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I'd like to speak to you
about the use of cloning and stem cells to resurrect life.
As you know, there are 2 ways to make copies of cells and organisms.
The first and most controversial
is cloning,
and that is also known as somatic cell nuclear transfer.
The concept is very simple,
you start out with an empty egg, that's the large circle you see
and then you place the cell you want to clone,
the smaller somatic cell right next to it,
then you send an electrical charge through the unit
and it damages the membrane between the two
and the nucleus of the cell you want to clone
dumps into that empty egg;
then you add some chemicals,
you fool that unit into thinking that it is fertilised,
it starts to divide
and you end up with what is known as preimplantation embryo.
Then you can do one of 2 things with that.
You can place that in a Petri dish
where you can turn that into embryonic stem cells
which are the master cells of the body
and they can turn into virtually every cell type.
And the other alternative
is that you can place that into a surrogate animal
to create an entire organism.
Another approach that is newer is known as Cell Reprogramming.
And that leads to what is known as induced pluripotent stem cells
or iPS cells.
You start out with a somatic cell on a piece of skin,
you throw in some transcription factors
and bring that differentiated cell back to a state of pluripotency
very much like an embryonic stem cell.
And we have new tricks now,
we can actually turn those cells into an entire organism as well.
So, to date, about 2 dozen different species have been cloned.
Back in 1958 John Gurdon cloned the first animal,
that was a frog,
In fact he was just recognised for that feat
a few months ago with the Nobel Prize,
and since that time, of course, there's been Dolly the cloned sheep,
and we and other groups have cloned mice and goats and even cats and dogs.
In fact, back in the 1990's, we cloned an entire herd of cows
from genetically modified cells.
So what you actually see here
are animals that are making human albumin in their milk,
So we could use the same approach to reconstruct extinct animals
à la Jurassic Park.
So in this case we took a skin biopsy from the ear of a cow,
we grew up the cells knocked in a gene cassette,
and then used ordinary eggs to create that herd of animals.
So similarly, as George Church would describe,
we can then take, say, an elephant cell, knock in the genes for tusks, or long ear,
or haemoglobin so he can live in a cold climate,
and then using the technique that I'll describe later,
we can create *** and eggs and an entire organism from that.
So, there are 2 types of cloning.
One is known as interspecies cloning
and the other is intraspecies.
With the intraspecies,
you actually use the egg and the cell from the same species you want to clone,
but using this cross-species approach,
we can take the egg of one species to clone the cell from another.
And that's very important if you want to resurrect extinct animals
or if you want to clone endangered animals.
Back in 2000 we used this cross-species technique
to clone the first endangered species.
In this case it was a gaur,
which is a wild ox on the verge of extinction.
At the time everyone said, "That's not going to work, that's impossible."
and the reason for that
is that a clone isn't really entirely a clone.
It turns out that every cell has 2 genomes.
One is the mitochondrial genome,
and the mitochondria
are the organelles in the cell that make energy.
That's maternally inherited, so that will come from the egg.
And the other genome is the nuclear genome,
and that contains the genes that distinguish you and I
from an elephant or a mouse.
So those 2 genomes have to talk to one another,
and there's evidence that it can only occur
within 8 to 18 million years species radiation.
We got around that problem by using very closely related species,
concord and xenograft combinations.
In this particular case we had a gaur and a cow
and they are both in the Bos family.
Using that approach,
we were able to reconstruct these clone gaur embryos,
that may look like little circles to you,
but these are actually beautiful little gaur blastocysts.
The idea here was to create these embryos,
send them by FedEx off to a farm in Iowa
where they would be implanted into some ordinary cows.
It turned out that the first round we made
and put outside the door for the delivery truck guy to pick up,
unfortunately, we came the next morning, and they were still there.
But eventually FedEx did deliver a new round of these embryos,
they were indeed implanted into some animals.
I went to Iowa entranced over
We had 25% pregnancy rate.
Two of those we let continue onto term.
Unfortunately one of those aborted at late stage,
it was 202 days.
We let one of them continue to just day.
And here's Bessy, 8 months pregnant.
We were a bit nervous.
The whole world was following us, CNN was running in almost everyday
and we were concerned, "What if Bessy gave rise to an ordinary cow?
That would be very embarrassing!"
(Laugher)
And that's happened before.
So fortunately it did give rise to a beautiful little baby gaur.
It's a bit surreal
seeing this exotic endangered animal
that is normally born in bamboo jungles of Southeast Asia,
being born out in an Iwoa farm that reeked of cow manure,
but it was alive.
Died unfortunately 2 days later.
Everyone said, "See Bob, the technology doesn't work."
About 2 years later, we approached the San Diego zoo
and they came up with an animal that's known as banteng.
Only about 2000 of these animals are left on the planet.
And he had cells from this animal
that had been frozen away for a quarter of a century.
So they sent us a vial of these frozen cells
and again we put those into cow eggs, sent them back off to Iowa,
and indeed on April Fool's Day in 2003 we had a beautiful little baby banteng
which was ultimately transferred to San Diego zoo
where it lived with the other bantengs.
So this technology does work.
There are some problems,
but we have new technologies that I'll mention
that can now solve many of these bottlenecks.
I collect dinosaur fossils.
So when you go to my front door
the first thing you see is this Brantosaur's femur.
It's about 6 feet long and weighs 800 pounds.
And everyone goes, "Bob, you gotta clone it!"
and that animal was bigger than my house,
I don't know what the surrogate would be, although it is an egg!
(Laughter)
In any case, I actually live on an island,
and one day a USA Today reporter was there and said,
"You know, you have the island, you need the electric fence."
and I told him, "You can't clone from stone."
So you are not likely to see any dinosaurs in your back yard
any time soon.
But that doesn't mean extinction is necessarily forever.
You just heard from Alberto, about Celia,
so that was the first short-term success.
I remember back in 2000 going to Zaragoza, Spain
and meeting with them, meeting with the ministers.
That was only a few months after Celia had died
and we said we wanted to clone it.
They almost laughed and basically said that that was science fiction.
I actually still have a bottle of wine from one of the ministers
and I'm waiting I'm going to open it
when the first bucardos are released in the Pyrenees.
There are other species.
Mike Archer mentioned the gastric-brooding frog,
frozen cells, so hopefully we'll be able to resurrect that
using the cross species cloning.
But those techniques are limited as I mentioned,
so recently, a few months ago,
he shared the Nobel Prize with John Gurdon,
Dr Yamanaka discovered iPS cells,
these are the reprogrammed cells that I mentioned to you,
and using that approach we now have a new tool
for conservation biology.
So when Yamanaka published his paper showing for the first time
that we can make human iPS cells,
I published a letter in Science, saying that this could also be used
for conservation biology to restore genes
from endangered and extinct animals.
And that has been used successfully in some animals.
There are many techniques, this is just one of them here:
something known as Tetraploid complimentation.
What happens is, you start with your fertilised egg,
you let it divide the 2 cell stage,
and then you fuse those 2 cells so there's twice as much DNA in it,
that is why it is called the tetraploid.
And then you let that divide
and it continues to divide into what's known as a blastocyst.
That will only create the placenta, and extra embryonic membranes,
it will not create the embryo per say.
So you can inject iPS cells into that blastocyst
and they all to go on to become the animal
So you can start out with an embryo, surrogate that's white,
inject your iPS cells from a pigmented animal
and get all iPS animals, essentially clones.
So we can do that
and we can make iPS cells from almost any animals,
from horses, from avian species.
So you can make them very readily unlike the normal cloning procedure.
But the more likely way this is going to occur
is to actually turn the iPS cells into eggs and ***.
You have just a little piece of skin from any endangered animal
or a closely related, say,
for the mammoth you can start with an elephant,
you add the transcription factors,
turn them into iPS cells
and then those can be coaxed into premodial germ cells
and then turn into either *** or eggs.
And indeed that does work.
A few months ago for the first time
a group in Japan turned iPS cells into eggs
that resulted in live pups,
and a year before the same group turned iPS cells into ***
that could create live pups as well.
So the goal for these extinct species is simply to start like an elephant cell,
upregulate the various genes for tusks, long ear, whatever,
and then you just create *** and eggs,
and then you create an entire organism.
But just in case that doesn't work,
and for those of you who are Jurassic Park fans,
I actually have a piece of amber in my pocket
and it really does have a mosquito in it.
Thank you.
(Laughter)
(Applause)