Kind: captions
Language: en
So the two things that I I want to
define or describe from you, one is, you
know, what does it really mean to
deextinct? And the second thing I want
you to get into is like how do you do
it, right? Like you know, yeah, what
what is what what's happening in the
lab?
>> How long is this podcast?
>> As long as you want it cuz I'm
interested. How often do I get this
opportunity? You know, I got Dr. Beth
Shapiro. I'm asking
I want to know, you know, I
>> So, our goal with deextinction is to be
able to create um versions of these
extinct species that are able to thrive
in habitats of today that resurrect
using DNA, using ancient DNA, extinct
traits. And by creating these extinct
species, by bringing extinct species
back to life, our goal is to restore
missing ecological interactions so that
we can make ecosystems more robust and
more resilient. So Romulus, Remis, and
Kesi, we intended to bring back traits
including the size and the musculature.
And we really liked the the the light
colored coat. This was we didn't know
that direwolves were light colored until
we sequenced the ancient DNA and were
able to see in the sequence of their DNA
that the animals whose genomes we'd
sequenced both had light colored coats.
And this is a actually a really
important way of of really showcasing
how we are concentrating on deextinction
but also on animal welfare. So we knew
that we wanted to make these light
colored animals. The gene variants that
were in our ancient direwolf fossils
were in a gene that in modern
greywolves, if individuals have variance
in those genes, they can sometimes be
blind or deaf. It's not the same variant
that we saw in the direwolf fossils, but
it's in the same gene. And we thought
that's a little bit risky. But since our
goal is to bring back phenotypes, we
know that we can make a greywolf
background into a white animal because
there are white greywolves today. So we
will use those variants to bring back to
deextinct this direwolf light colored
coat. And in this way we are ensuring
that we are bringing back we are
deextincting direwolf traits in the
safest most ethical way possible. So how
do we do it?
>> Wait wait wait let me let me ask a
question about that. So I I I've heard
this in with respect to the human
genome, but you can
map specific physical characteristics to
specific genes and you can say okay this
particular gene you know like for
example light skin occurring in in
humans and anatolia or something like
that. We know what gene created that.
Um, so is it the case that you take a
existing genome of say a greywolf oh you
know what I'm getting to the question
I'm about to ask you and then you say
okay let me add the particular genes
that give me the direwolf
characteristics to that existing
existing one or do you say hey I have
this direwolf incomplete direwolf DNA
profile and let me fill in the gaps with
living greywolf which
>> you know what That is the Jurassic Park
versus the way we're actually doing it
conversation, right? Which you had said.
So I think that's why people are
confused because Jurassic Park, which I
can I just remind everyone who's
watching right now that Jurassic Park
was not a documentary that uh this was a
a
science fiction. I think sometimes
people get a little confused and they
think this is what we're doing. And I'm
also going to admit that um I am an
ancient DNA scientist who has attempted
to extract DNA from insects preserved in
amber. And the hardest because of course
I did. And the hardest part about that
was actually smashing the amber cuz it's
so sticky. I had to freeze it really
hard and then take a sledgehammer and
whack the crap out of it so it would
shatter and then try to find the pieces
with the Anyway, there is no authentic
insect ancient DNA or authentic dinosaur
ancient DNA in amber. Amber is actually
a really bad
material for for the long-term
preservation of DNA because it forms in
really hot places and that's terrible
for DNA preservation. It's also super
porous, so microbes can get into those
pores and they'll just chew up the DNA
that's in there, and that is also
terrible for DNA preservation. The
oldest DNA that has been recovered so
far is from mammoth bones
>> uh that were preserved in in Siberia in
perafrost, frozen dirt. So, the the
bones were defleed probably by pred
predators and then buried and then
frozen solid. and they are probably
around 1 to 2 million years old which is
really old. Most of the DNA we have is
dates to within the last 50,000 years or
so. Um there's actually DNA that's been
isolated from dirt directly from
sediment from Greenland from a place
called Cap Copenhagen which is
potentially slightly older pyene in age
just before the ice ages started. It's
really hard to know exactly how old
things are around that time point but
that could be the oldest DNA still.
Dinosaurs have been extinct for more
than 66 million years. And so we do not
have DNA. That is that is that old. So
in Jurassic Park, they got dinosaur DNA,
which isn't possible, out of amber,
which doesn't have DNA. And they pieced
it together and then they saw that there
were holes in this, not surprising,
giant holes as in none of it was real.
But we're going here because this is
this is like it's a it's a movie. All
right. So these things were there and
then they thought, there are holes in
DNA. I'm going to use
frog DNA to fill in those gaps, which
was a weird choice even then, right?
Because we already knew that birds are
dinosaurs, right? But whatever, frogs
shoved in the middle and that meant that
somehow they turned into girls. Is that
what happened? I can't really remember
something.
>> So, so set it up, right? This is how it
had to happen. So now when people
imagine what we're doing, they're
thinking, "Oh, you're going out. You're
getting these DNA sequences directly
from these bones and you're like somehow
holding on to them maybe with a really
tiny pipeter and then you have another
one with another tiny pipeter and you're
super gluing those things together and
you still can't do it. So you're and
that just that it's it's not going to
work. The the the DNA is is broken in a
way. And it's also really hard. We
actually have a much easier way
>> to be successful doing deextinction.
Think about the the mammoth project for
example.
>> We know that mammoths and Asian
elephants, that's their closest living
relative. Hey, fun fact. Mammoths and
Asian elephants are more closely related
to each other than Asian elephants and
African elephants are related to each
other.
>> Right? All right. So we have mammoths
and Asian elephants that are only about
five million years diverged from each
other. That means that they share a lot
of their DNA. In fact, they share more
than 99% of the DNA sequence between
them. They're identical to each other,
but it's somewhere around 99 and a half%
depending on how you count. Which means
if you want to change an Asian elephant
into a mammoth, that is a lot easier of
a task than piecing together a mammoth
by taking little tiny fragments of DNA
with little tiny tweezers and shoving
them together, which is also impossible.
So now you have this great great
shortcut that you can use where you can
start with Asian elephant cells growing
in a dish in a lab and you can use the
tools of genome editing. The most famous
one that most people have heard about
now is crisper because it allows us some
really nice precision to be able to make
these changes. And then if you can think
about it like this, gradually go in and
cut out
>> the version of the elephant DNA and
paste in its place the mammoth version.
So we're cutting and pasting our way to
a mammoth starting with this template
that is already 99.5%
mammoth. Right? So that is way easier
than piecing it together.
>> So here's a question now. So are you in
is this DNA manipulation happening
outside the context of a cellular
nucleus? It's it's free floating in some
medium.
>> No, it is happening in the nucleus of
living cells that are growing in media
in a dish in a lab. Yes.
>> But we've missed a really important part
that you actually highlighted earlier,
right? which is how do we know what to
change, right? Um, being 99.5% the same
is great, but that.5% difference is
still a lot of genetic differences
between a mammoth and an Asian elephant.
And we can't make hundreds of millions
or tens of millions or even millions of
changes right now. The technology isn't
there yet. It it will get there
eventually. So, you're limiting the
number of changes you can make.
>> We're limited. And at Colossal, we're
really trying to push the limit of that.
How many edits can we make
simultaneously? Um, can we cut and paste
large pieces of DNA, maybe even to the
scale of whole chromosome arms at some
point so we can make lots of changes at
the same time? Because every time we go
into that nucleus of the cell with the
machinery that we need to make the
edits, we stress that cell out and the
cell has to be able to recover after
that before it can do something else. So
we have to focus on keeping cells
healthy on maximizing the number of
changes we can make at the same time so
that the number of times we stress out
the cell can be really limited. So these
are all the technologies that we're
pushing forward here. And I like to
point this out as we make these changes
as we figure out how to do multipplex
genome editing which is just making lots
of changes at the same time or replacing
whole genes. These are technologies that
can be immediately applied to human
health, to animal health. Once we figure
out how we can edit birds and pass those
DNA changes down between generations of
birds, we could do things like modify
genomes in Hawaiian honey creepers so
that they can be resistant, resilient to
aven malaria so that these species may
not become extinct. These technologies
are critical tools in what should be an
advanced toolkit for biodiversity
preservation. And those tools are being
developed right now on the path to a
mammoth and a dodo and a moa and a
thyloine. And I it to me it's such an
exciting environment to be part of. But
we still haven't gotten to a very hard
thing that you pointed out at the
beginning which was how do I know what
to change?
>> Yeah.
>> And that is where these ancient genomes
come in handy. So we can go out into
Siberia and we can collect hundreds,
thousands of mammoth bones and extract
DNA from them and piece together using
these tiny fragments and computers
sequences of mammoth genomes. And we can
compare all of these to each other and
compare them to elephant genomes and ask
where are all the mammoth genomes the
same as each other but different from
elephants? Because if they're the same
as each other, then that means that
they're probably important to making
them a mammoth. You and I, for example,
share a lot of our genomes, 99.9 blah
blah blah blah blah percent, because
we're both anatomically monitored
humans, right? We have we're pretty much
identical genetically, right?
>> Yeah. Yeah. But you could compare our
our genomes to Neandertols and to uh any
other of Denisven the other archaic
hominin that's our cousin that has
genome sequence that's been and you
could ask where are we the same as each
other and different from them
>> and that will start to narrow it down
what it is that makes all of us what it
is that makes anatomically modern humans
distinct as a lineage. One thing we can
also do there that's very useful for us
is we can look at where you are
different from me and where we are
different from anybody else that we
encounter and we can say those aren't
important changes to being a human
because they're not shared by all
humans. So we can throw those out and
that is important because that means we
can throw out a whole bunch of places in
the genome where the mammoths are all
different from each other because those
aren't things we have to change. We know
that they're not important to making a
mammoth a mammoth.