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Biologist Explains One Concept in 5 Levels of Difficulty - CRISPR

CRISPR is a new biomedical technique that enables powerful gene editing. WIRED challenged biologist Neville Sanjana to explain CRISPR to 5 different people; a child, a teen, a college student, a grad student, and a CRISPR expert.

Released on 05/24/2017

Transcript

My name is Neville Sanjana.

I'm a biologist at New York University,

and the New York Genome Center.

And I've been challenged today to teach one concept

in five levels of increasing complexity.

My topic is CRISPR.

CRISPR is a new area of biomedical science

that enables gene editing,

and it's helping us understand the genetic basis

of many diseases, like autism or cancer.

I think today everyone can leave with understanding

something about CRISPR at some level.

Hey Teigen, do you know what we're here to talk about today?

Science.

We are here to talk about science.

We're here to talk about something called CRISPR.

Have you heard of that?

No.

CRISPR is a tool that scientists are using

to edit, or change, genomes.

Do you know what a genome is?

No.

It's kind of like an instruction manual.

The instruction manual that makes you who you are.

Sometimes, there's mistakes in the instruction manual.

Like people get sick.

Like allergies?

Like allergies.

Do you have friends at school that have allergies?

Well, I have allergies to penicillin and azithromycin.

They're a type of medicine.

It's good that you actually know exactly

what you're allergic to.

For people that have really severe allergies,

we could erase where, in that big instruction manual,

where they have those allergies,

and maybe make it so that they

don't have those allergies anymore.

Blowing my mind.

(laughing)

Do you know what CRISPR is?

Absolutely not.

No, not at all.

CRISPR is a way to edit the genome.

Do you know what a genome is?

Yeah, it's the DNA.

DNA is kind of the language that the genome is written in,

and the genome itself is an instruction manual

that describes how to make you,

how tall you should be,

what color hair you have,

or what color eyes you have.

So, what CRISPR is, and an easy way to think about,

it's like a molecular pair of scissors

that can go through that long, long genome

and find specific places, make small cuts, and edit it.

What do you think about being able to edit genomes?

It's actually kind of cool 'cause then you could change,

can't you technically change things about a person

if you edit the DNA?

Sure.

So, how do we determine what's the right uses then?

I don't think it should be used for almost

cosmetology reasons.

Okay.

Or people just to be like oh I wanna be 5'6

instead of 5'4.

Or like reasons that aren't necessarily the most important.

I just think if it could genuinely help someone.

Like if someone had cancer, and there was a way to fix it.

Or like slow down the growth.

So, a lot of the work that we do in my lab

is about being engineers of DNA.

We try and look to see what mutations cause diseases,

and see if when we change those mutations,

if we can take a sick cell, or organism,

and make it healthy again.

Do you know how CRISPR works?

So, it works where you have this CRISPR,

well, this cas9 complex, and--

Protein. Cas9 protein.

Cas9 protein complex along with

something called a guide RNA.

That's right. That's right.

And that RNA will, basically, tell this protein

where to go, and what gene to sort of cut out.

From what I've heard, they're like close to almost

curing Muscular Dystrophy with it.

But there's a lot of, I guess, ethical issues

that come up with it too.

One of the really nice things, actually, about CRISPR

is that we can use it in human cells.

You know, if you ask most people,

should you use it to cure cancer?

Most people would say, yeah those are good uses.

But there are other areas that are a little bit

more problematic, like editing the germline.

Which means something that could be passed on.

So, I think a lot of people are concerned maybe

that CRISPR'll be used in kind of frivolous ways.

Maybe just to choose somebody's eye color,

or how tall they are,

or what color hair they have.

And I think what a lot of people don't realize,

maybe, is that the state of genetics is not quite there.

It's nice to think that I can go in and choose

exactly what eye color I want,

but fundamentally, science doesn't exactly

know all of that yet.

We don't know every single gene related to eye color,

nor the regulatory mechanisms, nor the epigenetics.

This is a huge--

Right, so we can use CRISPR now to try and understand

better how do our gene relate to these different features,

these different phenotypes that we have.

There's a lot of work left to do before

we even know what are the knobs and dials.

What are the controls--

Right.

That, you know, affect eye color, or how tall you are.

So, I think this question right now,

even though it's important to discuss,

I kind of feel like it's more theoretical right now.

Yeah, or is it really even a point necessary

for conversation,

because people are going out every single day

and getting plastic surgery to change how they look.

How is this any different?

So, Matt what are you doing right now in the lab,

and how are you using gene editing in your own work?

Right now, one of the questions I've been

very much interested in is trying to understand

the effect of human genetic variation

using CRISPR Cas9 reagents.

Because, you and I, just sitting here,

differ in millions of different locationss within our genome.

We use these guide RNAs which are 20-base pairs,

and we match it to different places in the genome,

but what if there's a mutation at that site,

and how does that affect--

A mutation that's different between you and me.

It's the same site, but there's a slight difference

in the DNA between you and me there.

Exactly.

Let's say in you it's a perfect match,

and in me there's one that's actually a mismatch.

And how does that affect things in the lab?

Because maybe it won't be as efficient,

it won't be able to bring Cas9 to the correct site,

and cut there.

So, when people are using CRISPR now in the lab,

are they really sequencing the exact cell type they use.

Sequencing, reading out the genome of that cell

before they use CRISPR?

Not many do that.

It would ultimately, the best way to do it for sure,

because the reference genome that was published in 2001

was kind of just one person's genome.

And as we know very well from sequencing many

different individuals, there are a lot of differences.

And so, there are some concerns that when you

use these in the lab that you're intending

for a cut to be made in this one place in the genome.

But if there happens to be a mismatch there,

because of some variant in the cells that you're studying,

maybe it won't cut there at all,

and even maybe worse,

is that maybe it'll cut somewhere else.

Because maybe now it can match elsewhere.

So, you're saying right now,

that it's kind of early days with CRISPR,

and that there's a lot of technical issues

that really need to be ironed out.

That it's not anything can be targeted at any time.

We're trying to develop the scientific steps

that will take us to that kind of total genome control.

It is still the early days.

And as much progress has been done,

which is actually quite remarkable given

how new this technology is.

I mean, we're just a few years away from when

it was really started being used for these applications.

However, having said that, it holds a lot of potential,

and I think can get there,

but there's a lot of issues,

and concerns that need to be worked out.

I think it's great for people of all ages

to understand CRISPR,

and at least a little bit about genome engineering.

Because so much of the world today revolves around biology.

Also, there's something about self-understanding.

We really wanna understand ourselves,

and what makes up ourselves.

And CRISPR and gene editing is another way

to get at what is the substance underlying us.

Starring: Neville Sanjana, Dr. Matthew Canver, Lauren Schiff, Christopher Reid, Teigen River, Bella DiDomenico

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