When I was a young boy,

I used to gaze
through the microscope of my father

at the insects in amber
that he kept in the house.

And they were remarkably well preserved,
morphologically just phenomenal.

And we used to imagine that someday
they would actually come to life,

and they would crawl out of the resin,
and if they could, they would fly away.

If you would ask me ten years ago
wether or not we would ever be able

to actually sequence
the genome of extinct animals

I would have told you:
Meh, it is unlikely.

If you would ask wether or not
we would be able

to revive an extinct species,
I would have said, pipe dream.

But I'm actually standing here today,
amazingly, to tell you

that not only are the sequencing
of extinct genomes a possibility,

are actually a modern day reality,

but the revival of an extinct species
are actually within reach.

Maybe not from the insects in amber.

In fact, this mosquito was actually used
for the inspiration for Jurassic Park,

but from woolly mammoths,

the well preserved remains
of woolly mammoths in the permafrost.

Woollies are a particularly interesting
quintessencial image of the Ice Age.

They were large, they were hairy,
they had large tusks,

and we seem to have a very deep connection
with them, like we do with elephants.

Maybe it's because elephants
share many things in common with us.

They bury their dead,
they educate the next of kin,

they have social knits 
that are very close,

or maybe it's actually because
we are bound by deep time,

because elephants, like us,
share their origins in Africa

some seven million years ago.

And as habitats changed
and environments changed,

we actually, like the elephants,
migrated out into Europe and Asia.

So the first large mammoth
that appears on the scene

is meridionalis, which was standing
four meters tall, weighing about 10 tons.

And was a woodland-adapted species
and spread from Western Europe

clear across central Asia,
across the Bering land bridge

and into parts of North America.

And then again, as climate changed
as it always does,

and new habitats opened up,

we had the arrival
of a steppe-adapted species,

called trogontherii in Central Asia,

pushing meridionalis
out into Western Europe.

And the open grassland savannas
of North America opened up

leading to the Columbian mammoth,
a large hairless species in North America.

It was really only
about 500,000 years later

that we had the arrival of the woolly,
the one that we all know and love so much,

spreading from an east Beringian
point of origin across Central Asia,

again pushing the trogontherii
out through Central Europe,

and over hundreds of thousands of years
migrating back and forth

across the Bering land bridge,
during times of glacial peaks,

and coming into direct contact
with the Columbian ancestors,

relatives living in the south.

And there, they survived
over hundreds of thousands of years

during traumatic climatic shifts.

So that is a highly plastic animal

dealing with great transitions
in temperature and environment

and doing very very well.

And there they survived on the mainland
until about 10,000 years ago,

and actually surprisingly
on the small islands

off of Siberia and Alaska
till about 3,000 years ago.

So Egyptians are building pyramids
and Woollies are still living on islands.

And then, they disappear,

like 99% of all the animals
that once lived, they go extinct,

likely due to a warming climate

and fast-encroaching dense forests
that are migrating north

and also, as the late, great
Paul Martin once put it:

Probably pleistocene overkill,

so the large game hunters
that took them down.

Fortunately, we find millions
of their remains,

strewn across the permafrost,
buried deep in Siberia and Alaska.

We can actually go up there
and actually take them out.

And the preservation is again,
like those insects in [amber], phenomenal.

So you have teeth, bones with blood,
which looked like blood.

You have hair, and you have
intact carcasses or heads

which still have brains in them.

So the preservation of the survival of DNA
depends on many factors

and I have to admit most of which
we still don't quite understand,

but depending upon when an organism dies
and how quickly he is buried,

the depth of that burial,

the constancy of the temperature
of that burial environment

will ultimately dictate
how long DNA will survive

over geologically meaningful time frames.

And it's probably surprising
to many of you sitting in this room

that it's not the time that matters,
it's not the length of preservation,

it's the consistency of the temperature
of that preservation that matters most.

So if we were to go deep now
within the bones and the teeth

that actually survived
the fossilization process

the DNA which was once intact
tightly wrapped around histone proteins

is now under attack by the bacteria

that lives symbiotically with the mammoth
for years during its lifetime.

So those bacteria
along with the environmental bacteria,

free water and oxygen,
actually break apart the DNA

into smaller and smaller DNA fragments
until all you have

are fragments
that range from 10 base pairs

to, in the best case scenarios,
a few hundred base pairs in length.

So most fossils out there
in the fossil record

are actually completely devoid
of all organic signatures,

but a few of them
actually have DNA fragments

that survived for thousands,
even a few millions of years in time.

And using state-of-the-art
clean room technology

we've devized ways that we can actually

pull these DNAs away
from all the rest of the gunk in there.

And it's not surprising
to any of you sitting in the room

that if I take a mammoth bone or a tooth

and I extract its DNA
that I will get mammoth DNA.

But I'll also get all the bacteria
that once lived with the mammoth

and more complicated, I'll get all the DNA
that survived in that environment with it.

So the bacteria, the fungi,
and so on and so forth.

So, not surprising then again
that a mammoth preserved in the permafrost

will have something on the order
of 50% of its DNA being mammoth,

where something
like the Columbian mammoth,

buried in a temperate environment
over its laying-in

will only have 3% to 10% endogenous.

But we've come up with very clever ways
that we can actually discriminate,

capture and discriminate the mammoth
from the non-mammooth DNA.

And with the advances
in high-troughput sequencing

we can actually pull out
and bioinformatically re-jig

all these small mammoth fragments

and place them onto a backbone

of an Asian or
African elephant chromosome.

And so, by doing that,
we can actually get all the little points

that discriminate between a mammoth
and an Asian elephant

and what do we know, then,
about the mammoth?

Well, the mammoth genome
is almost at full completion

and we know that it's actually really big,
it's mammoth.

So a hominid genome
is about three billion base pairs,

but an elephant and mammoth genome
is about two billion base pairs larger,

and most of that is composed
of small repetitive DNAs

that make it very difficult to actually
re-jig the entire structure of the genome.

So, having this information
allows us to answer

one of the interesting
relationship questions

between mammoths
and their living relatives,

the African and the Asian elephant,

all of which shared an ancestor
seven million years ago,

but the genome of the mammoth shows it
to share a most recent common ancestor

with Asian elephants
about six million years ago,

so slightly closer to the Asian elephant.

With advances in ancient DNA technology

we can actually now start
to begin to sequence

the genomes of those other
extinct mammoth forms that I mentioned.

And I just wanted to talk
about two of them:

The woolly and the Columbian mammoth.

Both of which were living very close
to each other during glacial peaks,

so when the glaciers
were massive in North America

the woollies were pushed
into these subglacial ecotones

and came into contact with their relatives
living to the south.

And there they shared refugia

and a little bit more
than the refugia, it turns out.

It looks like they were interbreeding.

And this is not an uncommon feature
in Proboscideans

because it turns out
that large savanna male elephants

will outcompete the smaller
forest elephants for their females.

So, large hairless Columbians,
outcompeting the smaller male woollies.

It reminds me a bit of high school,
unfortunately.

(Laughter)

So, this is not trivial,

given the idea that we want
to revive extinct species,

because it turns out that an African
and an Asian elephant

can actually interbreed
and have live young

and this has actually occurred by accident
in a zoo in Chester, UK in 1978.

So that means we can actually take
Asian elephant chromosomes,

modify them into all those positions

we have actually now been able
to discriminate with the mammoth genome.

We can put that into an enucleated cell,

differentiate that into a stem cell,

subsequently differentiate that
maybe into a sperm,

artificially inseminate
an Asian elephant egg

and over a long and arduous procedure

actually bring back
something that looks like this.

Now, this would not be an exact replica

because the short DNA fragments
that I told you about,

would prevent us from building
the exact structure.

But it would make something
that looked and felt

very much like a woolly mammoth did.

And when I bring up this with my friends,
we often talk about:

well, where would you put it?
Where are you going to house a mammoth?

There's not climates or habitats suitable.

Well, that is not actually the case.

It turns out that there are
swaths of habitat

in the north of Siberia and Yukon
that actually could house a mammooth.

Remember this was a highly plastic animal

that lived over tremendous
climate variation.

So this landscape
would be easily able to house it.

And I have to admit that there is
a part of the child in me, the boy in me,

that would love to see
these majestic creatures

walk across the permafrost
of the north once again.

But I do have to admit
that part of the adult in me,

sometimes wonders
wether or not we should.

Thank you very much.

(Applause)