Kind: captions
Language: en
Could you take embryionic hakee, stick a
needle in me, change a instruction, and
I now have fangs [music] and venom?
[snorts]
Yep. [laughter]
[music]
>> Sean Carol, welcome to Particles of
Thought.
>> Thanks for having me. Yeah, I'm so happy
to have you here, man. So, you are an
evolutionary biologist and you study the
evolution of new species coming into
existence. And when I hear that, I think
about us humans. We've changed a lot in
a very short period of time. What are we
going to evolve into and when?
[laughter]
Boy, wouldn't we like to know? Yeah,
it's hard to predict the course of
evolution because there's a lot of
ingredients that go in. You know, for
most of the story of
>> life on Earth, you know, the earth
changes and life changes along with it
>> and you know, we're creatures of that.
We're kind of creatures of the ice age.
Um, but then we've started to control
our own environment and that's now we're
we're kind of in a whole different
realm. Uh, I would say, you know,
because we get along we get across the
globe relatively easily. We mix with
each other very easily.
Um, you know, I think our future is
going to be of one one big kind of
intermixed population. That's real real
different from the past when you would
we had a lot more isolation, you know,
people on islands, people living at high
altitude, all that kind of stuff. And
that that would make
>> that makes us all look more different,
>> right?
>> I think in the future we're that one
that that gene pool is all mixing. So
maybe we're going to be a little more
similar to one another.
>> Yeah.
>> And uh but I don't I don't see any
superpowers coming. I
>> No. Well, I'm just hoping we don't lose
what we already got, which is, you know,
libraries, the scientific method, you
know, little things that help us cope.
>> Well, according to Stan Lee, right, we
evolve into homo superior and we do have
superpowers. Yeah. Before we get too
deep into the conversation, you know,
we're using terms and, you know,
sometimes we say phrases all the time
which makes us think we know what we're
saying, but actually we don't. I've
experienced this in my field with the
phrase big bang. And I think when people
hear a word like evolution, a lot of
people go monkeys to humans, right?
[laughter] Not happening. Let's go into
what evolution really is and how it
really works.
>> Sure. Evolution is change over time.
>> That's it. Just just just let that
settle for a second. That's all it
really is.
>> Okay?
>> Change over time. So you can think about
those two things. What's what do we mean
by change? Well, that's change in
appearance, change in the properties of
something, right?
>> Um, and time, time's a big ingredient.
Yeah.
>> And time is really the hard thing that
>> for people to get their heads around.
And Darwin really appreciated this
because in his day
>> where the entire mindset was one of
creation or essentially instantaneous
creation of things. He had really two
big challenges which was to get people
out of that mindset to understand that
natural processes were sufficient to
explain what you saw in the world and
that there had been immense amounts of
time available to do it
>> and these were big scientific gaps right
and even Darwin who thought oh maybe the
world was as much as 300 million years
old I mean he was off by a factor of 10
right there was a lot more time than
even
>> Darwin realized okay so let's just start
with change over time and we can break
that down in any direction you want. How
does the change happen,
>> right?
>> And then, you know, small amounts of
time, big amounts of time, you know, the
degree of change is somewhat going to be
proportional to time, right?
>> But, you know, things can change
rapidly. If things on Earth have changed
rapidly, you'll you'll see rapid
evolutionary change. If the Earth is
fairly stable, you'll see relatively
gradual evolutionary change.
>> Oh, interesting. Interesting. Yeah. I
know there was that geological time
that's called the boring billion just
before the Cambrian explosion. So does
that mean that geologically things were
boring? So life was boring?
>> No. Well, I mean I think any geologist,
you know, sitting here would say nothing
was nothing's ever been boring about the
planet because the planet has changed
tremendously.
>> Um especially things like oxygen levels
and and the sort of which means the
metabolism of life has changed a lot.
>> I think the boring comes from just our
perspective which is life was really
small. Life was micro microbial for
those billion years, right? So if you
visited Earth from somewhere else during
that billion before the Cine, you kind
of look around, you go, "Okay, I I see
some algae. I see some bacteria, you
know, next." Okay, [laughter]
>> but we're animals, so we get excited by
bigger things, right? And animal
evolution really kicks into high gear
and the Cambrian and then when life gets
to land, of course, then you get, you
know, plants and trees and all this sort
of stuff and the world that's, you know,
much more familiar to us. So, right,
>> you know, it's uh that perspective
depends upon maybe what kind of creature
you are. If you were if you were a
cyanobacterium,
>> you know, a billion and a half years
ago, the planet was wonderful. It was
paradise.
>> Yeah. Now, it's kind of [laughter]
>> now I got to share it with all these
clowns. Yeah. Yeah. Yeah.
>> And feed them their oxygen. And so,
>> the idea of new species evolving, like
it's pretty obvious when a species goes
extinct, there's no more of them. How do
you know when a new species has become?
>> This is a great question. This is a
tremendously great question. I think you
know we kind of grow up getting species
a concept of species sort of very static
and very like as though these are
categories that are very cleanly
delineated and that's it and there's no
mixing or anything like that. But that's
not the case. In fact, I just saw in the
news it's a really cool story about the
green jay and the blue jay. Green j for
Mexico. Blue Jay is familiar to us in uh
here in the United States.
>> Hybrids have been observed in Texas and
the hybrid doesn't look like exactly
like either parent.
>> So when these groups can come in contact
even though we would have called them
separate species,
>> you can get hybrid forms.
>> Okay,
>> that's not like a cement wall
necessarily between one population and
another. It can be a leaky barrier.
>> Right
>> now, let's go to the speciation process
itself. when it's happening, how can you
tell when something is split into two?
Because you got to realize
>> that those things are those populations
are probably so difficult to distinguish
from each other.
>> So if you take something like uh a
mountain range or a river that might
>> a lot of species form because of
isolation between populations. Okay, so
let's back up a little bit about process
and say all right
>> mountain ranges or you look on different
islands or something like that. So if
you start out with two populations that
are really similar
>> and given time there's been isolation
between them that they live on opposite
sides of some kind of barrier.
>> How do you know when they're different
species?
>> Yeah. What is that when does that switch
flip to
>> and it's not it's not a switch because a
I tell you it's a leaky barrier and and
second it depends on time
>> and is there a little bit is there just
a little bit of intermingling between
them which will sort of keep those
barriers lower. So you know we humans we
like to classify things. So of course
it's useful to classify things as
species but we don't want to give people
a hard and fast idea that these things
are sort of some kind of absolute you
know you know totally self-contained
population because they can mix.
>> And then in that process of speciation
it's a gradual separation of populations
one and two. So speciation is splitting.
>> Yeah.
>> One becomes two.
>> Right.
>> And that's happening all over the tree
of life. Right. Yeah.
>> Um, and it may be driven by different
conditions that the two populations
experience. So maybe think about maybe
up a mountain side, the things that are
adapting to maybe, you know, near or
above the tree line are different than
those that are living below the tree
line and eventually they sort of divide.
We can see that happening with things
like insects and all that.
>> Um, but uh, you know, no biologist can
walk in and say, well, this is the day,
you know, this is the day the species
happened. It's a gradual change. And for
some population, say animals, you know,
it might be a a two million yearlong
process of essentially becoming so
distinct that there's no going back.
>> You just gave me a movie in my mind of
of a of an experiment where you have
these two you take one species separated
on two islands, then you have
generations of scientists observe them.
>> Yeah.
>> And then you can say, "Aha."
>> Yeah. on July 8th, 2027.
Like, but even if you were to do that,
would you do it based on taking two
members and seeing if they mate? Would
you do it based would you figure out
that they were different species by
looking at their genetics? Like, how
would you figure that out? I I think
functionally we'd say two things. If
they wouldn't mate, okay, then that's
it. They're separate. There's no there's
no putting things back together if they
won't mate. or if they mate and their
offspring are inviable or infertile.
Yeah. Then that's it. Okay.
>> But often the case is going to be I my
prediction is this. Let's say we'll do
this with two birds on islands. It's
kind of been done a few times in
[laughter] nature. All right.
>> Yeah.
>> And those scientists are on those
islands a long time.
>> 10,000 years, 50,000 years, 100,000
years. I think when you do that
experiment, they're still going to mate
and their offspring are still going to
be viable. 200,000 years, 300,000 years,
400,000 years, somewhere maybe half
million years, million years. Okay. Now,
maybe they start to they their behaviors
are different enough they're not going
to mate or they're genetically distinct
enough that if they do mate, yeah, the
the offspring aren't viable. So, that's
that's the long gradual ticking of the
of sort of the clock. And what do we
mean by the ticking of the clock? Is it
under isolation,
>> you know, mutations happen in
populations,
traits change a little bit, etc. So
eventually either behavior or biology
may be different enough that you can't
mix them back together again.
>> But there's a long window where things
are permeable, right?
>> Yeah.
>> And you know taking you started out with
a question about us. You know, one of
the most mind-blowing discoveries of the
last 20 25 years
>> was the Neanderl contribution to Homo
sapiens, right? You know, so for a long
time we thought, okay, here's our
species. We're different from everything
else, right?
>> Yeah. But now we know
>> there's a little bit of Neanderl in most
of us, right?
>> Yes. Exactly. So it's a much more
complex
>> um history than just split split split.
You know the the the convenient picture
of the tree of life is
>> you just keep splitting species, you
know, one and two, one and two, some go
extinct, some keep going, etc., etc.
>> But those splits, they come back into
contact. And why do they come back into
contact? Well, they come back into
contact because we have a changing
Earth. Think about the ice ages here,
okay?
>> How many times in North America ice
sheets have covered North America,
right? So that's going to drive life
into into refugeia, right? Into places
that aren't that aren't ice covered,
right? And things are going to be mixing
and then
>> the the sheets retract again and things
spread back out again and you know and
this population's on one side of the
Rockies and that you know some somewhere
else and then here comes the ice again
back in. So with a changing planet,
you're going to have populations driven
apart and populations driven back
together again. So speciation is we'll
just call it sloppy.
>> Yeah. And not only that,
>> it's not a clean cleaving of one into
two.
>> Yeah. And the other thing that you just
pointed out how these geological changes
drive that. And since the time of Homo
sapiens sapiens having civilization,
we've been pretty stable, right? We
haven't we haven't had major geological
upheavalss like super volcanoes and ice
ages hitting us. So what we think now is
a normal
>> is not really a normal.
>> Yeah. It's in a short little interval,
right? I mean
>> the last you know civilizations the last
10 or 12,000 years
>> or at least you know farming and
domestication and all that kind of
stuff, right? But our species is 300,000
years old.
>> So they saw it.
>> They saw some serious stuff and they've
been through bottlenecks. I mean,
>> yeah,
>> we may have been down to, I don't know,
maybe 1,200 breeding pairs.
>> That's what I've heard. Yeah. Around
900,000 years ago, we're down to like
1300.
>> Yeah. Under some climate duress.
>> Let that be a lesson to us all.
>> Yeah. It lasted about 100,000 years. But
it also talks about our resilience. We
We made it through that. And you know,
>> we're a we got a lot more technology
than those hippies,
>> right? I [laughter] mean,
>> yes. Yes, we do. We absolutely do.
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So there have been a lot of transitions
that have occurred over life. These
stories that we hear, right? Going from
land to air, animals going from sea to
land and back to the sea. There was even
this idea that humans were water
monkeys. [laughter] Remember that idea.
Yes.
>> Uh
>> occasionally comes up in seminars I
give. But uh
>> Oh, no way. Yeah. Yeah. So, how do these
transitions happen and how long do they
take? If if a if if if walking a
tetropod is going to become a whale
>> or seal and then you have animals like
otter that are somewhere in between, you
know, how how does that
>> Well, it's a paleontologist, so that's a
different branch than myself. I'm not a
fossil hunter. You've had you've had
you've had a
>> So, that's where that story is written
is right.
>> Yeah, that story is in the fossils. And
um you know I think it's reasonable to
think I I think the estimate let's look
at a big one. Let's let's look at um
backboneed animals coming to land. So
fish
>> to land right going from fin to limb
walking on limbs
>> that takes longer and a lot of
speciation events. You don't just go
from being a fish to an amphibian in one
step. You don't go from being you know
ground dwelling to flying in one step.
>> Right? And you know roughly speaking
from the fossil record of various things
I'd say you know 10 15 20 million years
to execute a change like that
>> because there's a lot there's a lot of
anatomy changing. If you look at all the
remodeling of the skeleton and you're
going from something that's very
flippery to something that we think is
you know a little more digity you know.
>> Yeah.
>> Yeah. Takes a while. But
>> the paleontologists are out there
looking at for the fossils that sort of
mark that transition. And this has been
again really an exciting time. It's been
a golden age for paleontology to
>> Well, it makes me think of the the the
animations you see. You know, the
animations show a little fish and then
they like come up on the land and then
they transform into an amphibian, then
they transform into a reptile and Yeah.
You know, each of [clears throat] those
steps is
>> that's sped up. Yeah. [laughter] But,
you know, you we know there are
creatures that will live in the shallows
and then maybe do a little air
breathing, right, when they're in the
shallows. And you can start to imagine
because other things are happening. It's
not just the limbs that are changing.
For example, yeah, remember they got to
breathe air. Yeah.
>> So they got to go from gill to lung.
>> Yeah. So a lot simultaneous.
>> Yeah. A lot of things are changing. And
then probably you're seeing the position
of the eyes and the head changing from
maybe being out here
>> to being up top or being facing forward.
>> Recently was the limbs that spllay out
to being directly underneath.
>> Yeah. You got to support because you
come gravity is different, right? You
come on to land, you got to support that
whole body
>> whereas you're floating water otherwise.
>> How does it happen then? So all of these
changes of l gill to lung, fin to limb.
Yeah.
>> Uh and I would imagine if you are in
water then there's some sort of
balancing act with salinity that your
body has to undertake.
>> Physiology is changing etc. Yeah. So so
how do those
>> diet's going to change right the whole
thing right? What you're going to eat is
going to change the whole thing right.
Yeah. In fact it might be food that's
driving you onto land right. sometime of
scarcity you start finding there's stuff
on land
>> or you are the food
>> or you are the food let's get out of
here
>> absolutely let's get out of here
>> like the flying fish or something like
how
>> those things are driving things but
>> what what what drives that from the
inside so I I so the story of evolution
is you have some advantage to become an
adult and reproduce so you pass that
trait forward that's right
>> right and so there's going to be some
variation in that trait ac across that
species so is it the case that It's very
slow although you it's fast to you or
does it happen that these mutations are
occurring and then a mutation occurs and
hey look look we suddenly made a leap
>> it's not very leapy you know I think 100
years ago we entertain the thought of
things could be kind of
>> uh could move in jumps like that but
it's it's it's really not like that when
we really break down these transitions
it it's a lot of anatomy that's changing
that's a lot of physiology that's
changing right
>> and it's happening in increments and at
the increment isn't like, oh, this
generation is, you know, 1% better, the
next generation's 2% better. That's
that's even pretty fast.
>> There's going to have to be a lot of
concerted changes. And we also see when
these things are happening, lines go
extinct. You can see something kind of
getting there, but that branch doesn't
make it. It's something else that does
better and and is, you know, a more
direct ancestor to what we finally see
on land and things like this. So, it's a
process ridden with extinction because
in 10 million years,
>> there's a lot of extinction. You know,
probably most species only last a
million years or two.
>> Oh, wow.
>> So,
>> well, is that Wait a minute. So, there's
there's two ways to go extinct.
>> It's not a oneway I just want to get
this picture. It's not a one-way street
that
>> that line that starts to make its way
onto land. That's, you know, that's like
a, you know, a super lineage or
something like that. No, it's going to
it's going to experience extinction as
well. Branches are going to die off,
etc. It's a it's a messy process. So
what about something like a mental
change? So apes going from uh you know
from oropythecus to homohabilis and now
you're making tools and you're designing
tools and you come up with multi-art
tools like how does that you know
>> that's a great one boy wouldn't we love
to know a lot of those details right but
look what we do know you know two and a
half million years ago or so we're we're
starting to to make tools
>> that's fine motor skills
>> right and um we're living a more
visually driven lifestyle so one thing
you can relative to other mammals is
that like our visual system is we we
dedicate a fair amount of brain space to
visuals and for example less to scent.
Yeah.
>> So if you look at compare it with
mammals that um may make their way along
the ground you know even our favorite
companions like dogs etc. They're
devoting a lot of brain space and a lot
actually of genome
>> to the things that are going to help
them smell their way through the world.
We're kind of seeing our way through the
world. So, is it because we're upright
because you you you made this this
relation to the ground?
>> We're we're upright. So, we're away from
kind of odors as much, right? Because if
you're living, you know, close to the
ground and if that's where your food is
and you're trying to find scent trail,
that's where your mates are,
>> right? So, just I mean, whether you
think of a rodent or a canine or
something like that, close to the ground
kind of smelling its way through the
world.
>> Um, you know, look, we use dogs to
detect things. They're they're so much
better at it than we are. Well, they've
got a bigger repertoire of um receptors
for smell and they devote more of their
brain space and um to to uh detecting
these smells.
>> Well, we've adopted a different
lifestyle. We've actually given up a lot
of the
capability of for smell that existed in
more distant ancestors.
>> Yeah,
>> you can ask me later how we can see some
of that those vestigages. And we're
living a more visual lifestyle. And the
great apes have full color vision,
right? So we're we're we in the
>> Is that unusual?
>> Very unusual. So our other mammals don't
have it. Okay. So we there was a
evolution
I'm gonna go 25 30 million years ago
where we picked up uh another light
receptor in our uh in our retinas but it
connected to our brain. So we can
distinguish for example red, green,
blue. Mhm.
>> Well, really useful when you're like
grazing on leaves in the jungle and you
can tell the ripe ones from the unripe
ones, etc. Okay.
>> So, we see in full color.
>> So, this our we're more, as I said,
we're more visual species.
>> Yeah.
>> And we've traded off that that sort of
smell driven, old factory driven uh
lifestyle. And so, when you say, you
know, about change, this is manifested
in all sorts of ways. is you know in the
brain how much is dedicated to visual
processing versus old factory processing
in the genome a mouse or a dog might
have a thousand genes for scent
reception
>> where we've inactivated hundreds of them
you actually still see them in our
genome so in other words we know they
were there in our ancestor and these are
like little fossil texts they're like
they're like little redacted text almost
there but with mistakes in them that
have accumulated over time and it's a
great it's a really cool way to sort of
look back at our past is that there are
fossilized genes in our DNA and that's
telling us about lifestyles of our past
ancestors.
>> So if by some alien invasion or
something like that we find like oh we
better keep your head below 4T off the
ground we still have that ancient genome
in us to go back to smelling
>> we'd have to do some repair we'd have to
do some repairs. Yeah, which of course
now we have technology to do those
repairs to change our own DNA. But yeah,
it it's uh these these the lifestyle of
creatures and the lifestyles of their
ancestors. This is something again that
that we sort of didn't imagine decades
ago is that in DNA we we can see the
vestages of the past may not be used
anymore, but it's some of that text is
still there in the DNA. And it's a
really cool clue to look back and say,
well, what were our ancestors doing that
we're not doing anymore?
>> Well, what about like conversion
evolution? So there there are many
species that fly. So we have insects
flying, we have uh had flying reptiles.
Yeah.
>> We have flying mammals. So all of these
>> created a wing of some sort, right? Not
necessarily the same physics with each
one. No.
>> So it it how does a wing So I'm a
tetropod. Yeah.
>> But now I feel like I need to fly. How
do I go from
>> uh you know being me with arms to me
with wings? Well, they've all done it
differently. So, terasaurs, the dinosaur
you're referring to.
>> Yeah.
>> Uh, and birds, which of course were also
flying reptiles essentially.
>> And, uh, bats,
>> the anatomical details are all
different. Now, they all had to create
this
>> surf. They had to create some kind of
surface, right?
>> The the the part of the gene that
activates these.
>> They've all done it differently.
>> Okay. But they've all modified their
forearm. Okay. So, they've all worked
with this. Yeah. Okay. But where they've
made the webbing essentially to create
that wing surface is different. So, um,
you can sort of do this out more on the
hand. You can sort of create maybe a and
I got to think of my details a little
bit. I'd have to almost check this. Um,
but bats, birds, terasaurs, and this is
why we know they they're they're all
independent inventions is that when you
kind of look at the design of the wing,
they're they're using different pieces
of the forearm anatomy to to create that
wing surface. Okay. So this is the you
you're inventing a wing. Yeah.
>> You're working from a similar starting
point.
>> But it turns out they engineered three
different pathways
>> bats, birds, and terasaurus to to make
wings.
>> Now the the origin of novelty that the
general thing that I'm interested in,
lots of evolutionary biologists are
interested in is okay. Well, that's cool
to look at the finished wing and go,
"Wow, look at that. Terasaurus, amazing.
Bats amazing." But how does that even
happen?
>> Yeah. How do you get there?
>> Okay. How do you get there?
>> This is a question that it's really
central to evolutionary biology. It
worried Darwin from the start because
he'd look at these things and he'd say,
"Well,
you know, his description of evolution
was this very incremental process." And
if you think about something like an eye
or a wing, well, what good is half a
wing or what good is, you know, half an
eye, right? Uh how how do you so how do
you get there? So you have to start
thinking about maybe it was first a
little bit of membrane. It was a gliding
surface, right? Until you before you had
powered flight, right? And we think
about things that glide like there's
squirrels that are glide. There's snakes
that are glide for goodness sakes,
right?
>> Oh jeez.
>> So So we have to we have to sort of
either think our way through what the
value of sort of intermediate stages
would be. And of course the
paleontologists are trying to help us by
actually finding the fossils that tell
us what these intermediate stages look
like. Right? So that transition from fin
to limb looks pretty good. From to wing
is a little bit tougher like like
batwing. I mean those are tough fossils
to find like bat fossils or or bat
relatives and things like that.
>> We've got tons and tons of bird fossils.
>> Um which uh I I think we and we got a
pretty good story about feather
evolution, right? Because we think
>> here's here's another thing I'll just
jump into. You know, when we think about
feathers, we think about flight,
>> right? But you may now know from finding
dinosaurs that didn't fly but had
feathers.
>> Oh, feathers came before flight.
>> So, let's think about that one for a
second, right? Because again, humans
come in, we think like engineers. We
think, okay, I want to get up in the
air. How do I get up in the air? Let's,
you know,
>> we we design it, right? But that's
evolution,
>> you know. No, no. Evolution has to kind
of improvise its way there, right?
>> And [snorts]
feathers are just a great
>> illustrator of the evolutionary process
because they weren't there first for
flight. They were probably there for
either insulation, maybe a little bit of
>> um display, maybe a little bit of
camouflage, etc.
>> But as you start making these flaps or
whatever, now you got something out
there that can catch the air and then
you start to, you know, you evolve
flight feathers. You're like,
>> so feathers are a great illustration of
this thing of often
>> in biology there's this process we call
co-option. It we use something that
first existed for some other use,
>> right? and co-opt it into another
purpose. Yeah. So, evolution has to work
with the materials that are already
there, right?
>> It doesn't get to invent them from
scratch, right? In fact, evolution
doesn't work from scratch. It always has
to work on the pre-existing materials.
>> And so, it over time,
>> not even via mutation, not even via
mutation.
>> No, but no, mutation is it. So mutation
is the fuel that gives you
>> like could you could you for example
like uh have a mutation where suddenly
your kid is born and it has feathers.
[laughter]
>> It's a big step
>> or a feather-like
>> you could have a kid. It it's it's more
about if you already had for example if
you already had some kind of
feather-like structure
>> yeah you could have a kid with feathers
all over. Right.
>> Right. Okay.
>> But to create a feather out of nothing
>> Yeah.
>> is tricky.
>> It's not going to happen. What about
what about getting rid of something?
Because if we we look at the transition
from fish to land animals for
vertebrates,
>> the fish probably had a dorsal fin.
>> Yeah.
>> So, where dorsal fin go, right?
>> Stuff goes away all the time. That's a
great question. That's a great question
because
>> we often think about evolution being
this process of accumulation of new
stuff coming. We're getting rid of stuff
all the time. You may notice,
>> where's our tail?
>> Yeah, exactly. It's gone.
>> Right. It's gone. Right. cuz all our
relatives that have tails, right? So,
we've stopped that part of the
developmental process, we we we have the
capability to make a tail, but we don't
make it. Okay.
>> Um, so this goes on in evolution all the
time. Loss of stuff.
>> Do you think the loss is it more common
to lose than to reurpose?
Yeah, I probably I'd probably stick my
neck out and say that that loss is going
on all the time because as conditions
change, it's essentially a case of use
it or lose it.
>> Is there is there so there you think
there's some efficiency principle
underlying our design.
>> Yeah. Or the design of animals.
>> Yeah. Yeah. Because either making that
body part comes at some cost or
operating that body part comes at some
cost. So if it's not contributing to
performance
>> Yeah.
>> then here's the logic. mutations that
start to inhibit its formation or reduce
its size or whatever.
>> Those things are either of no cost to us
or they're actually beneficial because
we're not wasting
>> energy.
>> Yeah.
>> Building things that don't affect our
performance. So these things go away,
right? They go away over time. So
evolution sport, we can't plan for the
future, right? So we don't we don't we
didn't hang on to our tails just in case
we might need them. Okay? [laughter]
Right? It can't it can't wait. It can't
change that. It's it's all sort of being
weighed in the moment.
>> So things that enhance our performance
or are important to performance, we
retain. That's that natural selection
happening.
>> But things that don't affect performance
um survival, reproduction, etc.
>> Those things those those things go away.
>> Yeah. Yeah. So um loss is really common
when we look um you know through
evolution. I mean, you know, look at
things that creatures that are kind of
marked by loss. One of my favorite
groups are snakes, right?
>> Oh, the legs.
>> Where are those legs,
>> right? Well, they became burrowing
creatures, a whole lifestyle. So, they
evolved from lizards, right? So, they
evolved from four-legged animals, but
you have this whole group of animals.
They just
>> ditched their legs, right? Ditch their
ears, too.
>> Oh, geez.
>> No ears on snakes either, right?
>> So, um, yeah, loss is pretty common.
pretty efficient.
>> Snakes are pretty efficient.
>> They just reduce themselves to a tube.
>> To a tube. They're a tube. Yes. With
great muscles,
>> but they've been doing a lot of
inventing. Yeah.
>> Venomous snakes.
>> Venom. Yes.
>> Venomous snakes. And are have been
incredibly uh creative in the last 30 or
40 million years, inventing all sorts of
venom toxins to take down their prey.
And that's another example we see
throughout the animal kingdom.
Independent examples, right? You know
about spider venom, you know about bee
venom, you know about scorpion venom,
you know about, you know, uh, venomous
jellyfish and stuff. All independent
inventions.
>> Wow.
>> Of venom. So these are new molecules
that get invented, right? So this is
inventions going all the time, but that
helps those animals get their supper.
And that's a really powerful force in
evolution, right? If if this if you have
a way to get your prey, you have a way
to get food, this is a really this is
like evolution almost in uh fast
forward.
>> So language for humans is like venom for
the other [laughter] animals, right? You
can cooperate and hunt.
>> Well, in our culture today, language is
very much like venom. Yeah. But I think
you're making that analogy. But yeah,
these are this is uh you know, venom is
a special power that these animals have
and it's vital to essentially their
their daily being. And you know,
language is something. Yeah. We came up
with walking on two legs and and
language.
>> Uh pretty big inventions. You bet. And
you know, and vocalization,
>> right?
>> You know, to make that language.
>> So, let's dig a little bit deeper into
these transitions. So, the you know, we
have the transition of vertebbrates
going from sea to land. So, you know,
sometimes I come up with a crazy idea.
It makes sense to me and then I look it
up later, right? So, my crazy idea I
came up with was, hey, we have a tube
that goes from our mouth to our butt.
We're all worms. We just evolve, you
know, this extra stuff around the tube.
But then I went and looked where did
vertebrates come from. And the story was
something about some filter feeder that
um decided not to become a adult. And in
his laral stage, it was like a little
tadpole. Then it became the first um
cordate that eventually became something
like a lamprey and then a backbone. and
then on to land. It's an amazing story.
>> It is an amazing story. Yeah. Though
those early stages of of of backbone
creatures, you know, a little harder to
trace, you know, again, it's how good is
the fossil record. As we get a little
bit later, the fossils are great. You
know, the fish record and then the fish
that transition to land record. Thanks
to some brave paleontologists out there
who've gone to the far corners of the
world, we have a lot richer fossil
record now than we did just say 25 or 30
years ago. Really?
>> Yeah. Oh, yeah. Oh, yeah. No, we see
this in much better detail than we had.
Yeah. So, I think probably the
breakthrough fossil was something called
Tik Tok discovered by Neil Schubin and
his
>> tick tock.
>> Tik Talic. Tik Tok. No, no, it's
[laughter] not had nothing to do with
the social media app. Uh it has to do
with Inuit language. It was out of honor
to the Inuit. It was named um Tik Talic.
And it's uh this was a fossil discovered
in the Arctic. Um, that is just if you
had to draw a transitional fossil
between fish and four-legged animal,
this is it, right? This is what you
would essentially dream up. Sort of a
composite, right? Uh, or if you have
it's we call them fish and tetropods,
four-legged animals, tetropods. You
could say Tectalic is a fishopod.
>> Before I go into the detail, let me just
give you the significance of this, the
big picture significance. When Darwin
wrote the origin of species, he knew
that his theory had a lot of
predictions.
>> And one of those predictions was that
there should be intermediate creatures
out there between the great groups of
animals.
>> Yeah.
>> But he didn't have any.
>> I mean, he was essentially staking his
theory. And he in his book, he admitted
he said, "If these aren't found, you
know, my theory would be crushed."
>> Well, that's great science. He presented
his own falsifiable.
>> Absolutely. And this is what made the
origin of species one of the most
remarkable scientific works ever is
because he analyzed explicitly all the
weaknesses of his own theory. Like
where's the evidentiary holes right
>> now? Amazingly two years after the
origin of species somebody found this
creature out of a quarry in Germany
called archaopric you may have heard
about which had reptile characteristics
and bird characteristics. It was a
beautiful fit for Darwin's theory. And
it was 150 years almost 150 years later
that Neil Schubin and his colleagues
after a lot of searching find this
creature in the in the Arctic um that
has uh transitional features. It's its
eyes are more on the top of his head as
though it's kind of looking, you know,
looking up as opposed to looking, you
know, side to side a little bit. But
there's changes taking place in its
limbs. And so to come to land um the
fish lifestyle has to change quite a
great deal. It needs limb. It needs
those limbs to bear the weight of the
animal, right? Because it's up on up on
all fours as opposed to floating in
water.
>> Those articulated digits as opposed to
just a flipper that you could imagine is
clumsy. If we look at things like seals
on land, right? They don't look that
com. They don't look that agile. Right.
Okay. Right. But you know if you have a
much more mobile
>> so it had
>> Yeah. It has un it had the skeletal
makings of the digits. That's what we
can see in what we see in Tectalic is
it's a transitional creature. It's not a
full-fledged walking around tetropod but
it's heading that direction. That's what
we can see about it.
>> Um it's uh it has a neck that can move
relative
>> fish.
Yeah,
>> it's got a neck. How about that? Right.
>> So, that's where those are sort of the
giveaways if you're you're you know,
it's definitely not a fish. It's not a
full-fledged, you know, full-fledged
walking four-legged animal,
>> but you can see it head in that
direction. That's why it's such a
remarkable what we call these
transitional fossils because it's really
marking a big transition between two
groups. We're not talking about between
two species. We're talking about fish to
four-legged animals. One of the big one
of the big transitions. If I could just
insert here, you know, when people um
criticize evolution, you know, they they
want to disbelieve it. They will point
out, they say, "Oh, we see micro
evolution, yes, but not macro
evolution." So, what you're describing
is what they would describe as
macroevolution, evidence of macro
evolution.
>> Yeah. You're seeing the big transitions
between the big groups, the big
classifications, right? The big
categories in this case of animals,
you're seeing this these transitional
forms. So I'm I'm just describing to you
the that the
features of this creature that so tell
you a little bit about its lifestyle and
how is it different from a fish and how
is it different from a four-legged
animal? But the evolutionary process is
also what's going on? How do you change
your body?
>> Yeah.
>> How does the body evolve?
>> Right.
>> Now this is a really interesting area.
Again 50 years ago couldn't have said
much.
And that's because the process of
development, the process of making an
individual from an egg to a complete
individual was a black box. I mean, we
could we could watch it maybe in a, you
know, under a microscope, watch a frog
egg develop or something like that. But
we were just spectators, right? We were
just
>> You're talking about at the process of
egg. Yes. Embryo.
>> Yes. All the way to animal, right? All
the way to whether it's, you know,
juvenile or adult animal.
>> That process we could watch it, right?
you know, with
>> I guess what I'm getting at with that
question is is all of this baked in at
those very earliest stages because, you
know, we talk about how humans have
gills in the womb, right, when we first
start and and this sort of thing, but
ultimately we become a full-fledged
human at some point.
>> That's right. That's right. So, that
developmental process and I let's just
take a second to to to appreciate this
because it's almost like it's an
everyday process going on around us. If
you've seen, you know, you mentioned
frog eggs, you know, you see a frog egg
in the pond, you know, that's about to
be one of the most spectacular
pageantss that exists on Earth. The
making of a complete individual from a
single-sellled egg
>> is remarkable. I've watched it millions
of times never bored me once. Still
remarkable. And of course, anyone who's
gone through, you know, having children,
oh yeah, you know, and you sort of
imagine all those stages and if you're
watching the ultrasound, you're like,
"Oh my gosh, look at this whole being
that's coming together that's going to
be this remarkable thing." So, I think
if we just appreciate that and we say
this, this has got to be also one of the
most complex things we can imagine. Yet,
it's every day, right?
>> Whether it's, you know, a tree, you
know, from a from a acorn or whether
it's, you know, you know, a elephant
from an egg. Yeah,
>> this is every day this is happening on
Earth, right? Is is this process of
development
>> and we really didn't have much insight
into it until I'm going to say about
beginning about 40 years ago, we were
able to start to understand what was
going on. What were the chemical changes
taking place in an egg
>> that would start to shape tissues,
organs form and start to say, "Okay,
here here comes the creature."
>> [snorts]
>> This is this was a huge revolution in
biology to to understand development.
Why is development important from an
evolutionary point of view? Because it's
changes in development that give you
different kinds of creatures.
>> That's the process. If you're going to
make a creature with a longer neck or
shorter limbs or whatever, that's all
going to happen in that process of
development.
>> Yeah.
>> So, the actual process that's being
tweaked with in evolution is the process
of development. So if you want to
understand how evolution works, you got
to know how development works. That's a
decision actually I made as a young
biologist. I said okay I want to know
how evolution works. I became a
developmental biologist first.
>> Okay.
>> I wanted to understand the embryionic
>> development process. And by
understanding that what that meant was
what are all for example all the genetic
ingredients? What's what's necessary to
make a complete creature for it to all
go right?
>> Yeah.
>> Okay. just and it's as I said I I you
see this smile on my face because it is
spectacular. It's it's amazing and you
know I think a lot of people who wrestle
with evolution they're like you know it
seems
hard you know it's hard to imagine you
know how you get a from a fish to an
amphibian or something like that. Well
let me tell you it's hard to imagine how
you get from a single-sellled egg to an
adult human with 37 trillion cells.
>> Right. Yeah. I mean we basically start
off as liquids. [laughter]
Yes, exactly.
>> But we can see it. And this is the
thing. We can see it with our own eyes,
right? And we just can't see evolution
with our own eyes. It happened in the
past. It's buried in the rocks, etc.,
etc. It's kind of hard for us. It's an
incredible amount of time. Exactly.
>> But whether it's a day, a week, a month,
or nine months, we can watch development
of creatures. And now we can go in there
and we can tinker with it. We can
understand how exactly this thing
unfolds.
>> And that's a remarkable set of insights.
How do you do that in the lab? Do you
have certain species that like how to
use mice quite often? Is
>> Yeah, you know the but we have to give
credit where credit is due and and the
big
>> catalyst for understanding development
is the fruit fly.
>> The fruit it's always the fruit fly.
Yeah. Well, let me tell you the fruitly
baby paid my mortgage. Okay. So,
[laughter] that's why we got to credit
where credit's due. A fruitly what
what's the advantage of the fruitly very
short life cycle just a couple weeks or
so. uh you can keep a lot of them in a
small amount of space and they're cheap
to keep but they are complex animals
right so you start you have a little
tiny animal like that it builds all
these kind of tissues right it's got
wings it's got limbs it's got a little
heart right it's got a brain it's got
eyes so we can watch we can watch the
development of these creatures and we
can change what's happening development
>> so let me so I'm assuming it's happening
in like a a egg pupa type transition
>> egg larva pupa adult yeah
>> so are
like scanning the larvae and
>> sure we can looking at the inside
>> we can put them we can put all those
stages under microscopes and see what's
happening but what gave us power was
>> genetic approach to it. So what a
genetic approach is we deliberately
induced mutations in fruit flies and
started studying the interesting flies
that would come out. So some like one of
the most famous fruit flies was fruit
flies that instead of antenna have legs
on their head.
>> Oh jeez. Yeah,
>> that doesn't sound very useful.
>> No, but it's a it's a laboratory mutant
except for as incredibly useful as a
laboratory mutant because those are
fully formed legs in the place of
antenna.
>> And you start thinking, how do you put
legs in the place of antenna?
>> And then you map where those mutations
are and it goes to a single gene
>> and that gene turns out to be a gene
that orchestrates a big part of the
>> So let's talk process. Yeah.
>> Is it the case you blindly
ch make a genetic change, you see what
the outcome is and then you go back and
look at the genome.
>> Bingo. Exactly. And you're you're
picking those flies that are
interesting, right? You're saying, uh,
well, maybe I have a fly that changes
eye color. I go map where that happened.
But in this case, I find change a take a
fly that has legs on the top of his head
and I say, what happened?
>> So, let me let me ask you a question
there. So in in in astronomy, yeah,
>> which I know a lot more about,
>> one of the ways that uh you discover
exploding stars and moving objects like
asteroids is you do an image
subtraction. Yeah. And what you know
everything that remain the same
disappears and the only thing that
remains is what changed, right?
>> Is it like that with DNA?
>> It's logically it's very similar to
that.
>> Okay. to a geneticist, it will map the
mutation because it can it can figure
out where in the genome the change has
happened. And you can do that at sort of
a low level of resolution, sort of
chromosomal level, and say, I think it's
in this part of the chromosome. Now,
with DNA sequencing tools,
>> we can just sequence the animal and go,
there it is right there. That's the
change. The parent didn't have it.
>> Wait, that's easy for you to say, man.
When I look at images of these DNA
sequences, I just see like barcodes, you
know? I just see dots of
>> Yeah. Well, we need help with computers
to to sift through all that DNA. But
yeah, we can now pinpoint mutations just
sequencing DNA. If you take an animal
that that doesn't have the change that
has antenna in the right place
>> and the animal that has the legs on top
of its head, you can see the difference.
Bang. Okay. Couldn't do it in 1983 when
I got into the game.
>> Got it. [snorts]
>> Didn't have those tools. We we've got
those tools now.
>> So, it was a it was a longer march to to
discovery in those days. But those
discoveries, what were really important
is it taught us that there was a small
subset of genes. So the fruitfly has
maybe 14,000 genes, something like that.
There was a small subset of genes that
kind of orchestrated development that
had a really outsized impact on
development. And if you messed up one of
those genes, weird things happened. Like
there were genes that you'd wind up with
half the number of segments.
>> So you know, if you've looked at
insects, you've also looked at, you
know, a lobster on a plate, whatever.
It's segmented, right? It's got uh some
segments of the thorax. It's got
segments of its abdomen. So there are
genes that in the fruitfly you mess them
up, it comes up with half the number of
segments, right?
>> Or there are genes you mess them up, it
has no eyes.
>> Oh wow.
>> Right. So you got a you got an eyeless
fly, an adult, a fly with no eyes,
>> right?
>> Well, why was that helpful? Well, we map
the gene for eyeless. It tells us a gene
that's necessary to make an eye.
>> And this is a different trajectory we're
this conversation is going to go on. And
then you know what blew our minds?
>> Humans have that same gene. And when you
mutate into humans, we don't have eyes.
>> What? That's what I was going to ask.
Does it translate to other species?
>> Yeah. No one expected that.
>> So that means that the eye making gene
preceded the split.
>> That's right.
>> Exactly. That's the correct inference.
Right. And that blew. No one expected
that. You think of a fruit light
fruitfly anatomy, human anatomy. Look,
>> I was I had a PhD. I was going off to do
this work and my mentor said, "You work
on fruit flies, you're walking off the
edge of the earth because nothing you're
going to find has anything to do with
making furry animals like us."
>> Yeah,
>> that was the bias that existed across
the world.
>> And then, you know, a little small group
of people studying fruit flies like,
"Hey, look at this gene. Hey, look, you
got it, too. We got it, too. Oh my gosh,
mess that up. We don't have eyes
either."
>> So, what about limbs? Right. So, like
the legs on the head. So, fish have
fins.
>> Yeah. Arthropods have limbs. So they
have some common ancestor for which the
limb gene exists that you could
manipulate.
>> Exactly. Actually uh shown in my lab
that that common limb bearing. Yeah.
>> I came too late to to get a
>> Yeah. You could you could get Yeah.
Yeah. 1997. You got If you got to my lab
in 96, you would have done it. Again,
surprised us because the dogma at the
time was these limbs were all
independently invented, right? Because a
fly walking leg is a hollow structure
it's walking around on and you know and
our limbs are got bone in the center all
that kind of stuff.
>> But essentially as appendages that stick
out from the main body.
>> Yeah.
>> Those instructions go all the way back
500 million years
>> and these are just unfolding differently
in in you and I from a fruitfly. So the
fruitly was a passport to the whole
animal kingdom.
>> Wow.
>> Nobody saw it coming. But I'm smiling
because I took the leap
>> and as I said it has paid off
handsomely. [laughter]
>> But it also besides now allowing us to
study development and all sorts of
creatures, it allowed us to study
evolution because then we find these
bodybuilding and body patterning genes.
Again, it's a small subset of genes that
are sort of devoted to that. A lot of
genes, they just kind of run the
physiology of normal cells, but there
are genes devoted to sort of sculpting
the body. They affect the number, the
size, the shape, the color of body
parts. And that's the stuff that's
really interesting in evolution. So then
we started studying things that look
different, either
>> insects versus other kinds of arthropods
or maybe just like, you know,
butterflies versus fruit flies. How do
you get, you know, spotted wings and
things like this?
>> And then we're starting to figure out,
oh, how do you make something new?
>> And the general rule, I'll just give you
the breakthrough. The general rule is
that basically you take old genes and
you use them in new ways.
>> Okay. Okay.
>> Isn't that a simple statement?
>> That's a very God.
>> If I had known that new creations,
>> if I had known that, I could have gone
to Wall Street and skipped my whole
career in biology. But it turns out
>> it was a much better journey. But yeah,
so these and this is also telling us why
these genes have been preserved for
hundreds and hundreds of millions of
years is they get used in new ways in
different creatures. Speaking of which,
you know, we we we mentioned how we
found this evidence of Neanderthal DNA
in humans and Denisin.
>> Yeah.
>> DNA in humans, but we have even more
viral DNA in our cells. Right. And so is
that a result of viral infections
happening in the animal across its
evolution or was it all early?
>> Oh, no. This is keeps it keeps
happening. Yeah. Yeah. Yeah. Yeah. Yeah.
So um yeah, we we'll see these viral
these vestigages essentially of of
viruses spreading through DNA. We see
this in all sorts of lines of of
evolution and it and it can happen a new
all over the all
>> well it first came to my attention when
there was a recent um mention of a
discovery that the sheath of our nerves
which allows fast long range nerve
signal transmission was inherited from a
virus. So talking about I don't see how
a virus needs that.
>> Yeah. Yeah. [laughter] But we hijack
that genetic information and and
repurpose it in a new way. Yeah.
>> And this is this is what I mean this
sort of repurposing this sort of
co-option. So we might take you know
animal bodybuilding genes and use them
in a new way. And that's in fact how a
butterfly puts spots on its wings.
That's how have you seen beetles with
really big horns? Yes. Okay. They're
taking limb building genes and they're
putting them out on and they're
activating them on their head and making
these appendage like things on their
horns as examples.
>> But we also we hijack that that viral
material and we use it um for for it's
it's just material to be used and
reused.
>> What about spots and stripes? Stripes
and spots. What What was that
originally?
>> Well, spots the the spot making program
in a butterfly actually uses a little
bit of the limb building program, but it
turns it on really late. Okay. So, if
you're just building, if you've got the
embryo and it's just really an insect
embryo, they often would look like
little mini footballs, okay? And you
know, like a little bit of an oval,
right, without any uh, you know, shape
or form, you know, no no specific
tissues, whatever. You activate, well,
you activate the limb program, then you
build limbs and you build the basic
limbs of that body.
>> [snorts]
>> But days and weeks later when you have
the pupa and you've already made limbs,
you've already made the wing. Turn that
limb building program on in the wing,
connect it to the pigmentation program.
Okay? So you make a new connection
>> and you build a pattern of spots.
>> That's a whole new realm you just
introduced into this conversation. It's
not just turning genes on and off. Now
you can connect them.
>> You can connect them. Right? So there's
this whole I'll kind of sort of say the
software which is how the genes are
connected in development. And it's those
changing of connections that's a big
part of the evolution of anatomy. Okay?
So, you could take the same I'll just
give you this thought experiment.
>> Take 14,000 genes and I think I can
build a fruitly, a lobster, a crab, a
dragonfly, and a butterfly out of those
same 14,000 genes. I don't need any new
genes. All I have to do is just keep
changing their wiring.
>> What?
>> That's the big discovery. That's the big
discovery. Yeah.
>> Holy cow. It's not the genes you have,
it's how you use them. And how you use
them is these connections between the
genes.
>> So the genes are like Lego bricks.
That's right.
>> You can build different animals.
>> You can build different animals out of
the same genes. Yeah.
>> Wow.
>> Yeah. Yeah. And [snorts] then we see
that that toolkit
>> a lot of homework.
>> I just got a lot of thinking to do now.
>> All right. Pretty.
>> But hopefully it's a little anchored.
It's a little anchored. But then you
say, "Okay, well I need to know more.
>> That tool kit's been preserved through
500 million years. We've got it.
Earthworms have it. Elephants have it.
Same set. Well, they've got the same
They got the number varies. We probably
got 20,000.
>> So, it wouldn't be the case that if you
look at species that evolve later, they
would have the, you know, so there's a
sort of core set and then you add
>> or so there's a core bodybuilding set.
>> Yeah.
>> There's a core kind of physiology set
that just has to run to run cellular
metabolism. That's probably I don't I'm
going to say five six thousand genes
that just to just to do what every cell
needs to do.
>> Couple thou in us a couple thousand
bodybuilding and body patterning genes.
Uh and then the rest may be you know
like we got a like we have genes for
immunity big number of genes involved in
immunity adaptive immunity to to deal
with infections. So there are inventions
that have come along. Our immune system
is far more sophisticated than what you
find in animals without backbones for
example. um where
a lot of mammals I said are good good at
smelling so are insects. They got a lot
of the same smell receptors and stuff
like that. So you see expansions and
contractions in some of these
capabilities as lifestyles change. But
there's sort of a core bodybuilding and
a core set of uh cell physiology genes
that you'll just find across the whole
animal kingdom.
>> Hey everyone, if you're loving this
podcast, please go ahead and like us or
leave a comment. And also make sure to
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Your support means everything and helps
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[music] Now back to the show.
So I want to bring up a word that um I
heard a concept and I looked it up when
I first heard it and it was when I was
preparing to have a conversation with
you, but I've since forgotten
>> and the phrase is Evo DVO. Sounds like a
a European band or something, right? Uh
>> so somehow what happened was this is
called evolutionary developmental
biology
>> got shortened to Evo DVO for the rhyme
with a little bit of a play on the DVO
thing. Okay, but I've really been
describing to you evolutionary
developmental biology because what
that's saying is
>> the DVO part is that changes in
development are what give us anatomical
changes in evolution. Okay.
>> And by development you mean embryionic
development?
>> Yes. So it it it it's changes that
happen during the process of making a
creature are what will give you
>> different appearing creatures. Right. So
if you're going to have changes in your
>> anatomy, those are taking place during
the process of development
>> during construction.
>> During construction. Exactly. [laughter]
So there must be some instructions that
have changed that change the
construction. So you get a different
kind of animal.
>> So Evo to constru from instruction to
construction.
>> That's right. That's right. So it
changes during the process of
construction. So all evo devo means is
that and it really focuses on changes in
form right changes in that
three-dimensional form that how we to
even describe creatures right
>> is it's saying I I I'm trying to
understand the evolutionary changes in
development that's what an evo scientist
does.
>> So here tell me this then Mr. Smarty
pants science evo devo guy. Could you
take embryionic hakee and stick a needle
in me change a instruction and I now
have fangs and venom?
[snorts]
>> Yep. [laughter]
>> Oh what what
>> now? I'm going to say in principle I
wouldn't say it's impossible. There's
probably a little bit of knowledge that
we would need to build for, but when you
know the program for making teeth and we
know a lot about it and when you know
how you might be able to sort of modify
that a little bit to make an elongated
tooth with a with a central canal, which
is a fang,
>> okay, then we could we could tweak that,
right?
>> Wow. So, so
>> and then you know I we know how to make
venom.
>> Wow. That's what I wanted to get into,
man. Because making this this molecule
venom it is such a mysterious thing to
me. I was like, how would that even come
about? Right?
>> Oh, it's the general idea here is this.
All these characteristics we're talking
about, all these creatures that
fascinate us, right? The instructions
for making them are in the DNA,
>> and that book has been blown wide open
to us, right?
>> So, let me ask you a question about that
then. This is I'm sorry to interrupt.
>> Oh, no. Go anytime.
>> Does every animal have all of the
instruction book? Is it or or is it
later animals have all of it because
they have everything that came earlier?
>> Well, everybody's got their own
instruction book. Sometimes some
chapters have been torn out and left
behind. Okay? And some have some new
chapters.
>> So, but they have a lot of instructions
in common because they have they have
their animalness in common. They have a
lot of cell biology in common which even
is deeper than animals that they got
cell biology that's in common with fungi
and bacteria and plants and stuff like
that. Right? So, there's there's some
common parts of the code book. There's
some unique parts. But that codebook
which was again not accessible to us in
starting to become accessible in the
early 1980s and then
>> today oh my goodness I mean you know the
speed and the cost involved is is now
almost trivial right where it used to be
you know too expensive or impossible
>> so yeah I mean we can we can look at any
animal we are having a great time we are
having a great time
>> and um so what we do it's kind of it's
it's a lot of science is detect
detective work, right? You're playing
hunches, you're trying to look around,
you're trying to find those clues, etc.
And kind of DNA science these days is
exactly detective work. You're saying, I
okay, I've got this creature here that
doesn't have this capability. I got this
creature here that does have this
capability, and I'm looking around to
try to figure out what does it have that
it doesn't have,
>> right? And if I compare, for example,
nonvenenomous
animals, take a lizard or something like
that to venomous snakes or nonvenenomous
snakes to venomous snakes, I can see
exactly what's going on when I look in
the right place in the genome.
>> And that's telling us that what's
happened is again this co-option thing,
>> taking something that was used for some
other purpose and repurposing it. And so
what's basically happening is that
snakes are taking proteins that have
been used inside the body to do
something normal.
They're making them usually in
significant amounts in a gland
and putting them into prey through that
fang and they're putting sort of
abnormal amounts of of some either the
same or a modified protein into that
prey and usually disrupting one of two
things. and and things like venomous
snakes, they're either messing up
>> blood hemostasis like clotting and heart
rate and and blood pressure
>> or the nervous system. They're stopping
the nervous system. So, for example,
respiratory arrest.
>> So, how does this begin before I'm sure
it doesn't start out as full-blown fang
venom gland.
>> So, they're so the chemicals just being
secreted in their mouth and they bite
and then
>> probably components of saliva. Yeah. And
imagine the way these animals were first
taken down their prey was they're biting
and holding on.
>> Yeah.
>> Now biting and holding on is kind of
dangerous. Yeah.
>> Right. You can go for a bad ride and get
really roughed up.
>> So you can imagine the ability to strike
and then sit back while the prey dies.
>> Yeah.
>> Is a little bit safer attack mode,
right? So if you can deliver something
in your prey during that initial bite
>> that will subdue it.
>> Yeah.
>> Then there you go. And so we've got a
lot of enzymes in our mouth. We had a
lot of enzymes in our saliva. Okay?
>> And so what what venom evolved from was
some basic capability of having, you
know, digestive enzymes and things like
this in our saliva. And instead of just
sort of those things passively getting
transferred during a bite uh through
this modified tooth, the fang, a a
delivery apparatus evolved that could
deliver a more potent wallup of that
kind of stuff.
>> Wow.
So you can sort of feel that transition
from a bite hold on with some kind of
weak saliva
>> right
>> to
>> strike sit back very potent venom
delivered and and let it do the job.
>> This sounds somewhat like what you
described earlier where you connect
>> genes but now you're connecting the a
saliva gland to a tooth formation gland.
Yeah.
>> And now they become a single system of
venom.
>> Now that's that's an apparatus. Yeah.
that that that then does your job. And
when we look at the venom components and
these are these are fascinating sorts of
things and I I I got so many stories I
want I'm trying I'm running my head and
say which one should I really tell you.
>> Yeah.
>> But I'll tell you one that's that's
really striking that one of my students
is studying right now. So I don't know
the reputation Australian snakes have.
Right. We've probably heard Australia's
dangerous.
>> Oh yeah. I was as we're having this
conversation I was sitting here thinking
about the box jellyfish which is another
>> another one. Yeah. So on land they had a
couple snakes called brown snakes and
taipans. And uh they make me nervous.
Okay.
>> And I like snakes. And here's the deal.
>> Have you been bitten?
>> Uh I've been bitten by nonvenenomous
snakes. Yeah. I got an old buddy that uh
uh he had a great saying which was he
said there were two kinds of snake
enthusiasts. Those who' never been
bitten and those have been bitten a lot.
[laughter]
>> So there's no if you know me where that
comes from. Yeah. Because Okay. You can
you can you can piece that together
[laughter] anyway.
>> Oh, I get it.
>> Yeah. Yeah. So,
>> uh, taipans and brown snakes, they're
remarkably toxic. So, so you know, ounce
for ounce of their venom, one of the
most toxic things on the planet. What
have they done? And this is just to give
you a picture of what what's the
strategy of venom.
If you look at what their venom does to
the prey blood, you can watch it in a
test tube. It will clot like that.
>> Okay. What they've done is they've taken
two clotting proteins, proteins that we
normally use to clot our blood in
response to injury.
>> Yeah.
>> Packed them into the venom gland. They
inject them into prey and that blood
clots like that.
>> So, [clears throat] it's essentially a
instantaneous stroke and loss of blood
pressure.
>> Prey down.
>> Wow. So they've taken proteins that are
used inside the body and then using them
kind of outside their own bodies onto
prey. Yeah.
>> And that's the strategy of the venom. So
you'd think venom, wait, what is this
kind of, you know,
>> special substance, etc.? No, it's using
existing proteins
>> in a new way.
>> Wow.
>> Right. Yeah. And you can see when you h
or when you already have that protein
that can clot blood, it's just a matter
of making more of it and delivering it
in a new way into another creature in an
unregulated way. So that creature that
creature balances blood clotting very
carefully. You just overwhelm it and it
clots instantly.
>> Do the prey respond with evolutionary
changes to resist.
>> Brilliant. It's it's an arms race out
there. It's an arms race out there. And
we see this all. Yeah, we see this all
over the world. When prey are being
prayed upon by venomous creatures,
they're evolving all sorts of
mechanisms. Some of those are
>> well, they're all sorts of levels. So,
the targets of the venom toxins are
evolving. There's a lot of pressure,
right? Because if you can be less
susceptible, then that means maybe you
you got better chance of surviving a
bite
>> or a bite that's sublethal is not as
>> hazardous, you know, that sort of thing.
It's going on all it's remarkable. So
this is the the joy to an evolutionary
biologist or you might say the purpose
to an evolutionary biologist is studying
this is that those arms races going on.
Meaning the the there's pressure for the
predator for the for the venomous animal
to keep coming up with more and more
potent venom and there's pressure for
the prey to keep coming up with ways to
evade that venom. So you sort of have
evolution and fast motion going on in
both sides and that allows us to to it
it makes the evolutionary process sort
of we just have more stuff we can dig
into when it's when it's happening on
that kind of time scale. So it's
measured countermeasure that's why we
call we refer to them as as arms races
obviously from from the human analogy.
>> It it's all over the place. You go out
west
>> there are you know rodents that are you
know resistant to rattlesnakes. There
are snakes that feed on rattlesnakes
that are resistant to rattlesnakes.
>> Oh yeah. So here here's a question. So
when we develop antivenenoms from the
movies I've watched.
>> Yeah. [laughter]
>> They we typically make the antivenenom
from the venom.
>> Yes.
>> Do we ever use the praise mechanism to
create antivenenom?
>> God, you got great questions. Nobody's
done it yet, but I think that's the I
think that's the new opportunity now
that we've learned enough. This is
actually something my lab works on. Now
as we learn enough about the natural
defense mechanisms, yeah, we can exploit
them. So what we did this antivenenoms
got started in the late 19th century. At
the same time we were making like
antitoxins for for things like dtheria
toxin and tetanus toxin and stuff. And
what we do is we would immunize an
animal like a horse
>> with these toxins or venoms take the
blood of that horse. We'd refine it and
that would be the product we would give
people who if they had tetanas or if
they got bitten by a snake. Okay. So
that's a 19th century. So you're using
that animal's immune system that has
been exposed.
>> That's right. That's right. And given
that um and you know we use antibodies
today, I mean you know half the drugs
that we use today are monocone
antibodies that we make in a lab that we
give people for everything from cancer
to eczema or whatever that sort of
thing.
>> But these natural defense mechanisms
some of them look really to me they look
really really potent and broadly acting.
And I think I think they're going to be
some antivenenoms coming out of this new
branch of knowledge from the from the
way that the prey defense mechanisms
work.
>> So given how advanced we are with our
capabilities, it it I wonder why there's
a certain capability that we don't have.
And here's what that is. We're
constantly, you know, I constantly hear
about researchers going to the Amazon,
finding some plant or animal that
creates some novel molecule that's
useful for us. But why can't we say,
"Oh, here's a problem we have. I'm going
to use my computational powers to
calculate what molecule I need to deal
with that problem. Then I'm going to
synthesize that." So instead of
searching for it in nature,
>> take on that role ourselves, but in a in
a direct way.
>> We do both. We really do both. And I'll
just I'll give an example. So, for
example, you know, we have so much
better control of AIDS now than we did
in the beginning or even the middle of
the AIDS crisis. And a lot of those
drugs are designed
by humans out of thin air. Okay? We're
saying, "Okay, I need to design a drug
that's going to fit into a pocket of an
enzyme and shut that thing down." And we
design that on computers and we make it
in the lab and then we test it and there
you go. Okay? So, that's drug design
sort of from scratch. We do it.
>> Okay. At the same time, nature has had
millions and millions and millions of
years to work on some of these things
and come up with sometimes pretty
complicated chemistry, a lot of
antibiotics, etc. Those aren't things
that a chemist would synthesize just in
their spare time someday, right? They've
got they're fancy looking molecules when
you first look at them
>> and you're like, "Yeah, nature's has
come up with." Sometimes those are
they're made by you know sort of longer
pathways lots of chemical modifications
because like those arms races that have
been happening between you know say a
fungus and bacterium in the soil oh my
gosh those are so old those so let's
exploit what nature's been tinkering
with for millions and millions of years
>> millions of millions you mean tens of
millions of millions hundreds of
millions of years etc.
I mean a great example of that
underappreciated story is the first
statin.
>> What is a statin?
>> Statin everybody. People aren't no stat
people are on Wuang clan is from
>> people are on statins to control their
cholesterol.
>> Oh right. Yeah.
>> Okay. the first statin came from a
fungus because a a Japanese researcher
I'm gonna say back in the early 80s
thought you know if I can stop the
cholesterol metabolism
uh I'm going to if I can get involved
with cholesterol metabolism I could
really benefit for example um
cholesterol levels in humans well I'm
betting that somewhere out there in
nature that's a strategy that some
fungus used to stop you know an invader
and he screened like 6,000 streams Wait
a minute. How do you make that
connection? Human cholesterol fungus
stopping bacteria. That's
>> Yeah. Well, it was kind of the same
strategy people use to find antibiotics,
right? Is is a lot of these things are
are fungal products or antibiotics. So,
he thought there must be like an
antibiotic I can use for cholesterol,
>> right?
>> Because cholesterol is used in making
membranes. He thought, okay, that that
might be a target that that fungus would
use.
>> I think he screened like 6,000 strains.
>> Wow.
>> Fungi.
>> And that launched a drug revolution. And
he came up with the f the first stat.
And once you got the first statin, you
got the first principle. And then the
chemists came along and they said,
"Okay, we'll modify this. We'll modify
that. We'll make this a little more
potent. We'll make this a little, you
know, easier on the stomach, whatever."
But the first statin was pulled out of
nature. So there's two strategies going.
Use nature if you can. And I I feel the
same way with antivenenoms.
>> These animals have had
>> tens of millions of years to work on
these defense mechanisms. Let's exploit
that knowledge while at the same time we
in the laboratory, we can also use our,
you know, we got ever more powerful
tools for designing drugs. But um
>> so you want to do both.
>> We live at a time we live in a time
where we can do both. We do do both and
let there and and let the competition
you know begin. We because
>> very often in drug development there's a
first generation where you didn't have
something then you have something
>> but you know it's like this was true for
AIDS. I mean you had to take so many
different pills and they were so big and
there were side effects and all that
stuff. So over the years what you work
on are more potent drugs operating off
those first principles, less toxic,
right? More convenient to take uh you
know and and it's the same thing going
on with with late weight loss drugs
right now. You know, you know the root
of this weight loss. Yeah. You know the
root of this?
>> The root of this.
>> Tell me [laughter]
monsters.
>> What? No way.
>> Yeah. This is a discovery. The weight
loss drugs are based on a discovery made
in Hila Monsters. So reptiles, you know,
can go a long time between meals.
>> Yeah. Yeah.
>> How do they do that? How do they control
their body physiology in these long
periods?
>> They're coldblooded.
>> No, they they're doing a little more
than that.
>> So the lead to what became OMIC and
Monaw and all that kind of stuff were
discoveries in Hila monsters.
>> Wow. This is why when you talk to
biologists, we plead for the support of
basic research.
>> Yeah.
>> Because we we we the more we learn about
how nature works, we come up with new
ideas of how to, for example, intervene
in in human medicine. And if it weren't
for people studying how Hila Monsters
regulate their physiology in the long
gaps between meals,
>> we wouldn't have these weight loss
drugs, which we now start to understand
are helping cardiovascular health, liver
health, all this kind of stuff. And
we're going from injectables, right?
Because you're watching the watching the
evolution of the drug making to now
oral, which is a lot more convenient, a
lot easier for compliance. We're also
reducing side effects, etc. It's the
same story being told. a lead from
nature.
>> Yeah.
>> A first inclass drug. Then
>> you know the create the collective human
creativity gets involved and we come up
with things that are more potent, safer
to take, etc.
>> Well, well, tell me this then. Tell me,
have we crossed the threshold as a
species? Because one of the things that
was pretty impressive is how fast we
developed a um
vaccine for this pandemic that we just
had.
>> It was amazing. So, is it the case now
that we've reached a a threshold in our
understanding of chemistry and biology
that we have freed ourselves from the
possibility of extinction from bacterial
and viral pandemics?
>> It's a great question. Obviously, we
know this has some pretty profound
implications right now. Um,
>> well, I mean, I would say I would say we
gotten better. we gotten and in my
lifetime I'm stunned. I'm stunned by the
rapidity of innovation. This is things
have gone faster farther than I ever
could have imagined. You know,
scientists are optimist. You have to be
an optimist to be in this game, right?
So even my most optimistic projections
of where we might be. We're far and far
beyond that. Okay.
>> So I would say yes, if we're on our
toes,
>> yeah,
>> our combinations of, you know, vaccine
development, drug development, etc.,
Yeah, I think we can handle what
>> basic research.
>> I think we can handle what's coming down
the pike. Obviously, what we're living,
what we're experiencing right now is
that we're having a little bit of
societal struggle of exactly
>> how those things are prioritized and
who's doing it. And we've got
>> a lot of misinformation out there about
um you know, actually what happened and
you know, what's safe and what's
effective and things like that. So,
we're we're we're struggling a little
bit on the information side of it, but
on the scientific prowess side, we're in
great shape.
>> We're in potentially great shape, I
should say. And and that's why it's, you
know,
massive layoffs in the scientific
community are worrisome. And obviously,
we don't want to get into the politics
of that. Let's but let's get into the
reality of that that that has to do with
our capabilities, right?
>> Yeah. There was a scientist at NIH
uh uh Kazika Corbett who was happened to
be studying what turned out to be a
relative of CO 19. She was studying
actually a thing something called uh
Middle Eastern respiratory syndrome
virus MS
and it and this has never touched our
shores or anything like that or never
gone pandemic. Okay. But it was a
problem in the Middle East and I believe
it was transmitted by camels.
And she was studying this spike protein
on that virus when along came this
report from Wuhan,
>> right?
>> What became, you know, COVID 19. So she
and her collaborators had knowledge,
basic knowledge about this family of
viruses and these spike proteins,
>> right? spike proteins are on the
exterior of the virus that allow
>> and it was a it was a vaccine target for
her for MS
>> and she could immediately translate that
knowledge. had taken her years working
on MS and go, "Okay, I got something new
here.
>> Activate the toolkit." Right.
>> So, we happened to be in a fortunate
position that there was some basic
knowledge about this kind of obscure
family of viruses, right?
>> Yeah.
>> And and we could activate it and then we
activated again sort of this knowledge
of mRNA vaccines which was had not
really been put to the test on a large
scale. So what I thought would have
happened postco is that we would have
also filled the shelves. You know,
mostly we've got paxid, right? And my
wife had it last week because she had co
Oh jeez.
>> Um
I thought we'd have more antivirals on
the shelves by now because what the
pandemic
uh which was based on this particular
family of viruses that co belongs to is
we didn't have anything ready to go.
Like for flu, I'm going to say my my
understanding is we've got about four
flu drugs to go. So if a if an influenza
virus gets out of control right now and
we don't have a vaccine, we do have
drugs and that might keep people at work
and people in school etc. Right? So the
LA not having a drug was a big challenge
of
>> COVID
>> and I would have thought we'd gotten
ahead of that now and we would try to
have essentially
ready to go antivirals
in the case of some other outbreak.
>> This is something I'm a little worried
that we didn't
>> fully implement the lessons of COVID,
right? Because while it takes time to
get to a vaccine, if you have some
off-the-shelf drugs, society can keep
functioning while we essentially, you
know, treat people that have the virus.
But we had no treatment for CO. We had
no specific antiviral treatment for CO.
>> So we've we've got to do a little more
>> both imagination and sort of
infrastructure
>> uh to be well prepared. So you're you're
going back to your question of have have
we crossed a threshold? I think we it's
it's it's probably within our reach, but
we haven't grasped it yet. And that's
just sort of a societal challenge of
investing the resources and saying,
"Hey, we want to have a shelf of
antivirals to throw at whatever comes
down the pike next."
>> Got it. So, the other question I have is
connecting this to evolution. Is there a
way to predict uh oh we see that these
viruses are likely going to evolve in
this way in the future or is there a way
to identify the vulnerabilities we have
biologically and say oh we might want to
plug this hole
>> yeah brilliant question brilliant
question so this question of predicting
the course of evolution particularly in
microbes you know bacteria and viruses
>> it's a it's a really fertile ground and
there there's some just brilliant people
working in this area and our tools.
>> So once you see something like the spike
protein and you say okay how does that
spike protein how does it work in
gaining access to our cells right
because it's it's the it's the root in
and then we're vaccinating against it
because we're trying to block that but
then as we vaccinate against it or as we
make antibodies against it in the course
of infection that puts pressure on the
virus to change. So how many different
ways how many different ways can the
spike protein change
>> and get and escape our immunity and get
inside our cells. So this is the sort of
thing the arms this is an arms race
right this is our immunity against the
virus
>> right
>> people are are are
>> plotting out that arms race and trying
to get ahead of the virus and say okay
>> the virus has how many roots open to it
can you know what do we need to do to
anticipate and block off all those
routes so for example people are working
on what they hope would be a universal
covid vaccine
>> so you wouldn't need strain by stop all
of them
>> and it's ant it's essentially just just
blocking out all pass right now. The
vaccines are changing, you know, season
to season because the virus as it
>> Yeah.
>> runs the gamut and then can't find any
more people. In fact, it's a that's the
pressure to evolve to do something new.
So, we we think about universal vaccines
and that that requires anticipating what
the virus could be doing, what that
virus could be doing in the future. Same
with flu, same with other sorts of
things. We also have problems on on
bacteria because we've we've kind of
emptied the microbial arsenal at you
know the antibiotic arsenal at at at
bacteria and there's
>> serious concerns about our ability to
deal with some of these
>> bacteria that have evolved superbugs
that have evolved resistance to most of
our arsenal. So a lot of innovation is
needed there because
>> you know I mean that the hard thing
about scientists again we're optimists
>> right
>> co even exceeded our imagination
society. I I never I I never imagined
something.
>> Well, some people weren't happy. Some
people weren't happy with the the you
know, our vaccine, you know, they they
they because I feel like they were like,
"Oh, I thought the vaccine meant you
weren't going to even get it." But
that's not how it turned out. You could
still get it. And then the people are
are are leaning on, "But natural
immunity. We should do natural
immunity."
>> Yeah. So this brings me to the question
of the of the role of chance because
nature does it by chance. It does run
all these experiments. We're more
directed.
>> Yeah.
>> But we don't have all those years and
chance. So talk a bit about the role of
chance in evolution and
>> it's huge. Well, this is this is a big
topic
>> underappreciated I think and chance in
our lives, chance and how we get there,
how we even got here.
>> So we can go we can stay down at the
scale of things like viruses etc. Well,
they're changing by chance mutations.
And what happens is is it the conditions
sift out the winners and the losers,
right? So the mutations that affect the
spike protein that that disable it so it
can't infect. Well, we never see those
mutations because that virus can't get
anywhere, right? But those mutations
that change the virus in a way that
evade our immune systems and it can
still infect cells, guess what? We know
those are going to happen for sure.
Okay? So basically the mutation the the
mutational process is like generating
you know random lottery tickets and the
cons the conditions sort out which ones
are the winners and losers and of course
the losers we just never see. The losers
are just filtered away you know they
don't they don't get a head start at
all.
>> Um this is this is the evolutionary
process as at its basic root. Mutations
take place all the time. Every human is
born with 30 to 50 mutations that didn't
exist in mom or dad.
>> Oh wow. single changes in our in the
text of our DNA
>> that just happen because
>> it's it's actually built in
>> to the DNA itself. It's it's not a bug.
It's a feature of DNA. We understand the
chemistry of DNA is such that there are
going to be changes in DNA in every
generation
>> and you know we pick up about 30 or 50.
>> So is that more fundamental than life?
It's really chemistry and physics.
>> Yes.
>> Yeah. And so it
>> it's it's the basic chemistry. It's a
it's a sorry it's a um it's a little
shift uh in the position of a hydrogen
in a in a DNA base
>> and that's going to happen that's sort
of flickering as a matter of uh of
physics.
>> Yeah.
>> And when it happens and gets locked in
in one position that's we we call that a
mutation. So that's happening. That's
that's just built in. There's going to
be now when you say 30 or 50 like oh my
goodness. But those are spread among
three billion bases. And most of the
time they're just landing nowhere.
>> Nowhere making no
>> no effect whatsoever. But every now and
then, of course, they're gonna they're
going to have an effect either to just
change us in a little way, make us a
little different from mom and dad. Of
course, sometimes they have
consequential consequential health
effects.
>> But that mutational process is going on
all the time. And it's going on in all
creatures and all this. And without it,
we'd have no biodiversity at all. Right?
life would be constantly would be would
be unchanging.
>> It's interesting because you know even
in my field of cosmology it's these
random quantum fluctuations that gave
rise to everything. And so now
[laughter]
>> well this is where this is where DNA
meets your world is is that there's
random uh fluctuations in DNA that are
the root of mutation.
>> So fluctuations are the sort of like
opportunity and possibility.
>> Yes.
>> That's what Yeah.
>> Yes. Yeah. It's it's going to give you,
you know, both spots on butterflies and
cancer,
>> right? I mean, cancer is a cancer is a
is a
>> is a genetic disease. It's due to
mutations taking place in cells that
then cause
>> the the normal process of controlling
cell multiplication to run a muck. So,
we got to understand these the era we're
living in now, the reason why we're
sequencing the DNA of people's tumor
samples is that's powerful information
that says your breast cancer is
different than somebody else's breast
cancer, and let's take now what we know
about the genes that are mutated in
breast cancer, drugs that we've
developed that target some of the those
mutations, and prognosis that we develop
based on the behavior of tumors that
have those mutations. So this is
powerful knowledge to understand
mutations and and what's going on. It's
revolutionized oncology you know
hopefully to longer better lives.
>> Yeah.
>> Yeah. So we this you know this
mutational I mean mutation has a
negative connotation and when I bring up
disease and cancer there is it but of
course it is the fuel of evolution and
that's why it's so important for us to
understand it both in health and
disease.
>> Wow. Wow man. Dr. Carol this was
amazing. Thank you sir. You are welcome
to come back anytime
>> because who doesn't have questions about
life?
>> You bet. Thanks so much.
>> Thank you, man.
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