Want to edit your DNA? | Nessa Carey | TEDxLiverpool

Scientists can now harness the unparalleled power of gene editing to change the genome of any organism on earth, including ourselves. This has the potential to tackle devastating genetic diseases with no other treatment options, removing them from affected families for all future generations.

So why is society so uncomfortable with this? Why does the thought of changing maybe just one letter of the 3 billion in our genetic alphabet, in the genes of a tiny fraction of the human population, worry us so much? Maybe it’s time to challenge our oddly possessive feelings about our DNA and accept that with gene editing the ethical game has changed forever.
Follow Nessa on @NessaCarey Nessa Carey is an expert in genetics. She’s written Hacking the Code of Life, Junk DNA and The Epigenetics Revolution. She’s formerly a Senior Lecturer in Molecular Biology at Imperial College and currently serves there as Visiting Professor. Nessa holds has a virology PhD from Edinburgh University, a degree in immunology and did post-doc research in human genetics.

In addition to her academic and writing experience, Nessa spent 13 years in industry working in drug discovery with senior science roles at startup companies all the way up to behemoths such as Pfizer.

This talk was given at a TEDx event using the TED conference format but independently organized by a local community. Learn more at https://www.ted.com/tedx

Okay, so it's absolutely
brilliant to be here today

talking to you about gene editing

because this is the biggest
game in biology now.

It is almost the only story,

and it is an absolutely
transformational technology,

which is going to change the lives
of multiple people and organisms

on this planet,

and we all need to have opinions
and express those

about how it should be used.

This technology only
really started in 2012,

when it was shown that a system
that evolved in bacteria

could be used to change the DNA
of any organism from any source

in a test tube.

In 2013, this was adapted
so that it could work in living cells,

and as Herb mentioned,
just a couple of weeks ago,

it was adapted yet again
to give it an exquisite sensitivity

that means we could now, in theory,

change genetic mutations
that cause 90% of human genetic disease.

It's incredible.

The technical term for it

is "clustered regularly interspaced
short palindromic repeats,"

which of course is why everyone
calls it CRISPR,

but an easier way to think of it
is gene editing.

Now, there is a form
of changing the genome

that has been used for a long time

called "genetic modification,"

and CRISPR gene editing
is different from this,

both in the way it works,

but more importantly,
in what it can achieve.

And I'm going to give you an analogy

to show you just how good gene editing is.

So, here we go.

Most famous line, I would argue,
in English literature to open any novel:

"It is a truth universally acknowledged

that a single man
in possession of a good fortune

must be in want of a wife."

Do not let me down now, Liverpool.

What is that the opening line from?
(Audience) Pride and Prejudice.

Thank God. Pride and Prejudice.

But of course, Jane Austen didn't write

"a single 'mam' in possession
of a good fortune."

That would have been
rather forward-thinking for Jane.

So there is a typo.

If we had wanted to use the equivalent
of the old-fashioned gene modification

to change that typo, to correct it,

here's what we'd probably
have ended up with:

"It is the truth universally acknowledged,

that a single man" - yeah, we changed it -

"I meant man reader I married him in in
want of a hell, what's this bit wife."

That's what we'd have ended up with.

I've snuck in another
famous line from literature,

slightly later.

Please tell me what it is.
(Audience) Jane Eyre.

Jane Eyre, fantastic -
"reader I married him."

Liverpool is doing very well
right now. Excellent.

What you can see

is that with the old technique
of gene modification,

we've corrected the bit
that was wrong,

but we've also introduced other bits
that we didn't want,

and we've lost bits of the original text.

But with gene editing,
you can make the perfect correction -

you don't lose anything,
you don't gain anything.

If you put that into the context
of the human genome,

our DNA,

you receive 3,000 million letters
of genetic information from your mother

and 3,000 million from your father.

And it is most precise exquisite form,

gene editing can find one typo,
one mutation and correct that -

one out of three billion.

That's extraordinary.

We've never had a technology
that could do anything like that before.

It's amazing and it has
very wide-ranging implications.

And today, I'm just going to talk
about its implications

for new treatments
for human health conditions

because, you see, gene editing

is an intensely tempting
therapeutic approach.

Once you make an edit in a cell,
once you've changed the DNA,

that change's there forever,

and it would also be passed on
to all cells that originate from that,

so every time a cell divides.

We are looking at the potential
to being able to cure genetic disease -

not treat it, not prolong life,
but actually cure it.

It won't even be restricted
to genetic disease,

because here's one
of the weirdest implications.

Lots of people die every day
waiting for an organ transplant

because they're in things
like end-stage kidney failure

or end-stage heart failure.

We don't have enough organ donors.

It's partly the law
of unintended consequences.

Governments brought
in seatbelt legislation;

people don't die so much in car crashes,
which is a good thing,

but they were one of the main sources
of organs for donation.

We don't have enough humans
to get the organs from,

but maybe we could use pigs.

If you think about something
like end-stage heart failure,

pigs are awesome

because their hearts
are very similar to ours.

They're about the same size,

same mechanical and electrical properties.

It'd be great if we could
just take hearts from pigs.

There's lots of pigs.

There are problems.

One of the problems is we would
reject pig hearts very quickly,

but another problem is that pig hearts
carry secret agents.

Lurking in their DNA are viruses,
ancient viruses, and they're not dead,

they're not inactivated,
they're just asleep.

Now, if the immune system, for example,
is not functioning very well -

and that would be the case in somebody
who had received a heart transplant

because they'd be
on immunosuppressive drugs -

the worry is that these pig hearts
could reactivate those viruses,

and those viruses could cause
an infection in that recipient

but also might even
spread to other people,

probably not to all of us,

but people at risk would be the very old,
the very young, and the very sick.

Heart transplants
would take place in a hospital.

Hospitals are typically
full of the very old,

the very young, and the very sick,

so you can see it might not go well.

Using gene editing,

a team in the States has managed
to inactivate all 65 of the viruses

that lurk in the pig genome.

That could never have been done
with the old technology.

And this is so intensely valuable
that a company set up from that team

has just received an investment
of a hundred million dollars

to keep progressing this technology

to get to where we can
have pig organs in humans.

But where we'll see
much more application of this

is in the treatment
of human genetic diseases,

particularly what we call
"somatic treatment,"

where we just treat the body cells.

So this is quite remarkable.

Right now, there are clinical trials

using gene editing in sickle cell disease
and beta thalassemia.

It's 2019.

That's just seven years

after this technology
was first demonstrated.

We've never seen progress like this,

and this is a beautiful use
of the technology

because what they're doing
is they're taking out bone marrow cells

from patients with sickle cell
disease or thalassemia.

And these patients have a mutation
in one of the hemoglobin genes.

Hemoglobin is the protein
that carries oxygen around in the blood.

And what they're doing

is they're taking the cells
out of the bone marrow,

editing them in the laboratory
to change the mutation,

and then they put them
back in the patient;

and these cells will migrate
back to the bone marrow,

and they will then
repopulate the bone marrow

and produce healthy red blood cells.

So we're looking at a case

where previously all we've had
are really quite inadequate treatments,

and we could cure these patients.

They would no longer have
sickle cell disease or thalassemia;

they would be cured.

This is a fairly non-controversial
application of this technology

because all it's doing is changing
the cells in the bone marrow.

The patients who receive this treatment,

they won't pass on the mutation
to their offspring.

A much more controversial use of this
is what's called "germline gene therapy" -

sorry, germline gene "editing" -

and this is where we would
use gene editing

on a very early embryo

to change a mutation
which we know will cause a disease.

And then the embryo will be implanted
back in the mother -

classic test-tube baby tech -

and then that individual,

when they grow up,
their genome has changed,

but we will also have changed
the genetic sequence

of all of their offspring,
and their offspring forever.

It's a permanent change
in human genetic makeup.

And the idea and
what we assumed would happen

is that this would initially be developed

for only devastatingly
life-threatening conditions,

something like Huntington's disease.

So behind me, you can see a slice
of the post-mortem brain

of somebody who was not suffering
from a degenerative disease,

and then you can also see the brain

of someone who was suffering
from Huntington's,

an appalling lethal
neurodegenerative condition.

You can see that the brain
has completely degenerated.

We could, in theory, stop that
in a family by using gene editing.

Now, this is an extraordinary development.

We have never had the opportunity
to do something like this before,

and what we have to think about is,
Should we take that opportunity?

The questions now start becoming
much more ethical

than they are scientific,

and a great source of discussion on this
is the Nuffield Council on Bioethics,

who published a brilliant report
about this kind of technology.

Among things it raises
is "Who has the right to give consent?"

because consent is vital
for any medical procedure.

And it's always tempting

to think that of course,
the parents will give consent,

but the parents aren't being edited.

But we can't ask an embryo
if it will give consent,

because an embryo is a few cells big.

So what do we do?

Would we then ask that person
when they were 18?

Do we say, "Do you mind
that we edited you?

Do you think you'd have been better off
if we hadn't edited you?"

Gene editing creates the potential

that we end up asking for informed consent

in an imaginary form

from an individual who never existed,
in an alternative universe.

That's not informed consent;
this is going to be very tricky.

Now, this technology
will only, in some ways,

be used for a relatively small number
of people, but that's not the point.

Ethics is ethics.

There isn't a number

at which it becomes
an important ethical question;

the question is important
right from the start.

And for once,

scientists have been very careful

recognizing that this is a question
that is so important and so fundamental

it needs to be addressed,
not just by scientists.

We need to involve regulators
and ethicists and philosophers

and particularly patient groups.

A very interesting statement on this

was made by somebody from a patient group,

who said, "Why are you all
having such a fuss?

All we're asking is that you change
the genome of our child

so it is the same as the other
7.5 billion people on this planet,"

which is an interesting way
of looking at it.

But it was going very well,
everyone wanted to build consensus,

everyone wants to take this stepwise,
and then this happened.

He Jiankui, a scientist in China,
stood up at a conference

and announced that he had
edited two embryos,

implanted them in their mother,
and the babies have been born.

He'd done germline gene editing,
and everybody was horrified.

They were horrified for various reasons.

You have to admire this guy;

he managed to mess up
politically, ethically, and technically,

which is quite impressive.

He did the editing really, really badly.

It's not at all clear that he had
any meaningful ethical consent,

either from the family involved
or from the regulators.

And he's in China,

and he's messed up
politically spectacularly

because China wants to be

part of the global international
scientific community

and now they look like a rogue state,

and he's now under house arrest.

And it's caused real ructions

because of course, that ability now
to discuss this in a measured way

has been taken away from everyone,

and the fear is that governments
will start saying,

"This technology is moving too fast;

we're going to have
a complete moratorium on it,"

which I think would be
a terribly retrograde step.

But one thing that we really
ought to think about

is actually, Why do we care so much?

Why do we worry
to such an enormous degree

about what happens to DNA
and to our genes?

If we're talking about gene therapy
and germline gene therapy

and changing the DNA
of future generations,

I think nobody really
has major concerns about this

if it's used

for an inevitably life-threatening,
life-limiting, horrific disorder,

something such as Huntington's disease.

But what if we start using it
for something like deafness?

You could quite easily
edit the DNA in an embryo

to make sure they never became deaf.

But deafness is associated
with major cultural groups.

Sign languages have developed
independently all over the world;

if we start using gene editing
to remove deafness

from certain families
and certain communities,

we could actually be wiping out
linguistic groups.

That's coming perilously close

to the UN definition
of what constitutes genocide.

So there will have to be decisions made

about where this technology
can and cannot be used

in terms of life-threatening
versus life-altering conditions.

There's also the argument
about the slippery slope -

Oh, my god, everyone's going to make
blue-eyed, blonde-haired babies

who will grow up
to be very tall, very strong,

great athletes, very intelligent.

Well, they won't.

They might want to,
but they won't be able to do it.

All of those traits
are influenced by multiple genes,

hundreds of genes throughout the genome;

you can't edit all of them,

and they're hugely influenced
by the environment.

So although, I think, it's good
we're aware of the slippery slope,

I don't think it's really, in real terms,
that much of an issue.

I think the other reason
why we care so much

is we have an odd proprietorial
feel about our genome.

It's mine; it's my DNA; it's who I am -

it's not who you are.

It is a starting point,

but we have become strangely proprietorial

about these three billion letters
of genetic information,

most of which we don't actually know.

But I think gene editing is amazing.

The best thing about it is it's so easy.

This means we can develop new treatments.

It also means it has implications,

like we can create new crops
for the poorest people in the world,

where plant breeders
never put in any effort.

So it's brilliant that it's so easy.

It's also disastrous that it's so easy.

This guy is called Josiah Zayner.

He's a self-start biohacker.

He tried to inject
gene-editing agents into his bicep

to make his bicep get really big.

It didn't work,
which i think is unfortunate

because it would've been just so funny
to see this guy with one huge bicep.

I'm not really worried
about garage biohackers.

I am worried about people
who can have access to this

to make pathogens more pathogenic.

It's not a technology
we can control easily.

We can also be pretty sure

that we will start seeing
disreputable clinics

in poorly regulated states

offering miracle cures with gene editing
and taking huge advantage of people.

So I think we are going to see problems.

But I think one thing
we have to be very aware of

if gene editing has absolutely changed
the default ethical position,

especially when it comes to treatment
of human diseases:

The question now is not
"Do we have the right to intervene?"

The technology is so good
that we have to ask ourselves now,

"Do we have the right not to use it?"

So the final thing
that I would leave you with

when you're thinking about gene editing

is to remember it's not
the technology that's good or bad,

it's what we do with it that counts.

Thank you very much.

(Applause)