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What I'm going to show you
are the astonishing molecular machines

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that create the living
fabric of your body.

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Now molecules are really, really tiny.

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And by tiny, I mean really.

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They're smaller
than a wavelength of light,

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so we have no way
to directly observe them.

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But through science,
we do have a fairly good idea

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of what's going on
down at the molecular scale.

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So what we can do is actually
tell you about the molecules,

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but we don't really have a direct way
of showing you the molecules.

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One way around this is to draw pictures.

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And this idea is actually nothing new.

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Scientists have always created pictures

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as part of their thinking
and discovery process.

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They draw pictures
of what they're observing with their eyes,

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through technology
like telescopes and microscopes,

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and also what they're thinking
about in their minds.

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I picked two well-known examples,

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because they're very well-known
for expressing science through art.

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And I start with Galileo,
who used the world's first telescope

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to look at the Moon.

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And he transformed
our understanding of the Moon.

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The perception in the 17th century

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was the Moon was a perfect
heavenly sphere.

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But what Galileo saw
was a rocky, barren world,

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which he expressed
through his watercolor painting.

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Another scientist with very big ideas,

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the superstar of biology
is Charles Darwin.

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And with this famous entry
in his notebook,

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he begins in the top left-hand
corner with, "I think,"

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and then sketches out
the first tree of life,

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which is his perception
of how all the species,

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all living things on Earth are connected
through evolutionary history --

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the origin of species
through natural selection

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and divergence
from an ancestral population.

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Even as a scientist,

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I used to go to lectures
by molecular biologists

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and find them completely incomprehensible,

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with all the fancy technical
language and jargon

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that they would use
in describing their work,

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until I encountered
the artworks of David Goodsell,

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who is a molecular biologist
at the Scripps Institute.

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And his pictures -- everything's accurate
and it's all to scale.

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And his work illuminated for me

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what the molecular world
inside us is like.

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In the top left-hand corner,
you've got this yellow-green area.

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This is a transection through blood.

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The yellow-green area is the fluid
of blood, which is mostly water,

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but it's also antibodies, sugars,
hormones, that kind of thing.

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And the red region is a slice
into a red blood cell.

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And those red molecules are hemoglobin.

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They are actually red;
that's what gives blood its color.

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And hemoglobin acts as a molecular sponge

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to soak up the oxygen in your lungs

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and then carry it
to other parts of the body.

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I was very much inspired
by this image many years ago,

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and I wondered whether
we could use computer graphics

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to represent the molecular world.

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What would it look like?

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And that's how I really began.

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So let's begin.

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This is DNA in its classic
double helix form.

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And it's from X-ray crystallography,
so it's an accurate model of DNA.

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If we unwind the double helix
and unzip the two strands,

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you see these things that look like teeth.

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Those are the letters of genetic code,

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the 25,000 genes
you've got written in your DNA.

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This is what they typically talk about --
the genetic code --

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this is what they're talking about.

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But I want to talk about
a different aspect of DNA science,

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and that is the physical nature of DNA.

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It's these two strands
that run in opposite directions

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for reasons I can't go into right now.

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But they physically run
in opposite directions,

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which creates a number of complications
for your living cells,

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as you're about to see,

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most particularly
when DNA is being copied.

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And so what I'm about to show you

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is an accurate representation
of the actual DNA replication machine

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that's occurring right now
inside your body,

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at least 2002 biology.

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So DNA's entering the production line
from the left-hand side,

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and it hits this collection,
these miniature biochemical machines,

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that are pulling apart the DNA strand
and making an exact copy.

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So DNA comes in and hits this blue,
doughnut-shaped structure

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and it's ripped apart
into its two strands.

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One strand can be copied directly,

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and you can see these things
spooling off to the bottom there.

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But things aren't so simple
for the other strand

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because it must be copied backwards.

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So it's thrown out
repeatedly in these loops

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and copied one section at a time,
creating two new DNA molecules.

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Now you have billions of this machine
right now working away inside you,

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copying your DNA with exquisite fidelity.

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It's an accurate representation,

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and it's pretty much at the correct speed
for what is occurring inside you.

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I've left out error correction
and a bunch of other things.

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(Laughter)

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This was work from a number of years ago--

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Thank you.

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(Applause)

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This is work from a number of years ago,

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but what I'll show you next
is updated science,

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it's updated technology.

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So again, we begin with DNA.

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And it's jiggling and wiggling there

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because of the surrounding
soup of molecules,

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which I've stripped away
so you can see something.

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DNA is about two nanometers across,
which is really quite tiny.

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But in each one of your cells,

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each strand of DNA is about
30 to 40 million nanometers long.

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So to keep the DNA organized

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and regulate access to the genetic code,

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it's wrapped around these
purple proteins --

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or I've labeled them purple here.

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It's packaged up and bundled up.

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All this field of view
is a single strand of DNA.

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This huge package of DNA
is called a chromosome.

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And we'll come back
to chromosomes in a minute.

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We're pulling out, we're zooming out,

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out through a nuclear pore,

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which is the gateway to this compartment
that holds all the DNA,

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called the nucleus.

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All of this field of view
is about a semester's worth of biology,

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and I've got seven minutes,

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So we're not going to be
able to do that today?

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No, I'm being told, "No."

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This is the way a living cell
looks down a light microscope.

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And it's been filmed under time-lapse,
which is why you can see it moving.

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The nuclear envelope breaks down.

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These sausage-shaped things
are the chromosomes,

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and we'll focus on them.

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They go through this very striking motion
that is focused on these little red spots.

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When the cell feels it's ready to go,
it rips apart the chromosome.

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One set of DNA goes to one side,

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the other side gets
the other set of DNA --

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identical copies of DNA.

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And then the cell splits down the middle.

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And again, you have billions of cells
undergoing this process

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right now inside of you.

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Now we're going to rewind
and just focus on the chromosomes,

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and look at its structure and describe it.

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So again, here we are
at that equator moment.

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The chromosomes line up.

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And if we isolate just one chromosome,

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we're going to pull it out
and have a look at its structure.

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So this is one of the biggest
molecular structures that you have,

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at least as far as we've discovered
so far inside of us.

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So this is a single chromosome.

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And you have two strands of DNA
in each chromosome.

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One is bundled up into one sausage.

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The other strand is bundled up
into the other sausage.

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These things that look like whiskers
that are sticking out from either side

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are the dynamic scaffolding of the cell.

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They're called microtubules,
that name's not important.

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But we're going to focus on
the region labeled red here --

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and it's the interface between
the dynamic scaffolding

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and the chromosomes.

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It is obviously central
to the movement of the chromosomes.

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We have no idea, really,
as to how it's achieving that movement.

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We've been studying this thing
they call the kinetochore

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for over a hundred years
with intense study,

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and we're still just beginning
to discover what it's about.

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It is made up of about
200 different types of proteins,

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thousands of proteins in total.

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It is a signal broadcasting system.

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It broadcasts through chemical signals,

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telling the rest of the cell
when it's ready,

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when it feels that everything
is aligned and ready to go

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for the separation of the chromosomes.

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It is able to couple onto the growing
and shrinking microtubules.

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It's involved with the growing
of the microtubules,

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and it's able to transiently
couple onto them.

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It's also an attention-sensing system.

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It's able to feel when the cell is ready,

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when the chromosome
is correctly positioned.

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It's turning green here because it feels
that everything is just right.

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And you'll see,
there's this one little last bit

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that's still remaining red.

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And it's walked away
down the microtubules.

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That is the signal broadcasting system
sending out the stop signal.

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And it's walked away --
I mean, it's that mechanical.

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It's molecular clockwork.

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This is how you work
at the molecular scale.

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So with a little bit
of molecular eye candy,

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(Laughter)

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we've got kinesins, the orange ones.

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They're little molecular courier
molecules walking one way.

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And here are the dynein,
they're carrying that broadcasting system.

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And they've got their long legs

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so they can step around
obstacles and so on.

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So again, this is all derived
accurately from the science.

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The problem is we can't show it
to you any other way.

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Exploring at the frontier of science,
at the frontier of human understanding,

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is mind-blowing.

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Discovering this stuff

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is certainly a pleasurable
incentive to work in science.

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But most medical researchers --

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discovering the stuff is simply steps
along the path to the big goals,

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which are to eradicate disease,
to eliminate the suffering

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and the misery that disease causes

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and to lift people out of poverty.

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And so with my remaining time,
my four minutes,

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I'm going to introduce you
to one of the most devastating

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and economically important diseases.

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Which inflicts hundreds of millions
of people worldwide every year.

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So again - sound, thank you.

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This parasite is an ancient organism.

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It has been with us
since before we were human.

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Famous victims include
Alexander the Great,

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Ghengis Khan

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and George Washington.

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This is the neck of a sleeping child

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just after the Sun has set.

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And it's feeding time for mosquitoes.

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It's dinner time.

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[The lifecycle of Malaria
Human Host]

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(Sound of mosquito buzzing)

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This mosquito is infected
with a malaria parasite.

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Now, mosquitoes are usually vegetarian,

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they drink honey dew nectar,
fruit juices, that kind of thing.

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Only a pregnant female will bite humans

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seeking nutrients from blood
to nourish her developing eggs.

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During the bite she injects saliva

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to stop the blood from clotting

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and to lubricate the wound.

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Because she is infected with malaria,

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her saliva also contains
the malaria parasite

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so it rides in during the bite.

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The parasite then exits the wound
and seeks out a blood vessel

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and uses the circulatory system

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as a massive freeway
heading for its first target -

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the core of your body's
blood filter system - the liver.

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Within two minutes of the bite,

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the malaria parasites arrive to liver.

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And sensing its arrival then looks
for an exit from the blood stream.

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And this is where malaria
is particularly devious

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because it uses
the very type of immune cell

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that is the resident in the blood stream.

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The immune system is supposed
to remove foreign invaders

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like bacteria and parasites.

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But somehow, we're not quite sure how,

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malaria uses a backdoor entry
into the liver tissue.

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So here's that immune cell.

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Malaria leaves the bloodstream

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and infects a liver cell

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killing one or more liver cells
on its way.

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So again, this is within
a couple of minutes

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of the mosquito bite.

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Once it's infected a liver cell,

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it takes the next five or six days.

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It incubates,
it copies its DNA over and over again

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creating thousands of new parasites.

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So, it's this delay of about a week
since you've had the mosquito bite

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before malaria symptoms start to appear.

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The malaria also transforms
its physical nature;

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it's heading for a new target.

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The next target is your red blood cells.

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Part of its transformation,
the malaria coates itself

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with a coating of molecular hairs
that act like velcro.

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To stick red blood cells
to the outer surface.

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And then they reorient themselves
and penetrate inside the red blood cell.

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This happens within 30 seconds
of leaving the liver.

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This is an aera of intense study -

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if we could stop this process

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we could create a vaccine for malaria.

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Once it's inside the red blood cell

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it can hide
from your body's immune system.

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It then, over the next few days,

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devours the contents of the infected cell

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and creates more parasites.

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It also changes the nature
of the red blood cell

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and makes it sticky

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so it sticks on the blood vessel walls.

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This gives the parasite enough time
to incubate and grow.

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Once it's ready,

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it then bursts out of the red blood cell

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spreading malaria
throughout the bloodstream.

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Malaria victims suffer fever,

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lots of blood, convulsions,
brain damage and coma.

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Countless millions have been killed by it.

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This year between
200 and 300 million people

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will be struct down with malaria.

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Most people who die from the disease

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are pregnant women
and children under the age of five.

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Thank you.

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(Applause)