0:00:14.996,0:00:17.491
I have a small goal this morning.

0:00:17.491,0:00:20.689
You have given me[br]your 18 minutes of your time,

0:00:20.697,0:00:22.434
and 18 minutes from now

0:00:22.448,0:00:26.897
I'm going to make you a little wiser,[br]a little smarter than now.

0:00:26.897,0:00:31.935
I'm going to share my thoughts[br]and wisdoms from my scientific activity.

0:00:32.555,0:00:35.915
I'm a synthetic biologist.

0:00:35.915,0:00:37.582
Being a synthetic biologist

0:00:37.582,0:00:42.310
I'm dreaming about applying[br]the principles of biology

0:00:42.310,0:00:49.343
to create synthetic signals in the body[br]or synthetic life forms.

0:00:49.628,0:00:57.215
Let me start off by telling you[br]what is actually killing us.

0:00:58.588,0:01:03.579
I'm using American statistics[br]to illustrate this point.

0:01:03.579,0:01:08.611
What's shown here are the cause of death[br]before you naturally die.

0:01:08.611,0:01:13.100
And you can see a number of things[br]that you're familiar with.

0:01:13.100,0:01:15.186
You may have already noticed

0:01:15.186,0:01:19.166
that the most three common reasons to die

0:01:19.166,0:01:21.840
are those infectious disease.

0:01:21.840,0:01:26.391
This is the data from 1900,[br]about a hundred years ago.

0:01:26.391,0:01:29.490
As of today, the year 2010,

0:01:29.490,0:01:33.605
you can see a different list[br]of cause of death here,

0:01:33.605,0:01:38.705
and you may have already noticed[br]that those diseases that you noticed,

0:01:38.705,0:01:44.530
that I grayed out here,[br]are infectious diseases.

0:01:44.530,0:01:46.030
And those diseases,

0:01:46.030,0:01:50.998
diphtheria or pneumonia[br]or tuberculosis,

0:01:50.998,0:01:55.082
those infectious diseases[br]have essentially been eradicated

0:01:55.082,0:02:00.210
thanks to the discovery[br]of antibiotics and vaccines.

0:02:00.210,0:02:05.155
And this is a remarkable achievement[br]by medical doctors and the drug industry.

0:02:05.155,0:02:08.578
Actually, it happened for the first time[br]in the human industry

0:02:08.578,0:02:13.126
that the life expectancy,[br]average life expectancy,

0:02:13.133,0:02:17.903
has increased from about 47 years[br]a hundred years ago

0:02:17.903,0:02:22.139
to about 79 years as of today.

0:02:22.139,0:02:26.744
Now, if you look at the list of things[br]that are killing us today,

0:02:26.744,0:02:31.221
they are difficult diseases:[br]cancers, cardiovascular disease.

0:02:31.248,0:02:34.343
These are not caused by infection.

0:02:34.343,0:02:38.202
These are caused by the breakdown[br]of internal systems.

0:02:38.202,0:02:44.970
Cellular messaging systems[br]inside your body are breaking down,

0:02:44.987,0:02:49.385
and that's when these diseases[br]start to occur.

0:02:49.423,0:02:54.348
And a couple of other diseases[br]that you notice are underlined in red:

0:02:54.400,0:02:57.463
suicide, Alzheimer's, diabetes,

0:02:57.463,0:03:00.278
these are lifestyle diseases.

0:03:00.278,0:03:03.136
So these diseases are very[br]difficult to address,

0:03:03.136,0:03:08.491
and possibly, if we manage[br]to cure these diseases,

0:03:08.491,0:03:13.058
can we actually aim or desire[br]to live even longer?

0:03:13.058,0:03:17.697
Have you actually thought about living[br]longer to 150 years or more?

0:03:19.252,0:03:22.758
But more importantly,[br]the real important question is:

0:03:22.758,0:03:29.019
If you were given 150 years or 200 years[br]or as long as you want,

0:03:29.019,0:03:31.630
what kind of living is it going to be?

0:03:31.630,0:03:34.922
And that's the topic[br]that I'm going to talk about today.

0:03:34.922,0:03:37.423
Is it going to be a smart living?

0:03:37.423,0:03:40.118
Or what kind of life is it going to be?

0:03:40.118,0:03:45.703
And a lot of things are happening[br]these days in biological field,

0:03:45.703,0:03:51.376
and I'm going to highlight that[br]this living longer is not a simple task.

0:03:51.484,0:03:57.254
Actually, we, our genome,[br]is already designed to terminate our body

0:03:57.254,0:03:59.817
after about 100 years or so.

0:03:59.817,0:04:02.016
This was discovered about 50 years ago

0:04:02.016,0:04:06.270
by a scientist, Leonard Hayflick,[br]at the University of Pennsylvania.

0:04:06.270,0:04:08.389
In the laboratory he discovered

0:04:08.389,0:04:10.774
that cells that make up our body

0:04:10.774,0:04:15.274
actually stop dividing[br]after about 50 times.

0:04:15.274,0:04:18.130
It was a very peculiar phenomenon.

0:04:18.130,0:04:21.682
Why did they stop dividing and die?

0:04:21.682,0:04:24.876
That means our physical limitations[br]are already imposed.

0:04:24.876,0:04:26.958
We cannot live forever.

0:04:26.958,0:04:29.782
And this mystery was partly solved

0:04:29.782,0:04:33.842
when Elizabeth Blackburn[br]at U.C. San Francisco

0:04:33.854,0:04:37.270
discovered that the tip of our chromosome,

0:04:37.270,0:04:39.333
actually called a telomere,

0:04:39.333,0:04:42.255
is getting shorter and shorter.

0:04:42.255,0:04:44.601
Whenever cells divide it gets shorter.

0:04:44.616,0:04:49.148
So, after about 50 cell divisions,[br]you have no more telomere left,

0:04:49.211,0:04:52.509
and that's when our body[br]starts to break down

0:04:52.528,0:04:55.629
and we cannot live any longer.

0:04:55.665,0:05:00.011
So the challenge you may have hoped for[br]a couple of minutes ago,

0:05:00.011,0:05:03.230
that you may be able[br]to live 300 years or longer,

0:05:03.230,0:05:04.729
is not that simple.

0:05:04.729,0:05:08.011
It's not going to happen[br]unless we do something about it.

0:05:09.731,0:05:12.260
OK. To get to that discussion

0:05:12.260,0:05:16.229
I'm going to remind you of three points[br]from your high school biology.

0:05:16.260,0:05:18.163
Just three points. OK?

0:05:18.163,0:05:22.672
Our body is made up[br]with 37 trillion cells,

0:05:22.672,0:05:25.672
give or take, 37 trillion cells.

0:05:25.672,0:05:27.080
Point number two:

0:05:27.080,0:05:33.402
Each cell that makes up our body[br]contains 23 pairs of chromosomes,

0:05:33.402,0:05:36.932
and chromosomes are where[br]genetic material is stored.

0:05:36.932,0:05:38.643
Remember that?

0:05:38.687,0:05:44.871
And each of this DNA is made up[br]with only four kinds of compounds.

0:05:44.871,0:05:46.638
We call them bases.

0:05:46.651,0:05:50.538
They are A, T, G and C.

0:05:50.547,0:05:52.097
Remember all this?

0:05:52.115,0:05:54.058
OK. You're ready.

0:05:54.058,0:05:58.423
OK. I'm going to highlight[br]only two major breakthrough discoveries

0:05:58.423,0:06:02.272
made in the past few decades[br]in modern biology.

0:06:02.276,0:06:06.141
In my mind, it was[br]the turning point for modern biology

0:06:06.141,0:06:11.555
when James Watson, American postdoc[br]who went to Cambridge University,

0:06:11.555,0:06:14.055
who worked with Francis Crick,

0:06:14.055,0:06:17.055
then a graduate student[br]at Cambridge University,

0:06:17.055,0:06:22.636
when they together worked out[br]a three-dimensional structure of DNA.

0:06:24.236,0:06:28.425
DNA is made up with the two spirals[br]as you can see in the slides.

0:06:28.466,0:06:30.119
And that was the first time,

0:06:30.136,0:06:34.045
with this visual confirmation[br]of what DNA looks like,

0:06:34.069,0:06:37.100
that people have been able to sort out

0:06:37.100,0:06:40.940
how genes are transferred[br]from parents to children,

0:06:40.940,0:06:42.329
how they are replicated

0:06:42.329,0:06:47.798
and how our characters are copied[br]from one generation to another.

0:06:47.822,0:06:53.496
Actually biology, for the first time[br]faced a solid principle.

0:06:53.700,0:06:56.430
In biology it's very hard[br]to find a principle.

0:06:56.430,0:07:01.869
This is the principle that all life[br]forms on Earth rely on.

0:07:01.895,0:07:07.444
DNA is the blueprint of our life[br]that transcribes into RNA,

0:07:07.452,0:07:11.170
and RNA is the messenger[br]to translate into a protein,

0:07:11.170,0:07:12.921
and protein is the component

0:07:12.921,0:07:17.212
that circulates within your body[br]to perform certain functions.

0:07:17.212,0:07:20.444
And this central dogma is unshaken,

0:07:20.444,0:07:23.460
and it's going to be[br]the principle of life.

0:07:23.482,0:07:26.512
The second major breakthrough discovery

0:07:26.530,0:07:30.219
happened in 2000, about 10 years ago.

0:07:30.219,0:07:32.949
It was a lucky case for Bill Clinton,

0:07:32.949,0:07:35.624
it was towards the end[br]of his term in 2000,

0:07:35.624,0:07:38.837
and two main scientists,

0:07:38.837,0:07:41.438
Craig Venter on the left,[br]and then Francis Collins,

0:07:41.438,0:07:45.417
they announced the completion[br]of the human genome.

0:07:45.417,0:07:49.239
Before then, we didn't really know[br]for sure what we are made up with.

0:07:49.239,0:07:50.721
After this work

0:07:50.737,0:07:57.030
we now know we are made up with[br]3 billion base pairs of A, T, G and C.

0:07:57.030,0:07:59.769
And that's the blueprint we have.

0:07:59.769,0:08:04.623
That's what we're going to deal with[br]to make smarter living.

0:08:04.623,0:08:08.400
This is what happens during the process[br]of what we call development.

0:08:08.400,0:08:11.650
We all start out with a single embryo.

0:08:11.650,0:08:13.278
You understand this, right?

0:08:13.278,0:08:17.011
This single embryo goes[br]through the process of development.

0:08:17.011,0:08:18.544
We call it development.

0:08:18.544,0:08:21.654
Through this process[br]to turn into a tissue and a body,

0:08:21.654,0:08:24.182
there are number of developmental signals.

0:08:24.190,0:08:25.819
The names are not important.

0:08:25.819,0:08:29.266
Those are protein molecules[br]that go around in your body

0:08:29.266,0:08:34.289
to tell the cell to turn into[br]a heart or pancreas or skin

0:08:34.289,0:08:36.313
and that forms into a body.

0:08:36.323,0:08:43.799
And this green arrow is unfortunately[br]designed and blueprinted in your genome,

0:08:43.823,0:08:46.134
and it's a one-way street.

0:08:46.211,0:08:49.255
So if something goes wrong[br]in your pancreas,

0:08:49.311,0:08:51.511
you're going to have diabetic conditions.

0:08:51.549,0:08:53.534
If your heart stops working

0:08:53.569,0:08:57.500
then you will have a heart disease[br]and skin problems, things like that.

0:08:57.514,0:09:00.451
And those are the barriers[br]we want to overcome.

0:09:00.451,0:09:06.632
And the major technological discovery

0:09:06.667,0:09:10.865
was made by a scientist[br]almost single-handedly

0:09:10.865,0:09:13.761
- his name is Yamanaka[br]from Kyoto University -

0:09:13.761,0:09:15.699
about 10 years ago.

0:09:15.699,0:09:19.352
And he was able to take[br]one of these skin cells,

0:09:19.352,0:09:21.935
differentiated skin cells,

0:09:21.935,0:09:26.782
and then induced a certain set of genes[br]called transcription factors

0:09:26.782,0:09:28.669
by use of a virus,

0:09:28.669,0:09:33.542
and then made them[br]into almost like embryo-like cells.

0:09:33.542,0:09:35.041
It's not exactly an embryo.

0:09:35.041,0:09:38.832
It's cells in a Petri dish,[br]but it works like an embryo,

0:09:38.832,0:09:42.123
so that you have a second chance[br]to restart this engine,

0:09:42.123,0:09:45.864
go through the green arrow all over again,

0:09:45.864,0:09:50.322
so that you now can have[br]possibly fresh new tissue.

0:09:50.322,0:09:52.407
If you happen to have a bad heart,

0:09:52.417,0:09:56.762
then you can possibly create[br]this Petra dish of cells,

0:09:56.785,0:10:02.373
and then differentiate back to a fresh[br]new heart and put it back in your body.

0:10:02.373,0:10:07.904
Now that's something we can use[br]to make this longer, smart living.

0:10:07.904,0:10:10.395
What's missing though[br]in this red arrow

0:10:10.395,0:10:15.665
are the synthetic signals[br]that put this back on time,

0:10:15.665,0:10:18.349
because nature has never intended

0:10:18.364,0:10:25.483
to dedifferentiate back from skin cells[br]back to embryo-like cells.

0:10:25.483,0:10:29.682
So these synthetic signals are something[br]that never existed in nature,

0:10:29.682,0:10:32.421
and that's when my research[br]got really kicked in.

0:10:32.421,0:10:36.065
I was interested in attempting[br]to see something we can do.

0:10:36.065,0:10:38.940
Before I tell you about[br]the second major breakthrough,

0:10:38.940,0:10:44.039
I prepared one slide to illustrate[br]AB204 highlighted in yellow.

0:10:44.039,0:10:46.138
It mimics BMP2.

0:10:46.138,0:10:51.199
BMP2 is a natural signal[br]that tells the cell to turn into bone.

0:10:51.199,0:10:54.053
Can we do better than Mother Nature?

0:10:54.053,0:10:58.612
And that technology is the first[br]technology that I just told you about.

0:10:58.677,0:11:02.572
Here's the bone,[br]the top of the skull of a mouse.

0:11:02.572,0:11:07.427
We made a little hole,[br]about 5mm diameter hole,

0:11:07.427,0:11:10.820
and if the hole is too big,[br]they don't fuse back.

0:11:10.820,0:11:13.585
If you have a little crack,[br]they generally fuse back,

0:11:13.585,0:11:17.965
but the adult bones are not that good[br]in repairing themselves.

0:11:17.965,0:11:20.969
So, after three months[br]it remains like a hole.

0:11:20.969,0:11:25.830
With BMP2 natural signals[br]soaked into a piece of sponge

0:11:25.830,0:11:28.772
and put it on to that little 5mm hole,

0:11:28.788,0:11:30.450
then after three months

0:11:30.476,0:11:34.366
you can see the big part of that hole[br]has been sealed back.

0:11:34.381,0:11:36.834
And you can see[br]X-ray photography underneath,

0:11:36.855,0:11:39.671
so that you can see[br]a significant recovery.

0:11:39.671,0:11:42.562
This is the synthetic signal[br]that I created,

0:11:42.590,0:11:46.187
AB204 with a 0.1 microgram.

0:11:46.200,0:11:51.390
You notice it's a one-tenth of material[br]soaked in the same piece of sponge,

0:11:51.390,0:11:53.244
and put it on to that hole,

0:11:53.244,0:11:56.534
you can see a much better[br]recovery of the bone.

0:11:56.534,0:11:58.244
Actually, it's too much.

0:11:58.244,0:12:00.410
So probably you don't need even 0.1,

0:12:00.410,0:12:05.772
you maybe be OK with even 0.01 microgram.

0:12:05.772,0:12:12.522
So synthetic signals that do better[br]than Mother Nature are a possible thought.

0:12:12.522,0:12:17.462
And I think people can realize[br]that we are not really bound

0:12:17.462,0:12:22.482
by what Mother Nature intended for[br]through our genome.

0:12:22.482,0:12:24.544
Now, the second technology.

0:12:24.544,0:12:26.916
This is not my work[br]but this is very important.

0:12:26.916,0:12:29.539
If you haven't heard about this,[br]you should know this.

0:12:29.539,0:12:31.959
It's pronounced as "crisper."[br][IPA: krɪspə]

0:12:31.959,0:12:37.533
CRISPR is a piece of DNA[br]originally discovered by microbiologists.

0:12:37.533,0:12:44.593
And by combining with this[br]bacterial protein called Cas

0:12:44.593,0:12:48.414
a piece of RNA that works[br]as a guidance molecule,

0:12:48.414,0:12:53.496
now we have a technology[br]that fixes, that changes,

0:12:53.513,0:12:57.195
each of these 3 billion bases[br]one at a time.

0:12:57.248,0:12:58.565
It's true.

0:12:58.633,0:13:01.665
Your gene that's made up[br]with 3 billion base pairs

0:13:01.665,0:13:06.076
can be changed at any place you want.

0:13:06.076,0:13:08.559
It never happened.[br]It was never possible.

0:13:08.559,0:13:13.021
All these things happened[br]because of these breakthrough technologies

0:13:13.021,0:13:15.911
that happened starting[br]from Watson and Crick's DNA structure

0:13:15.911,0:13:18.381
and up until now.

0:13:18.381,0:13:23.424
What it means is it's great news for those[br]who are born with a birth defect.

0:13:23.475,0:13:29.217
We typically have 30,000 genes,

0:13:29.217,0:13:32.681
and 8,000 different kinds[br]of genetic disorders.

0:13:32.681,0:13:37.004
You know some people are born[br]with defects in a certain enzyme

0:13:37.004,0:13:39.324
because one base has changed.

0:13:39.324,0:13:40.732
It's called mutations.

0:13:40.732,0:13:42.429
It happens in cancer patients.

0:13:42.429,0:13:44.823
When we discovered that,

0:13:44.823,0:13:49.679
we can zoom into that one particular[br]base on the DNA strand

0:13:49.679,0:13:52.044
that's 3 billion base pairs long

0:13:52.044,0:13:53.396
and fix them.

0:13:53.396,0:13:59.273
Changing from either A, T, G and C[br]to one of those right base.

0:13:59.273,0:14:05.416
The alphabets of this genome is[br]as simple as that: A, T, G and C.

0:14:05.416,0:14:08.262
It's made up with by four letters.

0:14:08.262,0:14:13.250
So if we do this to a human,[br]it's a fantastic news.

0:14:13.250,0:14:17.896
We can actually change those genetic[br]defects that you're born with,

0:14:17.896,0:14:22.758
and some people may even wish[br]to have different characters.

0:14:22.786,0:14:26.654
I want something something,[br]and I want genetic changes,

0:14:26.654,0:14:30.624
and this happened actually[br]four months ago by Chinese scientists.

0:14:30.624,0:14:32.477
They reported for the first time

0:14:32.477,0:14:37.550
that this CRISPR-mediated technology[br]was used on a human embryo

0:14:37.550,0:14:40.779
so that the human genome[br]can be now edited.

0:14:40.779,0:14:45.360
It's a very scary thought to some extent.

0:14:45.360,0:14:47.443
Your gene can be edited.

0:14:47.443,0:14:50.239
But it's coming.

0:14:50.239,0:14:56.432
Combined with stem cell technology[br]that tracks back in time,

0:14:56.432,0:15:01.224
you have a second chance to restart[br]your developmental process.

0:15:01.224,0:15:06.545
Now, you have a second technology[br]that fixes or changes those genes.

0:15:06.545,0:15:11.214
Even if you're born with A[br]and you're an adult,

0:15:11.224,0:15:13.979
you can click the change from A to G,

0:15:13.986,0:15:17.534
and then backtrack[br]to all your embryonic state,

0:15:17.534,0:15:21.096
and restart your heart,[br]and you can have a new heart.

0:15:21.096,0:15:26.139
Let me end my thoughts[br]with the following two slides.

0:15:26.139,0:15:29.822
Now it's time to make some imaginations.

0:15:29.847,0:15:33.202
100 years from now,[br]maybe 200 years from now,

0:15:33.230,0:15:35.679
what kind of life would that be

0:15:35.679,0:15:40.366
if our genes have been modified[br]to live longer?

0:15:40.366,0:15:45.847
I already told you our genomes[br]are not designed to live long.

0:15:45.847,0:15:48.843
It's already built to terminate[br]after about a 100 years,

0:15:48.843,0:15:51.313
maybe 142 years or so.

0:15:51.313,0:15:55.134
But with these new technologies[br]called stem cell technologies

0:15:55.134,0:15:57.239
and gene-editing technologies,

0:15:57.239,0:15:59.986
our life form will be somewhat different.

0:15:59.986,0:16:02.332
It may not be our body, actually.

0:16:02.332,0:16:07.444
It may be based on our genomes,[br]but it may not be our body anymore.

0:16:07.444,0:16:09.679
What scares me even more is:

0:16:09.679,0:16:12.723
What's the definition of me?

0:16:12.723,0:16:15.954
Who am I? What am I?

0:16:15.954,0:16:19.486
My body doesn't really define me anymore.

0:16:19.486,0:16:22.017
It's the brain that goes on,

0:16:22.017,0:16:24.461
and you already heard several times

0:16:24.461,0:16:27.597
that the genetic framework

0:16:27.610,0:16:32.022
that fills the thoughts[br]and the characters or behaviors

0:16:32.053,0:16:34.818
are built in the brain circuitry.

0:16:34.824,0:16:37.884
And the physical framework[br]of that brain circuitry

0:16:37.903,0:16:41.677
is actually written out[br]in the form of genes.

0:16:41.677,0:16:49.662
So this scary thought was the theme[br]of a [1997] movie, the title is "Gattaca."

0:16:49.662,0:16:53.181
Ironically, this spells G-A-T-T-A-C-A.

0:16:53.188,0:16:55.680
I think director meant it that way.

0:16:55.691,0:17:00.287
And in this movie, the director[br]wanted to say something like this:

0:17:00.379,0:17:02.598
He raised the question

0:17:02.598,0:17:08.169
can our will play a part in deciding[br]our fate beyond our genes.

0:17:08.169,0:17:13.670
In this movie Ethan Hawke is born[br]to be a second-class citizen,

0:17:13.670,0:17:15.974
and then Uma Thurman was born

0:17:15.979,0:17:21.138
and her gene was engineered[br]to become an upper-class citizen,

0:17:21.150,0:17:22.934
and he fell in love with her,

0:17:22.961,0:17:28.542
and he overcame this genetic barrier[br]by the power of love.

0:17:28.542,0:17:34.179
I don't fully understand if it's going[br]to be the most sensible solution to this.

0:17:34.179,0:17:40.078
But to some extent I share the thoughts

0:17:40.106,0:17:46.562
that in a not-too-far-distant future[br]we will face a very profound question.

0:17:46.562,0:17:48.293
What am I?

0:17:48.293,0:17:54.694
In fact, even as of now, my body[br]consists of 37 trillion cells, I told you,

0:17:54.716,0:17:59.086
but it also contains[br]more than 100 trillion bacterial cells,

0:17:59.106,0:18:00.949
in your guts, on your skin.

0:18:00.968,0:18:06.712
So in a nutshell,[br]I'm 30% human and 70% bacteria.

0:18:07.544,0:18:10.633
It's true.[br]So that's not really me.

0:18:10.633,0:18:14.029
What if we start to change[br]those body parts

0:18:14.029,0:18:17.771
using stem cell technologies[br]and CRISPR technology?

0:18:17.771,0:18:23.623
Our body parts will be derived[br]from those synthetic materials.

0:18:23.623,0:18:25.290
Is that me?

0:18:25.290,0:18:29.206
Now the even scarier thoughts[br]are of artificial intelligence,

0:18:29.206,0:18:32.466
when our brain activity is aided or fused

0:18:32.466,0:18:37.195
to circuitry aided by computer chips[br]and algorithms.

0:18:37.195,0:18:39.425
How much is me?

0:18:39.425,0:18:43.277
And that's a really difficult question[br]to address in a simple way.

0:18:43.277,0:18:47.590
But at least I think I gave you[br]a right question to ponder on.

0:18:47.590,0:18:50.449
And this is my thought.[br]This is my solution.

0:18:50.449,0:18:53.444
I am not really defined by my body.

0:18:53.444,0:18:58.641
I am defined by the networks and impacts[br]I make on my neighbors and friends.

0:18:58.641,0:19:02.556
So thank you for being[br]my friends and neighbors in my lifetime,

0:19:02.556,0:19:04.682
and I appreciate your attention.

0:19:04.682,0:19:06.859
Thank you very much.

0:19:06.871,0:19:08.321
(Applause)