Hendrik Poinar: Bring back the woolly mammoth!

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Hendrik Poinar: Bring back the woolly mammoth!

小さいことは気にすんなッ、主題と主張をつかもう！

永久凍土の下から発掘されるマンモスの死体からDNAを抽出して、それをアジアゾウの核に組み込んで幹細胞化し、マンモスに近い生物を作ろうという計画です。NHKのスーパープレゼンテーションでジャック・ホーナー博士の「ニワトリから恐竜を作る」をやっていましたが、アプローチの方法が違いますね。つい最近、韓国の学者がマンモスの血液（液体の状態のもの）を採取したとの報道がありました。

→ 1万年前のマンモスから「液体の血液」を採取

【話題】マンモス復活計画

【時間】 10分22秒
【要約】
０．子供の頃の妄想
　父親が持っていた琥珀の中の蚊が、いつか飛び出してくるのではないかと妄想していた。

１．絶滅した生物の復活
　10年前までは、絶滅した生物を復活させるなどという話は夢物語だと思っていた。しかし今では、現実に可能だと信じている。

２．マンモスについて
　ケナガマンモスは氷河期の象徴的な生物だが、マンモスには数種類が存在した。アフリカを起源とし、気候変動と共にヨーロッパ、アジア、ベーリング陸峡、北アメリカを数千年に渡って行ったり来たりしながら、種が分化していった。マンモスは環境の変化に対して柔軟性をもった生物だった。

３．DNAの保存状態について
　マンモスは絶滅したが、シベリアの永久凍土からその死体が発掘される。数千年、数万年経っているにもかかわらず保存状態が驚異的に良いのは、瞬間的に埋められて一定の低温状態が保たれていたからだ。そして、50％以上のDNAが微生物に分解されずに残っているケースがある。

４．DNAを区別する技術
　マンモスのDNAとその他（微生物など）のDNAを区別する技術を開発した。そして、マンモスから抽出したDNAをアフリカゾウやアジアゾウのDNAに組み込むことができる。

５．マンモスとゾウの系統と分類
　マンモスは、アフリカゾウよりもアジアゾウに近い。過去において、ケナガマンモスとコロンビアマンモス同士が交配したと考えられ、またアフリカゾウとアジアゾウが交配した事実がある。

６．マンモスを復活させる方法
　発掘したマンモスから抽出したDNAをアジアゾウの細胞に組み込み、幹細胞にすれば、マンモスを復活させることができる。もちろん完全なマンモスではないが、それに近い生物を作ることができる。シベリア北部とユーコン川の間に、マンモスの住み処として最適な場所がある。マンモスは環境に柔軟な生物だということを思い出してほしい。

７．やるべきか、やらざるべきか
　決して興味本位ではないが、マンモスを復活させるべきか否か、葛藤する自分がいると言わざるを得ない。実行する前に十分な議論が必要だと感じる。

【語彙】

morphologically ：形態学的に

phenomenal ：驚異的な

resin ：樹脂

sequence ：配列を決定する

pipe dream ：夢物語

permafrost ：永久凍土

quintessential ：典型的な

the next of kin ：最近親者

meridionalis ：メリディオナス、最古の化石がみつかっているマンモス

Bering land bridge ：ベーリング地峡、シベリアとアラスカをつなぐ

trogontherii ：ステップマンモス

glacial peaks ：氷河期のピーク

traumatic ：衝撃的な

plastic ：柔軟な

fast-encroaching ：高速侵入する

Pleistocene ：更新世、更新世のほとんどは氷河期

strewn ：ばらまかれた

intact carcasses ：無傷の死体

preservation ：保全

consistency ：一貫性

fossilization ：化石

intact ：無傷の

histone proteins ：ヒストンタンパク質

be devoid of ：～を欠いている

gunk ：カス

endogenous ：内因性の

re-jig ：再治

hominid ：ヒト科の動物

ecotone ：推移帯

refugia ：退避地

enucleated cell ：徐核細胞

arduous ：つらい

differentiate ：分化する

swaths ：帯状の領域

reticence ：遠慮？

ramification ：波及効果

【transcripts】

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 had asked me 10 years ago whether or not we would ever be able to sequence the genome of extinct animals, I would have told you, it's unlikely. If you had asked whether or not we would actually 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 is the sequencing of extinct genomes a possibility, actually a modern-day reality, but the revival of an extinct species is 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, quintessential 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're 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. And 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 relatives living in the south, and there they survive over hundreds of thousands of years during traumatic climatic shifts. So there's a highly plastic animal dealing with great transitions in temperature and environment, and doing very, very well. And there they survive on the mainland until about 10,000 years ago, and actually, surprisingly, on the small islands off of Siberia and Alaska until about 3,000 years ago. So Egyptians are building pyramids and woollies are still living on islands.

And then they disappear. Like 99 percent of all the animals that have 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, and 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 look like blood, you have hair, and you have intact carcasses or heads which still have brains in them.

So the preservation and 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's 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 lived 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 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 survive for thousands, even a few millions of years in time. And using state-of-the-art clean room technology, we've devised 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'll 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. Not surprising then again that a mammoth preserved in the permafrost will have something on the order of 50 percent of its DNA being mammoth, whereas something like the Columbian mammoth, living in a temperature and buried in a temperate environment over its laying-in will only have 3 to 10 percent endogenous.

But we've come up with very clever ways that we can actually discriminate, capture and discriminate, the mammoth from the non-mammoth DNA, and with the advances in high-throughput 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 a 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 the 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 that 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.

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, U.K., in 1978. So that means that we can actually take Asian elephant chromosomes, modify them into all those positions we've 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 wouldn't be an exact replica, because the short DNA fragments that I told you about will prevent us from building the exact structure, but it would make something that looked and felt very much like a woolly mammoth did.

Now, 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 no climates or habitats suitable. Well, that's 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 mammoth. 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 isn't 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 whether or not we should.

Thank you very much.

Ryan Phelan: Don't go away. You've left us with a question. I'm sure everyone is asking this. When you say, "Should we?" it feels like you're reticent there, and yet you've given us a vision of it being so possible. What's your reticence?

Hendrik Poinar: I don't think it's reticence. I think it's just that we have to think very deeply about the implications, ramifications of our actions, and so as long as we have good, deep discussion like we're having now, I think we can come to a very good solution as to why to do it. But I just want to make sure that we spend time thinking about why we're doing it first.

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

HP: Thank you.

ヘンドリック・ポイナー「マンモス復活計画」