, I think, more so, I think than
with the worms at this point.
Speaker 1 (43:16):
Oh yeah, we never said what kind of an organism
malaria is. So the first example we talked about was
a nematode, the second one was a trematode, and malaria
is a protozoan protist.
Speaker 3 (43:25):
Yeah.
Speaker 1 (43:26):
Why is it so much harder to make vaccines for
parasites than for bacteria and viruses? And so my first
question is that actually true? I feel like the answer
is yes. And then is there a big picture reason
for why?
Speaker 5 (43:41):
Uh?
Speaker 6 (43:41):
Well, okay, it's generally it's true. But think about HIV.
I haven't had a vaccine against that yet, right, Yeah,
so it's not always easy to do, but I think
it's because the immune system seems to be much better
able to handle small things. Right. You can make an
antibody response, it'll bind to the bacterium or to the
(44:04):
viral particle, and then you can get your complement system
involved to destroy it. But you know the pathogens have
ways to get around the immune system as well, right,
So your bacteria and your viruses could subvert the immune
system too.
Speaker 3 (44:19):
Wait, I didn't understand that first thing you said, and
it reminds me of a big puzzle in physics, you know,
you said, essentially, the immune system is better at attacking
small things, but big things are all made out of
small things. So why can't you just attack all the
small things that a big thing is made out of.
It's like the puzzle of like every classical object is
made of quantum particles. Why can't we understand it? I'm
(44:39):
not suggesting this quantum mechanical magic happening here, but what
keeps the immune system from attacking each individual cell inside
one of these bigger objects.
Speaker 6 (44:49):
In case of the worms, they all have a cuticle
that protects the inner cells from damage. Right In the
case of like the hookworms, the immune system's able to
go after the small part of the worm, which is
the gut right that is exposed. It also takes a
lot of cells to kill, you know, a bigger worm.
It's just harder to do, I think. And like I said,
(45:12):
a lot of the mechanisms get where the worms involve
things like, well, we're just gonna flush them out, right,
We're not going to try to kill them. We're just
to try to flush them out. Whereas we have cells
that will actually ingest viruses and opsonize viruses at least
and bacteria, right, they recognize the antibody and they bind
to it and then ingest it and destroy it. Right.
(45:35):
So it's a lot easier to do that than it
is to try to kill a big worm that's got
this protective armor around it and is living in the gut,
for instance.
Speaker 1 (45:45):
Yeah, So as a biologist, one of the things I
think is super interesting about this conversation is not just
how do the parasites evaide the immune system, but it's
also just that they have such complicated life cycles. There's
so many different places where you could choose to try
to protect against parasites. So you know, for mosquitos, you
can pay for bed nets because the mosquitos are most
active at night, and maybe you just keep the mosquitos
from biting, and maybe that's even you know, better than
(46:07):
some of the medicines. Just you know, if you don't
encounter with them in the first place, that's hopeful. But
you know, all of these systems are evolving, so if you,
for example, go after the mosquitoes with pesticides, they evolve
resistance and anyway, it's a very complicated problem, and all
of those complications is sort of what got me interested
in parasitology in the first place. Anyway, back to Kelly's
(46:27):
origin story, but this has been a fascinating, fascinating chat.
Thanks so much, John for coming on the show to
tell us all about the parasites you study and the
parasites you don't study that I put you on the
spot to talk about.
Speaker 2 (46:39):
Anyway.
Speaker 6 (46:39):
Ah, well, you know, all these years of teaching, I've
learned something.
Speaker 2 (46:43):
So that's excellent.
Speaker 3 (46:45):
You've learned how to nail a snail joke or snail
it I guess.
Speaker 2 (46:48):
Yeah, well, John, let's save those for another episode. We
don't want to overwhelm the audience.
Speaker 6 (46:52):
Thank you was fun.
Speaker 1 (47:01):
Daniel and Kelly's Extraordinary Universe is produced by iHeartRadio.
Speaker 2 (47:05):
We would love to hear from you, We really would.
Speaker 3 (47:08):
We want to know what questions you have about this
Extraordinary Universe.
Speaker 1 (47:12):
We want to know your thoughts on recent shows, suggestions
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Speaker 2 (47:16):
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Speaker 3 (47:19):
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Speaker 1 (47:25):
Dot org, or you can find us on social media.
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all of those platforms.
Speaker 2 (47:32):
You can find us at D and K Universe.
Speaker 3 (47:35):
Don't be shy, write to us,
Hosts And Creators
Daniel Whiteson
Kelly Weinersmith
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