WEBVTT

00:00:14.825 --> 00:00:20.142
What I'm going to show you
are the astonishing molecular machines

00:00:20.166 --> 00:00:23.466
that create the living
fabric of your body.

00:00:23.490 --> 00:00:27.273
Now molecules are really, really tiny.

00:00:27.297 --> 00:00:30.177
And by tiny, I mean really.

00:00:31.245 --> 00:00:33.247
They're smaller
than a wavelength of light,

00:00:33.271 --> 00:00:35.576
so we have no way
to directly observe them.

00:00:36.351 --> 00:00:38.694
But through science,
we do have a fairly good idea

00:00:38.718 --> 00:00:40.930
of what's going on
down at the molecular scale.

00:00:41.399 --> 00:00:44.176
So what we can do is actually
tell you about the molecules,

00:00:44.200 --> 00:00:47.437
but we don't really have a direct way
of showing you the molecules.

00:00:47.461 --> 00:00:49.711
One way around this is to draw pictures.

00:00:49.735 --> 00:00:52.275
And this idea is actually nothing new.

00:00:52.299 --> 00:00:54.587
Scientists have always created pictures

00:00:54.611 --> 00:00:57.397
as part of their thinking
and discovery process.

00:00:57.421 --> 00:01:00.296
They draw pictures
of what they're observing with their eyes,

00:01:00.320 --> 00:01:02.712
through technology
like telescopes and microscopes,

00:01:02.736 --> 00:01:05.175
and also what they're thinking
about in their minds.

00:01:05.899 --> 00:01:07.701
I picked two well-known examples,

00:01:09.850 --> 00:01:13.455
because they're very well-known
for expressing science through art.

00:01:13.680 --> 00:01:17.383
And I start with Galileo,
who used the world's first telescope

00:01:17.407 --> 00:01:18.593
to look at the Moon.

00:01:18.617 --> 00:01:22.023
And he transformed
our understanding of the Moon.

00:01:22.848 --> 00:01:24.481
The perception in the 17th century

00:01:24.505 --> 00:01:26.562
was the Moon was a perfect
heavenly sphere.

00:01:26.875 --> 00:01:29.859
But what Galileo saw
was a rocky, barren world,

00:01:29.883 --> 00:01:32.276
which he expressed
through his watercolor painting.

00:01:36.811 --> 00:01:39.106
Another scientist with very big ideas,

00:01:39.234 --> 00:01:41.758
the superstar of biology
is Charles Darwin.

00:01:41.782 --> 00:01:44.325
And with this famous entry
in his notebook,

00:01:44.350 --> 00:01:47.190
he begins in the top left-hand
corner with, "I think,"

00:01:47.214 --> 00:01:49.921
and then sketches out
the first tree of life,

00:01:49.945 --> 00:01:53.174
which is his perception
of how all the species,

00:01:53.199 --> 00:01:56.780
all living things on Earth are connected
through evolutionary history --

00:01:56.881 --> 00:01:59.128
the origin of species
through natural selection

00:01:59.152 --> 00:02:01.476
and divergence
from an ancestral population.

00:02:05.015 --> 00:02:06.476
Even as a scientist,

00:02:06.888 --> 00:02:09.401
I used to go to lectures
by molecular biologists

00:02:09.425 --> 00:02:12.150
and find them completely incomprehensible,

00:02:12.174 --> 00:02:14.442
with all the fancy technical
language and jargon

00:02:14.466 --> 00:02:16.590
that they would use
in describing their work,

00:02:16.614 --> 00:02:19.665
until I encountered
the artworks of David Goodsell,

00:02:20.189 --> 00:02:22.930
who is a molecular biologist
at the Scripps Institute.

00:02:22.954 --> 00:02:26.523
And his pictures -- everything's accurate
and it's all to scale.

00:02:27.747 --> 00:02:30.176
And his work illuminated for me

00:02:30.200 --> 00:02:32.515
what the molecular world
inside us is like.

00:02:33.515 --> 00:02:36.521
In the top left-hand corner,
you've got this yellow-green area.

00:02:36.546 --> 00:02:38.300
This is a transection through blood.

00:02:38.325 --> 00:02:41.481
The yellow-green area is the fluid
of blood, which is mostly water,

00:02:41.506 --> 00:02:44.493
but it's also antibodies, sugars,
hormones, that kind of thing.

00:02:44.616 --> 00:02:47.104
And the red region is a slice
into a red blood cell.

00:02:47.128 --> 00:02:48.994
And those red molecules are hemoglobin.

00:02:49.218 --> 00:02:51.913
They are actually red;
that's what gives blood its color.

00:02:51.937 --> 00:02:53.904
And hemoglobin acts as a molecular sponge

00:02:53.928 --> 00:02:55.605
to soak up the oxygen in your lungs

00:02:55.629 --> 00:02:57.742
and then carry it
to other parts of the body.

00:02:57.766 --> 00:03:00.797
I was very much inspired
by this image many years ago,

00:03:00.822 --> 00:03:03.373
and I wondered whether
we could use computer graphics

00:03:03.397 --> 00:03:05.001
to represent the molecular world.

00:03:05.025 --> 00:03:06.176
What would it look like?

00:03:07.100 --> 00:03:08.983
And that's how I really began.

00:03:10.163 --> 00:03:12.547
So let's begin.

00:03:13.700 --> 00:03:16.484
This is DNA in its classic
double helix form.

00:03:16.509 --> 00:03:19.865
And it's from X-ray crystallography,
so it's an accurate model of DNA.

00:03:20.289 --> 00:03:23.260
If we unwind the double helix
and unzip the two strands,

00:03:23.284 --> 00:03:25.303
you see these things that look like teeth.

00:03:25.327 --> 00:03:27.144
Those are the letters of genetic code,

00:03:27.168 --> 00:03:29.437
the 25,000 genes
you've got written in your DNA.

00:03:29.461 --> 00:03:32.397
This is what they typically talk about --
the genetic code --

00:03:32.421 --> 00:03:34.112
this is what they're talking about.

00:03:34.136 --> 00:03:36.906
But I want to talk about
a different aspect of DNA science,

00:03:36.930 --> 00:03:38.818
and that is the physical nature of DNA.

00:03:38.843 --> 00:03:41.428
It's these two strands
that run in opposite directions

00:03:41.452 --> 00:03:43.622
for reasons I can't go into right now.

00:03:43.646 --> 00:03:45.854
But they physically run
in opposite directions,

00:03:45.878 --> 00:03:49.509
which creates a number of complications
for your living cells,

00:03:49.533 --> 00:03:50.762
as you're about to see,

00:03:50.786 --> 00:03:53.148
most particularly
when DNA is being copied.

00:03:53.172 --> 00:03:55.090
And so what I'm about to show you

00:03:55.114 --> 00:03:59.130
is an accurate representation
of the actual DNA replication machine

00:03:59.154 --> 00:04:01.211
that's occurring right now
inside your body,

00:04:01.235 --> 00:04:03.047
at least 2002 biology.

00:04:03.357 --> 00:04:06.368
So DNA's entering the production line
from the left-hand side,

00:04:06.734 --> 00:04:09.901
and it hits this collection,
these miniature biochemical machines,

00:04:09.925 --> 00:04:13.069
that are pulling apart the DNA strand
and making an exact copy.

00:04:13.093 --> 00:04:18.382
So DNA comes in and hits this blue,
doughnut-shaped structure

00:04:19.326 --> 00:04:21.632
and it's ripped apart
into its two strands.

00:04:22.119 --> 00:04:23.743
One strand can be copied directly,

00:04:23.767 --> 00:04:26.690
and you can see these things
spooling off to the bottom there.

00:04:26.714 --> 00:04:28.974
But things aren't so simple
for the other strand

00:04:28.998 --> 00:04:30.763
because it must be copied backwards.

00:04:30.787 --> 00:04:32.897
So it's thrown out
repeatedly in these loops

00:04:32.921 --> 00:04:36.965
and copied one section at a time,
creating two new DNA molecules.

00:04:36.989 --> 00:04:42.272
Now you have billions of this machine
right now working away inside you,

00:04:42.296 --> 00:04:44.513
copying your DNA with exquisite fidelity.

00:04:45.376 --> 00:04:46.910
It's an accurate representation,

00:04:46.934 --> 00:04:50.463
and it's pretty much at the correct speed
for what is occurring inside you.

00:04:50.787 --> 00:04:53.604
I've left out error correction
and a bunch of other things.

00:04:53.628 --> 00:04:55.387
(Laughter)

00:04:55.911 --> 00:04:58.032
This was work from a number of years ago--

00:04:58.056 --> 00:04:59.225
Thank you.

00:04:59.249 --> 00:05:00.621
(Applause)

00:05:00.645 --> 00:05:02.574
This is work from a number of years ago,

00:05:02.598 --> 00:05:04.865
but what I'll show you next
is updated science,

00:05:04.889 --> 00:05:06.051
it's updated technology.

00:05:06.075 --> 00:05:07.435
So again, we begin with DNA.

00:05:07.459 --> 00:05:09.177
And it's jiggling and wiggling there

00:05:09.201 --> 00:05:11.382
because of the surrounding
soup of molecules,

00:05:11.406 --> 00:05:13.789
which I've stripped away
so you can see something.

00:05:13.813 --> 00:05:16.788
DNA is about two nanometers across,
which is really quite tiny.

00:05:18.412 --> 00:05:19.846
But in each one of your cells,

00:05:20.070 --> 00:05:23.679
each strand of DNA is about
30 to 40 million nanometers long.

00:05:24.314 --> 00:05:26.250
So to keep the DNA organized

00:05:27.975 --> 00:05:29.975
and regulate access to the genetic code,

00:05:30.000 --> 00:05:32.136
it's wrapped around these
purple proteins --

00:05:32.161 --> 00:05:33.743
or I've labeled them purple here.

00:05:34.267 --> 00:05:35.851
It's packaged up and bundled up.

00:05:36.275 --> 00:05:38.676
All this field of view
is a single strand of DNA.

00:05:39.311 --> 00:05:42.393
This huge package of DNA
is called a chromosome.

00:05:42.417 --> 00:05:44.776
And we'll come back
to chromosomes in a minute.

00:05:45.215 --> 00:05:47.281
We're pulling out, we're zooming out,

00:05:47.305 --> 00:05:49.273
out through a nuclear pore,

00:05:49.300 --> 00:05:52.960
which is the gateway to this compartment
that holds all the DNA,

00:05:52.984 --> 00:05:54.403
called the nucleus.

00:05:54.557 --> 00:05:58.788
All of this field of view
is about a semester's worth of biology,

00:05:58.812 --> 00:06:00.177
and I've got seven minutes,

00:06:00.201 --> 00:06:02.889
So we're not going to be
able to do that today?

00:06:02.913 --> 00:06:04.875
No, I'm being told, "No."

00:06:05.316 --> 00:06:08.681
This is the way a living cell
looks down a light microscope.

00:06:08.705 --> 00:06:12.203
And it's been filmed under time-lapse,
which is why you can see it moving.

00:06:12.227 --> 00:06:13.808
The nuclear envelope breaks down.

00:06:13.832 --> 00:06:16.077
These sausage-shaped things
are the chromosomes,

00:06:16.101 --> 00:06:17.282
and we'll focus on them.

00:06:17.306 --> 00:06:21.344
They go through this very striking motion
that is focused on these little red spots.

00:06:23.068 --> 00:06:27.303
When the cell feels it's ready to go,
it rips apart the chromosome.

00:06:27.327 --> 00:06:29.368
One set of DNA goes to one side,

00:06:29.392 --> 00:06:31.415
the other side gets
the other set of DNA --

00:06:31.439 --> 00:06:33.276
identical copies of DNA.

00:06:33.300 --> 00:06:35.260
And then the cell splits down the middle.

00:06:35.284 --> 00:06:38.143
And again, you have billions of cells
undergoing this process

00:06:38.167 --> 00:06:39.524
right now inside of you.

00:06:40.342 --> 00:06:43.198
Now we're going to rewind
and just focus on the chromosomes,

00:06:43.222 --> 00:06:45.464
and look at its structure and describe it.

00:06:46.388 --> 00:06:48.813
So again, here we are
at that equator moment.

00:06:49.794 --> 00:06:50.994
The chromosomes line up.

00:06:51.018 --> 00:06:52.845
And if we isolate just one chromosome,

00:06:52.869 --> 00:06:55.686
we're going to pull it out
and have a look at its structure.

00:06:55.710 --> 00:06:59.171
So this is one of the biggest
molecular structures that you have,

00:06:59.196 --> 00:07:02.251
at least as far as we've discovered
so far inside of us.

00:07:03.226 --> 00:07:05.202
So this is a single chromosome.

00:07:05.226 --> 00:07:07.827
And you have two strands of DNA
in each chromosome.

00:07:07.851 --> 00:07:09.572
One is bundled up into one sausage.

00:07:09.596 --> 00:07:12.329
The other strand is bundled up
into the other sausage.

00:07:12.353 --> 00:07:15.915
These things that look like whiskers
that are sticking out from either side

00:07:15.939 --> 00:07:17.845
are the dynamic scaffolding of the cell.

00:07:17.869 --> 00:07:20.780
They're called microtubules,
that name's not important.

00:07:20.804 --> 00:07:23.535
But we're going to focus on
the region labeled red here --

00:07:23.559 --> 00:07:26.096
and it's the interface between
the dynamic scaffolding

00:07:26.120 --> 00:07:27.287
and the chromosomes.

00:07:27.311 --> 00:07:30.416
It is obviously central
to the movement of the chromosomes.

00:07:30.440 --> 00:07:34.012
We have no idea, really,
as to how it's achieving that movement.

00:07:34.036 --> 00:07:36.683
We've been studying this thing
they call the kinetochore

00:07:36.707 --> 00:07:38.779
for over a hundred years
with intense study,

00:07:38.803 --> 00:07:41.629
and we're still just beginning
to discover what it's about.

00:07:41.653 --> 00:07:44.407
It is made up of about
200 different types of proteins,

00:07:44.431 --> 00:07:46.142
thousands of proteins in total.

00:07:46.930 --> 00:07:49.750
It is a signal broadcasting system.

00:07:49.774 --> 00:07:51.938
It broadcasts through chemical signals,

00:07:51.962 --> 00:07:54.706
telling the rest of the cell
when it's ready,

00:07:54.730 --> 00:07:57.561
when it feels that everything
is aligned and ready to go

00:07:57.585 --> 00:07:59.563
for the separation of the chromosomes.

00:07:59.587 --> 00:08:03.497
It is able to couple onto the growing
and shrinking microtubules.

00:08:04.943 --> 00:08:07.341
It's involved with the growing
of the microtubules,

00:08:07.366 --> 00:08:09.561
and it's able to transiently
couple onto them.

00:08:09.899 --> 00:08:11.719
It's also an attention-sensing system.

00:08:11.743 --> 00:08:13.719
It's able to feel when the cell is ready,

00:08:13.743 --> 00:08:15.977
when the chromosome
is correctly positioned.

00:08:16.001 --> 00:08:19.814
It's turning green here because it feels
that everything is just right.

00:08:19.838 --> 00:08:22.096
And you'll see,
there's this one little last bit

00:08:22.120 --> 00:08:23.553
that's still remaining red.

00:08:23.577 --> 00:08:26.110
And it's walked away
down the microtubules.

00:08:27.689 --> 00:08:30.868
That is the signal broadcasting system
sending out the stop signal.

00:08:30.892 --> 00:08:33.587
And it's walked away --
I mean, it's that mechanical.

00:08:33.611 --> 00:08:35.179
It's molecular clockwork.

00:08:35.203 --> 00:08:37.775
This is how you work
at the molecular scale.

00:08:38.409 --> 00:08:40.673
So with a little bit
of molecular eye candy,

00:08:40.697 --> 00:08:41.895
(Laughter)

00:08:41.919 --> 00:08:43.869
we've got kinesins, the orange ones.

00:08:43.893 --> 00:08:46.666
They're little molecular courier
molecules walking one way.

00:08:46.690 --> 00:08:49.836
And here are the dynein,
they're carrying that broadcasting system.

00:08:49.860 --> 00:08:51.404
And they've got their long legs

00:08:51.428 --> 00:08:53.494
so they can step around
obstacles and so on.

00:08:53.518 --> 00:08:56.545
So again, this is all derived
accurately from the science.

00:08:56.569 --> 00:08:59.119
The problem is we can't show it
to you any other way.

00:09:02.143 --> 00:09:06.977
Exploring at the frontier of science,
at the frontier of human understanding,

00:09:07.001 --> 00:09:08.236
is mind-blowing.

00:09:09.614 --> 00:09:10.792
Discovering this stuff

00:09:10.816 --> 00:09:14.344
is certainly a pleasurable
incentive to work in science.

00:09:14.860 --> 00:09:16.766
But most medical researchers --

00:09:17.541 --> 00:09:21.754
discovering the stuff is simply steps
along the path to the big goals,

00:09:21.778 --> 00:09:26.199
which are to eradicate disease,
to eliminate the suffering

00:09:26.223 --> 00:09:28.298
and the misery that disease causes

00:09:28.322 --> 00:09:30.002
and to lift people out of poverty.

00:09:30.022 --> 00:09:32.283
And so with my remaining time,
my four minutes,

00:09:33.220 --> 00:09:37.418
I'm going to introduce you
to one of the most devastating

00:09:37.433 --> 00:09:39.212
and economically important diseases.

00:09:40.268 --> 00:09:43.482
Which inflicts hundreds of millions
of people worldwide every year.

00:09:45.569 --> 00:09:47.450
So again - sound, thank you.

00:09:48.934 --> 00:09:51.401
This parasite is an ancient organism.

00:09:52.022 --> 00:09:54.711
It has been with us
since before we were human.

00:09:55.307 --> 00:09:57.909
Famous victims include
Alexander the Great,

00:09:58.155 --> 00:09:59.155
Ghengis Khan

00:09:59.179 --> 00:10:00.646
and George Washington.

00:10:01.965 --> 00:10:03.925
This is the neck of a sleeping child

00:10:03.957 --> 00:10:06.307
just after the Sun has set.

00:10:06.895 --> 00:10:09.013
And it's feeding time for mosquitoes.

00:10:09.673 --> 00:10:10.806
It's dinner time.

00:10:11.309 --> 00:10:13.842
[The lifecycle of Malaria
Human Host]

00:10:14.825 --> 00:10:16.625
(Sound of mosquito buzzing)

00:10:17.368 --> 00:10:20.768
This mosquito is infected
with a malaria parasite.

00:10:20.852 --> 00:10:22.764
Now, mosquitoes are usually vegetarian,

00:10:22.800 --> 00:10:25.831
they drink honey dew nectar,
fruit juices, that kind of thing.

00:10:26.030 --> 00:10:28.545
Only a pregnant female will bite humans

00:10:28.665 --> 00:10:31.807
seeking nutrients from blood
to nourish her developing eggs.

00:10:38.465 --> 00:10:40.837
During the bite she injects saliva

00:10:41.107 --> 00:10:43.377
to stop the blood from clotting

00:10:47.101 --> 00:10:48.901
and to lubricate the wound.

00:10:51.093 --> 00:10:53.560
Because she is infected with malaria,

00:10:54.347 --> 00:10:57.561
her saliva also contains
the malaria parasite

00:10:57.609 --> 00:10:59.676
so it rides in during the bite.

00:11:04.234 --> 00:11:07.377
The parasite then exits the wound
and seeks out a blood vessel

00:11:10.528 --> 00:11:12.107
and uses the circulatory system

00:11:12.157 --> 00:11:16.378
as a massive freeway
heading for its first target -

00:11:17.323 --> 00:11:20.490
the core of your body's
blood filter system - the liver.

00:11:22.347 --> 00:11:24.021
Within two minutes of the bite,

00:11:24.061 --> 00:11:26.410
the malaria parasites arrive to liver.

00:11:27.696 --> 00:11:31.624
And sensing its arrival then looks
for an exit from the blood stream.

00:11:32.149 --> 00:11:34.490
And this is where malaria
is particularly devious

00:11:34.506 --> 00:11:36.640
because it uses
the very type of immune cell

00:11:36.649 --> 00:11:38.696
that is the resident in the blood stream.

00:11:39.514 --> 00:11:42.180
The immune system is supposed
to remove foreign invaders

00:11:42.205 --> 00:11:43.656
like bacteria and parasites.

00:11:44.006 --> 00:11:45.839
But somehow, we're not quite sure how,

00:11:45.864 --> 00:11:48.339
malaria uses a backdoor entry
into the liver tissue.

00:11:48.403 --> 00:11:50.136
So here's that immune cell.

00:11:50.252 --> 00:11:52.021
Malaria leaves the bloodstream

00:11:52.046 --> 00:11:53.646
and infects a liver cell

00:11:53.665 --> 00:11:56.180
killing one or more liver cells
on its way.

00:11:56.212 --> 00:11:58.283
So again, this is within
a couple of minutes

00:11:58.308 --> 00:11:59.521
of the mosquito bite.

00:12:00.276 --> 00:12:01.886
Once it's infected a liver cell,

00:12:01.911 --> 00:12:04.177
it takes the next five or six days.

00:12:04.228 --> 00:12:07.386
It incubates,
it copies its DNA over and over again

00:12:07.411 --> 00:12:09.811
creating thousands of new parasites.

00:12:10.085 --> 00:12:13.410
So, it's this delay of about a week
since you've had the mosquito bite

00:12:13.450 --> 00:12:16.378
before malaria symptoms start to appear.

00:12:19.696 --> 00:12:22.705
The malaria also transforms
its physical nature;

00:12:22.872 --> 00:12:24.872
it's heading for a new target.

00:12:29.920 --> 00:12:32.587
The next target is your red blood cells.

00:12:38.180 --> 00:12:40.759
Part of its transformation,
the malaria coates itself

00:12:41.601 --> 00:12:45.775
with a coating of molecular hairs
that act like velcro.

00:12:48.604 --> 00:12:51.737
To stick red blood cells
to the outer surface.

00:12:51.813 --> 00:12:55.344
And then they reorient themselves
and penetrate inside the red blood cell.

00:12:55.368 --> 00:12:57.899
This happens within 30 seconds
of leaving the liver.

00:13:00.609 --> 00:13:02.704
This is an aera of intense study -

00:13:02.736 --> 00:13:04.156
if we could stop this process

00:13:04.657 --> 00:13:07.190
we could create a vaccine for malaria.

00:13:07.553 --> 00:13:09.251
Once it's inside the red blood cell

00:13:09.292 --> 00:13:11.553
it can hide
from your body's immune system.

00:13:15.403 --> 00:13:17.363
It then, over the next few days,

00:13:17.403 --> 00:13:19.775
devours the contents of the infected cell

00:13:19.910 --> 00:13:21.710
and creates more parasites.

00:13:28.705 --> 00:13:31.126
It also changes the nature
of the red blood cell

00:13:31.150 --> 00:13:32.340
and makes it sticky

00:13:32.364 --> 00:13:34.897
so it sticks on the blood vessel walls.

00:13:35.101 --> 00:13:38.466
This gives the parasite enough time
to incubate and grow.

00:13:39.228 --> 00:13:40.426
Once it's ready,

00:13:40.871 --> 00:13:43.236
it then bursts out of the red blood cell

00:13:43.363 --> 00:13:46.430
spreading malaria
throughout the bloodstream.

00:13:48.582 --> 00:13:50.757
Malaria victims suffer fever,

00:13:50.852 --> 00:13:54.526
lots of blood, convulsions,
brain damage and coma.

00:13:55.162 --> 00:13:57.503
Countless millions have been killed by it.

00:13:58.157 --> 00:14:01.228
This year between
200 and 300 million people

00:14:01.253 --> 00:14:03.116
will be struct down with malaria.

00:14:03.895 --> 00:14:06.053
Most people who die from the disease

00:14:06.109 --> 00:14:09.259
are pregnant women
and children under the age of five.

00:14:09.726 --> 00:14:10.998
Thank you.

00:14:11.022 --> 00:14:16.219
(Applause)