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)