Playing God Horizon


Playing God

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Over billions of years,

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the natural world has evolved exquisite beauty and complexity.

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But just recently, we've started to do something remarkable.

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We've found a way to take life and radically re-design it.

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We have put ourselves in this extraordinary position,

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where nature itself can be disassembled into spare parts.

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And now we can put them back together, just as we please.

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Incredible as it sounds, life itself has become a programmable machine.

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These new machines aren't mechanical or electrical, but biological.

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And they're starting to change our world.

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I'm Dr Adam Rutherford

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and I want to explore what we're able to do with this new power.

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So what you're telling me is that somewhere on this farm

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there is an animal which is part spider, part something else?

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This new science can be as unsettling as it is intriguing.

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We're in the matrix here, aren't we?

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We're granting ourselves unprecedented control

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over living things. That is a high-stakes game

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and with it comes a question - can this power be abused?

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'KSL News Radio, and this is Utah's morning news,

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-'I'm Grant Nielson...

-..And I'm Amanda Dickson.

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'Right now, down town it's cloudy, 60 degrees,

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'a roll over blocking traffic on I-80...'

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Logan County, Utah.

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Heartland America.

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Where farming is a way of life.

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Now I've come here to see something

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which I think is truly, truly extraordinary.

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This may look like a fairly typical farm -

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there's grain over there, there are horses and cows and sheep -

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and it certainly smells like a real farm,

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but there's one animal here which I think shouldn't really exist.

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This isn't your usual farm. It's part of Utah State University.

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Professor Randy Lewis is working on a project that shows

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if you combine the principles of farming with the latest science,

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you quickly find yourself in a very odd place.

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It starts with spiders.

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Randy.

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-So what is it about spiders?

-Well, the spider that we have here

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is called an orb-weaver

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and she makes six different kinds of silk and the silk we're interested in

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is called drag-line silk, they catch themselves with it when they fall.

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It's actually stronger than Kevlar. So it really has some amazing properties for any kind of a fibre.

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So you've got this amazing property of silk which, I mean,

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it's stronger than anything we can make ourselves?

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Correct, correct.

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So that's an attractive material that we want to get some of.

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That's right, we want to make a lot of it.

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So we're on a farm here, why don't you just farm the spiders?

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They're very cannibalistic so they'll basically kill each other

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till everybody has enough room to do it.

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So basically spiders are un-farmable.

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-Spiders are absolutely un-farmable.

-Can we get her out?

-Sure.

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Ah, she's so... She's beautiful, look at that.

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Why would anyone be afraid of that? I just think she's gorgeous.

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My hands are actually getting bound in silk as she runs round them,

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-I'll be cocooned soon.

-And that's why they call it drag-line.

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I mean, she leaves it there the entire time.

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We've spent a very long time trying to figure out a way to produce lots of silk

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and the only way we've got it is that we have to take the spider silk gene

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and transfer it to an animal

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that can produce large quantities of the silk.

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So what you're telling me is that, somewhere on this farm,

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there is an animal which is part spider and part something else.

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There are and they will produce large amounts of spider silk

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protein for us to turn into fibres.

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I think you need to show me that.

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-These? Goats?

-These are our goats.

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-So they're just regular goats.

-They're absolutely regular goats.

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Except they're not, they're totally incredible goats.

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So, over here, we have the kids that were born this year

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and the older goats are all on that side.

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-And these are your spider goats.

-These are the spider goats.

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And they're eating my top.

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Hey, come on. OK, hey, hey! Behave! Just cos you're on camera.

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And so these kids have the genes for a spider in them.

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-Yeah.

-This is, it's insane.

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And where does the spider silk actually come from?

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I mean, where do you get it?

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It was designed so it comes in the milk.

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They look like such normal goats but in fact they're totally unique

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and bizarre. I mean, this is bizarre.

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I guess I would not say it's bizarre.

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I think that it's certainly different but, you know,

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they're absolutely normal, I don't think there's anything different about them.

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Hey, Freckles. Come here.

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-"Freckles"?

-Come over here. Right, so we have names for all the goats.

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She's actually one of the very original goats that was created.

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Can we actually milk them now?

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Yeah, we can, the two that are standing right here, 57 and 59

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who are Pudding and Sweetie. We can milk those and you can see the milk.

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-Pudding and Sweetie.

-Pudding and Sweetie.

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-Freckles, Pudding and Sweetie the spider goats.

-Yes.

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-Just a totally regular farm(!)

-That's right, that's right.

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Come on.

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Ah, so well behaved as well!

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That's right, that's right, they know. Get that out of the way.

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There you go, there you go.

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So the pumps just go on like that?

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That's all there is to it.

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Oh, you can see it. You can actually see it coming out.

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Yep, you can see milk coming out.

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So this is exactly the same as any normal goat milking process.

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Absolutely, absolutely. Do exactly the same.

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All right, so she's about done and we can disconnect this.

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We can now get this open and you can take a look and see.

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-Well, just looks like normal milk.

-Looks like absolutely normal milk.

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If you do an analysis of it and look at all the components of the milk,

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the only thing you'll find is different is one extra protein and that's the spider silk protein.

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All the rest looks like normal goats milk.

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You make it sound all really matter-of-fact.

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I mean, we've just milked a goat,

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we're on a farm, it's all rather mundane but, I mean,

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this is really cutting-edge science isn't it?

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It's much more difficult than it certainly sounds like.

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Once you get the embryo, the gene into the embryo

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then it really is farming.

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So you take the gene from a spider

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and then you put it in the goat

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but that's not what's in here is it?

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-There's no, there are no genes in here.

-No, it's the protein

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and spider silk is made out of proteins

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same as your hair, same as your skin,

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same as all the proteins in your body that digest your food,

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that carry oxygen around from your lungs,

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-it's exactly the same kind of a protein.

-And the gene itself

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-is the code to make that protein.

-Exactly, we take the gene

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and that gives in this case the goat instructions to say, "Make spider silk protein,"

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and they produce it only when they're lactating.

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Well, I'm still not entirely convinced, it looks a lot like normal milk to me,

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so can you show actually how to get the silk out?

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-Sure. We'll take it back to the lab and we'll purify the protein and then we'll spin some fibres.

-OK.

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The milk is filtered to remove the fats

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and leave only the proteins.

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A2nd from this purified protein comes the silk.

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Mimicking the spider's behaviour in nature, the silk is pulled out.

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And then it can be simply laced onto a spool.

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It's incredible, it just looks like spider silk. It's exactly the same.

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It looks very much the same.

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-So this is one continuous thread.

-And then we wrap it up on a reel.

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I can't quite believe that you can make something

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that's taken millions of years to evolve,

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you can just make it and put it on a roll and we can just pass it between each other.

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-And even more, we started with the goats.

-But it's not just for fun, though, is it?

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No, there are a lot of applications that we think of, especially in the medical field.

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We already know we can produce spider silk

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that's good enough to be used in both tendon and ligament repair.

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We already know we can make it strong enough and elastic enough,

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we've done some studies that show it's biocompatible,

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you can put it in the body and you don't get immune response,

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you don't got inflammation, you don't get ill, so we hope within even a couple of years,

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that we're going to be testing to see exactly the best designs

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and the best materials that we make that would be used for that.

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Spider silk, made from a goat, implanted into humans.

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Exactly.

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HE LAUGHS

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Now, I don't know what these animals think about being spider goats

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or whether they've got any idea at all,

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but we've been farming goats for thousands of years now

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to make them bigger and stronger and to produce more milk.

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And in the space of just one generation, a few years,

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these animals have been created

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and they couldn't possibly have existed otherwise.

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And no matter how amazing or unsettling or just plain bizarre

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you think that is, this is just the beginning.

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Transferring a single gene from a spider to a goat is one thing,

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but what if we had power over the entire genetic code of a life form?

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Very recently, we created that power.

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And it's raised key questions about how far we should take it.

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To really get a grip on where this field is at

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we don't have to go back very far.

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In just 2010, a team of scientists created something

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that generated shock and awe in the press but left the rest of the world

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not really quite sure what to make of it all.

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A familiar but powerful term was used to describe it - "Playing God".

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'In an amazing scientific breakthrough,

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'researchers say they've created the first ever synthetic life form.

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'They hope it will create life saving medicine and new forms of energy,

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'but the development is not without controversy.'

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'We're here today to announce the first synthetic cell.

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'The electronics industry only had a dozen or so components

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'and look at the diversity that came out of that.

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'We're limited here primarily by biological reality and our imagination.'

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After 15 years and 40 million of research,

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Dr Craig Venter had created something unique.

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A completely synthetic life form, that was nicknamed Synthia.

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But who or what was Synthia?

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So this it, Synthia, or to give it its proper name,

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Mycoplasma mycoides JCVI-syn 1.0.

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It's the very simplest of bacterial cells. Really not much to look at,

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but what's truly impressive about this

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is the fact that Synthia was not born from another bacteria.

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This is the only life form on Earth whose parent is a computer.

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'By moving the software of DNA around,

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'we can change things dramatically.'

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To make Synthia, Craig Venter took a simple cell.

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And he took all of its DNA code and plugged that into a computer.

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Once the code is in a computer, it's effectively DNA software.

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Next, he extracted the DNA from a similar cell...

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..discarded it and went back to the DNA software he'd created.

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And then came the really clever bit.

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Venter synthesised all of that DNA, just like printing it out.

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Now he had a physical version of that DNA software

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ready to be inserted into the empty cell.

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And with a spark, he booted it up, just like powering up a computer.

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Except by any definition, this thing was now a living organism.

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Had Craig Venter created life? Not really.

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But he had recreated it and, in a sense, rebooted it.

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Synthia may have been something quite simple,

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a fairly straightforward bacteria, but, after you've set aside

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all of the hype, the fact remains that Venter had done something

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that has never been achieved in 4 billion years of life on Earth -

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he'd made an organism whose parent was a computer.

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And that, more than anything else,

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demonstrated an unprecedented degree of control over a living thing.

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This blurring of the boundaries between computer code

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and biology has fuelled a whole new field of science.

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With our new-found ability to engineer life,

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we can start to think of organisms as biological machines

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that are under our control.

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And to see where these bold ideas are taking us,

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I've come here, to high-tech America.

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I reckon these are all quite tricky concepts to get your head around -

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things like biological machines,

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or that DNA is like software that you can just print out.

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This approach has a name, and it's synthetic biology.

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Now, even for a biologist this is pretty bewildering stuff

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but that is also exactly why it's so exciting.

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Professor Ron Weiss was one of the founders of synthetic biology,

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there at the beginning of it all, and he started out

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not as a biologist, but a computer scientist.

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So at first I was interested in understanding how we can take

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what we know about biology and apply that to computing.

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And at some point, I decided to flip that around and try to take

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what we understand in computing and apply that to programming biology

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and, to me, that's really the essence of synthetic biology.

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And what do you need to get started?

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Actually, all that we need is available right here in my bag.

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There's one major advantage of having life written in computer code.

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All you have to do to access it is get online.

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It's an approach that's led to a visionary new take on biology.

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We want to think about DNA as parts that we can then glue together

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to make more parts, putting systems together,

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putting maybe circuits together, built out of these DNA parts.

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But where do you get these parts from? They're in our cells.

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Right, but the cool thing is you can actually go online

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and get new DNA parts.

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Let's say for example we want a part that make a blue protein,

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so here's that arrow, you see that arrow right,

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that arrow is a part that tells the cell,

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"Make a protein that creates a blue colour."

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That's what it is, and I can put that into my circuit and those parts -

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we call them biobricks - and so we can take these biobricks

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and actually put them together to assemble, you know, biocircuits.

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You said that very casually.

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You said that like it hasn't been 4 billion years of evolution

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which has got my cells doing what they do.

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Right, they do it quite well, and they have a piece of DNA...

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-QUITE well?!

-Quite well. It's not perfect though, right?

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We die on occasion, we get cancer on occasion.

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-And you think you can do it better?

-Um, sometimes, perhaps.

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What about actual, useful, real world applications?

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So, what else could you do? So, for example,

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imagine this program, this piece of DNA which goes into the cell

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and it says, "If cancer cell,

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"then make a protein that kills the cancer cell, if not just go away."

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That's another kind of program that we're able to write and implement

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-and test in living cells right now.

-You can do that?

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-We have done that.

-It's like a targeted assassin.

-Yes.

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This works in the lab.

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It doesn't work quite in a clinic yet, that would be the next step.

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That's radical thinking!

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It's radically different from anything that's come before.

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'Ron doesn't even need to be in a lab

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'to put the strands of DNA together to make a biological circuit.'

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We actually have biobricks, pieces of DNA here.

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So let me put them together.

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So I'll take this biobrick and I want say,

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I want to put these two together, so I'm going to open up pieces of DNA,

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I'm going to take some from here...

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..mix it right there, OK?

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We've put two parts together, I'm done with this biobrick.

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I need one last component which is the glue,

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I need to be able to glue them together, so here's my glue.

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I'm going to take that out,

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make sure I have just right amount of glue, I'm going to mix them together

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and then it's done.

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And so, now, in this tube, you've got this circuit,

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you've just built a biological machine...

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That may never have existed before.

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-That we've just done in a cafe in downtown San Francisco.

-In a cafe, you and me together.

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A lot of people can now do this.

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We have the information, we have the technology now.

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-Astonishing.

-Brave new world.

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Ron's simple demonstration of al fresco biology has shown

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that with a new level of simplicity and accessibility

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you can build biological circuits that programme biological machines.

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The democratic nature of having biological parts,

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or biobricks, readily available online,

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has proved particularly appealing to one group of innovators.

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Students.

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Now, it's not unusual, in university corridors,

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to come across adverts on notice boards

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for things like cocktail societies or sports clubs.

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This one's slightly different and I want to read you a couple of lines.

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"Removal of metal ions from contaminated water."

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How about, "Repair of human tissue using bacteria"?

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Or this one says, "A biofilter for radioactive waste."

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Now, these are not clubs.

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These are entries from universities around the world for IGEM,

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the International Genetically Engineered Machine Contest.

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Basically, they're all ideas for saving the world.

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Here at the University of Cambridge the IGEM team leader,

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Cat McMurran, has asked to meet somewhere a little unusual

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to tell me about their entry.

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'The story of this particular biological machine

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'begins at a fish restaurant.

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'And with one particular dish - squid.'

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They're essentially masters of disguise.

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They have fantastic abilities to camouflage themselves

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so when they're hiding from predators

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they can very carefully match the colour

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and kind of even approximate what the texture of background there is.

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What is it about this beast

0:22:320:22:33

that gives it the ability to camouflage itself?

0:22:330:22:36

The really cool bit that inspired us

0:22:360:22:38

is that underneath that layer of skin you can see some shiny cells.

0:22:380:22:43

They're not very clear there, you can see it better in the eye.

0:22:430:22:46

Oh, I see. It looks a bit like tin foil.

0:22:460:22:49

Yeah, it's essentially the same.

0:22:490:22:51

There's some of it leaking out of the eye.

0:22:510:22:53

'The team wanted turn the camouflage system into a new biobrick,

0:22:530:22:58

'so a whole new range of biological machines could use the colour change

0:22:580:23:03

'just like the squid does so effortlessly.'

0:23:030:23:05

This is some images of what the squid cells look like under the microscope.

0:23:050:23:10

-You can really see the coloured patterns of reflectin that are formed.

-It's really beautiful.

0:23:100:23:15

It's kind of psychedelic.

0:23:150:23:17

'Reflectin is the protein that makes this spectacle possible.'

0:23:170:23:21

'The team ordered a series of biobricks online

0:23:220:23:25

'and used them to build a biological circuit

0:23:250:23:28

'that could make the same protein that the squid does.'

0:23:280:23:32

-So does it work?

-It does and I can prove it.

0:23:320:23:34

So we have the purified reflectin that we made using this circuit,

0:23:340:23:38

and we've taken and spun it onto, well, a little disc of silicon,

0:23:380:23:43

so you can see the iridescent patterns on it as I move it.

0:23:430:23:47

-Looks like a drop of oil.

-But what's really cool about it is if you breathe on it.

0:23:470:23:51

-What, just breathe on it?

-Yes.

-Right.

0:23:510:23:53

Oh, cool! So that's the squid protein reacting to my breath?

0:23:550:24:00

Yeah, it's the humidity in the air you're breathing out that's making the structure of the protein change.

0:24:000:24:05

You're very, very casual about this

0:24:050:24:07

but we've gone from a squid in a restaurant that can change colour,

0:24:070:24:11

even though it was dead, to getting that synthesised in a cell factory

0:24:110:24:15

via the internet, onto a plate

0:24:150:24:17

that can change colour when I breathe on it.

0:24:170:24:20

In a summer, yeah.

0:24:200:24:22

In a summer.

0:24:220:24:23

It's almost annoying, to hear you say that,

0:24:230:24:26

cos the prospect of me doing that

0:24:260:24:29

five years ago, ten years ago in the lab

0:24:290:24:31

would have taken, you know, hundreds of thousands of pounds

0:24:310:24:35

and years, but you can knock that out in a summer.

0:24:350:24:41

It's the beauty of synthetic biology

0:24:410:24:43

is that we don't have to go through...

0:24:430:24:45

Quite a lot of the hard work has been done for us.

0:24:450:24:48

The work we've done this summer has now been put back into the registry

0:24:480:24:52

so all the parts for making biobricks

0:24:520:24:54

are now something that anyone next year,

0:24:540:24:57

or a research lab right now, can e-mail

0:24:570:24:59

and ask for the DNA to be sent out,

0:24:590:25:00

and then they can start working on reflectin

0:25:000:25:03

and that's what's really exciting

0:25:030:25:05

about the open-source ideal,

0:25:050:25:07

is that now it's out there, anyone can use it.

0:25:070:25:09

In a squid, this is a survival mechanism,

0:25:100:25:14

but Cat and her team have succeeded in turning it into a component

0:25:140:25:18

that future scientists can use to do anything they want with.

0:25:180:25:21

They're already thinking about sending

0:25:210:25:25

tools like these into water supplies to detect pollutants

0:25:250:25:29

and then change colour just like the squid does.

0:25:290:25:32

It's an astonishing idea that life can be programmed like a machine

0:25:340:25:39

and that the components can be simply ordered online from a standardised tool kit,

0:25:390:25:45

and this means that engineers and computer scientists

0:25:450:25:48

and mathematicians can come together with biologists.

0:25:480:25:51

This is a totally new way of doing science, and it's happening now.

0:25:510:25:57

You might think that harnessing the full power of synthetic biology was just out of reach.

0:26:020:26:08

Well, that's not the way they see it here in California.

0:26:120:26:16

In a sense, they're taking this idea of playing God

0:26:160:26:20

and turning it into a business, potentially a rather lucrative one.

0:26:200:26:26

This is the other end of synthetic biology.

0:26:260:26:30

However you feel about big corporations,

0:26:300:26:32

they have access to the kind of cash that makes the most exciting science possible.

0:26:320:26:37

This is Amyris, one of the world's biggest synthetic biology operations.

0:26:410:26:46

Their aim is simple - to develop technology that might just change the world.

0:26:490:26:55

And Dr Jack Newman is leading the project here.

0:26:580:27:01

Right, so this looks very familiar to me, molecular biology lab,

0:27:010:27:05

been in a few labs like this where genetics happen. What's going on?

0:27:050:27:09

Well, you see here, it's a lot of dedicated talented folks

0:27:090:27:14

that know a lot about what goes on inside yeast.

0:27:140:27:18

What we're doing is reprogramming that yeast

0:27:180:27:20

to meet the petroleum needs of the world.

0:27:200:27:23

This isn't tinkering with biological circuits,

0:27:230:27:28

this is synthetic biology at full tilt.

0:27:280:27:31

Petroleum fuels our world,

0:27:310:27:33

we have tremendous energy need both in the US, in Europe, in Asia

0:27:330:27:38

and here we're coming up with new solutions for meeting that energy or fuel need.

0:27:380:27:42

-By producing it using cells.

-That's right.

0:27:420:27:46

-And you can do that?

-Absolutely, that's what I'm going to show you.

0:27:460:27:51

This is synthetic biology on an industrial scale.

0:27:550:27:59

Scientists and robots working together.

0:28:020:28:05

Their aim, to reprogramme old-fashioned brewers' yeast,

0:28:050:28:09

by re-engineering the cell, so that rather than producing alcohol, it now produces diesel.

0:28:090:28:15

What you're doing, in terms of making this biological machine,

0:28:150:28:20

is getting it to do something that nothing in nature has ever done before.

0:28:200:28:25

Not quite nothing, actually, so the molecule farnesene,

0:28:250:28:29

which is the root of our diesel, is actually the same oil that coats the outside of apples.

0:28:290:28:34

It's the oil that nature uses to repel the water off of apples. It also happens to be in diesel fuel.

0:28:340:28:40

Kick-starting this fuel factory couldn't be easier.

0:28:420:28:46

Grab a toothpick, get a little bit of yeast,

0:28:460:28:49

and this is a 96 well plate, which is 96 little fermenters basically filled with sugar water.

0:28:490:28:54

Put some yeast in there, it'll start making that sugar into diesel.

0:28:540:28:59

Give it a shot.

0:28:590:29:01

I remember this sort of laborious work from work from my days in the lab.

0:29:010:29:06

You've got a bunch of toothpicks there, why don't you do the next 100?

0:29:060:29:10

-Um, I'm OK with that, thanks.

-Here's another way to do it.

0:29:100:29:12

What you see there is about 10,000 yeast and what the machine has done is image that with the camera,

0:29:120:29:20

it's taken a picture of that, and it knows where every colony is.

0:29:200:29:24

I've done this kind of stuff, it takes about two weeks, and you're saying that this can do...how many?

0:29:240:29:30

Just did 100 in the time it took you to do one.

0:29:300:29:33

The speed is phenomenal!

0:29:340:29:38

The core idea is that oil, which gets made from biological organisms,

0:29:380:29:44

-takes hundreds of thousands of years to produce a barrel...

-That's right.

0:29:440:29:49

And this process, using yeast...

0:29:490:29:51

Can take a day.

0:29:510:29:53

All they need is some basic old-school lab equipment,

0:30:000:30:04

and with it, I can see exactly what this new school of science is all about.

0:30:040:30:10

Now, what are we seeing here?

0:30:130:30:17

Here's one where you can see actually the farnesene on the inside,

0:30:170:30:22

see that bright little droplet?

0:30:220:30:25

So they just produce the diesel inside the cell

0:30:250:30:27

and then it just secretes out?

0:30:270:30:29

Just comes out in little droplets

0:30:290:30:31

and those little droplets come together the same way sort of

0:30:310:30:34

when salad dressing is separating, the oil goes to the top.

0:30:340:30:38

So if I pull focus from the bottom upwards then I can see the cells.

0:30:380:30:41

The cells will be on the bottom because they're heavy.

0:30:410:30:45

And if I keep going then, bing, you get the oil.

0:30:450:30:49

Yep, and the oil'll be at the top because it's lighter,

0:30:490:30:52

you know, oil rises to the top.

0:30:520:30:55

Crikey, that's amazing.

0:30:550:30:57

Scale this up, and you're on your way to having an industrial operation.

0:30:570:31:01

This is the pilot plant,

0:31:010:31:03

this is where we take what you saw at that small scale

0:31:030:31:06

and take it up to the next level.

0:31:060:31:08

Wow!

0:31:080:31:10

Inside these tanks, the same process is happening

0:31:100:31:13

that I saw under the microscope,

0:31:130:31:15

except instead of it being on a slide,

0:31:150:31:17

it's in these massive vats.

0:31:170:31:20

And at the end of this production line is the simplest process of all, separation.

0:31:220:31:28

There goes the yeast and the nasty bit...

0:31:370:31:41

here comes the fuel.

0:31:410:31:43

-That's it?

-That's diesel. That's diesel right there.

0:31:430:31:46

-That's just waste on that side?

-That's yeast and water, diesel on this side.

0:31:460:31:51

Do you think this is going to replace oil out of the ground, fossil fuels?

0:31:510:31:55

-I'll be excited about a billion litres.

-A billion litres?

-Yeah.

0:31:550:31:58

So how long is it going to be

0:31:580:32:01

before you can scale this already pretty impressive set-up to a billion litres?

0:32:010:32:06

So, we're already manufacturing on three continents,

0:32:060:32:09

we're in South America, North America and Europe,

0:32:090:32:12

and have two more major facilities under construction.

0:32:120:32:16

Er, you know. We're ramping this just absolutely fast as we can.

0:32:160:32:20

There are strict rules preventing synthetic cells from leaving the lab,

0:32:290:32:34

but the things they make, like the fuel, can.

0:32:340:32:37

It is still diesel, though, and still produces CO2 emissions,

0:32:370:32:42

so this car, fuelled by synethic biology,

0:32:420:32:46

is a symbol of the power this technology offers.

0:32:460:32:50

And the questions it raises for all of us.

0:32:500:32:53

Where should we draw the line between what synthetic biology

0:32:560:32:59

might be capable of doing and what we think is safe or desirable?

0:32:590:33:04

The closer you look, the more it appears to be an uneasy bargain.

0:33:050:33:10

Now there's a question we have to address before we go too far.

0:33:260:33:31

Should synthetic biology be allowed out of the lab at all?

0:33:310:33:35

Now this is a legitimate question,

0:33:350:33:37

albeit one fuelled by Hollywood, who imagine that synthetic lifeforms can escape from the lab

0:33:370:33:43

and go down drains and crawl up into your cappuccino,

0:33:430:33:47

but how real is that threat?

0:33:470:33:50

Leading scientists in synthetic biology have called for added measures

0:33:500:33:55

to prevent the accidental release of synthetic organisms into the wild.

0:33:550:34:00

So it seems that there is a contradiction here.

0:34:000:34:03

On the one hand, synthetic lifeforms should be contained within the lab,

0:34:030:34:07

and on the other they should be out in the world, actually doing stuff for our benefit.

0:34:070:34:14

Whether out in the world, or in the lab, the key is that the scientists

0:34:170:34:21

have control over the life-forms they create,

0:34:210:34:23

and the principles behind that are simple.

0:34:230:34:27

Now scientists design synthetic cells, so they have an inbuilt safety mechanism,

0:34:290:34:34

and they get called kill switches, which is slightly overly dramatic.

0:34:340:34:39

But I can show you how they work using just a box of matches.

0:34:390:34:42

In the olden days, matches could be struck on any surface.

0:34:430:34:46

But then safety conscious matchmakers introduced a feature which meant they could only ignite

0:34:460:34:51

in very precisely controlled conditions - that is the side of the box.

0:34:510:34:55

And that is the safety match.

0:34:570:34:59

Now kill switches work in much the same way.

0:35:000:35:02

The synthetic cells can only grow in very precisely controlled conditions.

0:35:020:35:08

On top of that, once they are alive, they have to be continually fed,

0:35:080:35:12

otherwise, just like the flame, they won't survive.

0:35:120:35:16

Pretty foolproof, except safety measures are never 100% effective.

0:35:160:35:22

In the right circumstances, even a safety match will still ignite.

0:35:240:35:29

We know life does tend to find a way.

0:35:310:35:34

Synthetic biology is about creating and manipulating lifeforms.

0:35:380:35:43

Things that grow, feed and reproduce.

0:35:430:35:46

This is a high stakes game.

0:35:510:35:53

Scientists can have control, but there is always a level of risk.

0:35:530:35:57

Jim Thomas works for a watchdog called Etcetera.

0:36:160:36:20

Having called for a ban on synthetic biology in its very early days,

0:36:220:36:25

the group have evolved their views, along with the technology.

0:36:250:36:29

So if you initial concern was the release of synthetic organisms into the wild,

0:36:300:36:37

how has that changed over the years, as the technology has developed?

0:36:370:36:40

Well, we're still very concerned about the release of synthetic organisms.

0:36:400:36:44

We still think that's a no-no.

0:36:440:36:46

But what's become clearer to us is that the bigger issues around synthetic biology

0:36:460:36:51

are how it's turning into an industry, and what industry is doing with that technology.

0:36:510:36:55

Because the synthetic organisms that are going to be used have to eat something.

0:36:550:36:59

What they have to eat is sugar - biomass. It's this stuff, it's the living world,

0:36:590:37:04

And you have an industry whose basic approach is to take living biomass,

0:37:040:37:10

liquidate it, feed it to synthetic organisms in order to create the plastics

0:37:100:37:14

and the fuels that previously were made from petroleum,

0:37:140:37:17

and as an industrial model that's a terrible industrial model.

0:37:170:37:21

Living things become part of these biological machines,

0:37:220:37:26

not just as components in the circuit, but as a feedstock.

0:37:260:37:29

Large companies are buying up bits of land so that they can grow sugarcane or eucaplypus,

0:37:310:37:36

so that they can feed those to vats of what will ultimately be synthetic microbes to make fuels.

0:37:360:37:43

As the global population soars, Jim's concern is that feeding these synthetic lifeforms

0:37:430:37:48

could ultimately threaten the livelihood of some of the poorest people in the world.

0:37:480:37:55

Synthetic biology has become a technological force,

0:38:050:38:08

and questions about how it should used and controlled are unavoidable.

0:38:080:38:13

But there's a darker side to consider.

0:38:160:38:19

What if this technology was used to intentionally do harm?

0:38:190:38:24

Through bio-terrorism.

0:38:240:38:25

Sunnyvale.

0:38:330:38:34

California.

0:38:360:38:39

A residential street, like so many others across America.

0:38:440:38:48

Dr Rob Carlson is an advisor to the UN and FBI,

0:38:530:38:58

and they ask his advice on the threats that could come from this field.

0:38:580:39:04

He knows his way around the subculture of synthetic biology.

0:39:040:39:08

He's brought me here, to introduce me to some people he knows.

0:39:120:39:17

Rob, we are a long way from high-tech labs and universities. What are we doing here?

0:39:220:39:29

Well, biotechnology has become less expensive and more accessible over the last 20 years,

0:39:290:39:33

especially in the last 10 years.

0:39:330:39:36

You can set up a lab in a kitchen or a garage or a store front anywhere around here.

0:39:360:39:40

So you're saying that in some garage over there, in the middle of suburbia,

0:39:400:39:43

some kid could be doing real synthetic biology.

0:39:430:39:46

In principle yeah.

0:39:460:39:47

I've seen that scientists can order parts they want, wherever they can get online.

0:39:470:39:52

So what would be available to someone who wanted to do harm?

0:39:520:39:57

So there are many parts in the registry. You can use them for making many different things.

0:39:570:40:01

Making biofuels, making vaccines.

0:40:010:40:03

There are some parts in here that look like they might have nefarious use,

0:40:030:40:07

so there are some viral vectors that could be used to infect human cells with some things.

0:40:070:40:11

They're very difficult to use.

0:40:110:40:14

They're more of an art than a bit of technology that anybody can make use of.

0:40:140:40:18

Now I'm going to push you on this, because you say the parts are individually innocuous,

0:40:180:40:22

but if I wanted to build a nailbomb, I could go to any hardware store and get all of the ingredients.

0:40:220:40:29

Individually, they're not for making a bomb, but you put them together in the right way

0:40:290:40:32

and you've got something lethal.

0:40:320:40:34

Surely you could say the same thing about the parts?

0:40:340:40:37

There aren't any parts in the biobrick registry that I'm aware of that can be used to cause any harm.

0:40:370:40:41

But a nail is for putting pieces of wood together, it's not for killing people.

0:40:410:40:45

I understand that, but there aren't any pieces that look even like a nail in the biobricks registry,

0:40:450:40:50

which is not to say that you can't make those parts, it's just they're not in the registry.

0:40:500:40:54

Over time we'll have many more parts that become available that are so useful,

0:40:540:40:58

but I think you've brought up an interesting point,

0:40:580:41:01

which is given the difficulty in building anything nefarious,

0:41:010:41:04

using biological parts right now, in this way we're discussing,

0:41:040:41:07

it's a lot easier to just go build a nailbomb if you want to cause a problem.

0:41:070:41:10

It's easier to fixate on the threat than it is to embrace the opportunity from these new technologies.

0:41:100:41:16

Those opportunities are all around us. We can go and have a look just a couple of blocks away.

0:41:160:41:21

So the idea here is you pay a monthly fee, just like you're going to a gym,

0:41:320:41:37

and instead you're doing biology here.

0:41:370:41:39

This is DIY biology.

0:41:430:41:46

And it's already become a movement, known as Biohacking.

0:41:460:41:51

This is really cool.

0:41:580:42:00

Really interesting this. It's like a very community-based project,

0:42:010:42:06

but they're doing real experimental science,

0:42:060:42:09

and the strangest thing about it is, even though there are school-age kids here,

0:42:090:42:13

if you just look on the shelves, this is standard lab equipment,

0:42:130:42:18

expensive equipment that you'd see in any hospital lab

0:42:180:42:21

or university lab, and it's just here in this community centre.

0:42:210:42:26

This is unusual. I've not seen this before.

0:42:280:42:31

So some of these guys call themselves biohackers,

0:42:380:42:41

which is quite a cool name but it also has a real,

0:42:410:42:43

quite a negative connotation about it. How does that work?

0:42:430:42:48

That depends on who you're talking to. They don't think it's negative.

0:42:480:42:51

There are hackers taking things apart, putting them back together,

0:42:510:42:54

whether it's computers or cars or boats.

0:42:540:42:57

Hacking is part of the way new stuff gets built.

0:42:570:42:59

Hacking is part of innovation.

0:42:590:43:01

We piloted a class this last month

0:43:040:43:07

where we took an E. coli bacteria and we brought in green fluorescent protein,

0:43:070:43:12

so it basically glows in the dark.

0:43:120:43:14

It's a protein from jellyfish.

0:43:140:43:17

-Can you show me that?

-You bet.

0:43:170:43:20

Seeing such a powerful science in here does throw the biologist in me a bit off balance.

0:43:270:43:35

What this is is a bacteria, a naturally occurring bacteria,

0:43:350:43:39

that some kid in this garage space has put a gene from a jellyfish in.

0:43:390:43:45

And the jellyfish kind of has a superpower of being fluorescent.

0:43:450:43:49

It glows in the dark basically.

0:43:490:43:51

So we borrowed that one piece and stuck in into this bacteria

0:43:510:43:54

that we can grow a lot easier than we can grow a jellyfish.

0:43:540:43:57

So I've done this a few years ago in the lab,

0:43:570:44:01

but you've done this in a garage... Who did this?

0:44:010:44:05

Rank amateurs, people who'd never picked up pipettes before,

0:44:050:44:07

we trained them in about an hour.

0:44:070:44:09

It wasn't a big deal, a lot of the things we got off the internet,

0:44:090:44:12

a lot of things came together really easily for amateurs.

0:44:120:44:15

That represents how the game has changed so significantly

0:44:150:44:20

in way less than a decade.

0:44:200:44:23

I mean, how long would that have taken five years ago?

0:44:230:44:26

That is a game-changer, I think.

0:44:260:44:29

In 2008, three scientists won a Nobel prize for doing this

0:44:290:44:33

and now anyone can do it in a garage.

0:44:330:44:36

You ain't seen nothin' yet.

0:44:380:44:40

So, what comes next? What's the ambition?

0:44:400:44:43

Well, like, I can see the day

0:44:430:44:45

whenever people are growing plastics, medicine...

0:44:450:44:49

You know, I think the future looks a lot less like

0:44:490:44:53

a big refinery stack and a lot more like a big brewing vat.

0:44:530:44:56

You know what it reminds me of? The legend of Microsoft,

0:44:570:45:01

that it started in Bill Gates' garage

0:45:010:45:04

where they were building computers from scratch in a garage

0:45:040:45:07

and now it is this, you know, global, enormous corporation.

0:45:070:45:11

Rather than being a backdrop for dark, scientific arts,

0:45:120:45:16

suburbia is clearly a place where synthetic biology can flourish.

0:45:160:45:22

So, from what I've seen, whether it's driven by universities,

0:45:220:45:25

large corporations or even bio-hackers,

0:45:250:45:28

it's clear this technology has breathtaking potential.

0:45:280:45:32

The innovation offered up by this science

0:45:370:45:40

is about to take us across another boundary

0:45:400:45:42

Hi, how are you?

0:45:420:45:43

Not just taking synthetic biology out into the world

0:45:430:45:48

but putting it inside people.

0:45:480:45:51

Attempting the impossible is what scientists

0:45:510:45:54

at the NASA Ames research facility are pretty good at.

0:45:540:45:57

Do you get blase about working here?

0:45:570:45:59

This is a lifelong childhood dream of mine.

0:45:590:46:02

I will come to work sometimes and I have to pinch myself.

0:46:020:46:06

Dr David Loftus is a medic to the astronauts.

0:46:110:46:14

He's a man with a rather unique commute into the office.

0:46:160:46:20

What is that?

0:46:200:46:21

That is the air intake for the world's largest wind tunnel

0:46:210:46:26

it's just a fantastic structure. It's just huge.

0:46:260:46:31

-You can put an actual, full-sized aircraft inside.

-Wow.

0:46:310:46:34

David is not just planning to put synthetic biology into outer space,

0:46:370:46:41

but into astronauts, to help them deal with something

0:46:410:46:45

that Californians often take for granted.

0:46:450:46:48

The sun.

0:46:480:46:51

We've got some UV radiation to deal with,

0:46:510:46:54

here in our convertible, from the sun,

0:46:540:46:57

but in space you've got particle radiation and high-energy radiation

0:46:570:47:01

that can really be quite damaging

0:47:010:47:04

and potentially fatal to the astronauts.

0:47:040:47:06

What's synthetic biology going to... How is that going to help?

0:47:060:47:09

We've come up with a technology that's pretty nifty

0:47:090:47:12

that allows us to engineer organisms and cells,

0:47:120:47:16

to make therapeutic molecules

0:47:160:47:19

that can be directly released into the body.

0:47:190:47:22

You're going to take engineered bacteria

0:47:220:47:25

and put them into astronauts to treat them for radiation sickness?

0:47:250:47:29

It seems pretty far-fetched

0:47:290:47:30

but that's exactly what we've been thinking about.

0:47:300:47:33

Putting synthetic biology inside people

0:47:420:47:45

has never been done before. It's unknown territory.

0:47:450:47:49

The key is locking the engineered bacteria away

0:47:500:47:53

and safely containing them.

0:47:530:47:55

And to do that, NASA is using nanotechnology

0:47:570:48:00

to make something truly remarkable.

0:48:000:48:02

A biocapsule.

0:48:030:48:05

-This is just a normal syringe needle...

-A normal syringe needle.

0:48:100:48:13

..and on the top, this is a mould...

0:48:130:48:15

Exactly, it's a plastic mould that's porous.

0:48:150:48:19

And needle goes in this liquid?

0:48:190:48:21

Exactly, you just plunge it right in.

0:48:210:48:23

-Turn the vacuum on...

-All right.

0:48:230:48:25

..and you should see things happening almost right away.

0:48:250:48:29

Carbon nanotubes suspended in the liquid are drawn onto the mould.

0:48:290:48:34

Ha, look at that it's instantaneous!

0:48:340:48:36

The result? A biocapsule.

0:48:360:48:39

It's gone black.

0:48:390:48:41

Turn the vacuum off and you can pull it out of the solution.

0:48:450:48:49

Well, that was not very hard.

0:48:490:48:51

And let it dry, it's very quick,

0:48:510:48:53

and you can just take it off of the tubing

0:48:530:48:56

and there's the capsule.

0:48:560:48:58

That's it, I've just made a biocapsule.

0:48:580:49:00

You've just made a biocapsule.

0:49:000:49:03

It may not look like much, but the genius of this biocapsule

0:49:030:49:07

comes by way of the tiny molecules that make up its structure,

0:49:070:49:10

a substance that the body won't reject.

0:49:100:49:13

Carbon nanotubes.

0:49:130:49:15

if we zoom in at higher power,

0:49:150:49:18

-we start to appreciate the pores of this structure.

-Wow!

0:49:180:49:21

You can actually see the bundles of carbon nanotubes

0:49:210:49:24

forming this meshwork across the surface.

0:49:240:49:26

The holes in the mesh are too small for the synthetic cells to escape,

0:49:260:49:30

but just the right size for the smaller therapeutic molecules

0:49:300:49:34

to leave the capsule and enter the body.

0:49:340:49:37

We'll get a sense for how it works

0:49:370:49:39

once it's actually implanted into a human,

0:49:390:49:41

so this is a schematic representation

0:49:410:49:43

of how we might implant the capsule under the skin and then the capsule

0:49:430:49:47

could potentially respond to the radiation exposure

0:49:470:49:50

and once it responds it will release the therapeutic molecule

0:49:500:49:54

or the protective molecule altering the physiology of the astronaut

0:49:540:49:58

and protecting that astronaut

0:49:580:49:59

from whatever threat exposure has happened.

0:49:590:50:02

You can think of this as a completely novel

0:50:020:50:05

drug delivery system.

0:50:050:50:06

So, it's triggered by the thing that it's trying to prevent.

0:50:060:50:10

-Exactly. That's the beauty of the system.

-It's so elegant.

0:50:100:50:13

We really think it is.

0:50:130:50:14

So, how close are you to getting it actually into a human test?

0:50:140:50:20

I think it's going to be ready in about two to five years.

0:50:200:50:24

-So, just around the corner?

-Just around the corner.

0:50:240:50:27

NASA are famous for their giant feats of machine engineering

0:50:280:50:32

but now they can apply their prowess at a microscopic level,

0:50:320:50:35

making biological machines.

0:50:350:50:39

It's the ground floor of a defining technology

0:50:390:50:42

and it might not only be for astronauts but every one of us.

0:50:420:50:46

Of all the weird things that I've seen,

0:50:460:50:49

I think this one is the one that impresses me the most,

0:50:490:50:52

because it's so real,

0:50:520:50:54

this means that a whole new range of biological machines

0:50:540:50:58

can be designed in the knowledge

0:50:580:51:00

that they can sit inside of us, actually under our skin.

0:51:000:51:05

As this technology is pushed further and further,

0:51:160:51:19

the line between what's intriguing and unsettling becomes even finer,

0:51:190:51:24

and the idea of playing God seems to draw closer.

0:51:240:51:27

But there's one corner that's left to turn.

0:51:290:51:32

Being able to programme biological machines

0:51:320:51:35

by having control of microbes is one thing.

0:51:350:51:37

But what if we took that control to more complex life forms?

0:51:380:51:43

What about if it was much more personal,

0:51:430:51:47

if we could actually control what's in our bodies or even in here?

0:51:470:51:52

Well, that would take us to a whole new level.

0:51:520:51:55

A level that takes the principles of synthetic biology

0:52:000:52:03

to the most precious part of our anatomy.

0:52:030:52:06

To the root of art, culture and the full spectrum of our emotions.

0:52:100:52:15

The brain.

0:52:150:52:17

This is the Massachusetts Institute of Technology,

0:52:210:52:24

a place where people who think differently

0:52:240:52:26

can explore the limits of their field.

0:52:260:52:28

Professor Ed Boyden began his academic career here

0:52:320:52:35

almost two decades ago at just 15 years of age,

0:52:350:52:39

today he's driving a totally new field called Synthetic Neurobiology.

0:52:390:52:44

Ed, this looks like an electronics lab to me, not a biology lab,

0:52:460:52:50

so how did you get here?

0:52:500:52:52

Well, I actually started out my education as an electrical engineer,

0:52:520:52:55

trying to build new kinds of computer and to figure out

0:52:550:52:58

how to repair and alter systems such as submarines

0:52:580:53:01

and quantum computers and other things like that,

0:53:010:53:03

and I got really interested in trying to engineer

0:53:030:53:06

the most complex computer there is, the brain.

0:53:060:53:08

Turns out the brain uses the same kinds of electrical pulses

0:53:080:53:11

to compute and communicate that computers do,

0:53:110:53:14

and if we could try to control those elements, that would allow us

0:53:140:53:17

to enter information into them, like you can enter information

0:53:170:53:20

into a computer circuit. So, what we're trying to do now

0:53:200:53:23

is use these illuminators, these lasers, to do exactly that.

0:53:230:53:26

But let me show you how it works, first.

0:53:260:53:27

What they've done here is taken a light source

0:53:310:53:34

and connected it directly into the mouse's brain.

0:53:340:53:38

Every time the mouse goes to this point

0:53:380:53:40

a pulse of light is being delivered

0:53:400:53:42

to a very specific point in the brain.

0:53:420:53:44

That point is actually a place deep in the brain

0:53:440:53:48

where neurons that mediate reward and pleasure, and so on,

0:53:480:53:51

are thought to be residing. So, basically, the mouse

0:53:510:53:54

is going to this little portal and putting its nose in there.

0:53:540:53:57

Every time it does that, he gets a pulse of light,

0:53:570:53:59

and he's, sort of, working for light.

0:53:590:54:01

This other portal, the mouse doesn't get anything,

0:54:010:54:04

so he prefers to go to that spot.

0:54:040:54:05

But I still don't understand how you actually make the brain

0:54:050:54:08

sensitive to light, because it's not, it's inside our dark skulls.

0:54:080:54:12

Well, neurons in the brain don't normally respond to light.

0:54:120:54:15

What we have to do is to find molecules that do

0:54:150:54:18

and put them into the neurons.

0:54:180:54:20

And it turns out that species out in the wild like this green algae

0:54:200:54:23

have to sense light in order to photosynthesize.

0:54:230:54:25

This species of algae has an eye spot that senses light

0:54:250:54:29

and converts light into electricity. That's how it's able to navigate,

0:54:290:54:32

by turning these little flagellas

0:54:320:54:34

so it can steer it toward the surface of pond.

0:54:340:54:37

If you zoom in on this little eye spot,

0:54:370:54:39

you'll find proteins that, when they are hit by light,

0:54:390:54:41

will actually generate little electrical pulses

0:54:410:54:44

and that's exactly what we need if we want to control a neuron.

0:54:440:54:49

Ed has programmed a virus to travel to specific neurons in the brain

0:54:490:54:53

and deposit the light sensitive molecule,

0:54:530:54:55

tiling the surface of the brain cells like solar panels.

0:54:550:54:59

This turns those specific neurons, and only those neurons,

0:55:010:55:05

into on/off switches activated by light.

0:55:050:55:09

So, this is the, sort of, synthetic biology angle to it,

0:55:090:55:11

you're taking algae and putting it into the mouse,

0:55:110:55:16

but it's, sort of, another level above this because you're also

0:55:160:55:19

controlling that by using an electrical circuit.

0:55:190:55:23

Effectively, this is plugged into the mouse's brain

0:55:230:55:26

and turning it on, which makes this mouse, effectively, a cyborg.

0:55:260:55:30

Absolutely. What we're trying to do is deliver information to the brain

0:55:300:55:34

so we can control its natural processing.

0:55:340:55:36

To do that, we've been working on ways

0:55:360:55:38

to go beyond just one light source.

0:55:380:55:40

For example, now we can beam light all over the brain in a 3D pattern,

0:55:400:55:43

turning on and off the circuits that are involved with emotions,

0:55:430:55:47

decision making, sensations and actions.

0:55:470:55:49

We're in the matrix here, aren't we? Is this not exactly the way

0:55:490:55:53

brain control is going to be in the future?

0:55:530:55:56

I think science fiction can be really inspiring for new technologies.

0:55:560:56:00

I mean, it sounds potentially terrifying.

0:56:000:56:03

Well, the ability to control brain circuits with precision

0:56:030:56:06

we're regarding as a scientific tool to allow us to understand brain

0:56:060:56:10

and also as a medical prototype.

0:56:100:56:11

If you look at the world, there's something like a billion people

0:56:110:56:14

who have some kind of brain disorder and many of them

0:56:140:56:17

like Alzheimer's and multiple sclerosis,

0:56:170:56:19

stroke, traumatic brain injury,

0:56:190:56:21

there's basically no treatment for those things.

0:56:210:56:23

The 20th century was all about pharmacology, right?

0:56:230:56:26

Drugs for treating epilepsy, Parkinson's disease and so on,

0:56:260:56:29

but the problem is, if you bathe the brain in a substance

0:56:290:56:31

you're going to affect normal neurons as well as neurons you want to fix,

0:56:310:56:35

and that can cause side effects.

0:56:350:56:36

So, imagine that we go back to example of epilepsy.

0:56:360:56:39

What if we could turn off just the little piece of brain,

0:56:390:56:41

just for the time of a seizure and block it?

0:56:410:56:43

And therefore we won't have the side effects associated with it

0:56:430:56:47

other than that time.

0:56:470:56:48

So, what you're trying to do is hit the defective bit, ignore the rest?

0:56:480:56:51

Absolutely.

0:56:510:56:52

Having control over simple cells is one thing

0:56:570:57:00

but introducing control into our brains?

0:57:000:57:03

Well, that is something else,

0:57:030:57:05

this is the absolute cutting edge, not just of the science,

0:57:050:57:09

but also of the ethical debate.

0:57:090:57:11

We're talking about introducing control

0:57:110:57:14

into the most complex circuitry that there is,

0:57:140:57:17

our own minds.

0:57:170:57:19

I've seen some extraordinary things on this trip...

0:57:320:57:36

All based on the idea that you can treat the natural world

0:57:380:57:41

as spare parts for machines that can be rebuilt and reprogrammed.

0:57:410:57:45

And the result? Entirely new lifeforms

0:57:480:57:51

or biological machines that tread a line

0:57:510:57:54

somewhere between controversy and opportunity.

0:57:540:57:57

And so, it's easy to see

0:57:590:58:01

why some people might think of it as playing God.

0:58:010:58:04

What's really struck me about all of this,

0:58:080:58:10

whether you're in a small community garage or a colossal corporate lab,

0:58:100:58:15

is the number of people who have access to this technology

0:58:150:58:18

and the speed at which it's happened has been breathtaking.

0:58:180:58:22

Now, whatever you think of the uneasy bargain

0:58:220:58:25

that surrounds synthetic biology, one thing is absolutely clear.

0:58:250:58:29

We have created for ourselves

0:58:290:58:31

unprecedented power over life itself.

0:58:310:58:35

Adam Rutherford meets a new creature created by American scientists - the spider-goat. It is part goat, part spider, and its milk can be used to create an artificial spider's web.

It is part of a new field of research, synthetic biology, with a radical aim - to break down nature into spare parts so that we can rebuild it however we please.

This technology is already being used to make bio-diesel to power cars. Other researchers are looking at how we might, one day, control human emotions by sending 'biological machines' into our brains.


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