0:00:02.776,0:00:05.250
When I was a young boy,

0:00:05.250,0:00:08.476
I used to gaze[br]through the microscope of my father

0:00:08.476,0:00:11.741
at the insects in amber[br]that he kept in the house.

0:00:11.741,0:00:15.920
And they were remarkably well preserved,[br]morphologically just phenomenal.

0:00:15.920,0:00:19.972
And we used to imagine that someday[br]they would actually come to life,

0:00:19.972,0:00:24.311
and they would crawl out of the resin,[br]and if they could, they would fly away.

0:00:25.221,0:00:28.285
If you would ask me ten years ago[br]wether or not we would ever be able

0:00:28.285,0:00:30.631
to actually sequence[br]the genome of extinct animals

0:00:30.631,0:00:32.986
I would have told you:[br]Meh, it is unlikely.

0:00:32.989,0:00:35.296
If you would ask wether or not[br]we would be able

0:00:35.296,0:00:38.922
to revive an extinct species,[br]I would have said, pipe dream.

0:00:38.922,0:00:41.765
But I'm actually standing here today,[br]amazingly, to tell you

0:00:41.765,0:00:45.549
that not only are the sequencing[br]of extinct genomes a possibility,

0:00:45.549,0:00:47.765
are actually a modern day reality,

0:00:47.765,0:00:51.843
but the revival of an extinct species[br]are actually within reach.

0:00:51.843,0:00:54.113
Maybe not from the insects in amber.

0:00:54.113,0:00:57.852
In fact, this mosquito was actually used[br]for the inspiration for Jurassic Park,

0:00:57.852,0:00:59.790
but from woolly mammoths,

0:00:59.790,0:01:02.755
the well preserved remains[br]of woolly mammoths in the permafrost.

0:01:02.755,0:01:07.257
Woollies are a particularly interesting[br]quintessencial image of the Ice Age.

0:01:07.257,0:01:10.453
They were large, they were hairy,[br]they had large tusks,

0:01:10.453,0:01:14.169
and we seem to have a very deep connection[br]with them, like we do with elephants.

0:01:14.169,0:01:18.062
Maybe it's because elephants[br]share many things in common with us.

0:01:18.062,0:01:20.997
They bury their dead,[br]they educate the next of kin,

0:01:20.997,0:01:24.227
they have social knits [br]that are very close,

0:01:24.227,0:01:26.899
or maybe it's actually because[br]we are bound by deep time,

0:01:26.899,0:01:30.289
because elephants, like us,[br]share their origins in Africa

0:01:30.289,0:01:32.569
some seven million years ago.

0:01:32.569,0:01:35.545
And as habitats changed[br]and environments changed,

0:01:35.545,0:01:40.980
we actually, like the elephants,[br]migrated out into Europe and Asia.

0:01:41.620,0:01:44.373
So the first large mammoth[br]that appears on the scene

0:01:44.373,0:01:49.765
is meridionalis, which was standing[br]four meters tall, weighing about 10 tons.

0:01:49.765,0:01:53.705
And was a woodland-adapted species[br]and spread from Western Europe

0:01:53.705,0:01:57.084
clear across central Asia,[br]across the Bering land bridge

0:01:57.084,0:01:59.743
and into parts of North America.

0:01:59.743,0:02:02.350
And then again, as climate changed[br]as it always does,

0:02:02.350,0:02:04.230
and new habitats opened up,

0:02:04.230,0:02:06.528
we had the arrival[br]of a steppe-adapted species,

0:02:06.528,0:02:08.764
called trogontherii in Central Asia,

0:02:08.764,0:02:11.238
pushing meridionalis[br]out into Western Europe.

0:02:11.238,0:02:14.294
And the open grassland savannas[br]of North America opened up

0:02:14.294,0:02:18.592
leading to the Columbian mammoth,[br]a large hairless species in North America.

0:02:18.592,0:02:21.784
It was really only[br]about 500,000 years later

0:02:21.784,0:02:26.251
that we had the arrival of the woolly,[br]the one that we all know and love so much,

0:02:26.251,0:02:31.275
spreading from an east Beringian[br]point of origin across Central Asia,

0:02:31.275,0:02:34.749
again pushing the trogontherii[br]out through Central Europe,

0:02:34.749,0:02:37.942
and over hundreds of thousands of years[br]migrating back and forth

0:02:37.942,0:02:41.475
across the Bering land bridge,[br]during times of glacial peaks,

0:02:41.475,0:02:45.268
and coming into direct contact[br]with the Columbian ancestors,

0:02:45.268,0:02:47.341
relatives living in the south.

0:02:47.341,0:02:50.997
And there, they survived[br]over hundreds of thousands of years

0:02:50.997,0:02:52.974
during traumatic climatic shifts.

0:02:52.974,0:02:55.008
So that is a highly plastic animal

0:02:55.008,0:02:58.419
dealing with great transitions[br]in temperature and environment

0:02:58.419,0:03:00.052
and doing very very well.

0:03:00.052,0:03:04.281
And there they survived on the mainland[br]until about 10,000 years ago,

0:03:04.281,0:03:06.629
and actually surprisingly[br]on the small islands

0:03:06.629,0:03:09.749
off of Siberia and Alaska[br]till about 3,000 years ago.

0:03:09.749,0:03:13.648
So Egyptians are building pyramids[br]and Woollies are still living on islands.

0:03:14.528,0:03:16.324
And then, they disappear,

0:03:16.324,0:03:19.758
like 99% of all the animals[br]that once lived, they go extinct,

0:03:19.758,0:03:21.775
likely due to a warming climate

0:03:21.775,0:03:25.195
and fast-encroaching dense forests[br]that are migrating north

0:03:25.195,0:03:28.265
and also, as the late, great[br]Paul Martin once put it:

0:03:28.265,0:03:30.097
Probably pleistocene overkill,

0:03:30.097,0:03:32.625
so the large game hunters[br]that took them down.

0:03:32.625,0:03:35.105
Fortunately, we find millions[br]of their remains,

0:03:35.105,0:03:39.182
strewn across the permafrost,[br]buried deep in Siberia and Alaska.

0:03:39.182,0:03:42.626
We can actually go up there[br]and actually take them out.

0:03:42.626,0:03:46.960
And the preservation is again,[br]like those insects in [amber], phenomenal.

0:03:46.960,0:03:51.201
So you have teeth, bones with blood,[br]which looked like blood.

0:03:51.201,0:03:53.734
You have hair, and you have[br]intact carcasses or heads

0:03:53.734,0:03:56.638
which still have brains in them.

0:03:56.638,0:04:00.466
So the preservation of the survival of DNA[br]depends on many factors

0:04:00.466,0:04:03.512
and I have to admit most of which[br]we still don't quite understand,

0:04:03.512,0:04:07.998
but depending upon when an organism dies[br]and how quickly he is buried,

0:04:07.998,0:04:10.369
the depth of that burial,

0:04:10.369,0:04:13.294
the constancy of the temperature[br]of that burial environment

0:04:13.294,0:04:16.047
will ultimately dictate[br]how long DNA will survive

0:04:16.047,0:04:18.673
over geologically meaningful time frames.

0:04:18.673,0:04:21.647
And it's probably surprising[br]to many of you sitting in this room

0:04:21.647,0:04:25.369
that it's not the time that matters,[br]it's not the length of preservation,

0:04:25.369,0:04:29.749
it's the consistency of the temperature[br]of that preservation that matters most.

0:04:29.749,0:04:32.720
So if we were to go deep now[br]within the bones and the teeth

0:04:32.720,0:04:35.684
that actually survived[br]the fossilization process

0:04:35.684,0:04:39.636
the DNA which was once intact[br]tightly wrapped around histone proteins

0:04:39.636,0:04:41.904
is now under attack by the bacteria

0:04:41.904,0:04:45.470
that lives symbiotically with the mammoth[br]for years during its lifetime.

0:04:45.470,0:04:48.582
So those bacteria[br]along with the environmental bacteria,

0:04:48.582,0:04:52.380
free water and oxygen,[br]actually break apart the DNA

0:04:52.380,0:04:56.243
into smaller and smaller DNA fragments[br]until all you have

0:04:56.243,0:04:58.745
are fragments[br]that range from 10 base pairs

0:04:58.745,0:05:01.968
to, in the best case scenarios,[br]a few hundred base pairs in length.

0:05:01.968,0:05:04.651
So most fossils out there[br]in the fossil record

0:05:04.651,0:05:07.587
are actually completely devoid[br]of all organic signatures,

0:05:07.587,0:05:10.032
but a few of them[br]actually have DNA fragments

0:05:10.032,0:05:15.027
that survived for thousands,[br]even a few millions of years in time.

0:05:15.797,0:05:18.113
And using state-of-the-art[br]clean room technology

0:05:18.113,0:05:19.979
we've devized ways that we can actually

0:05:19.979,0:05:23.155
pull these DNAs away[br]from all the rest of the gunk in there.

0:05:23.155,0:05:25.758
And it's not surprising[br]to any of you sitting in the room

0:05:25.758,0:05:27.726
that if I take a mammoth bone or a tooth

0:05:27.726,0:05:30.295
and I extract its DNA[br]that I will get mammoth DNA.

0:05:30.295,0:05:34.016
But I'll also get all the bacteria[br]that once lived with the mammoth

0:05:34.016,0:05:38.645
and more complicated, I'll get all the DNA[br]that survived in that environment with it.

0:05:38.645,0:05:42.124
So the bacteria, the fungi,[br]and so on and so forth.

0:05:42.124,0:05:46.221
So, not surprising then again[br]that a mammoth preserved in the permafrost

0:05:46.221,0:05:49.988
will have something on the order[br]of 50% of its DNA being mammoth,

0:05:49.988,0:05:51.964
where something[br]like the Columbian mammoth,

0:05:51.964,0:05:54.238
buried in a temperate environment[br]over its laying-in

0:05:54.238,0:05:57.522
will only have 3% to 10% endogenous.

0:05:57.522,0:06:01.586
But we've come up with very clever ways[br]that we can actually discriminate,

0:06:01.586,0:06:04.880
capture and discriminate the mammoth[br]from the non-mammooth DNA.

0:06:04.880,0:06:07.268
And with the advances[br]in high-troughput sequencing

0:06:07.268,0:06:11.240
we can actually pull out[br]and bioinformatically re-jig

0:06:11.240,0:06:13.262
all these small mammoth fragments

0:06:13.262,0:06:15.329
and place them onto a backbone

0:06:15.329,0:06:18.022
of an Asian or[br]African elephant chromosome.

0:06:18.022,0:06:20.934
And so, by doing that,[br]we can actually get all the little points

0:06:20.934,0:06:23.671
that discriminate between a mammoth[br]and an Asian elephant

0:06:23.671,0:06:26.752
and what do we know, then,[br]about the mammoth?

0:06:26.752,0:06:29.897
Well, the mammoth genome[br]is almost at full completion

0:06:30.727,0:06:33.749
and we know that it's actually really big,[br]it's mammoth.

0:06:33.749,0:06:36.876
So a hominid genome[br]is about three billion base pairs,

0:06:36.876,0:06:40.461
but an elephant and mammoth genome[br]is about two billion base pairs larger,

0:06:40.461,0:06:44.159
and most of that is composed[br]of small repetitive DNAs

0:06:44.159,0:06:48.600
that make it very difficult to actually[br]re-jig the entire structure of the genome.

0:06:48.600,0:06:50.824
So, having this information[br]allows us to answer

0:06:50.824,0:06:52.983
one of the interesting[br]relationship questions

0:06:52.983,0:06:55.140
between mammoths[br]and their living relatives,

0:06:55.140,0:06:57.231
the African and the Asian elephant,

0:06:57.231,0:07:00.388
all of which shared an ancestor[br]seven million years ago,

0:07:00.388,0:07:04.643
but the genome of the mammoth shows it[br]to share a most recent common ancestor

0:07:04.643,0:07:07.146
with Asian elephants[br]about six million years ago,

0:07:07.146,0:07:09.497
so slightly closer to the Asian elephant.

0:07:10.247,0:07:13.387
With advances in ancient DNA technology

0:07:13.387,0:07:15.587
we can actually now start[br]to begin to sequence

0:07:15.587,0:07:18.899
the genomes of those other[br]extinct mammoth forms that I mentioned.

0:07:18.899,0:07:20.909
And I just wanted to talk[br]about two of them:

0:07:20.909,0:07:22.771
The woolly and the Columbian mammoth.

0:07:22.771,0:07:26.555
Both of which were living very close[br]to each other during glacial peaks,

0:07:26.555,0:07:28.937
so when the glaciers[br]were massive in North America

0:07:28.937,0:07:31.577
the woollies were pushed[br]into these subglacial ecotones

0:07:31.577,0:07:34.752
and came into contact with their relatives[br]living to the south.

0:07:34.752,0:07:36.763
And there they shared refugia

0:07:36.763,0:07:39.224
and a little bit more[br]than the refugia, it turns out.

0:07:39.224,0:07:41.517
It looks like they were interbreeding.

0:07:41.517,0:07:44.238
And this is not an uncommon feature[br]in Proboscideans

0:07:44.238,0:07:47.031
because it turns out[br]that large savanna male elephants

0:07:47.031,0:07:50.870
will outcompete the smaller[br]forest elephants for their females.

0:07:50.870,0:07:55.593
So, large hairless Columbians,[br]outcompeting the smaller male woollies.

0:07:55.593,0:07:57.989
It reminds me a bit of high school,[br]unfortunately.

0:07:57.989,0:07:59.986
(Laughter)

0:08:00.247,0:08:02.608
So, this is not trivial,

0:08:02.608,0:08:05.553
given the idea that we want[br]to revive extinct species,

0:08:05.553,0:08:08.284
because it turns out that an African[br]and an Asian elephant

0:08:08.284,0:08:10.418
can actually interbreed[br]and have live young

0:08:10.418,0:08:15.237
and this has actually occurred by accident[br]in a zoo in Chester, UK in 1978.

0:08:15.947,0:08:18.799
So that means we can actually take[br]Asian elephant chromosomes,

0:08:18.799,0:08:20.643
modify them into all those positions

0:08:20.643,0:08:23.850
we have actually now been able[br]to discriminate with the mammoth genome.

0:08:23.850,0:08:26.885
We can put that into an enucleated cell,

0:08:27.952,0:08:29.984
differentiate that into a stem cell,

0:08:29.984,0:08:32.376
subsequently differentiate that[br]maybe into a sperm,

0:08:32.376,0:08:35.243
artificially inseminate[br]an Asian elephant egg

0:08:35.243,0:08:38.104
and over a long and arduous procedure

0:08:38.104,0:08:41.364
actually bring back[br]something that looks like this.

0:08:41.364,0:08:43.493
Now, this would not be an exact replica

0:08:43.493,0:08:46.032
because the short DNA fragments[br]that I told you about,

0:08:46.032,0:08:48.352
would prevent us from building[br]the exact structure.

0:08:48.352,0:08:50.517
But it would make something[br]that looked and felt

0:08:50.517,0:08:53.313
very much like a woolly mammoth did.

0:08:53.353,0:08:56.838
And when I bring up this with my friends,[br]we often talk about:

0:08:56.838,0:09:00.124
well, where would you put it?[br]Where are you going to house a mammoth?

0:09:00.124,0:09:02.091
There's not climates or habitats suitable.

0:09:02.091,0:09:03.850
Well, that is not actually the case.

0:09:03.850,0:09:06.378
It turns out that there are[br]swaths of habitat

0:09:06.378,0:09:09.844
in the north of Siberia and Yukon[br]that actually could house a mammooth.

0:09:09.844,0:09:12.212
Remember this was a highly plastic animal

0:09:12.212,0:09:14.946
that lived over tremendous[br]climate variation.

0:09:14.946,0:09:17.823
So this landscape[br]would be easily able to house it.

0:09:17.823,0:09:21.757
And I have to admit that there is[br]a part of the child in me, the boy in me,

0:09:21.757,0:09:24.081
that would love to see[br]these majestic creatures

0:09:24.081,0:09:26.808
walk across the permafrost[br]of the north once again.

0:09:26.808,0:09:29.482
But I do have to admit[br]that part of the adult in me,

0:09:29.482,0:09:32.247
sometimes wonders[br]wether or not we should.

0:09:32.247,0:09:33.919
Thank you very much.

0:09:33.919,0:09:35.521
(Applause)