How to pronounce "spliced"

Translator: Joseph Geni Reviewer: Morton Bast

I do want to test this question we're all interested in:

Does extinction have to be forever?

I'm focused on two projects I want to tell you about.

One is the Thylacine Project.

The other one is the Lazarus Project,

and that's focused on the gastric-brooding frog.

And it would be a fair question to ask,

why have we focused on these two animals?

Well, point number one, each of them represents a unique family of its own.

We've lost a whole family.

That's a big chunk of the global genome gone.

I'd like it back.

The second reason is that we killed these things.

In the case of the thylacine, regrettably, we shot every one that we saw.

We slaughtered them.

In the case of the gastric-brooding frog, we may have "fungicided" it to death.

There's a dreadful fungus that's moving through the world

that's called the chytrid fungus,

and it's nailing frogs all over the world.

We think that's probably what got this frog,

and humans are spreading this fungus.

And this introduces a very important ethical point,

and I think you will have heard this many times

when this topic comes up.

What I think is important

is that, if it's clear that we exterminated these species,

then I think we not only have a moral obligation

to see what we can do about it,

but I think we've got a moral imperative to try to do something, if we can.

OK. Let me talk to you about the Lazarus Project.

It's a frog. And you think, frog.

Yeah, but this was not just any frog.

Unlike a normal frog, which lays its eggs in the water

and goes away and wishes its froglets well,

this frog swallowed its fertilized eggs,

swallowed them into the stomach, where it should be having food,

didn't digest the eggs, and turned its stomach into a uterus.

In the stomach, the eggs went on to develop into tadpoles,

and in the stomach, the tadpoles went on to develop into frogs,

and they grew in the stomach

until eventually the poor old frog was at risk of bursting apart.

It has a little cough and a hiccup, and out comes sprays of little frogs.

Now, when biologists saw this, they were agog.

They thought, this is incredible.

No animal, let alone a frog, has been known to do this,

to change one organ in the body into another.

And you can imagine the medical world went nuts over this as well.

If we could understand

how that frog is managing the way its tummy works,

is there information here that we need to understand

or could usefully use to help ourselves?

Now, I'm not suggesting we want to raise our babies in our stomach,

but I am suggesting it's possible

we might want to manage gastric secretion in the gut.

And just as everybody got excited about it, bang!

It was extinct.

I called up my friend,

Professor Mike Tyler in the University of Adelaide.

He was the last person who had this frog, a colony of these things, in his lab.

And I said, "Mike, by any chance --" This was 30 or 40 years ago.

"By any chance had you kept any frozen tissue of this frog?"

And he thought about it,

and he went to his deep freezer, minus 20 degrees centigrade,

and he poured through everything in the freezer,

and there in the bottom was a jar and it contained tissues of these frogs.

This was very exciting,

but there was no reason why we should expect that this would work,

because this tissue had not had any antifreeze put in it,

cryoprotectants, to look after it when it was frozen.

And normally, when water freezes, as you know, it expands,

and the same thing happens in a cell.

If you freeze tissues, the water expands, damages or bursts the cell walls.

Well, we looked at the tissue under the microscope.

It actually didn't look bad. The cell walls looked intact.

So we thought, let's give it a go.

What we did is something called somatic cell nuclear transplantation.

We took the eggs of a related species, a living frog,

and we inactivated the nucleus of the egg.

We used ultraviolet radiation to do that.

And then we took the dead nucleus from the dead tissue of the extinct frog

and we inserted those nuclei into that egg.

Now, by rights, this is kind of like a cloning project,

like what produced Dolly,

but it's actually very different,

because Dolly was live sheep into live sheep cells.

That was a miracle, but it was workable.

What we're trying to do is take a dead nucleus from an extinct species

and put it into a completely different species and expect that to work.

Well, we had no real reason to expect it would,

and we tried hundreds and hundreds of these.

And just last February, the last time we did these trials,

I saw a miracle starting to happen.

What we found was most of these eggs didn't work,

but then suddenly, one of them began to divide.

That was so exciting.

And then the egg divided again. And then again.

And pretty soon, we had early-stage embryos

with hundreds of cells forming those.

We even DNA-tested some of these cells,

and the DNA of the extinct frog is in those cells.

So we're very excited. This is not a tadpole. It's not a frog.

But it's a long way along the journey

to producing, or bringing back, an extinct species.

And this is news.

We haven't announced this publicly before.

We're excited.

We've got to get past this point.

We now want this ball of cells to start to gastrulate,

to turn in so that it will produce the other tissues.

It'll go on and produce a tadpole and then a frog.

Watch this space.

I think we're going to have this frog hopping

glad to be back in the world again.

(Applause)

Thank you.

(Applause)

We haven't done it yet, but keep the applause ready.

The second project I want to talk to you about is the Thylacine Project.

The thylacine looks a bit, to most people, like a dog,

or maybe like a tiger, because it has stripes.

But it's not related to any of those. It's a marsupial.

It raised its young in a pouch, like a koala or a kangaroo would do,

and it has a long history, a long, fascinating history,

that goes back 25 million years.

But it's also a tragic history.

The first one that we see occurs in the ancient rain forests of Australia

about 25 million years ago,

and the National Geographic Society

is helping us to explore these fossil deposits.

This is Riversleigh.

In those fossil rocks are some amazing animals.

We found marsupial lions.

We found carnivorous kangaroos.

It's not what you usually think about as a kangaroo,

but these are meat-eating kangaroos.

We found the biggest bird in the world,

bigger than that thing that was in Madagascar,

and it too was a flesh eater.

It was a giant, weird duck.

And crocodiles were not behaving at that time either.

You think of crocodiles as doing their ugly thing,

sitting in a pool of water.

These crocodiles were actually out on the land

and they were even climbing trees and jumping on prey on the ground.

We had, in Australia, drop crocs. They really do exist.

(Laughter)

But what they were dropping on was not only other weird animals

but also thylacines.

There were five different kinds of thylacines in those ancient forests,

and they ranged from great big ones to middle-sized ones

to one that was about the size of a chihuahua.

Paris Hilton would have been able

to carry one of these things around in a little handbag,

until a drop croc landed on her.

At any rate, it was a fascinating place,

but unfortunately, Australia didn't stay this way.

Climate change has affected the world for a long period of time,

and gradually, the forests disappeared, the country began to dry out,

and the number of kinds of thylacines began to decline,

until by five million years ago,

only one left.

By 10,000 years ago, they had disappeared from New Guinea,

and unfortunately, by 4,000 years ago, somebodies, we don't know who this was,

introduced dingoes -- this is a very archaic kind of a dog --

into Australia.

And as you can see,

dingoes are very similar in their body form to thylacines.

That similarity meant they probably competed.

They were eating the same kinds of foods.

It's even possible that aborigines were keeping some of these dingoes as pets,

and therefore they may have had an advantage in the battle for survival.

All we know is, soon after the dingoes were brought in,

thylacines were extinct in the Australian mainland,

and after that they only survived in Tasmania.

Then, unfortunately,

the next sad part of the thylacine story is that Europeans arrived in 1788,

and they brought with them the things they valued,

and that included sheep.

They took one look at the thylacine in Tasmania,

and they thought, hang on, this is not going to work.

That guy is going to eat all our sheep.

That was not what happened, actually.

Wild dogs did eat a few of the sheep, but the thylacine got a bad rap.

But immediately, the government said, that's it, let's get rid of them,

and they paid people to slaughter every one that they saw.

By the early 1930s,

3,000 to 4,000 thylacines had been murdered.

It was a disaster, and they were about to hit the wall.

Have a look at this bit of film footage.

It makes me very sad because, while it's a fascinating animal,

and it's amazing to think that we had the technology to film it

before it actually plunged off that cliff of extinction,

we didn't, unfortunately, at this same time,

have a molecule of concern about the welfare for this species.

These are photos of the last surviving thylacine, Benjamin,

who was in the Beaumaris Zoo in Hobart.

To add insult to injury,

having swept this species nearly off the table,

this animal, when it died of neglect --

The keepers didn't let it into the hutch on a cold night in Hobart.

It died of exposure, and in the morning, when they found the body of Benjamin,

they still cared so little for this animal that they threw the body in the dump.

Does it have to stay this way?

In 1990, I was in the Australian Museum.

I was fascinated by thylacines.

I've always been obsessed with these animals.

And I was studying skulls,

trying to figure out their relationships to other sorts of animals,

and I saw this jar,

and here, in the jar, was a little girl thylacine pup,

perhaps six months old.

The guy who had found it and killed the mother

had pickled the pup, and they pickled it in alcohol.

I'm a paleontologist, but I still knew alcohol was a DNA preservative.

But this was 1990, and I asked my geneticist friends,

couldn't we think about going into this pup

and extracting DNA, if it's there,

and then somewhere down the line in the future,

we'll use this DNA to bring the thylacine back?

The geneticists laughed. But this was six years before Dolly.

Cloning was science fiction.

It had not happened.

But then suddenly cloning did happen.

And I thought, when I became director of the Australian Museum,

I'm going to give this a go.

I put a team together.

We went into that pup to see what was in it,

and we did find thylacine DNA.

It was a eureka moment. We were very excited.

Unfortunately, we also found a lot of human DNA.

Every old curator who'd been in that museum

had seen this wonderful specimen,

put their hand in the jar, pulled it out and thought,

"Wow, look at that," plop, dropped it back in the jar,

contaminating this specimen.

And that was a worry.

If the goal here was to get the DNA out

and use the DNA down the track to try to bring a thylacine back,

what we didn't want happening

when the information was shoved into the machine

and the wheel turned around and the lights flashed,

was to have a wizened old horrible curator pop out the other end of the machine.

It would've kept the curator very happy, but it wasn't going to keep us happy.

So we went back to these specimens and we started digging around,

and particularly, we looked into the teeth of skulls,

hard parts where humans had not been able to get their fingers,

and we found much better quality DNA.

We found nuclear mitochondrial genes.

It's there. So we got it.

OK. What could we do with this stuff?

Well, George Church, in his book, "Regenesis,"

has mentioned many of the techniques that are rapidly advancing

to work with fragmented DNA.

We would hope that we'll be able to get that DNA back into a viable form,

and then, much like we've done with the Lazarus Project,

get that stuff into an egg of a host species.

It has to be a different species. What could it be?

Why couldn't it be a Tasmanian devil?

They're related, distantly, to thylacines.

And then the Tasmanian devil is going to pop a thylacine out the south end.

Critics of this project say, hang on.

Thylacine, Tasmanian devil? That's going to hurt.

No, it's not. These are marsupials.

They give birth to babies that are the size of a jelly bean.

That Tasmanian devil's not even going to know it gave birth.

It is, shortly, going to think

it's got the ugliest Tasmanian devil baby in the world,

so maybe it'll need some help to keep it going.

Andrew Pask and his colleagues have demonstrated

this might not be a waste of time.

And it's sort of in the future, we haven't got there yet,

but it's the kind of thing we want to think about.

They took some of this same pickled thylacine DNA

and they spliced it into a mouse genome,

but they put a tag on it

so that anything that this thylacine DNA produced

would appear blue-green in the mouse baby.

In other words, if thylacine tissues were being produced by the thylacine DNA,

it would be able to be recognized.

When the baby popped up, it was filled with blue-green tissues.

And that tells us if we can get that genome back together,

get it into a live cell,

it's going to produce thylacine stuff.

Is this a risk?

You've taken the bits of one animal

and you've mixed them into the cell of a different kind of an animal.

Are we going to get a Frankenstein? Some kind of weird hybrid chimera?

And the answer is no.

If the only nuclear DNA that goes into this hybrid cell is thylacine DNA,

that's the only thing that can pop out the other end of the devil.

OK, if we can do this, could we put it back?

This is a key question for everybody.

Does it have to stay in a laboratory, or could we put it back where it belongs?

Could we put it back in the throne of the king of beasts in Tasmania,

restore that ecosystem?

Or has Tasmania changed so much that that's no longer possible?

I've been to Tasmania.

I've been to many of the areas where the thylacines were common.

I've even spoken to people, like Peter Carter here,

who when I spoke to him, was 90 years old,

but in 1926, this man and his father and his brother

caught thylacines.

They trapped them.

And when I spoke to this man, I was looking in his eyes and thinking,

"Behind those eyes is a brain that has memories of what thylacines feel like,

what they smelled like, what they sounded like."

He led them around on a rope.

He has personal experiences

that I would give my left leg to have in my head.

We'd all love to have this sort of thing happen.

Anyway, I asked Peter, by any chance,

could he take us back to where he caught those thylacines.

My interest was in whether the environment had changed.

He thought hard. It was nearly 80 years before this that he'd been at this hut.

At any rate, he led us down this bush track,

and there, right where he remembered,

was the hut,

and tears came into his eyes.

He looked at the hut. We went inside.

There were the wooden boards on the sides of the hut

where he and his father and his brother had slept at night.

And he told me, as it all was flooding back in memories.

He said, "I remember the thylacines going around the hut

wondering what was inside,"

and he said they made sounds like "Yip! Yip! Yip!"

All of these are parts of his life and what he remembers.

And the key question for me was to ask Peter, has it changed?

And he said no.

The southern beech forests surrounded his hut

just like it was when he was there in 1926.

The grasslands were sweeping away.

That's classic thylacine habitat.

And the animals in those areas were the same that were there

when the thylacine was around.

So could we put it back? Yes.

Is that all we would do? And this is an interesting question.

Sometimes you might be able to put it back,

but is that the safest way to make sure it never goes extinct again?

And I don't think so.

I think gradually, as we see species all around the world,

it's kind of a mantra that wildlife is increasingly not safe in the wild.

We'd love to think it is, but we know it isn't.

We need other parallel strategies coming online.

And this one interests me.

Some of the thylacines that were being turned in to zoos,

sanctuaries, even at the museums,

had collar marks on the neck.

They were being kept as pets,

and we know a lot of bush tales and memories

of people who had them as pets,

and they say they were wonderful, friendly.

This particular one

came in out of the forest to lick this boy

and curled up around the fireplace to go to sleep.

A wild animal.

And I'd like to ask the question. We need to think about this.

If it had not been illegal to keep these thylacines as pets then,

would the thylacine be extinct now?

And I'm positive it wouldn't.

We need to think about this in today's world.

Could it be that getting animals close to us so that we value them,

maybe they won't go extinct?

And this is such a critical issue for us

because if we don't do that,

we're going to watch more of these animals plunge off the precipice.

As far as I'm concerned,

this is why we're trying to do these kinds of de-extinction projects.

We are trying to restore that balance of nature

that we have upset.

Thank you.

(Applause)