0:00:00.868,0:00:02.654
When I was a young boy,

0:00:02.654,0:00:05.262
I used to gaze through the microscope of my father

0:00:05.262,0:00:08.620
at the insects in amber that he kept in the house.

0:00:08.620,0:00:11.177
And they were remarkably well preserved,

0:00:11.177,0:00:13.422
morphologically just phenomenal.

0:00:13.422,0:00:15.616
And we used to imagine that someday,

0:00:15.616,0:00:17.225
they would actually come to life

0:00:17.225,0:00:19.222
and they would crawl out of the resin,

0:00:19.222,0:00:21.966
and, if they could, they would fly away.

0:00:21.966,0:00:24.342
If you had asked me 10 years ago whether or not

0:00:24.342,0:00:27.540
we would ever be able to sequence the genome of extinct animals,

0:00:27.540,0:00:30.015
I would have told you, it's unlikely.

0:00:30.015,0:00:31.910
If you had asked whether or not we would actually be able

0:00:31.910,0:00:34.062
to revive an extinct species,

0:00:34.062,0:00:35.721
I would have said, pipe dream.

0:00:35.721,0:00:38.246
But I'm actually standing here today, amazingly,

0:00:38.246,0:00:40.253
to tell you that not only is the sequencing

0:00:40.253,0:00:44.443
of extinct genomes a possibility, actually a modern-day reality,

0:00:44.443,0:00:48.736
but the revival of an extinct species is actually within reach,

0:00:48.736,0:00:50.575
maybe not from the insects in amber --

0:00:50.575,0:00:52.535
in fact, this mosquito was actually used

0:00:52.535,0:00:54.887
for the inspiration for "Jurassic Park" —

0:00:54.887,0:00:57.447
but from woolly mammoths, the well preserved remains

0:00:57.447,0:00:59.654
of woolly mammoths in the permafrost.

0:00:59.654,0:01:01.727
Woollies are a particularly interesting,

0:01:01.727,0:01:04.273
quintessential image of the Ice Age.

0:01:04.273,0:01:06.098
They were large. They were hairy.

0:01:06.098,0:01:08.082
They had large tusks, and we seem to have

0:01:08.082,0:01:10.982
a very deep connection with them, like we do with elephants.

0:01:10.982,0:01:13.497
Maybe it's because elephants share

0:01:13.497,0:01:15.319
many things in common with us.

0:01:15.319,0:01:18.047
They bury their dead. They educate the next of kin.

0:01:18.047,0:01:21.067
They have social knits that are very close.

0:01:21.067,0:01:23.937
Or maybe it's actually because we're bound by deep time,

0:01:23.937,0:01:27.275
because elephants, like us, share their origins in Africa

0:01:27.275,0:01:29.398
some seven million years ago,

0:01:29.398,0:01:32.192
and as habitats changed and environments changed,

0:01:32.192,0:01:35.802
we actually, like the elephants, migrated out

0:01:35.802,0:01:38.022
into Europe and Asia.

0:01:38.022,0:01:40.725
So the first large mammoth that appears on the scene

0:01:40.725,0:01:44.131
is meridionalis, which was standing four meters tall

0:01:44.131,0:01:47.963
weighing about 10 tons, and was a woodland-adapted species

0:01:47.963,0:01:50.925
and spread from Western Europe clear across Central Asia,

0:01:50.925,0:01:53.175
across the Bering land bridge

0:01:53.175,0:01:55.485
and into parts of North America.

0:01:55.485,0:01:58.173
And then, again, as climate changed as it always does,

0:01:58.173,0:01:59.683
and new habitats opened up,

0:01:59.683,0:02:02.159
we had the arrival of a steppe-adapted species

0:02:02.159,0:02:04.407
called trogontherii in Central Asia

0:02:04.407,0:02:07.157
pushing meridionalis out into Western Europe.

0:02:07.157,0:02:09.552
And the open grassland savannas of North America

0:02:09.552,0:02:11.712
opened up, leading to the Columbian mammoth,

0:02:11.712,0:02:14.252
a large, hairless species in North America.

0:02:14.252,0:02:17.163
And it was really only about 500,000 years later

0:02:17.163,0:02:19.868
that we had the arrival of the woolly,

0:02:19.868,0:02:21.896
the one that we all know and love so much,

0:02:21.896,0:02:25.206
spreading from an East Beringian point of origin

0:02:25.206,0:02:28.092
across Central Asia, again pushing the trogontherii

0:02:28.092,0:02:29.743
out through Central Europe,

0:02:29.743,0:02:31.809
and over hundreds of thousands of years

0:02:31.809,0:02:34.893
migrating back and forth across the Bering land bridge

0:02:34.893,0:02:36.920
during times of glacial peaks

0:02:36.920,0:02:38.716
and coming into direct contact

0:02:38.716,0:02:41.520
with the Columbian relatives living in the south,

0:02:41.520,0:02:44.808
and there they survive over hundreds of thousands of years

0:02:44.808,0:02:46.985
during traumatic climatic shifts.

0:02:46.985,0:02:51.201
So there's a highly plastic animal dealing with great transitions

0:02:51.201,0:02:54.049
in temperature and environment, and doing very, very well.

0:02:54.049,0:02:58.040
And there they survive on the mainland until about 10,000 years ago,

0:02:58.040,0:03:01.193
and actually, surprisingly, on the small islands off of Siberia

0:03:01.193,0:03:03.667
and Alaska until about 3,000 years ago.

0:03:03.667,0:03:05.356
So Egyptians are building pyramids

0:03:05.356,0:03:08.122
and woollies are still living on islands.

0:03:08.122,0:03:09.671
And then they disappear.

0:03:09.671,0:03:11.925
Like 99 percent of all the animals that have once lived,

0:03:11.925,0:03:15.188
they go extinct, likely due to a warming climate

0:03:15.204,0:03:17.286
and fast-encroaching dense forests

0:03:17.286,0:03:18.787
that are migrating north,

0:03:18.787,0:03:21.760
and also, as the late, great Paul Martin once put it,

0:03:21.760,0:03:23.511
probably Pleistocene overkill,

0:03:23.511,0:03:26.084
so the large game hunters that took them down.

0:03:26.084,0:03:28.346
Fortunately, we find millions of their remains

0:03:28.346,0:03:31.023
strewn across the permafrost buried deep

0:03:31.023,0:03:34.148
in Siberia and Alaska, and we can actually go up there

0:03:34.148,0:03:36.058
and actually take them out.

0:03:36.058,0:03:37.582
And the preservation is, again,

0:03:37.582,0:03:40.152
like those insects in [amber], phenomenal.

0:03:40.152,0:03:43.672
So you have teeth, bones with blood

0:03:43.672,0:03:45.712
which look like blood, you have hair,

0:03:45.712,0:03:47.239
and you have intact carcasses or heads

0:03:47.239,0:03:50.182
which still have brains in them.

0:03:50.182,0:03:52.553
So the preservation and the survival of DNA

0:03:52.553,0:03:54.625
depends on many factors, and I have to admit,

0:03:54.625,0:03:56.953
most of which we still don't quite understand,

0:03:56.953,0:03:59.025
but depending upon when an organism dies

0:03:59.025,0:04:03.514
and how quickly he's buried, the depth of that burial,

0:04:03.514,0:04:06.816
the constancy of the temperature of that burial environment,

0:04:06.816,0:04:09.384
will ultimately dictate how long DNA will survive

0:04:09.384,0:04:12.245
over geologically meaningful time frames.

0:04:12.245,0:04:13.889
And it's probably surprising to many of you

0:04:13.889,0:04:17.029
sitting in this room that it's not the time that matters,

0:04:17.029,0:04:18.656
it's not the length of preservation,

0:04:18.656,0:04:22.638
it's the consistency of the temperature of that preservation that matters most.

0:04:22.638,0:04:25.457
So if we were to go deep now within the bones

0:04:25.457,0:04:28.432
and the teeth that actually survived the fossilization process,

0:04:28.432,0:04:31.824
the DNA which was once intact, tightly wrapped

0:04:31.824,0:04:34.192
around histone proteins, is now under attack

0:04:34.192,0:04:37.158
by the bacteria that lived symbiotically with the mammoth

0:04:37.158,0:04:38.968
for years during its lifetime.

0:04:38.968,0:04:42.169
So those bacteria, along with the environmental bacteria,

0:04:42.169,0:04:45.872
free water and oxygen, actually break apart the DNA

0:04:45.872,0:04:48.417
into smaller and smaller and smaller DNA fragments,

0:04:48.417,0:04:50.738
until all you have are fragments that range

0:04:50.738,0:04:53.419
from 10 base pairs to, in the best case scenarios,

0:04:53.419,0:04:55.792
a few hundred base pairs in length.

0:04:55.792,0:04:58.103
So most fossils out there in the fossil record

0:04:58.103,0:05:00.816
are actually completely devoid of all organic signatures.

0:05:00.816,0:05:03.249
But a few of them actually have DNA fragments

0:05:03.249,0:05:05.123
that survive for thousands,

0:05:05.123,0:05:08.872
even a few millions of years in time.

0:05:08.872,0:05:11.060
And using state-of-the-art clean room technology,

0:05:11.060,0:05:13.724
we've devised ways that we can actually pull these DNAs

0:05:13.724,0:05:16.228
away from all the rest of the gunk in there,

0:05:16.228,0:05:18.427
and it's not surprising to any of you sitting in the room

0:05:18.427,0:05:20.548
that if I take a mammoth bone or a tooth

0:05:20.548,0:05:23.547
and I extract its DNA that I'll get mammoth DNA,

0:05:23.547,0:05:27.358
but I'll also get all the bacteria that once lived with the mammoth,

0:05:27.358,0:05:29.605
and, more complicated, I'll get all the DNA

0:05:29.605,0:05:31.789
that survived in that environment with it,

0:05:31.789,0:05:34.963
so the bacteria, the fungi, and so on and so forth.

0:05:34.963,0:05:37.368
Not surprising then again that a mammoth

0:05:37.368,0:05:39.040
preserved in the permafrost will have something

0:05:39.040,0:05:41.908
on the order of 50 percent of its DNA being mammoth,

0:05:41.908,0:05:43.931
whereas something like the Columbian mammoth,

0:05:43.931,0:05:46.548
living in a temperature and buried in a temperate environment

0:05:46.548,0:05:50.365
over its laying-in will only have 3 to 10 percent endogenous.

0:05:50.365,0:05:52.808
But we've come up with very clever ways

0:05:52.808,0:05:55.914
that we can actually discriminate, capture and discriminate,

0:05:55.914,0:05:57.889
the mammoth from the non-mammoth DNA,

0:05:57.889,0:06:00.439
and with the advances in high-throughput sequencing,

0:06:00.439,0:06:03.276
we can actually pull out and bioinformatically

0:06:03.276,0:06:06.245
re-jig all these small mammoth fragments

0:06:06.245,0:06:08.542
and place them onto a backbone

0:06:08.542,0:06:11.101
of an Asian or African elephant chromosome.

0:06:11.101,0:06:13.677
And so by doing that, we can actually get all the little points

0:06:13.677,0:06:16.502
that discriminate between a mammoth and an Asian elephant,

0:06:16.502,0:06:19.541
and what do we know, then, about a mammoth?

0:06:19.541,0:06:22.694
Well, the mammoth genome is almost at full completion,

0:06:22.694,0:06:26.235
and we know that it's actually really big. It's mammoth.

0:06:26.235,0:06:29.420
So a hominid genome is about three billion base pairs,

0:06:29.420,0:06:30.997
but an elephant and mammoth genome

0:06:30.997,0:06:33.653
is about two billion base pairs larger, and most of that

0:06:33.653,0:06:36.277
is composed of small, repetitive DNAs

0:06:36.277,0:06:40.910
that make it very difficult to actually re-jig the entire structure of the genome.

0:06:40.910,0:06:43.271
So having this information allows us to answer

0:06:43.271,0:06:45.406
one of the interesting relationship questions

0:06:45.406,0:06:47.578
between mammoths and their living relatives,

0:06:47.578,0:06:49.622
the African and the Asian elephant,

0:06:49.622,0:06:52.789
all of which shared an ancestor seven million years ago,

0:06:52.789,0:06:54.878
but the genome of the mammoth shows it to share

0:06:54.878,0:06:57.658
a most recent common ancestor with Asian elephants

0:06:57.658,0:06:59.074
about six million years ago,

0:06:59.074,0:07:01.547
so slightly closer to the Asian elephant.

0:07:01.547,0:07:04.271
With advances in ancient DNA technology,

0:07:04.271,0:07:06.224
we can actually now start to begin to sequence

0:07:06.224,0:07:09.535
the genomes of those other extinct mammoth forms that I mentioned,

0:07:09.535,0:07:11.422
and I just wanted to talk about two of them,

0:07:11.422,0:07:13.476
the woolly and the Columbian mammoth,

0:07:13.476,0:07:15.894
both of which were living very close to each other

0:07:15.894,0:07:18.519
during glacial peaks,

0:07:18.519,0:07:20.682
so when the glaciers were massive in North America,

0:07:20.682,0:07:23.277
the woollies were pushed into these subglacial ecotones,

0:07:23.277,0:07:26.488
and came into contact with the relatives living to the south,

0:07:26.488,0:07:28.500
and there they shared refugia,

0:07:28.500,0:07:30.884
and a little bit more than the refugia, it turns out.

0:07:30.884,0:07:33.384
It looks like they were interbreeding.

0:07:33.384,0:07:35.017
And that this is not an uncommon feature

0:07:35.017,0:07:36.655
in Proboscideans, because it turns out

0:07:36.655,0:07:39.568
that large savanna male elephants will outcompete

0:07:39.568,0:07:42.936
the smaller forest elephants for their females.

0:07:42.936,0:07:45.248
So large, hairless Columbians

0:07:45.248,0:07:47.051
outcompeting the smaller male woollies.

0:07:47.051,0:07:49.669
It reminds me a bit of high school, unfortunately.

0:07:49.669,0:07:52.008
(Laughter)

0:07:52.008,0:07:54.702
So this is not trivial, given the idea that we want

0:07:54.702,0:07:56.907
to revive extinct species, because it turns out

0:07:56.907,0:07:58.727
that an African and an Asian elephant

0:07:58.727,0:08:00.822
can actually interbreed and have live young,

0:08:00.822,0:08:02.963
and this has actually occurred by accident in a zoo

0:08:02.963,0:08:06.005
in Chester, U.K., in 1978.

0:08:06.005,0:08:09.151
So that means that we can actually take Asian elephant chromosomes,

0:08:09.151,0:08:11.309
modify them into all those positions we've actually now

0:08:11.309,0:08:13.693
been able to discriminate with the mammoth genome,

0:08:13.693,0:08:16.474
we can put that into an enucleated cell,

0:08:16.474,0:08:18.733
differentiate that into a stem cell,

0:08:18.733,0:08:21.053
subsequently differentiate that maybe into a sperm,

0:08:21.053,0:08:23.677
artificially inseminate an Asian elephant egg,

0:08:23.677,0:08:26.784
and over a long and arduous procedure,

0:08:26.784,0:08:30.293
actually bring back something that looks like this.

0:08:30.293,0:08:31.983
Now, this wouldn't be an exact replica,

0:08:31.983,0:08:34.465
because the short DNA fragments that I told you about

0:08:34.465,0:08:36.946
will prevent us from building the exact structure,

0:08:36.946,0:08:38.482
but it would make something that looked and felt

0:08:38.482,0:08:41.589
very much like a woolly mammoth did.

0:08:41.589,0:08:44.333
Now, when I bring up this with my friends,

0:08:44.333,0:08:46.941
we often talk about, well, where would you put it?

0:08:46.941,0:08:48.629
Where are you going to house a mammoth?

0:08:48.629,0:08:50.669
There's no climates or habitats suitable.

0:08:50.669,0:08:52.009
Well, that's not actually the case.

0:08:52.009,0:08:54.902
It turns out that there are swaths of habitat

0:08:54.902,0:08:57.237
in the north of Siberia and Yukon

0:08:57.237,0:08:58.443
that actually could house a mammoth.

0:08:58.443,0:09:00.688
Remember, this was a highly plastic animal

0:09:00.688,0:09:03.349
that lived over tremendous climate variation.

0:09:03.349,0:09:06.231
So this landscape would be easily able to house it,

0:09:06.231,0:09:09.891
and I have to admit that there [is] a part of the child in me,

0:09:09.891,0:09:11.176
the boy in me, that would love to see

0:09:11.176,0:09:14.022
these majestic creatures walk across the permafrost

0:09:14.022,0:09:16.477
of the north once again, but I do have to admit

0:09:16.477,0:09:18.621
that part of the adult in me sometimes wonders

0:09:18.621,0:09:21.026
whether or not we should.

0:09:21.026,0:09:22.711
Thank you very much.

0:09:22.711,0:09:27.909
(Applause)

0:09:27.909,0:09:29.426
Ryan Phelan: Don't go away.

0:09:29.426,0:09:31.158
You've left us with a question.

0:09:31.158,0:09:34.682
I'm sure everyone is asking this. When you say, "Should we?"

0:09:34.682,0:09:37.291
it feels like you're reticent there,

0:09:37.291,0:09:40.269
and yet you've given us a vision of it being so possible.

0:09:40.269,0:09:41.595
What's your reticence?

0:09:41.595,0:09:42.901
Hendrik Poinar: I don't think it's reticence.

0:09:42.901,0:09:46.699
I think it's just that we have to think very deeply

0:09:46.699,0:09:49.250
about the implications, ramifications of our actions,

0:09:49.250,0:09:51.450
and so as long as we have good, deep discussion

0:09:51.450,0:09:53.466
like we're having now, I think

0:09:53.466,0:09:56.172
we can come to a very good solution as to why to do it.

0:09:56.172,0:09:57.809
But I just want to make sure that we spend time

0:09:57.809,0:09:59.658
thinking about why we're doing it first.

0:09:59.658,0:10:02.439
RP: Perfect. Perfect answer. Thank you very much, Hendrik.

0:10:02.439,0:10:04.903
HP: Thank you. (Applause)