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When I was a young boy,

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I used to gaze through the microscope of my father

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

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And they were remarkably well preserved,

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morphologically just phenomenal.

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And we used to imagine that someday,

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they would actually come to life

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and they would crawl out of the resin,

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and, if they could, they would fly away.

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If you had asked me 10 years ago whether or not

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we would ever be able to sequence the genome of extinct animals,

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I would have told you, it's unlikely.

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If you had asked whether or not we would actually be able

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to revive an extinct species,

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I would have said, pipe dream.

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But I'm actually standing here today, amazingly,

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to tell you that not only is the sequencing

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of extinct genomes a possibility, actually a modern-day reality,

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but the revival of an extinct species is actually within reach,

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maybe not from the insects in amber --

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in fact, this mosquito was actually used

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for the inspiration for "Jurassic Park" —

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but from woolly mammoths, the well preserved remains

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of woolly mammoths in the permafrost.

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Woollies are a particularly interesting,

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quintessential image of the Ice Age.

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They were large. They were hairy.

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They had large tusks, and we seem to have

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a very deep connection with them, like we do with elephants.

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Maybe it's because elephants share

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many things in common with us.

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They bury their dead. They educate the next of kin.

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They have social knits that are very close.

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Or maybe it's actually because we're bound by deep time,

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because elephants, like us, share their origins in Africa

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some seven million years ago,

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and as habitats changed and environments changed,

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we actually, like the elephants, migrated out

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into Europe and Asia.

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So the first large mammoth that appears on the scene

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is meridionalis, which was standing four meters tall

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weighing about 10 tons, and was a woodland-adapted species

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and spread from Western Europe clear across Central Asia,

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across the Bering land bridge

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and into parts of North America.

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

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and new habitats opened up,

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we had the arrival of a steppe-adapted species

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called trogontherii in Central Asia

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pushing meridionalis out into Western Europe.

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And the open grassland savannas of North America

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opened up, leading to the Columbian mammoth,

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a large, hairless species in North America.

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And it was really only about 500,000 years later

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that we had the arrival of the woolly,

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the one that we all know and love so much,

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spreading from an East Beringian point of origin

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across Central Asia, again pushing the trogontherii

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out through Central Europe,

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and over hundreds of thousands of years

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migrating back and forth across the Bering land bridge

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during times of glacial peaks

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and coming into direct contact

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with the Columbian relatives living in the south,

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and there they survive over hundreds of thousands of years

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during traumatic climatic shifts.

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So there's a highly plastic animal dealing with great transitions

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in temperature and environment, and doing very, very well.

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

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and actually, surprisingly, on the small islands off of Siberia

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and Alaska until about 3,000 years ago.

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So Egyptians are building pyramids

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and woollies are still living on islands.

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And then they disappear.

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Like 99 percent of all the animals that have once lived,

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they go extinct, likely due to a warming climate

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and fast-encroaching dense forests

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that are migrating north,

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

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probably Pleistocene overkill,

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so the large game hunters that took them down.

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Fortunately, we find millions of their remains

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strewn across the permafrost buried deep

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in Siberia and Alaska, and we can actually go up there

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and actually take them out.

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And the preservation is, again,

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like those insects in [amber], phenomenal.

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So you have teeth, bones with blood

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which look like blood, you have hair,

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and you have intact carcasses or heads

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which still have brains in them.

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So the preservation and the survival of DNA

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depends on many factors, and I have to admit,

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most of which we still don't quite understand,

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but depending upon when an organism dies

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and how quickly he's buried, the depth of that burial,

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the constancy of the temperature of that burial environment,

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will ultimately dictate how long DNA will survive

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over geologically meaningful time frames.

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And it's probably surprising to many of you

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sitting in this room that it's not the time that matters,

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it's not the length of preservation,

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

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So if we were to go deep now within the bones

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and the teeth that actually survived the fossilization process,

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the DNA which was once intact, tightly wrapped

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around histone proteins, is now under attack

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by the bacteria that lived symbiotically with the mammoth

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for years during its lifetime.

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So those bacteria, along with the environmental bacteria,

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free water and oxygen, actually break apart the DNA

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into smaller and smaller and smaller DNA fragments,

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until all you have are fragments that range

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from 10 base pairs to, in the best case scenarios,

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a few hundred base pairs in length.

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So most fossils out there in the fossil record

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are actually completely devoid of all organic signatures.

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But a few of them actually have DNA fragments

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that survive for thousands,

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even a few millions of years in time.

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

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we've devised ways that we can actually pull these DNAs

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away from all the rest of the gunk in there,

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

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that if I take a mammoth bone or a tooth

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and I extract its DNA that I'll get mammoth DNA,

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

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and, more complicated, I'll get all the DNA

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that survived in that environment with it,

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

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Not surprising then again that a mammoth

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preserved in the permafrost will have something

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on the order of 50 percent of its DNA being mammoth,

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whereas something like the Columbian mammoth,

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living in a temperature and buried in a temperate environment

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over its laying-in will only have 3 to 10 percent endogenous.

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But we've come up with very clever ways

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that we can actually discriminate, capture and discriminate,

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the mammoth from the non-mammoth DNA,

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and with the advances in high-throughput sequencing,

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we can actually pull out and bioinformatically

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re-jig all these small mammoth fragments

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and place them onto a backbone

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of an Asian or African elephant chromosome.

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

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that discriminate between a mammoth and an Asian elephant,

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

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Well, the mammoth genome is almost at full completion,

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

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So a hominid genome is about three billion base pairs,

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but an elephant and mammoth genome

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is about two billion base pairs larger, and most of that

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is composed of small, repetitive DNAs

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

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So having this information allows us to answer

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one of the interesting relationship questions

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between mammoths and their living relatives,

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the African and the Asian elephant,

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all of which shared an ancestor seven million years ago,

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but the genome of the mammoth shows it to share

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a most recent common ancestor with Asian elephants

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about six million years ago,

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so slightly closer to the Asian elephant.

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With advances in ancient DNA technology,

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we can actually now start to begin to sequence

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

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and I just wanted to talk about two of them,

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the woolly and the Columbian mammoth,

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both of which were living very close to each other

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during glacial peaks,

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so when the glaciers were massive in North America,

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the woollies were pushed into these subglacial ecotones,

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and came into contact with the relatives living to the south,

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and there they shared refugia,

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

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It looks like they were interbreeding.

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And that this is not an uncommon feature

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in Proboscideans, because it turns out

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that large savanna male elephants will outcompete

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the smaller forest elephants for their females.

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So large, hairless Columbians

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outcompeting the smaller male woollies.

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It reminds me a bit of high school, unfortunately.

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(Laughter)

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So this is not trivial, given the idea that we want

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to revive extinct species, because it turns out

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that an African and an Asian elephant

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can actually interbreed and have live young,

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and this has actually occurred by accident in a zoo

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in Chester, U.K., in 1978.

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So that means that we can actually take Asian elephant chromosomes,

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modify them into all those positions we've actually now

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been able to discriminate with the mammoth genome,

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we can put that into an enucleated cell,

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differentiate that into a stem cell,

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subsequently differentiate that maybe into a sperm,

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artificially inseminate an Asian elephant egg,

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and over a long and arduous procedure,

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actually bring back something that looks like this.

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Now, this wouldn't be an exact replica,

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because the short DNA fragments that I told you about

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will prevent us from building the exact structure,

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but it would make something that looked and felt

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very much like a woolly mammoth did.

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Now, when I bring up this with my friends,

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we often talk about, well, where would you put it?

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Where are you going to house a mammoth?

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There's no climates or habitats suitable.

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Well, that's not actually the case.

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It turns out that there are swaths of habitat

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in the north of Siberia and Yukon

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that actually could house a mammoth.

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Remember, this was a highly plastic animal

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that lived over tremendous climate variation.

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So this landscape would be easily able to house it,

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and I have to admit that there [is] a part of the child in me,

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the boy in me, that would love to see

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these majestic creatures walk across the permafrost

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of the north once again, but I do have to admit

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that part of the adult in me sometimes wonders

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whether or not we should.

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Thank you very much.

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(Applause)

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Ryan Phelan: Don't go away.

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You've left us with a question.

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I'm sure everyone is asking this. When you say, "Should we?"

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it feels like you're reticent there,

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and yet you've given us a vision of it being so possible.

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What's your reticence?

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Hendrik Poinar: I don't think it's reticence.

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I think it's just that we have to think very deeply

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about the implications, ramifications of our actions,

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and so as long as we have good, deep discussion

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like we're having now, I think

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we can come to a very good solution as to why to do it.

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But I just want to make sure that we spend time

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thinking about why we're doing it first.

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RP: Perfect. Perfect answer. Thank you very much, Hendrik.

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HP: Thank you. (Applause)