How to pronounce "replication"

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

that create the living fabric of your body.

Now molecules are really, really tiny.

And by tiny, I mean really.

They're smaller than a wavelength of light,

so we have no way to directly observe them.

But through science, we do have a fairly good idea

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

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

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

One way around this is to draw pictures.

And this idea is actually nothing new.

Scientists have always created pictures

as part of their thinking and discovery process.

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

through technology like telescopes and microscopes,

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

I picked two well-known examples,

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

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

to look at the Moon.

And he transformed our understanding of the Moon.

The perception in the 17th century

was the Moon was a perfect heavenly sphere.

But what Galileo saw was a rocky, barren world,

which he expressed through his watercolor painting.

Another scientist with very big ideas,

the superstar of biology is Charles Darwin.

And with this famous entry in his notebook,

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

and then sketches out the first tree of life,

which is his perception of how all the species,

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

the origin of species through natural selection

and divergence from an ancestral population.

Even as a scientist,

I used to go to lectures by molecular biologists

and find them completely incomprehensible,

with all the fancy technical language and jargon

that they would use in describing their work,

until I encountered the artworks of David Goodsell,

who is a molecular biologist at the Scripps Institute.

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

And his work illuminated for me

what the molecular world inside us is like.

So this is a transection through blood.

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

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

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

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

And those red molecules are hemoglobin.

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

And hemoglobin acts as a molecular sponge

to soak up the oxygen in your lungs

and then carry it to other parts of the body.

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

and I wondered whether we could use computer graphics

to represent the molecular world.

What would it look like?

And that's how I really began.

So let's begin.

This is DNA in its classic double helix form.

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

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

you see these things that look like teeth.

Those are the letters of genetic code,

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

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

this is what they're talking about.

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

and that is the physical nature of DNA.

It's these two strands that run in opposite directions

for reasons I can't go into right now.

But they physically run in opposite directions,

which creates a number of complications for your living cells,

as you're about to see,

most particularly when DNA is being copied.

And so what I'm about to show you

is an accurate representation of the actual DNA replication machine

that's occurring right now inside your body,

at least 2002 biology.

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

and it hits this collection, these miniature biochemical machines,

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

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

and it's ripped apart into its two strands.

One strand can be copied directly,

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

But things aren't so simple for the other strand

because it must be copied backwards.

So it's thrown out repeatedly in these loops

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

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

copying your DNA with exquisite fidelity.

It's an accurate representation,

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

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

(Laughter)

This was work from a number of years ago--

Thank you.

(Applause)

This is work from a number of years ago,

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

it's updated technology.

So again, we begin with DNA.

And it's jiggling and wiggling there

because of the surrounding soup of molecules,

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

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

But in each one of your cells,

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

So to keep the DNA organized and regulate access to the genetic code,

it's wrapped around these purple proteins --

or I've labeled them purple here.

It's packaged up and bundled up.

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

This huge package of DNA is called a chromosome.

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

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

out through a nuclear pore,

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

called the nucleus.

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

and I've got seven minutes,

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

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

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

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

The nuclear envelope breaks down.

These sausage-shaped things are the chromosomes,

and we'll focus on them.

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

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

One set of DNA goes to one side,

the other side gets the other set of DNA --

identical copies of DNA.

And then the cell splits down the middle.

And again, you have billions of cells undergoing this process

right now inside of you.

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

and look at its structure and describe it.

So again, here we are at that equator moment.

The chromosomes line up.

And if we isolate just one chromosome,

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

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

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

So this is a single chromosome.

And you have two strands of DNA in each chromosome.

One is bundled up into one sausage.

The other strand is bundled up into the other sausage.

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

are the dynamic scaffolding of the cell.

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

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

and it's the interface between the dynamic scaffolding

and the chromosomes.

It is obviously central to the movement of the chromosomes.

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

We've been studying this thing they call the kinetochore

for over a hundred years with intense study,

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

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

thousands of proteins in total.

It is a signal broadcasting system.

It broadcasts through chemical signals,

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

when it feels that everything is aligned and ready to go

for the separation of the chromosomes.

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

It's involved with the growing of the microtubules,

and it's able to transiently couple onto them.

It's also an attention-sensing system.

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

when the chromosome is correctly positioned.

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

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

that's still remaining red.

And it's walked away down the microtubules.

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

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

It's molecular clockwork.

This is how you work at the molecular scale.

So with a little bit of molecular eye candy,

(Laughter)

we've got kinesins, the orange ones.

They're little molecular courier molecules walking one way.

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

And they've got their long legs

so they can step around obstacles and so on.

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

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

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

is mind-blowing.

Discovering this stuff

is certainly a pleasurable incentive to work in science.

But most medical researchers --

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

which are to eradicate disease, to eliminate the suffering

and the misery that disease causes

and to lift people out of poverty.

Thank you.

(Applause)