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)