What you need to know about CRISPR

So has everybody heard of CRISPR?

I would be shocked if you hadn't.

This is a technology,
it's for genome editing,

and it's so versatile
and so controversial

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

Should we bring back
the woolly mammoth?

Should we edit a human embryo?

And my personal favorite,

how can we justify
wiping our an entire species

that we consider harmful to humans

off the face of the Earth

using this technology?

This type of science

is moving much faster

than the regulatory mechanisms
that govern it,

and so for the past six years,

I've made it my personal mission

to make sure that as many people
as possible understand

these types of technologies
and their implications.

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

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

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

and look into some of the myths
and the realities around CRISPR.

If you try to CRISPR a genome,

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

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

through the double helix,

and then the cellular repair
processes kick in,

and then we convince
those repair processes

to make the edit that we want

and not a natural edit.

That's how it works.

It's a two part system.

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

I like to think of it
as a guided missile.

So the Cas9 --
I love to anthropomorphize --

so the Cas9 is kind of this
Pac-Man thing

that wants to chew DNA,

and the guide RNA is the leash
that's keepIng it out of the genome

until it finds the exact spot
where it matches.

And the combination of those two
is called CRISPR.

It's a system that we stole
from an ancient, ancient

bacterial immune system.

The part that's amazing about it

is that the guide RNA

only 20 letters of it

are what target the system.

This is really easy to design,

and it's really cheap to buy.

So that's the part

that is modular in the system.

Everything else stays the same.

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

So the guide RNA and
the Cas9 protein complex together

go bouncing along the genome,

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

then it inserts between the two strands
of the double helix,

it rips them apart,

that triggers the Cas9 protein to cut,

and all of a sudden,

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

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

What does it do?
It calls its first responders.

There are two major repair pathways.

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

This isn't a very efficient system,

because what happens is
sometimes a base drops out

or a base is added.

It's an okay way to maybe, like,
knock out a gene,

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

The second repair pathway
is a lot more interesting.

In this repair pathway,

it takes a homologous piece of DNA.

And now mind you, in a diploid
organism like people,

we've got one copy of our genome
from our mom

and one from our dad,

so if one gets damaged, it can use
the other chromosome to repair it.

So that's where this comes from.

The repair is made,

and now the genome is safe again.

The way that we can hijack this

is we can feed it

a false piece of DNA,

a piece that has homology on both ends

but is different in the middle.

So now you can put whatever you want
in the center and the cell gets fooled.

So you can change a letter,

you can take letters out,

but most importantly, you can
stuff new DNA in,

kind of like a Trojan horse.

CRISPR is going to be amazing

in terms of the number of different
scientific advances

that it's going to catalyze.

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

I mean, we've been shoving DNA
into organisms for years. Right?

But because of the modular
targeting system, we can actually

put it exactly where we want it.

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

and it being easy,

and I run a community lab.

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

"Hey, can I come to your open night
and, like, maybe use CRISPR

and engineer my genome?"

Like, seriously.

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

"But I've heard it's cheap.
I've heard it's easy."

So we're going
to explore that a little bit.

So how cheap is it?

Yeah, it is cheap in comparison.

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

from thousands of dollars
to hundreds of dollars,

and it cuts the time a lot too.

It can cut it from weeks to days.

That's great.

You still need a professional lab
to do the work in.

You're not going to do anything meaningful
outside of a professional lab.

I mean, don't listen to anyone who says
you can do this sort of stuff

on your kitchen table.

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

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

so even if you do invent something,

the Broad Institute and UC Berkeley

are in this incredible patent battle.

It's really fascinating
to watch it happen,

because they're accusing each other
of fraudulent claims

and then they've got people saying,
"Oh, well I signed my notebook

here or there."

This isn't going to be settled for years,

and when it does, you can bet
you're going to pay someone

a really hefty licensing fee
in order to use this stuff.

So is it really cheap?

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

So how about easy?
Let's look at that claim.

The devil is always in the details.

We don't really know
that much about cells.

They're still kind of black boxes.

So for example, we don't know
why some guide RNAs work really well

and some guide RNAs don't.

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

and some cells would rather do the other.

And besides that,
there's the whole problem

of getting the system
into the cell in the first place.

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

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

it gets really tricky.

It's okay if you use something like blood
or bone marrow.

Those are the targets
of a lot of research now.

There was a great story
of some little girl

who they saved from leukemia

by taking the blood out, editing it,
and putting it back

with a precursor of CRISPR.

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

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

you're probably going
to have to use a virus.

So you take the virus,
you put the CRISPR into it,

you let the virus infect the cell.

But now you've got this virus in there,

and we don't know what the long term
effects of that are.

Plus, CRISPR has some off-target effects,

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

So what's going to happen
over time with that?

These are not trivial questions,

and there are scientists
that are trying to solve them,

and they will eventually
hopefully be solved.

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

So is it really easy?

Well, if you spend a few years
working it out

in your particular system,

yes it is.

Now, the other thing is we don't really
know that much about

how to make a particular thing happen

by changing particular spots
in the genome.

We're a long way away from figuring out
how to give a pig wings, for example,

or even an extra leg.

I'd settle for an extra leg.
That would be kind of cool, right?

But what is happening

is that CRISPR is being used
by thousands and thousands of scientists

to do really, really important work,

like making better models
of diseases in animals, for example,

or for taking pathways

that produce valuable chemicals

and getting them into industrial
production and fermentation vats,

or even doing really basic research
on what genes do.

This is the story of CRISPR
we should be telling,

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

are drowning all of this out.

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

and what's interesting to me

is that these scientists
are being supported by our society.

Think about it.

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

to spend all their time doing research.

That makes us all the inventors of CRISPR,

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

We all have a responsibility.

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

because really only in that way

are we going to be able to guide

the development of these technologies,
the use of these technologies,

and make sure that in the end,

it's a positive outcome

for both the planet and for us.

Thanks.

(Applause)