The CRISPR revolution: Healing or improving our genes? | Luciano Marraffini | TEDxRiodelaPlata

What technical and ethical challenges does DNA editing pose? In this talk, Luciano explains how CRISPR technology works and what social and scientific consequences it can have. Luciano is an Argentine-American microbiologist born in Rosario, and he currently works as a professor and director of The Bacteriology Laboratory at Rockefeller University, and as a researcher at HHMI. He is also one of the co-founders of Intellia Therapeutics. He is recognized for his research on the CRISPR-Cas system, which promises to correct genetic diseases. He was one of the first scientists to figure out how these systems work at the molecular level.

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

When I was a kid I used to watch
a lot of sci-fi movies

in which there were
genetically modified beings

to have superior bodies or intelligences.

I remember Blade Runner's replicants.

They really caused an impression on me.

Today, science is not that far
from that fiction.

In 2018 in China,

twins were born whose embryos
were genetically modified

with a mutation that would make them

HIV-resistant,

the virus that causes AIDS.

Since the mid-20th century

we know that the genes of all organisms

are made up of DNA molecules,

also known as
"the molecules of life".

Genes determine that a plant
has large or small leaves,

that an insect has wings or not,

or that a person has
brown or grey eyes.

When the chemical composition
of a gene's DNA changes,

the characteristics this gene defines
also change.

For many years, changing the chemical
composition of DNA in humans

had been very, very difficult.

But everything changed recently

when a revolutionary technique
called CRISPR was developed.

The birth of the twins in China

is the beginning of a new era
in modern medicine.

Genetic manipulation of
human beings is already possible.

Maybe some of you
already heard of this technique.

What is CRISPR?

It is much easier to modify
embryonic cells with CRISPR

than to explain the meaning
of the acronym.

For the curious, CRISPR means

"clustered regularly interspaced
short palindromic repeats."

Unfathomable, I know.

I would simplify it like this:

if an organism's DNA contains
all necessary instructions

to build that organism,

CRISPR is a text editor that can
easily change those instructions.

I was one of the first scientists

dedicated to CRISPR research.

My discipline is not genetic engineering
but microbiology.

I study how bacteria defend themselves
against their viruses.

Yes, it's not just human beings
and animals that get infected by viruses.

Also bacteria.

CRISPR is the immune system
these little single-celled guys have

to defend against viruses.

In 2008, together with my colleague
Erik Sontheimer,

we found out how CRISPR works.

Bacteria program CRISPR to cut viral DNA,

in that way destroy the virus
and cure themselves of the infection.

In the publication of this work
we proposed that this mechanism,

that evolved naturally in bacteria,

could be transplanted
to other organisms

for medical and biotechnological
applications.

In particular, we thought
it could be used

for the modification of human genes.

Why? Because two steps
are required to modify genes.

First, we have to cut the gene
we want to modify.

And second, we have to repair
or fix that gene

with a DNA sequence that is the one
we want to introduce,

which would modify the gene.

Repairing cut DNA is relatively simple

because cells can do it themselves.

Any damage to the DNA
immediately triggers mechanisms

that repair it with other DNA
from a similar sequence.

This other DNA, similar to the cut DNA,
is called template DNA.

And it's very easily introduced
by a researcher

after cutting the DNA with CRISPR.

What was always very difficult to achieve
was to develop a technique

that would cut specifically
a gene among all the genes

that we have in the cells.

So, along with Feng Zhang,
an expert in genetic engineering,

we decided to transport the CRISPR system
from bacteria to human cells

to have it do the same
it does in bacteria:

cut DNA specifically.

We program CRISPR to cut
the human gene EMX1,

and we repaired it with a template DNA

introducing three
modifications to the DNA.

After several tests
to fine-tune the technique

we got mutant cells
which had all the three modifications

that we designed ourselves.

We published our work in 2013

and because of the efficiency
and the simplicity of the technology,

it was adopted by research labs

around the world.

It was the beginning
of the CRISPR revolution.

This new technology has
two fundamental problems.

One is technical and the other, ethical.

The first, the technical one, is
that CRISPR can have "side effects".

What does that mean?

That CRISPR can cut not only
the gene you want to cut,

but also another gene,
therefore introducing mutations

you don't want to introduce.

To reduce this risk
CRISPR is usually programmed

in several different ways.

And only those

with minimal and acceptable risk
of side effects are adopted.

Taking these precautions,
today CRISPR is already being used

for multiple medical applications.

Although all of them are still
in an experimental phase.

For example, immune system cells
can be modified

to attack cancer cells
and therefore attack tumors.

Certain lymphomas and leukemias
are starting to be treated

with this technology.

Research is also after new therapies

to cure genetic diseases.

CRISPR is injected to modify
the defective gene

that causes that disease and correct it,

and in this way restore
the functions of the organs

that are affected by the deficient gene.

In other fields, it is already beyond
the experimental stage

and it's making significant impact.

In agriculture, for example,
CRISPR can be used

to have crops with higher yields,

resistant to certain
environmental conditions.

Livestock can be modified with CRISPR

to increase meat production

and be more resilient
certain diseases.

No doubt CRISPR
will be one of the technologies

that's going to help
feeding the world by 2050,

with its 10 billion inhabitants.

The second problem, the ethical one,
is much more serious.

Embryonic cell manipulation
that would result

in the creation of
genetically modified human beings

has been disapproved by all
scientific academies worldwide.

Because the modification of embryos
has a lot of troubles.

One is risk.

In all medical interventions
there are risks.

Another problem is the lack
of consent.

The person being born
from embryos modified with CRISPR

can't decide.

It is possible to imagine children
blaming their parents

for having introduced them traits
they didn't want to have.

There's also the problem
of inequality.

Not everyone will have the resources
to access this technology,

which would widen the gap even more
between the poor and the rich,

whether it's people or countries.

But the most complicated question is:

in which cases is acceptable
the "genetic improvement" of humans?

From a religious point of view
probably never.

From a medical point of view
it would only be accepted

if it is possible to cure genetic diseases

that have no other treatment available.

But what will happen if future parents
want to give their children advantages

by changing their genes?

Currently, doping is not accepted
in athletes.

Would we allow competitions with athletes

that were genetically modified?

The case of the CRISPR twins
makes it clear to us

how complex the problem is.

The researchers who performed
the treatment of the embryos

justified it by labeling it
as AIDS prevention,

but the rest of the
scientific community

saw it as a clear example
genetic improvement,

which was also carried out

regardless of
the possible side effects,

and not even calculating
the risks it might have.

The disapproval didn't just come
from the scientific world.

Researchers involved
were sentenced to three years in prison.

Today we all agree that
the experiment carried out in China

was completely irresponsible
and premature.

But it made it clear to us
that genetic modification of humans

is possible and that it will certainly
be part of the world to come.

It was the take-off of a ship to a future,
and there is no turning back.

While there's still a long way to go
to know what genes

we have to change in people

to create the "replicants"
of Blade Runner,

CRISPR gave us the tool to do it

when we have that knowledge.

But we can't wait arms crossed.

Now it's time to start
discussing and debating

how we are going to use
this new technology.