Transcriber: Jennifer Becerra Reviewer: aknv tso
(Applause)
I am a molecular paleontologist
Sounds sophisticated?
actually, I just made it up.
I spend most of my time
in the lab or in front of the computer
but during the summer,
I prefer to spend my days and nights
in the far north,
where I divide my time between
waging war against mosquitoes
and searching for the remains
of Ice Age animals,
which I bring back to the lab
to extract their ancient DNA.
As an early career scientist
I was interested in ancient DNA for three reasons:
First,
it was an oportunity
to combine my interests in paleontology,
geology and molecular evolution.
I could get DNA from fossils and use this
to watch species evolve through time.
Second, it was a brand new field
absolutely bursting with enthusiasm
and excitement,
a career in ancient DNA promised to be different,
definitely cool and hopefully useful.
And third,
I really wanted to go to the Arctic.
So, what about the Arctic is so good for DNA?
well, it is the best place
for the long term preservation of DNA,
and the reason why is quite straightforward
it's cold.
And it's been cold consistently
for at least the last million years.
This period was characterised by dramatic shifts
between very cold glacial intervals
and much warmer interglacial periods
like the one we're in today.
During the glacial periods, or ice ages,
the sea level was a lot lower than it is today,
because much of the planet's water
was taken up into the glaciers forming on the continents.
The lower sea level exposed a mass of land
that connected the Asian and North American continents,
this land mass was called Beringia,
and it's where I do much of my work.
Now crucially Beringia was not glaciated
during the last Ice Age, instead
it was a rich tundra grassland
that was home to an equally rich diversity
of Ice Age plants and animals.
Today, most of these species are extinct,
but their bones and other hard bits -
tusks, teeth, hair,
sometimes even full mummies, survived
frozen in the ground called permafrost.
We look for frozen bones
wherever the permafrost is melting
along riverbeds, around lakes
and at active gold mining sites
such as this in Canada's Yukon territory,
where the gold miners wash away the permafrost
to get to the gold there, in gravels beneath,
thousands of bones are unearthed.
Over the last decade
I and colleagues from around the world
have extracted DNA
from tens of thousands of these bones
and used them to better understand
how Ice Age animals
were affected by climate change,
in particular, the last Ice Age.
We learn, for example,
that bison, horses and mammoths
really liked it when it was cold,
this is when their populations were the biggest,
their genetic diversity, the most large.
As it got warmer
many of these populations started to decline
and eventually went extinct.
We watched brown bears during the last Ice Age
dispersed out of Alaska,
across Asia, and into Europe,
presumably chasing after this growing populations of herbivores
And we've asked questions such as
why do some species,
including the cave lion, go extinct?
while others
like the caribou, continue to thrive today.
And today we find ourselves in the middle of the genomics revolution,
once again
with growing enthusiasm to push this a little bit further,
we find ourselves more and more frequently
being asked and asking each other:
can we sequence a complete genome
of an extinct animal and,
dare we say it,
actually bring one back to life.
To answer this,
let me first recap, very quickly
what I'm going to call
the seven, badly described,
but deeply over-simplified steps,
to bring an extinct species back to life.
First,
you have to sequence the genome,
and somewhere in there are the genes
some of these As, Cs, Gs and Ts,
the genes that code for the proteins
that make the cells, the bodies and the behaviours
of the things we're trying to bring back.
Then, we have to
get this genomes under the chromosomes
because chromosomes are the way that genetic material
is carried in the cells,
then we have to get the chromosomes into the nucleus
and the nucleus into the cell
so they can start to divide
and then we have to get the cell at the embryo
into a surrogate mother
so that it can actually grow up and develop
and become something,
and presumably
her genome isn't going to have too much to say
about this developmental process.
And then,
she's got to take this developing embryo or fetus actually to term
in this case
this is also not simple,
there's a very large size difference
between the much large mammoth
and a smaller elephant
and it's not known whether it would actually be
physically possible for a female elephant
to carry a baby mammoth to term without disaster.
But assuming disaster is averted
then a mammoth can be born and learn how to be a mammoth
we then have to find a place for it to live
so it can go about doing mammothy stuff
and eventually make more mammoths.
Pretty straightforward.
Ok so, easy might be an exaggeration,
or an outright lie,
but let's get not caught on semantics.
So, where are we,
in this, with the mammoth?
The first attempt to sequence a complete genome of a mammoth
was published in 2008 in the journal Nature.
The authors managed to sequence
3.3 billion base pairs of mammoth DNA.
When all was put together and mapped to the elephant
it looked like about 50% of the mammoth genome had been sequenced.
50%, that's about half
so instead of this,
we're working with this,
but that's ok, that's great
that was state of the art in 2008,
and it's pretty much state of the art today,
in fact, does anybody know how many vertebrate genomes
have been completely sequenced,
including modern vertebrates, living vertebrate species?
Give you a hint, is not a very big number.
None.
Not even our own genome,
for which an honest to goodness ridiculous amount
of sequence data has been published.
We do not know the complete sequence of our own genome.
I'm being a little unfair.
We do know more than 99%
of the genome,
the part of our genome that actually codes for things,
where the genes live, the euchromatin.
It's the other part, the heterochromatin,
that is made of tightly condensed, repeat sequences,
that are just super hard to sequence through.
The heterochromatin doesn't make up a very big part of our genome,
and it might not actually be that important,
but we don't know,
because we haven't managed to sequence it
for a living thing.
For the mammoth,
we don't know the heterochromatin,
we also don't know where the genes are,
much less, where the specific genes,
that make a mammoth look like a mammoth, are,
so we can find them, and
use that to hybridise--
So what do we do, how do we fix this problem?
Well, seems pretty clear, let's finish it.
We go into the Arctic,
we find the really well-preserved mammoth bone,
we take a chunk out of it,
and bring it back to the lab, and we sequence its genome,
that's where the fun begins.
If I'm gonna sequence my own genome,
I could start with, say, a piece of my hair.
And I could dissolve it off
into extraction stuff,
and sequence everything that was in there,
and the results would look like this.
Pretty much everything inside that DNA extract
would be me, my own DNA,
that's because I'm alive,
my DNA is in good condition,
my hair hasn't been anywhere particularly weird.
Not so for the mammoth.
A similar experiment performed on the mammoth bone
from Alaska,
resulted in about 50%, a little more than half
of the sequences in that bone being mammoth.
The other half was a combination of plants, bacteria,
other stuff that had gotten into the bone
while it was in the soil,
and stuff that might have been introduced into the bone
during the process of excavation and sequencing,
we touch the bone and breath on the sample.
But this is still pretty good,
permafrost preserved more that 50%.
Here's a similar experiment,
for a Neanderthal, from a cave in Croatia.
Here, only 3% of the sequences in that extract
were actually primate,
and that includes both Neanderthal sequences
and any potentially contaminating human sequences,
but this is still good,
there's still Neanderthal DNA in this sample,
just not much of it,
so presumably, what that means is
all we have to do is
sequence a lot more of it.
And to some extent, that's absolutely true,
but there is another problem.
You imagine that our own DNA is like
a rope, or a ribbon, or
party streamers, say like those we're gonna put up
to celebrate the birth of our first cloned mammoth.
Then a mammoth DNA itself is actually going to be
more like...
confetti...
that's been run over by a herd of mammoths...
in the rain.
Water,
oxygen,
solar radiaton,
bacterial decay,
all of these things
will begin to act on the long strands of DNA
immediately after an organism dies.
And, eventually,
that DNA will be chopped down
into smaller and smaller fragments,
until there's nothing left.
So, this is what we have
to make this,
to make these,
and eventually that.
It's a hard problem,
it's a problem that probably won't be solved
without new and different biotechnology
than what's available today.
But as we progress toward this goal,
we're going to learn a tremendous amount
about these extinct animals,
knowledge that I have no doubt
will help us to win battles against the extinction
that are happening in our world today.
We'll learn where the genes are,
we'll learn what genes make them look and act
the way they did,
we'll learn a lot more about how genes interact with the environment.
And, we'll finally,
hopefully,
discover why some populations
and some species are so much more susceptible to extinction
than others are.
At the same time, we would get better at extracting DNA
from our ancient --
the ancient bones.
We will learn how to fix the broken bits
so we can start piecing together these little tiny fragments
into longer and longer fragments.
If it's what we want to do,
we will eventually be able to sequence
the complete genome of an extinct animal.
And then we will have completed step one.
Thank you.
(Applause)