i'd like to speak to you about the use of cloningand stem cells to resurrect life. as you know, there are 2 waysto make copies of cells and organisms. the first and most controversial is cloning, and that is also known assomatic 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 placethe cell you want to clone,
the smaller somatic cellright next to it, then you send an electrical chargethrough the unit and it damages the membranebetween the two and the nucleus of the cellyou want to clone dumps into that empty egg; then you add some chemicals, you fool that unit into thinkingthat it is fertilised, it starts to divide and you end up with what is knownas 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 intoembryonic stem cells which are the master cellsof the body and they can turn intovirtually every cell type. and the other alternative is that you can place thatinto a surrogate animal to create an entire organism. another approach that is neweris known as cell reprogramming.
and that leads to what is knownas induced pluripotent stem cells or ips cells. you start out with a somatic cellon a piece of skin, you throw in some transcription factors and bring that differentiated cellback to a state of pluripotency very much like an embryonic stem cell. and we have new tricks now, we can actually turn those cellsinto an entire organism as well. so, to date, about 2 dozen different species have been cloned.
back in 1958 john gurdoncloned the first animal, that was a frog, in fact he was justrecognised 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 clonedmice 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 approachto reconstruct extinct animals ã la jurassic park. so in this case we took a skin biopsyfrom the ear of a cow, we grew up the cellsknocked in a gene cassette, and then used ordinary eggsto 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 livein a cold climate,
and then using the techniquethat i'll describe later, we can create sperm and eggsand 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 cellfrom the same species you want to clone, but using this cross-species approach, we can take the egg of one speciesto clone the cell from another.
and that's very importantif you want to resurrect extinct animals or if you want to cloneendangered animals. back in 2000 we usedthis cross-species technique to clone the first endangered species. in this case it was a gaur, which is a wild oxon 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 cloneisn't really entirely a clone.
it turns out that every cellhas 2 genomes. one is the mitochondrial genome, and the mitochondria are the organelles in the cellthat make energy. that's maternally inherited,so that will come from the egg. and the other genomeis the nuclear genome, and that contains the genesthat distinguish you and i from an elephant or a mouse. so those 2 genomeshave to talk to one another,
and there's evidencethat it can only occur within 8 to 18 million yearsspecies radiation. we got around that problemby using very closely related species, concord and xenograftcombinations. in this particular casewe had a gaur and a cow and they are bothin 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 actuallybeautiful little gaur blastocysts. the idea here was to create these embryos, send them by fedex offto a farm in iowa where they would be implantedinto some ordinary cows. it turned out that the first round we made and put outside the doorfor the delivery truck guy to pick up, unfortunately, we came the next morning,and they were still there. but eventually fedex did delivera new round of these embryos, they were indeed implantedinto some animals.
i went to iowa entranced over we had 25% pregnancy rate. two of thosewe let continue onto term. unfortunately one of thoseaborted at late stage, it was 202 days. we let one of them continueto 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 riseto a beautiful little baby gaur. it's a bit surreal seeing this exotic endangered animal that is normally born in bamboo junglesof southeast asia, being born out in an iwoa farmthat 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 animalthat's known as banteng. only about 2000 of these animalsare left on the planet. and he had cells from this animal that had been frozen awayfor a quarter of a century. so they sent us a vialof 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 2003we had a beautiful little baby banteng which was ultimately transferredto san diego zoo where it livedwith the other bantengs. so this technology does work. there are some problems, but we have new technologiesthat i'll mention that can now solvemany of these bottlenecks. i collect dinosaur fossils.
so when you go to my front door the first thing you seeis this brantosaur's femur. it's about 6 feet longand 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 reporterwas 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 seeany dinosaurs in your back yard any time soon. but that doesn't mean extinctionis 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 monthsafter celia had died and we said we wanted to clone it. they almost laughed and basically saidthat that was science fiction. i actually still have a bottle of winefrom one of the ministers and i'm waitingi'm going to open it when the first bucardosare released in the pyrenees. there are other species. mike archer mentionedthe gastric-brooding frog, frozen cells, so hopefullywe'll be able to resurrect that
using the cross species cloning. but those techniques are limitedas i mentioned, so recently, a few months ago, he shared the nobel prizewith john gurdon, dr yamanaka discovered ips cells, these are the reprogrammed cellsthat i mentioned to you, and using that approachwe 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 biologyto restore genes from endangered and extinct animals. and that has been usedsuccessfully in some animals. there are many techniques,this is just one of them here: something known astetraploid complimentation. what happens is, you startwith your fertilised egg, you let it divide the 2 cell stage,
and then you fuse those 2 cellsso there's twice as much dna in it, that is why it is calledthe tetraploid. and then you let that divide and it continues to divideinto 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 cellsinto that blastocyst and they all to go onto become the animal so you can start out with an embryo,surrogate that's white,
inject your ips cellsfrom a pigmented animal and get all ips animals,essentially clones. so we can do that and we can make ips cellsfrom almost any animals, from horses,from avian species. so you can make them very readilyunlike the normal cloning procedure. but the more likely waythis is going to occur is to actually turn the ips cellsinto eggs and sperm. you have just a little piece of skinfrom any endangered animal
or a closely related, say, for the mammothyou can start with an elephant, you add the transcription factors, turn them into ips cells and then those can be coaxedinto premodial germ cells and then turninto either sperm or eggs. and indeed that does work. a few months agofor the first time a group in japanturned ips cells into eggs
that resulted in live pups, and a year before the same groupturned ips cells into sperm that could create live pups as well. so the goal for these extinct speciesis simply to start like an elephant cell, upregulate the various genesfor tusks, long ear, whatever, and then you just create sperm and eggs, and then you create an entire organism. but just in case that doesn't work, and for those of youwho are jurassic park fans,
i actually have a piece of amberin my pocket and it really does have a mosquito in it. thank you. (applause)
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