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I have a small goal this morning.

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You have given me
your 18 minutes of your time,

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and 18 minutes from now

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

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

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I'm a synthetic biologist.

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Being a synthetic biologist

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I'm dreaming about applying
the principles of biology

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

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

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I'm using American statistics
to illustrate this point.

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

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

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You may have already noticed

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that the most three common reasons to die

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are those infectious disease.

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

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As of today, the year 2010,

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

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

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that I grayed out here,
are infectious diseases.

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And those diseases,

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diphtheria or pneumonia
or tuberculosis,

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those infectious diseases
have essentially been eradicated

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thanks to the discovery
of antibiotics and vaccines.

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

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

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that the life expectancy,
average life expectancy,

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has increased from about 47 years
a hundred years ago

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to about 79 years as of today.

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

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they are difficult diseases:
cancers, cardiovascular disease.

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These are not caused by infection.

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These are caused by the breakdown
of internal systems.

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Cellular messaging systems
inside your body are breaking down,

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and that's when these diseases
start to occur.

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

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suicide, Alzheimer's, diabetes,

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these are lifestyle diseases.

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So these diseases are very
difficult to address,

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and possibly, if we manage
to cure these diseases,

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can we actually aim or desire
to live even longer?

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

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But more importantly,
the real important question is:

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

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what kind of living is it going to be?

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

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Is it going to be a smart living?

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Or what kind of life is it going to be?

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

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

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

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after about 100 years or so.

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This was discovered about 50 years ago

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

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In the laboratory he discovered

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that cells that make up our body

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actually stop dividing
after about 50 times.

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It was a very peculiar phenomenon.

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Why did they stop dividing and die?

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That means our physical limitations
are already imposed.

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We cannot live forever.

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And this mystery was partly solved

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when Elizabeth Blackburn
at U.C. San Francisco

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discovered that the tip of our chromosome,

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actually called a telomere,

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is getting shorter and shorter.

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Whenever cells divide it gets shorter.

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

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and that's when our body
starts to break down

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and we cannot live any longer.

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

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

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is not that simple.

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

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OK. To get to that discussion

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

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Just three points. OK?

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Our body is made up
with 37 trillion cells,

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give or take, 37 trillion cells.

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Point number two:

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

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and chromosomes are where
genetic material is stored.

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Remember that?

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

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We call them bases.

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They are A, T, G and C.

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Remember all this?

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OK. You're ready.

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

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made in the past few decades
in modern biology.

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

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

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who worked with Francis Crick,

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then a graduate student
at Cambridge University,

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

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

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And that was the first time,

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with this visual confirmation
of what DNA looks like,

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that people have been able to sort out

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how genes are transferred
from parents to children,

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how they are replicated

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

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

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

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

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

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and RNA is the messenger
to translate into a protein,

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and protein is the component

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that circulates within your body
to perform certain functions.

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And this central dogma is unshaken,

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

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The second major breakthrough discovery

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happened in 2000, about 10 years ago.

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It was a lucky case for Bill Clinton,

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it was towards the end
of his term in 2000,

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and two main scientists,

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Craig Venter on the left,
and then Francis Collins,

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they announced the completion
of the human genome.

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

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After this work

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

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And that's the blueprint we have.

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

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

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We all start out with a single embryo.

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You understand this, right?

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This single embryo goes
through the process of development.

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We call it development.

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

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there are number of developmental signals.

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The names are not important.

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Those are protein molecules
that go around in your body

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

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and that forms into a body.

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

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and it's a one-way street.

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So if something goes wrong
in your pancreas,

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you're going to have diabetic conditions.

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If your heart stops working

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

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And those are the barriers
we want to overcome.

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And the major technological discovery

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was made by a scientist
almost single-handedly

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- his name is Yamanaka
from Kyoto University -

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about 10 years ago.

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

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differentiated skin cells,

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and then induced a certain set of genes
called transcription factors

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by use of a virus,

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

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It's not exactly an embryo.

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

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

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go through the green arrow all over again,

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so that you now can have
possibly fresh new tissue.

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If you happen to have a bad heart,

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then you can possibly create
this Petra dish of cells,

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

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

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What's missing though
in this red arrow

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are the synthetic signals
that put this back on time,

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because nature has never intended

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

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

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

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

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Before I tell you about
the second major breakthrough,

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I prepared one slide to illustrate
AB204 highlighted in yellow.

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It mimics BMP2.

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

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Can we do better than Mother Nature?

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

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

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

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

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

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

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So, after three months
it remains like a hole.

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With BMP2 natural signals
soaked into a piece of sponge

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and put it on to that little 5mm hole,

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then after three months

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

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And you can see
X-ray photography underneath,

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so that you can see
a significant recovery.

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This is the synthetic signal
that I created,

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AB204 with a 0.1 microgram.

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

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and put it on to that hole,

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you can see a much better
recovery of the bone.

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Actually, it's too much.

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So probably you don't need even 0.1,

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you maybe be OK with even 0.01 microgram.

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

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

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by what Mother Nature intended for
through our genome.

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Now, the second technology.

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This is not my work
but this is very important.

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

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

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CRISPR is a piece of DNA
originally discovered by microbiologists.

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And by combining with this
bacterial protein called Cas

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a piece of RNA that works
as a guidance molecule,

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now we have a technology
that fixes, that changes,

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each of these 3 billion bases
one at a time.

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It's true.

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

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can be changed at any place you want.

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It never happened.
It was never possible.

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All these things happened
because of these breakthrough technologies

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that happened starting
from Watson and Crick's DNA structure

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and up until now.

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

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We typically have 30,000 genes,

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and 8,000 different kinds
of genetic disorders.

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

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because one base has changed.

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It's called mutations.

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It happens in cancer patients.

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When we discovered that,

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

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that's 3 billion base pairs long

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and fix them.

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

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

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It's made up with by four letters.

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

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

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and some people may even wish
to have different characters.

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I want something something,
and I want genetic changes,

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and this happened actually
four months ago by Chinese scientists.

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They reported for the first time

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

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so that the human genome
can be now edited.

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It's a very scary thought to some extent.

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Your gene can be edited.

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But it's coming.

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Combined with stem cell technology
that tracks back in time,

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you have a second chance to restart
your developmental process.

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

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

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you can click the change from A to G,

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and then backtrack
to all your embryonic state,

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00:15:17,534 --> 00:15:21,096
and restart your heart,
and you can have a new heart.

245
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Let me end my thoughts
with the following two slides.

246
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Now it's time to make some imaginations.

247
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100 years from now,
maybe 200 years from now,

248
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what kind of life would that be

249
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if our genes have been modified
to live longer?

250
00:15:40,366 --> 00:15:45,847
I already told you our genomes
are not designed to live long.

251
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It's already built to terminate
after about a 100 years,

252
00:15:48,843 --> 00:15:51,313
maybe 142 years or so.

253
00:15:51,313 --> 00:15:55,134
But with these new technologies
called stem cell technologies

254
00:15:55,134 --> 00:15:57,239
and gene-editing technologies,

255
00:15:57,239 --> 00:15:59,986
our life form will be somewhat different.

256
00:15:59,986 --> 00:16:02,332
It may not be our body, actually.

257
00:16:02,332 --> 00:16:07,444
It may be based on our genomes,
but it may not be our body anymore.

258
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What scares me even more is:

259
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What's the definition of me?

260
00:16:12,723 --> 00:16:15,954
Who am I? What am I?

261
00:16:15,954 --> 00:16:19,486
My body doesn't really define me anymore.

262
00:16:19,486 --> 00:16:22,017
It's the brain that goes on,

263
00:16:22,017 --> 00:16:24,461
and you already heard several times

264
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that the genetic framework

265
00:16:27,610 --> 00:16:32,022
that fills the thoughts
and the characters or behaviors

266
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are built in the brain circuitry.

267
00:16:34,824 --> 00:16:37,884
And the physical framework
of that brain circuitry

268
00:16:37,903 --> 00:16:41,677
is actually written out
in the form of genes.

269
00:16:41,677 --> 00:16:49,662
So this scary thought was the theme
of a [1997] movie, the title is "Gattaca."

270
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Ironically, this spells G-A-T-T-A-C-A.

271
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I think director meant it that way.

272
00:16:55,691 --> 00:17:00,287
And in this movie, the director
wanted to say something like this:

273
00:17:00,379 --> 00:17:02,598
He raised the question

274
00:17:02,598 --> 00:17:08,169
can our will play a part in deciding
our fate beyond our genes.

275
00:17:08,169 --> 00:17:13,670
In this movie Ethan Hawke is born
to be a second-class citizen,

276
00:17:13,670 --> 00:17:15,974
and then Uma Thurman was born

277
00:17:15,979 --> 00:17:21,138
and her gene was engineered
to become an upper-class citizen,

278
00:17:21,150 --> 00:17:22,934
and he fell in love with her,

279
00:17:22,961 --> 00:17:28,542
and he overcame this genetic barrier
by the power of love.

280
00:17:28,542 --> 00:17:34,179
I don't fully understand if it's going
to be the most sensible solution to this.

281
00:17:34,179 --> 00:17:40,078
But to some extent I share the thoughts

282
00:17:40,106 --> 00:17:46,562
that in a not-too-far-distant future
we will face a very profound question.

283
00:17:46,562 --> 00:17:48,293
What am I?

284
00:17:48,293 --> 00:17:54,694
In fact, even as of now, my body
consists of 37 trillion cells, I told you,

285
00:17:54,716 --> 00:17:59,086
but it also contains
more than 100 trillion bacterial cells,

286
00:17:59,106 --> 00:18:00,949
in your guts, on your skin.

287
00:18:00,968 --> 00:18:06,712
So in a nutshell,
I'm 30% human and 70% bacteria.

288
00:18:07,544 --> 00:18:10,633
It's true.
So that's not really me.

289
00:18:10,633 --> 00:18:14,029
What if we start to change
those body parts

290
00:18:14,029 --> 00:18:17,771
using stem cell technologies
and CRISPR technology?

291
00:18:17,771 --> 00:18:23,623
Our body parts will be derived
from those synthetic materials.

292
00:18:23,623 --> 00:18:25,290
Is that me?

293
00:18:25,290 --> 00:18:29,206
Now the even scarier thoughts
are of artificial intelligence,

294
00:18:29,206 --> 00:18:32,466
when our brain activity is aided or fused

295
00:18:32,466 --> 00:18:37,195
to circuitry aided by computer chips
and algorithms.

296
00:18:37,195 --> 00:18:39,425
How much is me?

297
00:18:39,425 --> 00:18:43,277
And that's a really difficult question
to address in a simple way.

298
00:18:43,277 --> 00:18:47,590
But at least I think I gave you
a right question to ponder on.

299
00:18:47,590 --> 00:18:50,449
And this is my thought.
This is my solution.

300
00:18:50,449 --> 00:18:53,444
I am not really defined by my body.

301
00:18:53,444 --> 00:18:58,641
I am defined by the networks and impacts
I make on my neighbors and friends.

302
00:18:58,641 --> 00:19:02,556
So thank you for being
my friends and neighbors in my lifetime,

303
00:19:02,556 --> 00:19:04,682
and I appreciate your attention.

304
00:19:04,682 --> 00:19:06,859
Thank you very much.