0:00:00.850,0:00:02.753
So, has everybody heard of CRISPR?

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I would be shocked if you hadn't.

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This is a technology --[br]it's for genome editing --

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and it's so versatile and so controversial

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that it's sparking all sorts[br]of really interesting conversations.

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Should we bring back the woolly mammoth?

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Should we edit a human embryo?

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And my personal favorite:

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How can we justify[br]wiping out an entire species

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that we consider harmful to humans

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off the face of the Earth,

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using this technology?

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This type of science[br]is moving much faster

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than the regulatory mechanisms[br]that govern it.

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And so, for the past six years,

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I've made it my personal mission

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to make sure that as many people[br]as possible understand

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these types of technologies[br]and their implications.

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Now, CRISPR has been the subject[br]of a huge media hype,

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and the words that are used most often[br]are "easy" and "cheap."

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So what I want to do is drill down[br]a little bit deeper

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and look into some of the myths[br]and the realities around CRISPR.

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If you're trying to CRISPR a genome,

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the first thing that you have to do[br]is damage the DNA.

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The damage comes in the form[br]of a double-strand break

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through the double helix.

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And then the cellular repair[br]processes kick in,

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and then we convince[br]those repair processes

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to make the edit that we want,

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and not a natural edit.

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That's how it works.

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It's a two-part system.

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You've got a Cas9 protein[br]and something called a guide RNA.

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I like to think of it as a guided missile.

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So the Cas9 --[br]I love to anthropomorphize --

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so the Cas9 is kind of this Pac-Man thing

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that wants to chew DNA,

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and the guide RNA is the leash[br]that's keeping it out of the genome

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until it finds the exact spot[br]where it matches.

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And the combination of those two[br]is called CRISPR.

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It's a system that we stole

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from an ancient, ancient[br]bacterial immune system.

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The part that's amazing about it[br]is that the guide RNA,

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only 20 letters of it,

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are what target the system.

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This is really easy to design,

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and it's really cheap to buy.

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So that's the part[br]that is modular in the system;

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everything else stays the same.

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This makes it a remarkably easy[br]and powerful system to use.

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The guide RNA and the Cas9[br]protein complex together

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go bouncing along the genome,

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and when they find a spot[br]where the guide RNA matches,

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then it inserts between the two strands[br]of the double helix,

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it rips them apart,

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that triggers the Cas9 protein to cut,

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and all of a sudden,

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you've got a cell that's in total panic

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because now it's got a piece[br]of DNA that's broken.

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What does it do?

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It calls its first responders.

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There are two major repair pathways.

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The first just takes the DNA[br]and shoves the two pieces back together.

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This isn't a very efficient system,

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because what happens is[br]sometimes a base drops out

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or a base is added.

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It's an OK way to maybe, like,[br]knock out a gene,

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but it's not the way that we really want[br]to do genome editing.

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The second repair pathway[br]is a lot more interesting.

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In this repair pathway,

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it takes a homologous piece of DNA.

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And now mind you, in a diploid[br]organism like people,

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we've got one copy of our genome[br]from our mom and one from our dad,

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so if one gets damaged,

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it can use the other[br]chromosome to repair it.

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So that's where this comes from.

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The repair is made,

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and now the genome is safe again.

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The way that we can hijack this

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is we can feed it a false piece of DNA,

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a piece that has homology on both ends

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but is different in the middle.

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So now, you can put[br]whatever you want in the center

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and the cell gets fooled.

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So you can change a letter,

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you can take letters out,

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but most importantly,[br]you can stuff new DNA in,

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kind of like a Trojan horse.

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CRISPR is going to be amazing,

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in terms of the number of different[br]scientific advances

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that it's going to catalyze.

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The thing that's special about it[br]is this modular targeting system.

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I mean, we've been shoving DNA[br]into organisms for years, right?

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But because of the modular[br]targeting system,

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we can actually put it[br]exactly where we want it.

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The thing is that there's[br]a lot of talk about it being cheap

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and it being easy.

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And I run a community lab.

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I'm starting to get emails from people[br]that say stuff like,

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"Hey, can I come to your open night

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and, like, maybe use CRISPR[br]and engineer my genome?"

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(Laugher)

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Like, seriously.

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I'm, "No, you can't."

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(Laughter)

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"But I've heard it's cheap.[br]I've heard it's easy."

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We're going to explore that a little bit.

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So, how cheap is it?

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Yeah, it is cheap in comparison.

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It's going to take the cost of the average[br]materials for an experiment

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from thousands of dollars[br]to hundreds of dollars,

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and it cuts the time a lot, too.

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It can cut it from weeks to days.

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That's great.

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You still need a professional lab[br]to do the work in;

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you're not going to do anything meaningful[br]outside of a professional lab.

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I mean, don't listen to anyone who says

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you can do this sort of stuff[br]on your kitchen table.

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It's really not easy[br]to do this kind of work.

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Not to mention,[br]there's a patent battle going on,

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so even if you do invent something,

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the Broad Institute and UC Berkeley[br]are in this incredible patent battle.

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It's really fascinating[br]to watch it happen,

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because they're accusing each other[br]of fraudulent claims

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and then they've got people saying,

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"Oh, well, I signed[br]my notebook here or there."

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This isn't going to be settled for years.

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And when it is,

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you can bet you're going to pay someone[br]a really hefty licensing fee

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in order to use this stuff.

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So, is it really cheap?

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Well, it's cheap if you're doing[br]basic research and you've got a lab.

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How about easy?[br]Let's look at that claim.

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The devil is always in the details.

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We don't really know[br]that much about cells.

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They're still kind of black boxes.

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For example, we don't know[br]why some guide RNAs work really well

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and some guide RNAs don't.

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We don't know why some cells[br]want to do one repair pathway

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and some cells would rather do the other.

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And besides that,

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there's the whole problem[br]of getting the system into the cell

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in the first place.

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In a petri dish, that's not that hard,

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but if you're trying to do it[br]on a whole organism,

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it gets really tricky.

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It's OK if you use something[br]like blood or bone marrow --

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those are the targets[br]of a lot of research now.

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There was a great story[br]of some little girl

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who they saved from leukemia

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by taking the blood out, editing it,[br]and putting it back

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with a precursor of CRISPR.

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And this is a line of research[br]that people are going to do.

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But right now, if you want to get[br]into the whole body,

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you're probably going[br]to have to use a virus.

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So you take the virus,[br]you put the CRISPR into it,

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you let the virus infect the cell.

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But now you've got this virus in there,

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and we don't know what the long-term[br]effects of that are.

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Plus, CRISPR has some off-target effects,

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a very small percentage,[br]but they're still there.

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What's going to happen[br]over time with that?

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These are not trivial questions,

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and there are scientists[br]that are trying to solve them,

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and they will eventually,[br]hopefully, be solved.

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But it ain't plug-and-play,[br]not by a long shot.

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So: Is it really easy?

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Well, if you spend a few years[br]working it out in your particular system,

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yes, it is.

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Now the other thing is,

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we don't really know that much about how[br]to make a particular thing happen

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by changing particular spots[br]in the genome.

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We're a long way away from figuring out

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how to give a pig wings, for example.

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Or even an extra leg -- I'd settle[br]for an extra leg.

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That would be kind of cool, right?

0:08:06.922,0:08:08.458
But what is happening

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is that CRISPR is being used[br]by thousands and thousands of scientists

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to do really, really important work,

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like making better models[br]of diseases in animals, for example,

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or for taking pathways[br]that produce valuable chemicals

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and getting them into industrial[br]production in fermentation vats,

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or even doing really basic research[br]on what genes do.

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This is the story of CRISPR[br]we should be telling,

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and I don't like it[br]that the flashier aspects of it

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are drowning all of this out.

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Lots of scientists did a lot of work[br]to make CRISPR happen,

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and what's interesting to me

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is that these scientists[br]are being supported by our society.

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Think about it.

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We've got an infrastructure that allows[br]a certain percentage of people

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to spend all their time doing research.

0:09:02.984,0:09:06.355
That makes us all the inventors of CRISPR,

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and I would say that makes us all[br]the shepherds of CRISPR.

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We all have a responsibility.

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So I would urge you to really learn[br]about these types of technologies,

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because, really, only in that way

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are we going to be able to guide[br]the development of these technologies,

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the use of these technologies

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and make sure that, in the end,[br]it's a positive outcome --

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for both the planet and for us.

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Thanks.

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(Applause)