Human Nature

Dr. Bonner, fellow prophets, and...

- -...ladies and gentlemen...

This summer, I traveled through

Northern Arizona and Southern Utah.

In this land, the rivers have carved

great gorges,

and on the sheer cliffs of these gorges,

one can read a billion years of the history of the Earth.

On that immense scale

of what represents the passage of perhaps 100,000 years,

all of man's recorded history

took place as an inch was deposited,

all of organized science, a millimeter,

all we know of genetics, a few tens of microns.

The dramatic advances of the past few decades

have led to the discovery of DNA

and to the decipherment of the universal hereditary code,

the age-old language of the living cell.

And with this understanding

will come the control of processes

that have known only the mindless discipline

of natural selection for two billion years.

And, now, the impact of science will strike straight home,

for the biological world includes us.

We will surely come to the time

when man will have the power to alter,

specifically and consciously, his very genes.

This will be a new event in the universe.

The prospect is, to me,

awesome in its potential for deliverance

or equally for disaster.

There we go. Much better.

You want to squeeze my hand?

Relax your shoulders.

Relax your toes.

Being in the hospital isn't scary to me.

Having a certain new problem isn't scary to me anymore

'cause it's happened so many times.

I don't know.

My blood just does not like me very much, I guess.

Your red cells are supposed to be round

and have oxygen in them.

Mine are half-moon-shaped, sickle-shaped,

which is why it's called sickle cell,

so I don't get the same amount of oxygen.

I always say, like, oil change, you know?

You're draining the dirty out and then put a clean in.

Yeah, so he just needs a tune-up

every four to six weeks, yeah, uh-huh.

Yeah. That okay?

-Okay. -Put this on.

Take deep breath and hold.

Mmm.

Okay.

You okay, David? Mmm-hmm?

He used to tell me, "Don't cry, Nonna. Why are you crying?"

I said, you know, "Love you, baby."

He goes, "Don't worry about it."

He says, "If I lose my life," he goes,

"You'll see me again,"

and I thought,

"This child has more strength and faith than I do."

It's often called the first molecular disease.

It's caused by a single change in the DNA sequence.

It's the letter A changed to a letter T.

- That's it? - That's it.

And that mutation causes a kink in the protein

that prevents it from folding properly.

If your folding structure of a protein is disrupted,

now that protein can't function.

It causes the red blood cell

to really collapse.

It becomes very stiff, and it can't squeeze through,

and you're not able to get red blood cells

to the tissues where they can deliver oxygen,

and if you block the ability of oxygen to get to those tissues,

those tissues won't work well, and they'll get damaged.

In Africa, the life expectancy for somebody with sickle cell disease

is on the order of five to eight years of age.

In the U.S., it's the early to mid-40s.

What do you say to a kid that their life is gonna be--

We avoid it. We avoid that conver--

-It's not a-- - Really?

It's not a conversation we're good at having.

Makes me very nervous.

David can go from crazy teenager,

joking, jumping around,

to a fetal position on his knees.

It's, like, pulsing.

"This hurts.

You're having a sickle cell crisis."

I can have, like, a little pain crisis where it really doesn't count,

and then I can have something really bad,

but I'm not just gonna not play basketball.

You can't just not play basketball.

This is David's old red blood cells.

We're gonna save for research.

How do you sing?

It's a genetic disorder,

so in order to cure a genetic disorder,

you literally have to go in, and fix the gene.

We just didn't have the tools

to make that single letter change in a precise fashion.

- Even one letter? -Especially one letter.

Deoxyribonucleic acid, or DNA for short,

is the material that's the basis of life.

Each living thing has its unique DNA

that determines what that living thing will be:

plant or animal, man or muskrat.

If we understood the structure of genes,

the structure of chromosomes and how genes work,

then we might better be able to understand

and treat genetic diseases which occur in humans.

The work that Paul Berg did,

that was probably the beginning.

This dream of gene therapy

was born out of those 1970s experiments,

and we were still very far away from it,

but you'll see people talking about that hope right away.

The hope is that the isolation of the gene

will lead to treatment of people with muscular dystrophy.

Scientists are working on genetic cures

for diseases such as Alzheimer's and Parkinson's.

A, T, A, G, C...

The idea behind gene therapy is really simple:

add in a copy of the gene that works.

Then they'll make the protein that works, and then they won't be sick anymore.

But the devil, as is often the case, is in the details.

Right now, we have the ability to identify the gene, to isolate it,

but the ability to put it where we want it is still a long ways away.

If you put a gene into a cell, you cannot tell exactly where that gene

is going to enter the cell's chromosome.

Conventional gene therapy is an essentially random process.

So imagine taking this century-long narrative,

which is human DNA,

which is a very, very long text,

and taking one paragraph and just sticking it somewhere random.

The change you are creating is not a controlled one.

They've done it!

Professor Alain Fischer's team is the first in the world

to cure a human being using gene therapy.

This method has been one of medicine's best hopes

for the past fifteen years.

There was a clinical trial that was done in France.

This was for really sick children. I want to be clear.

This was for children who would have died otherwise.

Four of these children developed cancer.

One of them died.

The gene went into the wrong place

because it's a random process, and, by chance,

it went into the wrong place,

and that random event caused cancer.

You know, you always think that what you know

is gonna get a little better and a little better

and a little better and soon will be there,

and what we knew how to do

wasn't getting a whole lot better.

It was getting a little bit better.

The technology was just too clumsy

to actually use it with human beings.

It became very, very clear to us

that we are at the foot of a very tall mountain

and we may not even have the right mountaineering gear.

I worked at this company called Sangamo Biosciences.

We decided to figure out a way

to change human genes in a precise fashion.

You know, this would be like word processors for your DNA.

This will get technical but good technical.

DNA breaks all the time.

You go get a dental X-ray.

The technician points this thing at your face...

And the X-rays actually hit your DNA, and they physically create a break,

so that the familiar double helix of DNA physically goes...

The good news is,

the cell has its own machine to fixing breaks.

Inside our cells, there are two identical DNA molecules

lying side by side, literally side by side.

If one is broken, it can say to its sister--

and that, in fact, is the technical term-- the sister.

"Hey, sis, I'm sorry. I've had a break.

I'm wondering if I can copy the missing genetic information."

And the sister goes, "Yeah."

Done.

"Chromosome broken

awaits sounds of strands pairing,

preserving the life's thread."

There's really a haiku about homology directed repair.

Why is that useful? So it's useful because

if you can cut a gene inside a cell,

so if you can create a break at a place of interest,

then you can change that gene.

You fool the cell,

give it a separate piece of DNA that you have made,

a piece of DNA which is identical

to the chromosome that you are cutting

except for the change that you wish to make.

And Mother Nature will not know she's being fooled.

She will repair the break

using this piece of DNA you provided as a template,

and so whatever change you brought in