How do we control mosquito populations?

Daniel, Kelly, and Katrine chat about how mosquitos find us, and what we can do to protect ourselves from the diseases they transmit.

See omnystudio.com/listener for privacy information.

Episode Transcript

Speaker 1 (00:09):
If you live in most places in the United States,
mosquitoes are a massive annoyance.

Speaker 2 (00:14):
They've ruined a good hike, They've ruined a.

Speaker 1 (00:16):
Beautiful night camping under the stars, They've ruined delicious picnics,
and they've ruin breathtaking sunsets.

Speaker 2 (00:23):
They are the worst.

Speaker 1 (00:25):
But if you live in an area where mosquitos carry
deadly diseases like malaria, dengey, yellow fever, or zeka, they're
also potentially deadly. According to the Centers for Disease Control,
malaria alone killed five hundred and ninety seven thousand people
in twenty twenty three.

Speaker 2 (00:43):
So what are our options.

Speaker 1 (00:45):
Mosquitoes have developed resistance to our insecticides, and insecticides in
general aren't great for ecosystems because they often kill a
bunch of other stuff as well. But what if we
could use new genetic tools to drive some mosquito species
to extend or make those mosquitoes resistant to diseases so
they can no longer transmit those diseases to us. Today,

(01:07):
we're going to respond to some listener questions about mosquitoes.
We'll chat about how mosquitoes find us, how genetic engineering
could be used to combat mosquitoes and how you undertake
the tricky task of estimating how mosquito population sizes are
changing over time. Welcome to Daniel and Kelly's Mosquito Infested Universe.

Speaker 3 (01:41):
Hi.

Speaker 4 (01:41):
I'm Daniel. I'm a particle physicist, and I have a
top five list of animals i'd like to see genocided
off the planet.

Speaker 1 (01:48):
Oh Man starting an episode with the word genocide.

Speaker 2 (01:52):
Not loving that. Hi, I'm Kelly Waiter Smith.

Speaker 1 (01:54):
I study parasites and space, and I was going to
say I'm buzzing with enthusiasm for this topic, but Daniel
started with genocides, So my enthusiasm has been shot through.

Speaker 4 (02:04):
Did that sting you a little bit? Scratching the wrong
itch over there?

Speaker 2 (02:09):
I can't, I can't, I can't. All right, what are
the five insects that you like the least, Daniel? We
could put it that way too, you know.

Speaker 4 (02:16):
Yeah, number five mosquitoes, Number four mosquitoes, number three mosquitoes,
number two mosquitoes, and number one coming in at the
top of the list is mosquito.

Speaker 2 (02:27):
Yes, predictable list. Yeah. I'm not a mosquito fan really either.

Speaker 4 (02:31):
Absolutely, And so I'm fascinated today that we're going to
be talking about the science of mosquitoes and learning about
everything that biologists can do to improve our quality of life.

Speaker 1 (02:42):
Yeah, I'm a biologists and engineers. A variety of folks
for many decades have been trying to do battle with mosquitoes,
and you know, in the last few decades, we now
have some genetic tools that we can use that might give.

Speaker 2 (02:54):
Us the leg up.

Speaker 4 (02:55):
And your focus, of course, is on eradicating disease, caring
mosquitoes because that kills people and all that stuff and
that along the way. Along the way, I would to
eradicate Daniel's suffering from mosquito bites, because that's what it's
really all about. In the end, It's about me and
my itches.

Speaker 1 (03:13):
Right, No, i'd say no, Yeah, I don't actually know that.
I would advocate for eliminating mosquitoes that are annoying but
don't transmit disease, although I guess in California do do
your mosquitoes transmit Wes Nile?

Speaker 4 (03:27):
I don't know. I have heard of cases, but I'm
not sure. But really, for me, it's just all about
the itches. I'm not a great sleeper and I'm very
responsive to mosquito bites, which means if I get too
many mosquito bites, then I'm up all nights scratching them.
So it's really a bummer. I would happily actually donate
my blood to the mosquitoes if we could make a deal,

(03:48):
like if I could just put out a little like
saucer of blood every night and be like, here's your
blood meal, leave me alone. I would make that deal
no trouble at all. So if the mosquito's lawyer wants
to reach out and to go she ates some sort
of settlement like that, I am open for business.

Speaker 1 (04:03):
All yes, So you give your fecal sample to your
wife and your blood sample to the mosquitoes.

Speaker 2 (04:08):
Everybody needs a part of Daniel.

Speaker 4 (04:10):
Come take a sample exactly. Matt will take an audio sample.
Here we go.

Speaker 2 (04:15):
All right.

Speaker 1 (04:16):
Well, then you will be very excited to hear today
that there are a variety of cutting edge techniques for
in some cases straight up eradicating mosquitos and in other
cases just trying to make it so that they can't
carry disease anymore.

Speaker 4 (04:29):
I like the sound a straight up eradication.

Speaker 1 (04:31):
Well, I reached out to our extraordinaries and asked them
what they think the most promising techniques for eradicating disease
carrying mosquitoes are and let's go ahead and hear what
they had to say, treat.

Speaker 5 (04:44):
The water where they breed, kill the larvae.

Speaker 6 (04:47):
Someone far smarter than I am must have a technique
to get them to stop breeding. I like what they've
done in the past with releasing genetically modified ones so
that it reduces the population and potentially targets those disease
carrying ones, because the generic sprays kill all sorts of
insects and they are beneficial for the ecosystem.

Speaker 7 (05:08):
Does the Geneva convention apply to mosquitoes? That does, I'd
have to say some bioengineered aerosol that wouldn't harm other
living creatures.

Speaker 8 (05:19):
The one technique I know right now is that some
larvacide is spread during mosquito season. I'm not so sure
that is the most promising technique, since that's been done
for a long time and we still get a lot
of mosquitos.

Speaker 9 (05:32):
It appears the sterile insect technique is the most promising method,
though I'm not sure if that will eradicate or just
vastly reduce population numbers, and is nowhere near as fun
as an electrified racket swater.

Speaker 10 (05:43):
We would genetically engineer some very attractive but sterile mosquitos,
dispatch them two the affected areas. Let dat run its course,
and over time the population will fade away.

Speaker 11 (05:57):
Do the thing they're doing with the screw worms and
doing like sterilized ones. And I really do hope that
you kill all mosquitos, because they love me. I am
foreign food here in the UK, even though I'm havy English,
So kill them all.

Speaker 1 (06:09):
I think a lot of people are on the same
page with you, Daniel eradicating mosquitos.

Speaker 2 (06:14):
They are on board.

Speaker 4 (06:15):
It sounds like somebody else spoke to the mosquito's lawyer
because they're referencing the Geneva Convention and like getting illegal
about it. Oh my gosh.

Speaker 1 (06:22):
I know, I know these things are intense well. And
you know, in the United States, if you do want
to release some method for eradicating mosquitos, you do need
to go through like the USDA, the EPA. We'll talk
about this a little bit more later. There's some legal
stuff involved.

Speaker 4 (06:36):
I think that probably makes sense. Somebody should think about
whether these are good ideas before we just like let
scientists do things. Willy nilly, I'm for that.

Speaker 1 (06:44):
I'm gonna let you in on a little secret. We've
messed things up a few times in the past.

Speaker 2 (06:49):
Yeah, I know, I know.

Speaker 4 (06:50):
Right now, we can't be trusted to make our own decisions.

Speaker 2 (06:53):
Well, I think some oversight is warranted.

Speaker 4 (06:56):
That's a good way to put it.

Speaker 2 (06:57):
We get a little over enthusiastic.

Speaker 4 (07:00):
Yeah, we knew because the universe is amazing and we
just want to learn stuff and we think we have
it figured out, and so yeah, we just want to
press the big red button sometimes.

Speaker 1 (07:09):
Well, today we're going to be learning specifically about answers
to questions that we got from listeners. And we called
in a little bit of backup because any biology topic
is improved by having Katrina Whiteson join the podcast. So
let's invite Katrina on the show.

Speaker 4 (07:24):
It's my great pleasure to welcome back to the podcast,
our most popular, our most frequent guest, also winner of
the whites In Unable to Say No To a Podcast
Invitation Award, doctor and Professor Katrina Whitson.

Speaker 5 (07:37):
Wow, thank you for the glamorous introduction.

Speaker 1 (07:43):
Thank you for being willing to come back on the
show again. We always love having you.

Speaker 5 (07:47):
Well. Thanks all around, all right.

Speaker 2 (07:52):
Let's dive right in.

Speaker 1 (07:53):
So we have a couple questions from Robert Shackelford, who
is a high school teacher who wanted to know about mosquito.

Speaker 2 (08:00):
Let's dive in.

Speaker 12 (08:01):
Hello, Daniel and Kelly, this is Robert on Samun Island
in Washington State. And I'm curious about mosquitoes. Well, it's
probably more accurate to say they seem to be curious
about me, unfortunately. And where we live there's a pond nearby,
and if you're anywhere near the pond, you will get
bidden right away. Further from the pond, it's not so

(08:21):
bad unless you're stationary, and then they will find you.
And when they find you, they really find you. And
that has me wondering if they are coordinating their attack somehow,
if they are watching each other, or if they are
our little mosquito walkie talkies I don't know, or they're
just acting individually on the same clues to find the victim.

(08:44):
And then similarly, I would love to know how many
mosquitoes I'm up against, right, it's important.

Speaker 4 (08:49):
To know your enemy.

Speaker 12 (08:51):
And how would you ever estimate a mosquito population? I
know there's some techniques for estimating wildlife, say birds, by
tagging them and then recapturing them later, But I can
imagine doing that with mosquitos. Sorry, Kelly, I can't imagine
even the best biologist having the ability to take little

(09:13):
tag number forty two and glue it to a mosquito's
leg and be able to capture it later. So I'm curious.
Is there a way Is that number even that knowable?
Is there a way to make a good estimate of
mosquito population? Really curious? Thank you so much for taking
on my question. Look forward to hearing from you soon.

Speaker 4 (09:30):
Wonderful question. I love hearing from high school teachers, and
thank you to all the teachers out there working on
the front lines of education to make society a better
place than everybody smarter.

Speaker 2 (09:40):
You all are heroes.

Speaker 1 (09:41):
Thank you so much, And I am thrilled to get
to educate folks about mosquitos, which I have to admit
I hate.

Speaker 4 (09:49):
It's not hard to admit you hate mosquitos. It's joyful.

Speaker 1 (09:52):
I guess don't know how many collegist I'm supposed to
like almost everything, but I have to admit dipterines, which
are like mosquitos and flies, I'm not a big fan
of well.

Speaker 4 (10:00):
You know, I used to say all the time that
mosquitos are the one thing you could like erase from
the planet and not have any negative effects. But then
some listeners sent me an article about how mosquitos helped
chocolate help cocoa beans pollinate each other, and I was like, uh, oh,
I'm not sure if I had to give up mosquitos
if I would also give up chocolate.

Speaker 1 (10:19):
It sounds a little bit tough at first, but when
you consider that mosquitoes transmit malaria, which kills almost six
hundred thousand people a year, I would give up chocolate
for that.

Speaker 4 (10:30):
I mean, I hear you, But we're talking about chocolate here, Kelly.

Speaker 2 (10:33):
We're talking about children, Daniel.

Speaker 1 (10:35):
But I have to remember that you are willing to
give up all of humanity to get one answer from
an alien.

Speaker 2 (10:40):
We had that discussion the.

Speaker 4 (10:41):
Other that juicy answer. But yes, yes, I am, that's true,
all right.

Speaker 1 (10:45):
I'll note that his wife was also shaking her head
in disbelief.

Speaker 4 (10:50):
I don't like this new number of podcast hosts where
I can get outvoted.

Speaker 2 (10:55):
We'll go back to mosquitoes.

Speaker 1 (10:58):
Mosquitos are often enlisted as the deadliest animals on the
planet Wow. And one of the problems caused by mosquitos
is that they transmit malaria. There are over five hundred
Anoplies mosquito species, so this is like a genus of mosquito,
and about sixty of those species are able to transmit malaria.
Mosquitos also transmit Dangae west Niles zega lymphatic philoriasis, and

(11:22):
so mosquitoes are estimated to kill indirectly up to a
million people a year. But I've never felt like this
is super fair to pin on mosquitos, even though I
hate mosquitoes, because it's like, isn't it the individual responsibility
of all of those diseases. It's not necessarily the mosquitoes.
But I get I get it.

Speaker 13 (11:43):
They were unwilling partners. Nobody like, they didn't say, yeah,
bring on that plasmodium. They were just like flying a rods.
But they do drink blood. I mean, I don't know.

Speaker 4 (11:53):
I mean, Kelly, if I came over to your house
and drank your blood and give you some weird disease,
I think you'd blame me for anything you got, wouldn't you?

Speaker 2 (11:59):
You wouldn't be invited again. That's true.

Speaker 1 (12:03):
And you would be breaking a lot of social wars
to do that, and laws and laws and laws. Right,
But does anybody want to guess? This surprised me a little,
But it shouldn't have. On the list of species that
kill humans, mosquitoes are at the top. What species is second?
The next most killing e species kills about half as

(12:24):
many humans each year. But what would you guess? That
species is?

Speaker 4 (12:28):
Raccoons? Those are ferocious? Have you heard that story about raccoons?
Don't have a pet raccoon? FYI, and don't google what
happens if you lead a raccoon in a room with
your baby.

Speaker 5 (12:40):
Oh, definitely don't google that.

Speaker 13 (12:41):
But I would guess it's microbial. I mean, it has
to be microbial. Microbes rule the world. So now I've
got to like pick from microbes, and I really should
know this.

Speaker 5 (12:51):
I mean, it could be tuberculosis.

Speaker 2 (12:53):
Bacteria that is still a problem which.

Speaker 5 (12:56):
Infects a third of humans. Or it could be real raccoons,
my gosh.

Speaker 13 (13:01):
Some kind of parasite, some kind of eukaryotic parasite.

Speaker 5 (13:04):
Is that what it is?

Speaker 2 (13:06):
It's humans?

Speaker 5 (13:07):
Oh my god?

Speaker 2 (13:09):
Oh that's so good.

Speaker 4 (13:10):
I think Katrina gets points because we are eukaryotic parasites, right,
So there you go.

Speaker 1 (13:15):
There you go point So Katrina essentially got it right.
One point for Katrina, zero points for raccoons.

Speaker 13 (13:21):
From Daniel, I'm not gonna I can't take any points.
I was going down a totally wrong road there, and
I really thought it was my crogial, you know.

Speaker 1 (13:29):
I also felt like you could just blame bacteria across
the board. But anyway, the list right now has humans.
I guess we kill about half a million of each
other every year, which is depressing.

Speaker 2 (13:39):
Wow.

Speaker 1 (13:40):
But all right, let's talk about the mosquito life cycle
real quick, because understanding the life cycle is necessary if
you're going to understand how you can try to eradicate
mosquitos by breaking part of the life cycle.

Speaker 2 (13:50):
So first, let's note.

Speaker 1 (13:51):
There's lots of mosquito species, like over three thousand, five
hundred mosquito species. They don't all bite humans. The ones
that you bite humans are females. The males actually don't
take blood meals, and the females apparently need the blood
to make eggs. Okay, so if you get bit it's
a female, don't blame the female. They're just doing what

(14:12):
evolution made them. Do but anyway, so they do the
blood meal. So they get a blood meal, they lay
their eggs in a body of water, the eggs hatch
in the water, and then they've got this aquatic stage
where they look like these sort of like frilly little
specks of dirt that kind of move around like crazy
all over the place. Sometimes you might see them in
like a bird feeder in the middle of the summer

(14:33):
or something. And then they have another stage where they
essentially like stay near the surface and they're kind of
getting oxygen from the surface. And then they emerge out
of the aquatic environment as adults and they go off
and you know, mate with each other and go off
in search of blood.

Speaker 4 (14:48):
And all this happens in hours or days.

Speaker 1 (14:50):
Or depends on the species. There's a lot of variability,
but an egg can take something like seven to ten
days to develop into an adult, and then when they're
an adult, I think they've got like a week or
a few weeks. They don't live for very long, so.

Speaker 4 (15:01):
When a mosquito is biting you, it's like one of
a few dozen meals it's gonna have in its lifetime,
or how many blood meals does a mosquito have in
their whole lifetime.

Speaker 1 (15:10):
They must be taking more than one blood meal. But
I think they only mate with a male once in
their life and lay eggs once, and that has to
be the case for a bunch of the techniques that
we talk about later to work.

Speaker 4 (15:23):
Well. I know that in southern California we have two
different kinds of mosquitos. So the ones that come and
give you one really big juicy bite and then move on,
and another tiny version that come in bye you like
four times in a row.

Speaker 2 (15:33):
Oh they're all awful.

Speaker 4 (15:35):
Though, they're all awful.

Speaker 1 (15:36):
Yeah, thumbs down. Well, so then how do they find you?
So Robert wanted to know if they're like communicating with
each other so that they can swarm and get to you,
and I don't think that that's what's happening. I didn't
find any evidence that a mosquito is like altruistic enough
to be like, hey, there's a snack over here, fellas,
or I guess, ladies, Hey, ladies, there's a snack over here,

(15:58):
because it's all females do in the feeding. I think
that the only times they swarm on purpose is when
they're trying to mate, and so usually they're not sharing information.
But the way they find you is a multi step process. First,
they detect the carbon dioxide that we breathe out, and
then they follow the carbon dioxide trail until they get
close to us. When they start getting close enough to us,

(16:19):
they start detecting some odors that we give off. And
these odors can be things like ketones, lactic acids, and Katrina,
I read that a lot of the odors we give
off are related to our microbiome exactly.

Speaker 13 (16:30):
I even had a whole grant once. I didn't get it,
but I wrote a grant with a bunch of people.
It was a military grant, and the goal was to
make soldiers invisible to mosquitoes. And you're going to do
it by changing their skin microbiomes. And you know, some
people are just so juicy to mosquitos and they get
bitten all the time and others don't. And we don't
know why really, but I think it could be related

(16:52):
to the microbiome and the volatiles that the microbes are
emitting that the mosquitoes can detect, and so anyway, it
might be that that's something we can change.

Speaker 5 (17:01):
Like, that's pretty amazing.

Speaker 4 (17:02):
Hold on a second, I just put two and two together.
I live in a house where I'm the one getting
bitten by mosquitoes all the time, and I also live
in a house where somebody knows how to manipulate people's microbiomes.
And I just heard that microbiomes are the number one
influence and who gets bitten by mosquitoes? Hmm, Okay, I'm
gonna have to think about that.

Speaker 13 (17:22):
Okay, This mosquito preference thing has been going on since
way before I learned about microbiomes.

Speaker 4 (17:30):
I see, so you've been guilty for a long time,
got it, got it all right?

Speaker 5 (17:34):
But it could be a life goal.

Speaker 4 (17:35):
But for the individual mosquito, Kelly, this is not, like
you know, they have complicated sensors. I'm imagining they're like
flying through the air and they sort of veer towards
the CO two instead of away from it. It's sort
of like moths being attracted to light. Is that how
it works?

Speaker 2 (17:49):
Yeah?

Speaker 1 (17:49):
I mean I think it might be under selling it
a little bit to say that they don't have complicated sensors.
So like moths, for example, the males who have to
find the females, they have super feathery antenna and nobody
can see.

Speaker 2 (17:59):
But I have hand antennas right now.

Speaker 4 (18:02):
You're looking very mathia, I thank.

Speaker 2 (18:03):
You, thank you.

Speaker 1 (18:04):
And they, you know, have an incredible surface area, and
they're able to detect chemicals that the females put into
the environment and follow that chemical trail to find a female.
And so, you know, like insects, they you know, they
might not look super impressive, but they do have pretty
impressive ways of detecting cues in the environment. Like I
can't detect CO two and use it to find my

(18:25):
dog when she's not coming in the middle of the
night when I call her. So anyway, I'm impressed. But yeah,
it's not super complicated.

Speaker 13 (18:32):
I mean, I think there's a lot of sensors that
we actually don't know what they are. That's something that
I'm so fascinated by that apparently, you know, we have
these sensory receptors that we know about in our nose
and our tongue, like you hear about the sense of taste,
But actually we have those kind of receptors all.

Speaker 5 (18:47):
Over the place.

Speaker 13 (18:48):
They're in our skin, they're in our guts, like babies
have them when they're developing, and so I think those
receptors are binding molecules we don't even know what they
are yet, and I would not be surprised the mosquitoes
have a lot of that going on.

Speaker 4 (19:00):
You're saying we can taste with our hands and stuff
like that, exactly. I see. So when I swat a
mosquito and I feel that like moment of satisfaction, it's like,
literally delicious.

Speaker 5 (19:09):
Let me just back up on that.

Speaker 13 (19:11):
I'm saying, there's receptors that are sensing those molecules and
you're having a response. The response is not lighting up
the taste receptors in your brain, at least.

Speaker 2 (19:20):
Not for me.

Speaker 13 (19:20):
I mean, I don't know about you, but I think
it's like lighting up something that not necessarily that we're
even aware of it in our brain, but it could
be like affecting our physiology.

Speaker 5 (19:32):
You know.

Speaker 1 (19:32):
We had Stephen Munger on the show to talk about
taste and smell, and he was talking about how we
have receptors for things like even in our hearts, and
it's not quite clear why we have them. So if
folks want to learn more about that, they should check
out the Manger episode because we talk about that for
a little bit. It's totally fascinating in my opinion.

Speaker 4 (19:47):
All Right, so, but we were talking about how mosquitoes
find hosts, and you're saying, at first they look for
clouds of CO two, and then as they get closer,
they're looking for skin odorans that give them cues to
where you are, and then what walk us through through
all the way to the bite.

Speaker 1 (20:01):
And then they're looking for heat and humidity. And so
I don't think we know exactly how they decide, like
I'm going to bite their arm as opposed to their leg.
It might be whatever they encounter first, because you want
to get the bite in there and get out. But yeah,
those are the cues that they use. The cues change
depending on how close they are to us. Some people
give off more cues, as Katrina mentioned, that could be
because of their microbiome. There's some evidence that women in

(20:23):
their third trimester are also more attractive to mosquitoes. And
the idea there is that we are breathing more and
more heavily and we give off more CO two, so
we're easier for mosquitos to find. I certainly was breathing heavily.
I remember my mom being like, do you have to
be so loud?

Speaker 2 (20:39):
And I was like I do. I'm breathing for two.

Speaker 8 (20:43):
Uh.

Speaker 1 (20:45):
But yeah, the mosquitoes apparently love that. All right, So
now we know how mosquitoes find us, But now how
do you figure out how many mosquitoes are in an area?
So Robert had this great insight, which is that often
when we are trying to faitigure out how many of
a certain species is in a particular environment, we use
this technique called mark recapture, and it would be really

(21:07):
hard to mark and recapture mosquito. So mark recapture is
a procedure where you essentially go out into an environment
twice to collect animals. The first time you go out,
you collect you know, as many animals as you can
with whatever technique. So, for example, I used to go
sample fish and I would use what's called fight nets.
You essentially put a net that goes one side of

(21:27):
it is in like the middle of a lake. The
other side goes to the shoreline. As the fish swim
along the shoreline, they hit the net that hits the
shoreline and they follow it essentially into a funnel that
they can't get out of. And then you sample that
once a day. Does that make sense mm hm? Okay,
So we trap fish, we take the fish out, we
tag the fish in a way where we will know

(21:48):
if we've seen them before or not, and then we
release them back into the environment. And then a week
or two later, we go out again and we use
another technique to catch as many fish as we can.
In this case, we're using an electro fishing boat where
you stun the fish temporarily, you bring them into a
live well on the boat where it's got a lot
of water circulating so that they can come to and

(22:08):
stay safe. And then you count how many fish you collected,
and you look to see how many of them you're
catching for the second time, so how many of them
showed up in both of your samples, And so then
you're making this assumption that the proportion of animals that
you re caught in your second sample is similar to
the proportion of animals that you caught the first time

(22:32):
in the entire population. So, for example, if I caught
fifty fish in my first sample and marked them all,
and then I went out and I caught one hundred
fish in my second sample, ten of which were already
marked individuals, the way that I would capture this is
I would say fifty times one hundred which is the
number of fish I captured in both of my samples,
and divide by ten, which is the number of individuals

(22:55):
I caught twice, and that would give me an estimate
that there's five hundred fish in the population, all right.

Speaker 4 (23:00):
So the goal here is to get a sense for
how many animals there are total. Of course, you can't
measure all of the animals, and so you measure twice
and then you look at the overlap because like, if
you have one hundred percent overlap between your two measurements,
that means you have a smaller population. If you have
no overlap between your two measurements, then you have a
bigger population because you're getting like different subsets of the

(23:20):
whole population. Is that the way to think.

Speaker 2 (23:22):
About it exactly?

Speaker 13 (23:23):
Yes, Yeah, Like if you mark one hundred fish and
then the next day every single fish is marked, it
suggests there's not really any other fish out there. But
if only ten percent of them are marked, then it
suggests that the population has another ninety percent out.

Speaker 4 (23:36):
There, right, cool, all right, So that's how mark and
recapture studies work to get a sense for like how
many birds are there, or how many cheetahs are there,
But what do you do for mosquitoes. You can't capture
and mark mosquitoes, can you.

Speaker 1 (23:49):
So first of all, thanks team, it was very helpful
to have your input on that. Yeah, so marking and
recapturing mosquitoes would be kind of nuts because they're so
small and so delicate that when you go to catch
them and count them, unfortunate, well maybe not unfortunately, you
usually kill them in the process of counting them. And
so how could you mark a mosquito and release it?
And the answer is they usually don't. So when a

(24:11):
lot of companies are trying, for example, to see how
many mosquitos are out there, what they'll do essentially is
grow males in the lab and they'll throw out all
of the females because you don't want to put any
extra mosquitos out there that will be biting anybody and
taking blood meals. But since the males don't take blood meals,
they hatch them out of eggs in the lab, and
then when they go to emerge to go from the
water to their like air phase, they put a powder

(24:34):
on the surface of the water and it's a fluorescent powder,
so as the mosquitoes emerge through it they get covered
in this fluorescent dust.

Speaker 4 (24:43):
Wow, and you get fabulous mosquitos.

Speaker 2 (24:45):
And you get fabulous mosquitos.

Speaker 1 (24:47):
You can also genetically modify them so that they fluoresc
green based on a protein that they're making themselves. But
one way or another, you're making it so that the
animals that you've released into the wild are detectable in
some way that it didn't require you to like handle them,
which could kill them. So now instead of doing mark
and recapture, you mark in the lab and then when

(25:09):
you go out you can put, for example, a giant
tub with dry ice which releases CO two that attracts
the mosquitoes, and so you find a way to capture them.
And then you look at the proportion of mosquitos that
you recapture that fluores when you look at them, and
you'll say, okay, those are the ones we added to
the environment from the lab. And then you compare that
to the number that didn't fluoresse, which were the wild

(25:31):
animals that you're catching for the first time. And this
process does kill them while you're doing the counting. Does
that make sense?

Speaker 4 (25:37):
Yes, So if you attract and capture a bunch of
mosquitos and they're all your fluorescent ones. It suggests that
your fluorescent ones are dominating the population. And if they
come back and you see almost none of your fluorescent ones,
it means that there are a tiny fraction of the population.
So there's a bunch out there. Exactly what I wonder is, like,
how many other crazy ideas did they come up with
before this crazy idea that they made work. I love

(26:00):
the experimental creativity of science this way, you know.

Speaker 3 (26:04):
Like this is a hilarious idea, But I would really
love to see the whiteboard where they came up with
all sorts of bizarre ideas, including like you know, laser
pointers or who knows what.

Speaker 1 (26:15):
There are some more complicated methods, so for example, you
can like look at how many batches of eggs appear
to have been laid in like some water that you
put out, and then you can try to extrapolate from
the batches of eggs how many females likely came by
to lay those eggs. And it's much more complicated and
there's a lot more guesswork because you have to like

(26:36):
have an estimate for the average number of eggs laid
by a female, for example. But yes, I think it
is a beautiful technique to release fluorescent mosquitoes who can't
bite you and then see how many of them you
get back.

Speaker 4 (26:47):
And this is important because it's like a basic element
of mosquito science. It just like to know what are
the populations and where are they, right, because without basic
knowledge you can't do anything. But I think a lot
of people underest to me, like how much work goes
into just getting some basic information. Like we had our
episode about weather, and like just knowing what is the

(27:08):
temperature everywhere on the Earth would be hugely helpful, and
we can't know that. We don't know that, and so
just like knowing where the mosquitoes are would be massively beneficial,
I imagine.

Speaker 2 (27:18):
Yeah.

Speaker 13 (27:19):
And actually, I don't know if you guys have ever
talked about the citizen science projects that are the reason
we have information about insect population size. But for example,
many of us have noticed that our windshields are not
covered in bugs when we go on a read trip
these days, and that's because the insect populations have declined
so much. And there are citizen science projects where people
will like put nets kind of like the one you

(27:39):
described on the top of their cars and drive around
and just catch all the insects and count them. And
there were people that were doing that in Germany throughout
the twentieth century, and that is a big part of
why we know about the insect decline. Like if they
hadn't done that, we just wouldn't even know.

Speaker 2 (27:54):
Wow, I didn't know about that.

Speaker 4 (27:56):
Yeah, that's amazing. Thank you. Weird German insects capture people.
There are people out there who have enthusiasm for everything.
It's incredible. Yes, well, I need a break from all
of these mosquitoes. I gotta go scratch some itches and
when we come back, we're going to talk more about
how mosquitoes do what they do and how we do
what we do best, which is kill mosquitoes. Wow.

Speaker 12 (28:19):
Thank you for those answers, Daniel and Kelly. What are
relief knowing that mosquitoes aren't able to coordinate their attacks?
Let's hope they do not evolve that ability anytime soon.
Also so amazed that biologists have figured out a way
to estimate mosquito populations. Sorry, Kelly, I will never doubt
biologists again. Let's get whoever came up with that idea

(28:41):
working on quantum gravity soon. Love the show. Thank you,
guys so much. Shout out to my Spring Street students.

Speaker 4 (29:07):
Okay, we're back and I'm very excited for this segment
of the podcast where we get to take scientific revenge
on all the mosquitoes that have caused me to suffer
so much.

Speaker 1 (29:16):
All right, so we have this question from a listener, James,
and let's go ahead and listen to James's question.

Speaker 14 (29:22):
Hi, Daniel and Kelly, I was wondering if you could
cover gene drives. It seems like this technology has been
out for a long time but hasn't been deployed. It
seems like a magical technology for wiping out invasive species.
When you have invasive mosquitoes wiping out the last native
Hawaiian songbirds with av and malaria, you have to ask
why you wouldn't test this out on such isolated islands.

(29:42):
What terrifying scenarios are keeping them from deploying gene drives
in the outside world. Are those scenarios realistic or is
the pesticide industry just bumping off gene drive researchers.

Speaker 1 (29:52):
Thanks, all right, So we have tried lots of things
to kill mosquitoes with varying success.

Speaker 2 (29:58):
One of the things we tried.

Speaker 1 (30:00):
Initially was spraying a bunch of insecticides, and that worked
for a while, but eventually the mosquitoes that happened to
be resistant to the insecticides had a lot more babies.
And now we have populations of insecticide resistant mosquitos.

Speaker 4 (30:14):
How does that even possibly work? I mean, I see
like trucks driving around spraying insecticide, but I'm like, you know,
what fraction of the mosquitoes are they going to be
hitting with that? It seems like, you know, shooting individual
pigeons in the park or something.

Speaker 1 (30:28):
It's like hopeless, right, Yeah, And sometimes they release it airborne.
Other times they'll specifically release insecticides into like waterways where
mosquitoes are breeding, and that's a little bit more targeted.
Either way, you're probably killing a bunch of stuff you
don't intend on killing as well, because a lot of
these things are not specific just for mosquitoes.

Speaker 4 (30:47):
And then aren't people going to end up drinking insecticide?

Speaker 2 (30:49):
Yeah, or breathing it in?

Speaker 1 (30:50):
I remember whenever the insecticide trucks would come through in California,
I would run inside the house or I'd bring my
baby inside of the house. And yeah, so you breathe
it in presumably. I mean they try to make it
so that these chemicals are specifically focusing in on things
mosquitoes and other insects do and not things that happen

(31:10):
inside the human body. I don't know how well we're
often able to do that, Katrina, do you have any
insights there?

Speaker 13 (31:16):
Yeah, oh, exactly, that's the idea, But I think that's
extremely hard. I mean, when it comes to viruses and microbes,
it's easier to come up with targets that are totally
orthogonal to what would happen to a person, But that's
so much harder for insects.

Speaker 5 (31:29):
Like we're a little more closely related, believe it or not.

Speaker 4 (31:31):
To insects than we are to microbes.

Speaker 13 (31:33):
Yeah, yeah, exactly, so it's harder to come up with
distinct targets.

Speaker 5 (31:36):
But yeah, that's definitely the goal.

Speaker 13 (31:38):
But I think there's all kinds of off target impacts.
Like I'm sure you guys remember hearing about the Peregon
falcons and the compromised egg structure that came from all
the insecticides being sprayed in the sixties.

Speaker 1 (31:51):
Yeah, right, the DDT. Yeah, I think Rachel Carson wrote
about that in silent spring. Yes, So we use these insecticides,
and we're trying to use them in a little bit
more specific ways. So, for example, you can dip a
bed net in insecticides, and then you can put the
bed net over your bed and then at the time
of day when mosquitos are most likely to bite, you're
protected inside of the bed net, and because it has

(32:12):
already soaked into the bed net, you're not breathing a
lot in or you're not drinking it in water. But
the problem is that there's very strong selection pressure for
mosquitoes to find routes around this. So, for example, if
you've got mosquitos that bite at night, if there's variability
and some mosquitoes are biting a little bit earlier in
the day, the ones that bite earlier in the day

(32:32):
are going to catch the early birds and then they're
going to have a lot more babies that go early
in the day. And now the bed net isn't as helpful.
And we've actually been finding that in some parts of
the world mosquitos are changing there the time of day
when they're most active, so that they are now going
after people when they're outside of the bed nets.

Speaker 4 (32:49):
Wow, And this is why when I came back from
a trip to Tahiti where we had to sleep with
bed nets every night, and I loved waking up without
any bites. I just set up the bed net on
our couch and then for weeks, I just like, anytime
I'm hanging on the couch, I'm under the mosquito net.
No big deal. I'm like impervious. I'm like laughing at
all the mosquitoes.

Speaker 2 (33:08):
Ha ha.

Speaker 13 (33:09):
It was a very interesting sight, Daniel, Like watching TV
while sitting inside the bed net.

Speaker 4 (33:15):
It's amazing, amazing because I don't feel any social pressure
to be bitten by mosquitos, so I don't look like
a weird under a bench. I was happy. It was great,
and now I know that ecologically I was, you know,
suppressing mosquitos in a balanced way. So yeah, I was
being responsible.

Speaker 2 (33:31):
Way to go, Daniel, Thank you, pat on the back.

Speaker 4 (33:33):
All right, that's what I wanted. Thank you very much.

Speaker 1 (33:35):
So mosquitos essentially are constantly providing a moving target where
there's selection for them to route around whatever methods that
we are using to try to keep them at bay.
People also use things like they'll dump mosquitofish into waterways.
These are tiny little fish that eat the aquatic stages
of the mosquito.

Speaker 4 (33:52):
My new favorite fish.

Speaker 1 (33:54):
Yeah, But then the problem is they also out compete
a bunch of native fish, and they cause problems in
the ecosystems that you introduce them in because they're not
native there. So it's not a perfect method, but it's
a method you can use in some areas at your
own house. Now that you know that there's an aquatic stage.
Maybe you already knew that, but you can make sure
that you dump any standing water and if you want to,
like have a bird bath, just dump it out every

(34:15):
day or two and then refill it because that won't
give the mosquitos time to hatch. But trying to like
up the complication level a little bit. The next thing
that we started in the nineteen fifties was using sterile
insect technique, and folks might remember that we talked about
this a bit for the screwworm episode, and the idea here,
essentially is that you blast mosquitoes with gamma rays or

(34:37):
other chemicals that sterilize them, and then you release just
the males into the environment. Female mosquitos mate once and
they'll mate with one of these sterile males, and then
if they're able to lay eggs, those eggs won't hatch,
And so essentially you are taking females out of the
population reproductively by having them mate with males where it

(34:58):
won't result in successful offspring. But this method has a
couple problems. First of all, if you are just like
randomly bombarding insects with gamma rays, yes you're gonna sterilize them,
but you also might beat them up in a bunch
of other ways. And so sometimes these males that you
release into the environment aren't as good at attracting the
ladies as the wild males, because these males have all

(35:20):
sorts of other things wrong with them.

Speaker 4 (35:22):
Since Kelly, I read a bunch of comic books, and
if you blasphamilar with gamma rays, it usually gives it superpowers. Right, Yeah,
are you telling me that particle physics isn't really connecting
with the biology there? Is that what's happening?

Speaker 1 (35:33):
I think that's what's happening, Daniel. I'm really sorry. Or
maybe it's a statistical thing. Sometimes it works out that way.
But the mosquitos just they there hasn't been the Spider
Man equivalent for mosquitoes yet.

Speaker 4 (35:43):
Yeah, I'm glad that we haven't turned any of these
mosquitoes into the incredible hulk mosquito. Yeah, that would be
really excite to see that.

Speaker 2 (35:49):
It would be mad.

Speaker 5 (35:50):
Yeah, I bet the fabulous mosquitos do great though.

Speaker 4 (35:53):
Yeah.

Speaker 13 (35:57):
And actually I have a colleague at the City of
Hawaii who's working on the microbiome. It's actually in the
context of gene drives, but they are working on making
the microbiome of the mosquitos robust to help the mosquitos
that they're engineering to go out there and succeed with
the ladies.

Speaker 5 (36:14):
As it were.

Speaker 2 (36:15):
Nice. Is this Wallbakia, No, it's mosquitos.

Speaker 5 (36:18):
It's a malaria project.

Speaker 13 (36:19):
It's Nicole Hinson at the University of Hawaii by Walbakia.

Speaker 1 (36:22):
I meant the bacteria that they're adding. But anyway, we'll
get back to Wallbachia.

Speaker 13 (36:26):
So no, I think that they are like more roundly
making the microbiome of the mosquito robust, so that in
general the mosquito is robust.

Speaker 4 (36:33):
I'm not sure, but again with this method, I wonder, like,
how many males do you have to put out there
to have this have any efficacy. It's not like the
males are reproducing and making more of themselves, right, so
like every one you put out, it's one that you
essentially manufactured. Is it really possible to have an impact
on the population.

Speaker 1 (36:50):
Yeah, great question. So there was an experiment done in Havana, Cuba.
Sorry I said that wrong, but that's what we expect
out of me. Where about one and a quarter million
or radiated mosquitos in this case, the species was eighties
jipdi were released and again all males, and they did
a twenty week trial and they looked at a fifty
hectare area, so a pretty big area, and they put

(37:12):
out what they called ovtraps, essentially just like areas where
mosquitoes could lay eggs, and they didn't find any eggs
in that fifty hectar area, suggesting that one in a
quarter million mosquitoes, which is a lot of mosquitoes, is
enough to essentially knock a population down in an area.
But the problem is you got to keep doing that
over and over and over again every year. So it's

(37:32):
an expensive process that needs to be maintained. But it
turns out it doesn't work well for anophlies mosquitos. So
we talked about eighties mosquitoes. There's another genus of mosquitos
called Anophlies that also tends to have a lot of
species that transmit diseases to us, and that species it
looks like it's a little bit harder at the early
stages of their life to figure out which ones are

(37:52):
males and which ones are females. And if you can't
be sure, then maybe you're releasing a bunch of extra
females into the environment who are like go and start
biting people and possibly transmit diseases. So it works okay
for eighties a jipdi if you're willing to release it
over and over again over a large area, But it
works less well for an off lease because there's this
step where you need to figure out if there are

(38:13):
boy mosquitos or girl mosquitos, and because that's hard to
do in the lab, that makes this technique a little
harder to use. So next, let's talk about bacteria. So
I suspect to have Katrina's attention. So Wolbakia is a
gram negative bacteria that's carried by a bunch of different
kinds of insects. It lives inside of insects cells and

(38:36):
it only passes down the female line, and so it's
found ways to manipulate a lot of different insects species
to help it transmit from one generation to another. So
if a male who has the bacteria mates with the
female who doesn't, the eggs that she produces won't hatch.
But if the female has Wolbachia and the male doesn't,

(38:58):
then she will lay as that all carry Woolbachia. And
so essentially the bacteria has a way of sort of
manipulating things so that eggs are produced in ways where
the bacteria can transmit and in instances where the bacteria
wouldn't be able to transmit. It just sort of like
stops reproduction dead, so that there's a line there where
nothing's happening. So in this way it can permeate the

(39:20):
entire population.

Speaker 4 (39:21):
That's mind boggling. The sort of like genetic engineering by
the bacteria to ensure that only lines that have the
bacteria continue, that's incredible.

Speaker 13 (39:30):
It is incredible. Yeah, I remember when I first learned
about this. It's kind of like blood types or something
that there's like this incompatibility. But I know it's given
people a real handle for engineering the populations. So I
can only imagine what you're going to say next.

Speaker 1 (39:45):
So what I'm going to say next is that Scott
O'Neill at Monash University noted that a different lab had
found that viruses and fruit flies have trouble growing when
they're infected by wolbachia.

Speaker 2 (39:58):
So this has nothing to do with REP production.

Speaker 1 (40:00):
This is just if wolbachia is there, it prevents the
growth of viruses that otherwise would have killed the fruit flies.
So O'Neil was like, well, what if we take wolbachia
out of fruit flies and put it in mosquito eggs
and then see if mosquitoes carrying this wolbachia are less
likely to transmit dengae, which is another yeah, mosquito transmitted

(40:21):
disease that can be lethal. And so essentially they did
the incredibly difficult job of extracting a teeny tiny bacteria
from a fruit fly sticking it into a teeny tiny
little mosquito egg. Apparently they had to do this like
thousands of times before it worked, but they eventually were
able to get a strain of mosquitoes that were infected
by the wolbachia that was found in these fruit flies.

Speaker 4 (40:43):
So you're telling me that they found a strain of
Wolbachia that kills viruses, and since dangay is a virus,
they were like, maybe this strain of Wolbachia is going
to also kill dngay. That's crazy.

Speaker 2 (40:56):
It doesn't necessarily kill the virus.

Speaker 1 (40:59):
But it makes it so the virus can't reproduce, and
if the virus can't reproduce, it can't go from mosquito
to mosquito. And so they did some lab experiments and
it was working well in the lab. And in fact,
one of our listeners, Joe, sent us an email that
included a link to an article where Wobakia infected mosquitoes
had been released in Florida. So we're trying this like

(41:19):
out in the wild.

Speaker 4 (41:21):
Wow.

Speaker 1 (41:21):
And so the question is does it work? And I
looked for a really long time to try to find
studies that had quantified this working, and I was able
to find one study and it was in Indonesia and
they released Wolbachia infected mosquitoes and it reduced the spread
of dengay by seventy seven percent.

Speaker 4 (41:38):
Wow.

Speaker 1 (41:39):
So not one hundred percent, but like, man, those are
much better odds. I'd take those odds. But then I
found a twenty twenty four review paper that was trying
to aggregate all of the Wobakia infected mosquito results, and
they reported that essentially the only paper they were able
to find was this paper from Indonesia. There were two
other ongoing studies collecting data, but they hadn't published results yet.

(42:01):
And so I would say at this point that this
is super promising. I'd like to see evidence that it's
working in some other areas before I could say like, ah, we.

Speaker 2 (42:09):
This is this might be the key.

Speaker 1 (42:11):
But for dengay, there's some preliminary evidence that this method
is promising.

Speaker 4 (42:16):
Well, I'm a big fan of anything that's anti mosquito,
and I'm a big fan of preventing dengay or other
kinds of diseases, but the idea of like intentionally infecting
mosquitoes with some kind of bacteria seems dangerous, like kind
of I know this thing is going to like mutate
and then all of a sudden it's some new horrible
face melting disease or something.

Speaker 1 (42:36):
So you know, this bacteria is pretty widespread in nature,
so it's not like we're introducing something super weird into
the environment, but it is a different strain. I don't know,
bacteria expert.

Speaker 15 (42:49):
What do you think, Katrina, Well, I guess I was
just going to say that this Wolbakia bacteria, I think
it's present in like forty percent of insects, and so
of course there's going to be very individual relationships that
each bacteria has with its own insect.

Speaker 13 (43:02):
But I don't know of the things that humans do
to manipulate the environment, this seems like a relatively innocuous one.

Speaker 5 (43:08):
I think it's really cool.

Speaker 13 (43:09):
It's like not so toxic to just kind of scramble
things around a little and hope for a better outcome.

Speaker 4 (43:14):
All right, Well, if people's faces get melted, it's on you.

Speaker 1 (43:16):
Oh no, well I think it's on Oxytech, which is
a company that is releasing some of these mosquitoes. I
don't know that we can blame Katrina, she didn't release them.

Speaker 16 (43:27):
But thank you for looking up for me. Kelly, Yeah,
you're welcome. I like when we can team up against
Daniel so well.

Speaker 4 (43:37):
You know, then maybe I need you to chime in
on a topic that's been discussed heatedly at the Whites
and Institute board meetings recently, really, which is you know
what is the source of all the mosquitoes at the
Whites and is too compound that are biting Daniel. And
for example, I'm against having sources of fresh water near
the house, but Katrina is growing vegetables hydroponically in our backyard.

(44:00):
H what do you think, Kelly, I need a ruling.

Speaker 13 (44:03):
There's no way for a mosquito to get into this
hydroponic growth chamber or for a mosquito to get out,
so I just really don't think it's possible for them
to be in there. But there is sometimes like a
bowl of water that collects from rain that I don't notice,
and I'm sorry if that caused any mosquito growing to happen.

Speaker 4 (44:21):
I mean, I'm hearing all of your fancy engineering explanations
for why this can't happen, but I'm taking measurements of
mosquito bites and I'm telling you it's high.

Speaker 13 (44:29):
It feels like there's been a lot of mosquitoes lately.
But I thought we could blame that shipping container of
the Port of Long Beach. Isn't that why?

Speaker 4 (44:36):
Well, what do you think, Kelly?

Speaker 1 (44:38):
I think that I like every opportunity that I can
have to side with Katrina, But I don't really want
to get in the middle of a marital spat, so
I'm going to run away and call a commercial break
and pretend none of this happened.

Speaker 2 (44:51):
When we get back, and we're back and we are talking.

Speaker 1 (45:14):
About genetic engineering techniques for controlling mosquito populations. This time around,
we're about to get to gene drives, which was the
listener's question. This is the most roundabout way of getting there.
But first let's talk about some genetic engineering where essentially
you take males and you make it so that if
they don't encounter tetracycline, they will die.

Speaker 4 (45:34):
What is tetracycline.

Speaker 1 (45:36):
Tetracycline is an antibiotic, and essentially you make it so
that the males are making a protein that when it's
made it messes up the cells activity. But in the
presence of tetracycline, that protein is suppressed so it doesn't
get made. So males in the lab are given tetracycline,
they act normal, but when they produce suns in the wild,

(45:58):
the suns start producing this protein like crazy. It messes
up their cell activity and they die. And so the
females do lay eggs but their eggs don't tend to survive.

Speaker 4 (46:07):
So you genetically engineer mosquitos to be dependent on this
thing that you can give them. So when they go
out there in the wild, their bodies are making this
protein and since they don't have this magic powder, they
end up killing themselves.

Speaker 2 (46:20):
They end up dying. Yeah.

Speaker 4 (46:21):
Wow.

Speaker 1 (46:21):
These are pretty complicated strategies, and they also are strategies
that tend to make a lot of people uncomfortable. So,
for example, this has been tried in the Cayman Islands, Panama, Brazil,
and Florida, and in the Florida Keys, for example, the
initial response was like massive backlash against the release of
these GMO mosquitoes. They ended up getting released anyway, but

(46:43):
there were people who were saying like, I'm gonna find
the boxes where there's these mosquitos are supposed to hatch from,
and I'm gonna dump them out or pour bleach in them.
And I think in general it's really important that you
have public buy in for these sorts of things, because
otherwise you just get you know, you get people who
are justifiably upset. They don't understand what's being released. They're
worried that the genes that got put in the mosquitoes

(47:04):
might jump into them.

Speaker 4 (47:06):
Is that what the concern is that the that they're
going to end up depending on tetracyclin also or is
it just a generic like I'm scared of GMO stuff.

Speaker 1 (47:14):
I think it's more of a generic. I'm scared of
GMO stuff. You know, folks don't want GMO foods. I
think they don't necessarily like the idea of getting bitten
by GMO mosquitos.

Speaker 13 (47:22):
I think they also don't like the idea of putting
an engineered gene out in the environment and not knowing
where it's going to end. So like these island capture experiments,
where of course the idea is that it's an island
so it's somewhat contained, are still unsettling because the world
is so connected right now, so it's hard to know
what the reach of an experiment like that.

Speaker 2 (47:42):
Will be exactly.

Speaker 1 (47:43):
And so while these releases do first have to go
through like a complicated series of approvals through groups like
the Food and Drug Administration, the United States Department of Agriculture,
the Environmental Protection Agency, it is still the first time
we're doing something like this, and so ox Tech did
release mosquitos that had this tetracycling thing happening, and some

(48:08):
of the genes from the mosquitoes did end up being
found in wild mosquito, so like those genes had escaped
into the population. There were some headlines at the time
that sort of were way overblown. They said things like,
these genes are going to make the wild mosquitoes even
better at biting us, and now we've just made our
problem worse. There wasn't necessarily any evidence for that, but

(48:30):
there was evidence that genes that were essentially manufactured in
a lab are now part of the wild population and
might be there forever. And we don't really understand if
that is going to do anything at all.

Speaker 4 (48:42):
I understand the concern that these genes that you've put
into one mosquito might end up in a wild mosquito,
and you don't know exactly what's going to happen. Maybe
it turns them into incredible hulk mosquitos, whatever. But how
does a gene go from that mosquito to the wild mosquitos.
Does it have to breed with those mosquitoes or is
there some other weird horizontal thing happening.

Speaker 1 (49:00):
So I think what happened in this case is that
one of the mosquito babies that was supposed to die
did not, and so it survived, had some of the
genes that it got from its genetically engineered dad, and
then is passing that through the generation.

Speaker 4 (49:15):
Okay, so it's through breeding.

Speaker 13 (49:16):
Yeah, you could imagine some compensation that allowed it to
survive with that toxic protein, and then the toxic protein
would stick in the population. I mean, I guess in
my mind, there's so much evolution and transfer of genetic
material all the time that any tiny little drop that
comes from a lab feels insignificant to me. But I

(49:38):
do understand why it feels unsettling.

Speaker 1 (49:41):
That's my gut feeling. Also, like horizontal gene transfer happens
between insects and our food, and just all sorts of
different transfers are happening all the time in nature. I'm
less worried about a genetic sequence that seems pretty benign
getting out into the wild. But on the other hand,
I'm somebody who is totally fine eating genetically modified foods.
But I understand that that's not true for everybody, and

(50:02):
so I can understand why this would be upsetting to
some people.

Speaker 4 (50:06):
I think generally, you know, biologists don't know how everything works,
and we're pushing buttons and pulling levers on a big,
complicated machine, and it does feel like one little button
on a huge machine. But you know, you release the
right pathogen and it can definitely have a big impact
on a population.

Speaker 2 (50:22):
Yeah, I think it's important to be humble.

Speaker 1 (50:23):
Yeah, So let's get to gene drives, which is probably
the most like ethically controversial thing that we'll be talking
about today. And you know, we bring Katrina on the
show because we generally love Katrina's input, but she also
understands gene drives. And I spent a day smashing my
head against a paper I could not understand. And so Katrina,
could you explain gene drives for us, please?

Speaker 13 (50:44):
So, a gene drive refers to when you use genetic
engineering to force a gene through a population at a
really high rate. So normally our genes are inherited approximately
fifty to fifty, so the chances of inheriting a pertinent
trait are not weighted in one direction or another. What
a gene drive does is it ensures or drives that

(51:07):
a particular trait will be more frequent in the population
and so, and we've actually been using this technique in
the context of mosquitos with a few different strategies in mind.
This it could be something that affects fertility, so then
you drive the population to extinction, So that would lead
to you know, fewer mosquitos is the goal there. But

(51:27):
then there's also strategies where you try to prevent the
mosquitoes from spreading malaria. So there's some mosquitos that are
naturally resistant to carrying the malaria parasite, and so spreading
that strategy is another gene drive technique.

Speaker 4 (51:41):
So can we dig a bit deeper, Like I understand
sort of the basics of genetics at the sort of
pea pod level, you know from Gregor Mendel, and you
have a fifty percent chance of getting the gene from
one parent or from the other. How does the gene
drive affect which genes you're going to end up with?

Speaker 13 (51:58):
Well, okay, the one really cool strategy that people use
to make gene drives work is to borrow the phage
defense system called Crisper cast nine. As you guys hopefully
know all about, there are these viruses called phages that
can infect bacteria and the bacteria defund themselves in all
kinds of interesting ways, and one of them has been

(52:20):
co opted for all kinds of genetic engineering. It's called
Crisper cast nine, and it turns out whenever the phage
infect the bacteria, the bacteria keep a little record of
little snippets of the genes that the phage was trying
to infect the bacteria with. And then they put a
little pair of scissors, a gene that can chop DNA

(52:41):
up next to the little memory bank of all the
little phage genes that were left behind. And then when
the phage tries to infect the scissors, the gene that
has the DNA cutting enzyme on it will match up
with the pieces of the phage gene and it'll chop
up the phage as it tries to enter. The Nobel
Prize last year to Jennifer Dawna and Manuel Sharpentier because

(53:05):
they had the idea of taking this tool and using
it to engineer genes in any system.

Speaker 4 (53:13):
So, just to back up and make sure we're understanding,
the Crisper idea is some sort of like bacterial immune
system where it remembers the viruses it's seen before and
has a bunch of guys floating around which will recognize
those viruses. Plus it comes with scissors so that when
the viruses come near, it latches on and then it
chops them up and then the viruses can't infect the
bacteria anymore. So the basics of how the Crisper system works, yeah.

Speaker 5 (53:36):
That is exactly the basics.

Speaker 13 (53:39):
But the idea of using it as a tool is
really cool because basically, now you have a system that
can go and find a particular DNA sequence and then
it's got scissors right next to it, so it can
go cleanly chop things out exactly next to whatever sequence is.

Speaker 5 (53:56):
Next to it.

Speaker 13 (53:57):
So with the phases, the bacteria using it to chop
up phages. But now imagine you wanted to go in
there and slice and dice a mutation that was causing
sickle cell anemia.

Speaker 5 (54:07):
You can do that.

Speaker 13 (54:08):
That actually is happening in people right now, which is amazing.
So people with sickle selenemia now can have some access
to Crisper CAST nine genetic engineering technology where you use
the same scissors, but this time you match it to
the gene causing the sickle cell disease and you have
the scissors go in there and snip out the problematic

(54:28):
gene and replace it with a healthy gene. And I mean,
that's to me amazing that that is actually working in people.
The idea is not that old. I mean the discovery
is somewhat recent. And so that's the same strategy that's
been used to build mosquito gene drives.

Speaker 4 (54:46):
So I understand how Crisper can let you edit your genes,
which on one hand sounds like why is that are
you know, you just like go in and edit the data.
But like this data stored on DNA, you can't just
go in there and like manipulate it with tweezers. You
need some of like microscopic manipulation tools, and that's what
Crisper is giving you. But how does that connect to
gene drives. How does Crisper let you enhance which genes

(55:09):
get passed down in the population.

Speaker 13 (55:11):
Well, you engineer mosquitos that contain a Crisper cast nine
gene set in there. And so you could put the
scissors right next to a gene that's important for fertility,
or you could put the scissors right next to a
gene that controls whether the mosquito is able to be
infected by the malaria parasite, and so if you put

(55:34):
that in there, then the crisper cast nine scissors will
go around spreading that gene even after the mosquito is born,
so it's throughout the mosquito's life the gene drive will
be active and it will continue to spread that gene.
So your opportunity for picking up your genetic traits will

(55:55):
not end right at the moment of Mendelian inheritance.

Speaker 5 (55:59):
The gene drive will can continued to be active after.

Speaker 4 (56:01):
Oh, in the same way that you go in and
edit somebody's genes when they're alive to remove the bit
that's giving them some condition, you're basically giving these mosquitoes
a little bit of genetic engineering during their whole lifetime,
so it's not just what they inherit. You're like changing
them after the fact. That's cool.

Speaker 13 (56:19):
Yeah, So basically, if that gene drive is in there,
every time the little cassette that has the scissors on
it encounters the gene that it can match to, it
will swap things around, so you can. Like one of
the examples that I really loved that I read about
was where they had a naturally malaria or resistant mosquito,

(56:40):
and it was just caused by one snip and a gene,
a single mutation, and they made a gene drive that
forced that mutation through the population. But it's it's a
naturally existing gene, so they're not making a Frankenstein mosquito here,
and it made it so that the malaria infectivity rate

(57:00):
of the mosquito population could go down.

Speaker 1 (57:02):
I found another paper where they were tinkering with the
gene that they called double sex, and essentially what happened
is they made sure, you know that everybody got two
versions of double sex, and if you're a female that
has the double sex genes, you are sterile and you
also look a little bit male like. But males who
get it are normal and they can go on spreading

(57:22):
the gene drive. So essentially every baby that's produced that's
a female is not going to make any more babies,
and males that are produced are going to be able
to go on in mate, but they're going to pass
this gene drive onto their offspring, and so they'll create
female babies that die and male babies that go off
and continue to pass the gene drive until it gets

(57:43):
through essentially the entire population. I think is the goal. Wow,
well yeah, and so this has not yet been released
into the environment, and so, as Katrina noted, there's two
different methods. You could try to either kill the mosquitoes directly,
or you could do something to the mosquito so they
can't transmit the dizzy anymore. There might be some other
options too, but those are the two things that people
are working on right now. But this, I think this

(58:06):
technique in particular, is a little scarier ecologically because you know, like,
what if that gene drive jumps to I don't know,
another mosquito species. Maybe having two mosquito species eradicated doesn't
sound so bad, but what if somehow that gene drive
is able to jump to I don't know, a ladybug
that helps control pests in agriculture or something. And now

(58:29):
we've got this thing that could lead to extinction, and
there's some concern that if you release it, you know,
where is it going to end up?

Speaker 4 (58:36):
But how do these jumps happen? Earlier we were saying
that the genetic engineering that you manufacturing your mosquitos can
spread to wild mosquitoes through inheritance, But we're not having
mosquitoes like having babies with ladybugs. How does that jump possible?

Speaker 1 (58:50):
So, as we're going to talk about in a future episode,
the definition of a species isn't always entirely crisp. Sometimes
you can get you know, individuals that are in the
same genus, for example, mating with each I don't know
if they get confused or they have very particular interests
something they're looking for in a partner.

Speaker 2 (59:05):
No judge, but no judgment, no judgment.

Speaker 1 (59:08):
But if you know the mosquito species, you put the
gene drive in mates with another mosquito species. Now you're
wiping out that species too.

Speaker 2 (59:17):
And you can.

Speaker 1 (59:17):
Imagine yourself jumping around the tree of life and whenever
you get some you know, cross species mating, you've now
got that species wiped out too.

Speaker 4 (59:27):
So crisper can move because species aren't crisp, is what
you're telling me.

Speaker 5 (59:30):
Ah, that's right, I mean, yeah, that's definitely.

Speaker 13 (59:34):
One way is through mating partners that might be a
little bit less related. But I mean another big strategy
is sometimes there are big leaps in genes that get
transferred across the tree of life, and that often is
facilitated by viruses. So, for example, eight percent of the
human genome is in the form of endogenous retroviruses. So

(59:57):
that means that one of our long ago ancestors had
a virus infect one of their germline cells, one of
their sex cells, and we have inherited that to the
tune of literally eight percent of our genome. Most of
them are pretty dormant and haven't really affected us that much,
but some of them have led to the biggest innovations
in biology. So like, for example, did you guys know

(01:00:19):
that the gene that led to the placenta evolving came
from a virus? So an endogenous retrovirus that infected one
of our ancestors back before mammals existed, had a gene
in it that helps with membrane fusion. So like that
gene in a virus is great for helping the cell
membrane fusee but in a mammal it allows for the

(01:00:42):
fusion between the uterus and the placenta cool, so those
kind of jumps can happen. And to me, that's a
really big question about gene drives because what if this
crisper gene gets transmitted farther afield. I think that's the
real concern, But keep in mind, in your own gut.
Right now, you have thousands of bacteria that contain all

(01:01:04):
kinds of crisper systems, and I'm not worried about those
transmitting into human cells.

Speaker 1 (01:01:09):
And I should note there are labs that are working
on anti gene drive techniques, like a gene that you
could release into the population that would sort of stop
the gene drive. And so there are some folks who
are forward thinking about this problem and are trying to
stop it. But then we can return to Daniel's earlier point,
which is that biology is complicated and biologists don't necessarily
know what's going to happen. So, like, what if we

(01:01:30):
knock out one mosquito species, a different mosquito species fills
that niche, and that species is even better at transmitting
the disease. Now we've you know, maybe we can release
gene drives again to control the problem. But like, it's
hard to know what's going to happen to a system
when you remove an animal that has you know, a
large number of individuals out in the population, and we

(01:01:51):
don't really understand the ecological impacts. So Daniel mentioned that
some mosquitoes pollinate chocolate, you know, may what if you
have a mosquite species that ends up being an important
food source, for example, for a fish species that is
an important source of protein for the local community. So like,
there's a lot of you know, ecological stuff that might
happen that we don't understand very well. And so making

(01:02:14):
the decision to knock out a species because we've decided
we wanted to do that, you know, could have some
other implications. But if, on the other hand, you're talking
about you know, more than half a million people dying
every year from malaria, my tolerance for taking risks goes
up a little bit. But those risks should be well
thought through, in my opinion, and I hope that.

Speaker 4 (01:02:31):
You're including my itchy ankles from mosquito bytes in your calculation.
I'm not away a lot.

Speaker 2 (01:02:36):
I'm not no.

Speaker 4 (01:02:39):
And of course Kitchen is going to vote. We do
so on that voted again.

Speaker 1 (01:02:44):
So where we are on this right now is that
some genetically modified mosquitoes have been released and we're doing
tests on those, but no gene drive mosquitoes have been
released yet. There was a target malaria was working in
Bikina Fassa to try to get community buy in, to
get people on board with this idea of releasing gene drives,
but recently their facility was essentially rated and they were

(01:03:07):
told that their project is being shut down. It was
a little bit unclear what happened because it seemed like
the Target Malaria group was in good with the local community,
in good with the government. There have been some like
think tanks that think that the problem actually is Russian disinformation,
where this message has been spread that we are using
genetic modification to make people sterile, and you know, releasing

(01:03:27):
these genetic mosquitos will sterilize the local population. So it
has become a complicated ethical, geopolitical problem, and that's where
we are right now. We are sort of trying to
decide as a society what we're going to do when
we have this technique that could be used to save
a bunch of lives from malaria, but has you know,
potential implications, some of which we know about and some

(01:03:50):
of which we might not even understand unless we were
to actually try the experiment.

Speaker 2 (01:03:55):
So it's complicated because it's biology, but.

Speaker 4 (01:03:57):
It's worthwhile because these are people's lives. It matters.

Speaker 13 (01:04:00):
Yeah, I think it's so interesting that it's more controversial
when we understand what we're doing better. I mean, for example,
in agriculture, we've been selecting for traits for thousands of
years that have all kinds of ecological impact, and we
don't find that to be controversial. But as soon as
we use molecular biology tools to genetically engineer things, it's
less understandable and somehow scarier, although the implications could be

(01:04:23):
the same.

Speaker 5 (01:04:24):
So I think that's really interesting.

Speaker 1 (01:04:25):
All right, So we have had a fun, complicated discussion
about mosquitos and genetic engineering, and Katrina, I have no
doubt we'll bring you back on the show five or
six more times before.

Speaker 2 (01:04:36):
The end of the year, which is only a couple
weeks off. Thanks for coming back on the show.

Speaker 5 (01:04:42):
Well, thank you for having me.

Speaker 1 (01:04:44):
Thank you to our listeners for submitting their questions. Let's
hear what they had to say about the episode.

Speaker 14 (01:04:49):
I really appreciate you getting to my question and in
the most relevant episode. I can't say that I'm entirely
convinced that the reason gene drives haven't been tested yet
aren't nefarious. After all, if your goal was eradication and
you released enough mosquitoes on a small island, and considering
the length of the mosquito life cycle, how long would
it take to eradicate the species entirely a short time

(01:05:10):
period leaves very little time for the genes to jump.
If the gene drive did jump species and eradicate another
species of mosquito, oh why has no native mosquitos to
worry about? In fact, the six to eight invasive mosquito
species on the islands would make a great test case
to see if the.

Speaker 4 (01:05:25):
Gene drives do jump species.

Speaker 14 (01:05:28):
Maybe some diligent pesticide use by the ports could keep
any modified mosquitos from leaving the island before total eradication. Overall,
it seems much less risky than Uruguay's plan to use
gene drives to eradicate screw worms. Given the biodiversity of
South America. Maybe the answer is in Wolbakia, which you covered.
Perhaps is just less risky. It looks like they started
attempting to use it to radicate coolx mosquitos on Maui

(01:05:51):
to save native birds. Thanks so much.

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