What kills us? | Senyon Choe | TEDxKFAS

Our genome is designed so our bodies break down after about a century. Synthetic biologist Dr. Senyon Choe highlights major discoveries in modern biology like stem cell therapy and CRISPR technology that may hold the answer to living longer, curing birth defects, and editing the human genome. He also discusses his work with synthetic signals which possess the potential to surpass the limitations set by nature.

This talk was given at a TEDx event using the TED conference format but independently organized by a local community.

Learn more at http://tedxkfas.com

I have a small goal this morning.

You have given me
your 18 minutes of your time,

and 18 minutes from now

I'm going to make you a little wiser,
a little smarter than now.

I'm going to share my thoughts
and wisdoms from my scientific activity.

I'm a synthetic biologist.

Being a synthetic biologist

I'm dreaming about applying
the principles of biology

to create synthetic signals in the body
or synthetic life forms.

Let me start off by telling you
what is actually killing us.

I'm using American statistics
to illustrate this point.

What's shown here are the cause of death
before you naturally die.

And you can see a number of things
that you're familiar with.

You may have already noticed

that the most three common reasons to die

are those infectious disease.

This is the data from 1900,
about a hundred years ago.

As of today, the year 2010,

you can see a different list
of cause of death here,

and you may have already noticed
that those diseases that you noticed,

that I grayed out here,
are infectious diseases.

And those diseases,

diphtheria or pneumonia
or tuberculosis,

those infectious diseases
have essentially been eradicated

thanks to the discovery
of antibiotics and vaccines.

And this is a remarkable achievement
by medical doctors and the drug industry.

Actually, it happened for the first time
in the human industry

that the life expectancy,
average life expectancy,

has increased from about 47 years
a hundred years ago

to about 79 years as of today.

Now, if you look at the list of things
that are killing us today,

they are difficult diseases:
cancers, cardiovascular disease.

These are not caused by infection.

These are caused by the breakdown
of internal systems.

Cellular messaging systems
inside your body are breaking down,

and that's when these diseases
start to occur.

And a couple of other diseases
that you notice are underlined in red:

suicide, Alzheimer's, diabetes,

these are lifestyle diseases.

So these diseases are very
difficult to address,

and possibly, if we manage
to cure these diseases,

can we actually aim or desire
to live even longer?

Have you actually thought about living
longer to 150 years or more?

But more importantly,
the real important question is:

If you were given 150 years or 200 years
or as long as you want,

what kind of living is it going to be?

And that's the topic
that I'm going to talk about today.

Is it going to be a smart living?

Or what kind of life is it going to be?

And a lot of things are happening
these days in biological field,

and I'm going to highlight that
this living longer is not a simple task.

Actually, we, our genome,
is already designed to terminate our body

after about 100 years or so.

This was discovered about 50 years ago

by a scientist, Leonard Hayflick,
at the University of Pennsylvania.

In the laboratory he discovered

that cells that make up our body

actually stop dividing
after about 50 times.

It was a very peculiar phenomenon.

Why did they stop dividing and die?

That means our physical limitations
are already imposed.

We cannot live forever.

And this mystery was partly solved

when Elizabeth Blackburn
at U.C. San Francisco

discovered that the tip of our chromosome,

actually called a telomere,

is getting shorter and shorter.

Whenever cells divide it gets shorter.

So, after about 50 cell divisions,
you have no more telomere left,

and that's when our body
starts to break down

and we cannot live any longer.

So the challenge you may have hoped for
a couple of minutes ago,

that you may be able
to live 300 years or longer,

is not that simple.

It's not going to happen
unless we do something about it.

OK. To get to that discussion

I'm going to remind you of three points
from your high school biology.

Just three points. OK?

Our body is made up
with 37 trillion cells,

give or take, 37 trillion cells.

Point number two:

Each cell that makes up our body
contains 23 pairs of chromosomes,

and chromosomes are where
genetic material is stored.

Remember that?

And each of this DNA is made up
with only four kinds of compounds.

We call them bases.

They are A, T, G and C.

Remember all this?

OK. You're ready.

OK. I'm going to highlight
only two major breakthrough discoveries

made in the past few decades
in modern biology.

In my mind, it was
the turning point for modern biology

when James Watson, American postdoc
who went to Cambridge University,

who worked with Francis Crick,

then a graduate student
at Cambridge University,

when they together worked out
a three-dimensional structure of DNA.

DNA is made up with the two spirals
as you can see in the slides.

And that was the first time,

with this visual confirmation
of what DNA looks like,

that people have been able to sort out

how genes are transferred
from parents to children,

how they are replicated

and how our characters are copied
from one generation to another.

Actually biology, for the first time
faced a solid principle.

In biology it's very hard
to find a principle.

This is the principle that all life
forms on Earth rely on.

DNA is the blueprint of our life
that transcribes into RNA,

and RNA is the messenger
to translate into a protein,

and protein is the component

that circulates within your body
to perform certain functions.

And this central dogma is unshaken,

and it's going to be
the principle of life.

The second major breakthrough discovery

happened in 2000, about 10 years ago.

It was a lucky case for Bill Clinton,

it was towards the end
of his term in 2000,

and two main scientists,

Craig Venter on the left,
and then Francis Collins,

they announced the completion
of the human genome.

Before then, we didn't really know
for sure what we are made up with.

After this work

we now know we are made up with
3 billion base pairs of A, T, G and C.

And that's the blueprint we have.

That's what we're going to deal with
to make smarter living.

This is what happens during the process
of what we call development.

We all start out with a single embryo.

You understand this, right?

This single embryo goes
through the process of development.

We call it development.

Through this process
to turn into a tissue and a body,

there are number of developmental signals.

The names are not important.

Those are protein molecules
that go around in your body

to tell the cell to turn into
a heart or pancreas or skin

and that forms into a body.

And this green arrow is unfortunately
designed and blueprinted in your genome,

and it's a one-way street.

So if something goes wrong
in your pancreas,

you're going to have diabetic conditions.

If your heart stops working

then you will have a heart disease
and skin problems, things like that.

And those are the barriers
we want to overcome.

And the major technological discovery

was made by a scientist
almost single-handedly

- his name is Yamanaka
from Kyoto University -

about 10 years ago.

And he was able to take
one of these skin cells,

differentiated skin cells,

and then induced a certain set of genes
called transcription factors

by use of a virus,

and then made them
into almost like embryo-like cells.

It's not exactly an embryo.

It's cells in a Petri dish,
but it works like an embryo,

so that you have a second chance
to restart this engine,

go through the green arrow all over again,

so that you now can have
possibly fresh new tissue.

If you happen to have a bad heart,

then you can possibly create
this Petra dish of cells,

and then differentiate back to a fresh
new heart and put it back in your body.

Now that's something we can use
to make this longer, smart living.

What's missing though
in this red arrow

are the synthetic signals
that put this back on time,

because nature has never intended

to dedifferentiate back from skin cells
back to embryo-like cells.

So these synthetic signals are something
that never existed in nature,

and that's when my research
got really kicked in.

I was interested in attempting
to see something we can do.

Before I tell you about
the second major breakthrough,

I prepared one slide to illustrate
AB204 highlighted in yellow.

It mimics BMP2.

BMP2 is a natural signal
that tells the cell to turn into bone.

Can we do better than Mother Nature?

And that technology is the first
technology that I just told you about.

Here's the bone,
the top of the skull of a mouse.

We made a little hole,
about 5mm diameter hole,

and if the hole is too big,
they don't fuse back.

If you have a little crack,
they generally fuse back,

but the adult bones are not that good
in repairing themselves.

So, after three months
it remains like a hole.

With BMP2 natural signals
soaked into a piece of sponge

and put it on to that little 5mm hole,

then after three months

you can see the big part of that hole
has been sealed back.

And you can see
X-ray photography underneath,

so that you can see
a significant recovery.

This is the synthetic signal
that I created,

AB204 with a 0.1 microgram.

You notice it's a one-tenth of material
soaked in the same piece of sponge,

and put it on to that hole,

you can see a much better
recovery of the bone.

Actually, it's too much.

So probably you don't need even 0.1,

you maybe be OK with even 0.01 microgram.

So synthetic signals that do better
than Mother Nature are a possible thought.

And I think people can realize
that we are not really bound

by what Mother Nature intended for
through our genome.

Now, the second technology.

This is not my work
but this is very important.

If you haven't heard about this,
you should know this.

It's pronounced as "crisper."
[IPA: krɪspə]

CRISPR is a piece of DNA
originally discovered by microbiologists.

And by combining with this
bacterial protein called Cas

a piece of RNA that works
as a guidance molecule,

now we have a technology
that fixes, that changes,

each of these 3 billion bases
one at a time.

It's true.

Your gene that's made up
with 3 billion base pairs

can be changed at any place you want.

It never happened.
It was never possible.

All these things happened
because of these breakthrough technologies

that happened starting
from Watson and Crick's DNA structure

and up until now.

What it means is it's great news for those
who are born with a birth defect.

We typically have 30,000 genes,

and 8,000 different kinds
of genetic disorders.

You know some people are born
with defects in a certain enzyme

because one base has changed.

It's called mutations.

It happens in cancer patients.

When we discovered that,

we can zoom into that one particular
base on the DNA strand

that's 3 billion base pairs long

and fix them.

Changing from either A, T, G and C
to one of those right base.

The alphabets of this genome is
as simple as that: A, T, G and C.

It's made up with by four letters.

So if we do this to a human,
it's a fantastic news.

We can actually change those genetic
defects that you're born with,

and some people may even wish
to have different characters.

I want something something,
and I want genetic changes,

and this happened actually
four months ago by Chinese scientists.

They reported for the first time

that this CRISPR-mediated technology
was used on a human embryo

so that the human genome
can be now edited.

It's a very scary thought to some extent.

Your gene can be edited.

But it's coming.

Combined with stem cell technology
that tracks back in time,

you have a second chance to restart
your developmental process.

Now, you have a second technology
that fixes or changes those genes.

Even if you're born with A
and you're an adult,

you can click the change from A to G,

and then backtrack
to all your embryonic state,

and restart your heart,
and you can have a new heart.

Let me end my thoughts
with the following two slides.

Now it's time to make some imaginations.

100 years from now,
maybe 200 years from now,

what kind of life would that be

if our genes have been modified
to live longer?

I already told you our genomes
are not designed to live long.

It's already built to terminate
after about a 100 years,

maybe 142 years or so.

But with these new technologies
called stem cell technologies

and gene-editing technologies,

our life form will be somewhat different.

It may not be our body, actually.

It may be based on our genomes,
but it may not be our body anymore.

What scares me even more is:

What's the definition of me?

Who am I? What am I?

My body doesn't really define me anymore.

It's the brain that goes on,

and you already heard several times

that the genetic framework

that fills the thoughts
and the characters or behaviors

are built in the brain circuitry.

And the physical framework
of that brain circuitry

is actually written out
in the form of genes.

So this scary thought was the theme
of a [1997] movie, the title is "Gattaca."

Ironically, this spells G-A-T-T-A-C-A.

I think director meant it that way.

And in this movie, the director
wanted to say something like this:

He raised the question

can our will play a part in deciding
our fate beyond our genes.

In this movie Ethan Hawke is born
to be a second-class citizen,

and then Uma Thurman was born

and her gene was engineered
to become an upper-class citizen,

and he fell in love with her,

and he overcame this genetic barrier
by the power of love.

I don't fully understand if it's going
to be the most sensible solution to this.

But to some extent I share the thoughts

that in a not-too-far-distant future
we will face a very profound question.

What am I?

In fact, even as of now, my body
consists of 37 trillion cells, I told you,

but it also contains
more than 100 trillion bacterial cells,

in your guts, on your skin.

So in a nutshell,
I'm 30% human and 70% bacteria.

It's true.
So that's not really me.

What if we start to change
those body parts

using stem cell technologies
and CRISPR technology?

Our body parts will be derived
from those synthetic materials.

Is that me?

Now the even scarier thoughts
are of artificial intelligence,

when our brain activity is aided or fused

to circuitry aided by computer chips
and algorithms.

How much is me?

And that's a really difficult question
to address in a simple way.

But at least I think I gave you
a right question to ponder on.

And this is my thought.
This is my solution.

I am not really defined by my body.

I am defined by the networks and impacts
I make on my neighbors and friends.

So thank you for being
my friends and neighbors in my lifetime,

and I appreciate your attention.

Thank you very much.

(Applause)