Michael Archer: How we'll resurrect the gastric brooding frog, the Tasmanian tiger

51,239 views ・ 2013-06-27

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Translator: Joseph Geni Reviewer: Morton Bast
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I do want to test this question we're all interested in:
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Does extinction have to be forever?
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I'm focused on two projects I want to tell you about.
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One is the Thylacine Project.
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The other one is the Lazarus Project,
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and that's focused on the gastric-brooding frog.
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And it would be a fair question to ask,
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why have we focused on these two animals?
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Well, point number one, each of them represents a unique family of its own.
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We've lost a whole family.
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That's a big chunk of the global genome gone.
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I'd like it back.
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The second reason is that we killed these things.
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In the case of the thylacine, regrettably, we shot every one that we saw.
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We slaughtered them.
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In the case of the gastric-brooding frog, we may have "fungicided" it to death.
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There's a dreadful fungus that's moving through the world
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that's called the chytrid fungus,
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and it's nailing frogs all over the world.
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We think that's probably what got this frog,
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and humans are spreading this fungus.
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And this introduces a very important ethical point,
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and I think you will have heard this many times
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when this topic comes up.
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What I think is important
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is that, if it's clear that we exterminated these species,
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then I think we not only have a moral obligation
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to see what we can do about it,
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but I think we've got a moral imperative to try to do something, if we can.
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OK. Let me talk to you about the Lazarus Project.
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It's a frog. And you think, frog.
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Yeah, but this was not just any frog.
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Unlike a normal frog, which lays its eggs in the water
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and goes away and wishes its froglets well,
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this frog swallowed its fertilized eggs,
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swallowed them into the stomach, where it should be having food,
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didn't digest the eggs, and turned its stomach into a uterus.
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In the stomach, the eggs went on to develop into tadpoles,
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and in the stomach, the tadpoles went on to develop into frogs,
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and they grew in the stomach
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until eventually the poor old frog was at risk of bursting apart.
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It has a little cough and a hiccup, and out comes sprays of little frogs.
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Now, when biologists saw this, they were agog.
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They thought, this is incredible.
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No animal, let alone a frog, has been known to do this,
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to change one organ in the body into another.
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And you can imagine the medical world went nuts over this as well.
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If we could understand
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how that frog is managing the way its tummy works,
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is there information here that we need to understand
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or could usefully use to help ourselves?
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Now, I'm not suggesting we want to raise our babies in our stomach,
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but I am suggesting it's possible
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we might want to manage gastric secretion in the gut.
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And just as everybody got excited about it, bang!
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It was extinct.
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I called up my friend,
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Professor Mike Tyler in the University of Adelaide.
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He was the last person who had this frog, a colony of these things, in his lab.
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And I said, "Mike, by any chance --" This was 30 or 40 years ago.
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"By any chance had you kept any frozen tissue of this frog?"
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And he thought about it,
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and he went to his deep freezer, minus 20 degrees centigrade,
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and he poured through everything in the freezer,
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and there in the bottom was a jar and it contained tissues of these frogs.
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This was very exciting,
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but there was no reason why we should expect that this would work,
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because this tissue had not had any antifreeze put in it,
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cryoprotectants, to look after it when it was frozen.
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And normally, when water freezes, as you know, it expands,
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and the same thing happens in a cell.
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If you freeze tissues, the water expands, damages or bursts the cell walls.
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Well, we looked at the tissue under the microscope.
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It actually didn't look bad. The cell walls looked intact.
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So we thought, let's give it a go.
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What we did is something called somatic cell nuclear transplantation.
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We took the eggs of a related species, a living frog,
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and we inactivated the nucleus of the egg.
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We used ultraviolet radiation to do that.
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And then we took the dead nucleus from the dead tissue of the extinct frog
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and we inserted those nuclei into that egg.
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Now, by rights, this is kind of like a cloning project,
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like what produced Dolly,
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but it's actually very different,
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because Dolly was live sheep into live sheep cells.
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That was a miracle, but it was workable.
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What we're trying to do is take a dead nucleus from an extinct species
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and put it into a completely different species and expect that to work.
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Well, we had no real reason to expect it would,
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and we tried hundreds and hundreds of these.
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And just last February, the last time we did these trials,
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I saw a miracle starting to happen.
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What we found was most of these eggs didn't work,
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but then suddenly, one of them began to divide.
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That was so exciting.
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And then the egg divided again. And then again.
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And pretty soon, we had early-stage embryos
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with hundreds of cells forming those.
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We even DNA-tested some of these cells,
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and the DNA of the extinct frog is in those cells.
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So we're very excited. This is not a tadpole. It's not a frog.
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But it's a long way along the journey
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to producing, or bringing back, an extinct species.
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And this is news.
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We haven't announced this publicly before.
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We're excited.
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We've got to get past this point.
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We now want this ball of cells to start to gastrulate,
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to turn in so that it will produce the other tissues.
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It'll go on and produce a tadpole and then a frog.
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Watch this space.
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I think we're going to have this frog hopping
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glad to be back in the world again.
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(Applause)
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Thank you.
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(Applause)
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We haven't done it yet, but keep the applause ready.
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The second project I want to talk to you about is the Thylacine Project.
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The thylacine looks a bit, to most people, like a dog,
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or maybe like a tiger, because it has stripes.
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But it's not related to any of those. It's a marsupial.
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It raised its young in a pouch, like a koala or a kangaroo would do,
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and it has a long history, a long, fascinating history,
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that goes back 25 million years.
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But it's also a tragic history.
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The first one that we see occurs in the ancient rain forests of Australia
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about 25 million years ago,
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and the National Geographic Society
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is helping us to explore these fossil deposits.
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This is Riversleigh.
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In those fossil rocks are some amazing animals.
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We found marsupial lions.
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We found carnivorous kangaroos.
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It's not what you usually think about as a kangaroo,
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but these are meat-eating kangaroos.
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We found the biggest bird in the world,
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bigger than that thing that was in Madagascar,
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and it too was a flesh eater.
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It was a giant, weird duck.
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And crocodiles were not behaving at that time either.
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You think of crocodiles as doing their ugly thing,
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sitting in a pool of water.
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These crocodiles were actually out on the land
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and they were even climbing trees and jumping on prey on the ground.
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We had, in Australia, drop crocs. They really do exist.
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(Laughter)
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But what they were dropping on was not only other weird animals
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but also thylacines.
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There were five different kinds of thylacines in those ancient forests,
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and they ranged from great big ones to middle-sized ones
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to one that was about the size of a chihuahua.
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Paris Hilton would have been able
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to carry one of these things around in a little handbag,
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until a drop croc landed on her.
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At any rate, it was a fascinating place,
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but unfortunately, Australia didn't stay this way.
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Climate change has affected the world for a long period of time,
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and gradually, the forests disappeared, the country began to dry out,
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and the number of kinds of thylacines began to decline,
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until by five million years ago,
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only one left.
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By 10,000 years ago, they had disappeared from New Guinea,
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and unfortunately, by 4,000 years ago, somebodies, we don't know who this was,
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introduced dingoes -- this is a very archaic kind of a dog --
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into Australia.
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And as you can see,
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dingoes are very similar in their body form to thylacines.
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That similarity meant they probably competed.
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They were eating the same kinds of foods.
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It's even possible that aborigines were keeping some of these dingoes as pets,
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and therefore they may have had an advantage in the battle for survival.
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All we know is, soon after the dingoes were brought in,
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thylacines were extinct in the Australian mainland,
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and after that they only survived in Tasmania.
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Then, unfortunately,
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the next sad part of the thylacine story is that Europeans arrived in 1788,
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and they brought with them the things they valued,
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and that included sheep.
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They took one look at the thylacine in Tasmania,
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and they thought, hang on, this is not going to work.
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That guy is going to eat all our sheep.
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That was not what happened, actually.
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Wild dogs did eat a few of the sheep, but the thylacine got a bad rap.
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But immediately, the government said, that's it, let's get rid of them,
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and they paid people to slaughter every one that they saw.
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By the early 1930s,
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3,000 to 4,000 thylacines had been murdered.
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It was a disaster, and they were about to hit the wall.
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Have a look at this bit of film footage.
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It makes me very sad because, while it's a fascinating animal,
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and it's amazing to think that we had the technology to film it
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before it actually plunged off that cliff of extinction,
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we didn't, unfortunately, at this same time,
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have a molecule of concern about the welfare for this species.
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These are photos of the last surviving thylacine, Benjamin,
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who was in the Beaumaris Zoo in Hobart.
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To add insult to injury,
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having swept this species nearly off the table,
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this animal, when it died of neglect --
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The keepers didn't let it into the hutch on a cold night in Hobart.
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It died of exposure, and in the morning, when they found the body of Benjamin,
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they still cared so little for this animal that they threw the body in the dump.
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Does it have to stay this way?
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In 1990, I was in the Australian Museum.
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I was fascinated by thylacines.
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I've always been obsessed with these animals.
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And I was studying skulls,
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trying to figure out their relationships to other sorts of animals,
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and I saw this jar,
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and here, in the jar, was a little girl thylacine pup,
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perhaps six months old.
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The guy who had found it and killed the mother
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had pickled the pup, and they pickled it in alcohol.
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I'm a paleontologist, but I still knew alcohol was a DNA preservative.
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But this was 1990, and I asked my geneticist friends,
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couldn't we think about going into this pup
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and extracting DNA, if it's there,
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and then somewhere down the line in the future,
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we'll use this DNA to bring the thylacine back?
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The geneticists laughed. But this was six years before Dolly.
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Cloning was science fiction.
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It had not happened.
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But then suddenly cloning did happen.
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And I thought, when I became director of the Australian Museum,
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I'm going to give this a go.
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I put a team together.
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We went into that pup to see what was in it,
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and we did find thylacine DNA.
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It was a eureka moment. We were very excited.
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Unfortunately, we also found a lot of human DNA.
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Every old curator who'd been in that museum
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had seen this wonderful specimen,
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put their hand in the jar, pulled it out and thought,
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"Wow, look at that," plop, dropped it back in the jar,
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contaminating this specimen.
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And that was a worry.
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If the goal here was to get the DNA out
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and use the DNA down the track to try to bring a thylacine back,
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what we didn't want happening
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when the information was shoved into the machine
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and the wheel turned around and the lights flashed,
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was to have a wizened old horrible curator pop out the other end of the machine.
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It would've kept the curator very happy, but it wasn't going to keep us happy.
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So we went back to these specimens and we started digging around,
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and particularly, we looked into the teeth of skulls,
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hard parts where humans had not been able to get their fingers,
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and we found much better quality DNA.
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We found nuclear mitochondrial genes.
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It's there. So we got it.
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OK. What could we do with this stuff?
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Well, George Church, in his book, "Regenesis,"
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has mentioned many of the techniques that are rapidly advancing
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to work with fragmented DNA.
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We would hope that we'll be able to get that DNA back into a viable form,
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and then, much like we've done with the Lazarus Project,
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get that stuff into an egg of a host species.
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It has to be a different species. What could it be?
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Why couldn't it be a Tasmanian devil?
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They're related, distantly, to thylacines.
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And then the Tasmanian devil is going to pop a thylacine out the south end.
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Critics of this project say, hang on.
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Thylacine, Tasmanian devil? That's going to hurt.
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No, it's not. These are marsupials.
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They give birth to babies that are the size of a jelly bean.
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That Tasmanian devil's not even going to know it gave birth.
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It is, shortly, going to think
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it's got the ugliest Tasmanian devil baby in the world,
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so maybe it'll need some help to keep it going.
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Andrew Pask and his colleagues have demonstrated
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this might not be a waste of time.
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And it's sort of in the future, we haven't got there yet,
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but it's the kind of thing we want to think about.
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They took some of this same pickled thylacine DNA
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and they spliced it into a mouse genome,
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but they put a tag on it
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so that anything that this thylacine DNA produced
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would appear blue-green in the mouse baby.
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In other words, if thylacine tissues were being produced by the thylacine DNA,
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it would be able to be recognized.
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When the baby popped up, it was filled with blue-green tissues.
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And that tells us if we can get that genome back together,
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get it into a live cell,
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it's going to produce thylacine stuff.
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Is this a risk?
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You've taken the bits of one animal
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and you've mixed them into the cell of a different kind of an animal.
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Are we going to get a Frankenstein? Some kind of weird hybrid chimera?
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And the answer is no.
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If the only nuclear DNA that goes into this hybrid cell is thylacine DNA,
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that's the only thing that can pop out the other end of the devil.
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OK, if we can do this, could we put it back?
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This is a key question for everybody.
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Does it have to stay in a laboratory, or could we put it back where it belongs?
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Could we put it back in the throne of the king of beasts in Tasmania,
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restore that ecosystem?
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Or has Tasmania changed so much that that's no longer possible?
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I've been to Tasmania.
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I've been to many of the areas where the thylacines were common.
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I've even spoken to people, like Peter Carter here,
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who when I spoke to him, was 90 years old,
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but in 1926, this man and his father and his brother
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caught thylacines.
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They trapped them.
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And when I spoke to this man, I was looking in his eyes and thinking,
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"Behind those eyes is a brain that has memories of what thylacines feel like,
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what they smelled like, what they sounded like."
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He led them around on a rope.
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He has personal experiences
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that I would give my left leg to have in my head.
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We'd all love to have this sort of thing happen.
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Anyway, I asked Peter, by any chance,
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could he take us back to where he caught those thylacines.
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My interest was in whether the environment had changed.
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He thought hard. It was nearly 80 years before this that he'd been at this hut.
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At any rate, he led us down this bush track,
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and there, right where he remembered,
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was the hut,
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and tears came into his eyes.
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He looked at the hut. We went inside.
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There were the wooden boards on the sides of the hut
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where he and his father and his brother had slept at night.
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And he told me, as it all was flooding back in memories.
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He said, "I remember the thylacines going around the hut
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wondering what was inside,"
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and he said they made sounds like "Yip! Yip! Yip!"
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All of these are parts of his life and what he remembers.
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And the key question for me was to ask Peter, has it changed?
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And he said no.
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The southern beech forests surrounded his hut
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just like it was when he was there in 1926.
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The grasslands were sweeping away.
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15:49
That's classic thylacine habitat.
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And the animals in those areas were the same that were there
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when the thylacine was around.
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So could we put it back? Yes.
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Is that all we would do? And this is an interesting question.
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Sometimes you might be able to put it back,
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but is that the safest way to make sure it never goes extinct again?
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And I don't think so.
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I think gradually, as we see species all around the world,
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it's kind of a mantra that wildlife is increasingly not safe in the wild.
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We'd love to think it is, but we know it isn't.
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We need other parallel strategies coming online.
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And this one interests me.
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Some of the thylacines that were being turned in to zoos,
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sanctuaries, even at the museums,
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had collar marks on the neck.
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They were being kept as pets,
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and we know a lot of bush tales and memories
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of people who had them as pets,
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and they say they were wonderful, friendly.
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This particular one
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came in out of the forest to lick this boy
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and curled up around the fireplace to go to sleep.
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A wild animal.
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And I'd like to ask the question. We need to think about this.
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If it had not been illegal to keep these thylacines as pets then,
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would the thylacine be extinct now?
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And I'm positive it wouldn't.
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We need to think about this in today's world.
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Could it be that getting animals close to us so that we value them,
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maybe they won't go extinct?
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And this is such a critical issue for us
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because if we don't do that,
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we're going to watch more of these animals plunge off the precipice.
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As far as I'm concerned,
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this is why we're trying to do these kinds of de-extinction projects.
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We are trying to restore that balance of nature
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that we have upset.
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Thank you.
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(Applause)
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