Secret Universe: The Hidden Life of the Cell

It takes 120 trillion cells to make a human.

They are the fundamental units of life,

making up our brain, muscles, organs - every part of us.

In the last decade,

scientists have been able to witness what once seemed impossible -

the world inside a human cell.

When I was a student,

the idea that we could burrow deep inside a living cell was unthinkable.

Recent advances have made it so scientists can see inside cells

like never before.

We can see the parts of single cells and how they work together.

The more we learn about the universe, the simpler it seems.

But the cell isn't like that.

The more we find out, the more complicated things get.

But these beautiful worlds are also on the front line of the longest war

in history.

This is a battle that goes back into the depths of time,

to a time when the earth was dominated by single cells and viruses.

Every day, our cells confront these ancient virus enemies,

tiny, ruthless machines that kill to reproduce.

There is this whole mechanism inside cells that are taking out viruses

that previously we just didn't know was there.

It is a four-billion-year-old struggle that has changed the course

of our evolution.

This battle of these viruses against your cells,

this amazing, epic science fiction movie,

it's going on inside your body all the time,

and you don't even know it.

Cells are the basic building blocks of living tissue,

and the smallest units of what makes us human.

And yet...

..beneath the surface of every one lies a world stranger

than any in science fiction.

A world in which a billion microscopic machines

all play their part, working in concert through every second

of our life.

Every one of us in made of 120 trillion cells,

and every one of those cells is different.

But they contain the same instructions.

Cells are a bit like babies. When they're born, they all look the same

but they change very quickly.

In different countries they learn to speak different languages,

and our bodies are like that - some cells speak heart,

and some cells speak liver.

The workers of this incredible world are proteins,

chains of complex chemicals

that can lock together to transform into spectacular machines.

Others work to create incredible structures,

like the internal skeleton that holds the cell together.

These great trusses are constantly adjusting to stresses and strains,

building and rebuilding to give the cell its shape and strength.

Then there are the motor-proteins, haulage workers that use

the cell's skeleton as highways to deliver food, chemicals

and the essential building materials of life to wherever they are needed.

They are just one of the astonishing micro machines that keep

this bustling community healthy.

Scientists are asked all the time, how do things in a cell know

how to get where they're supposed to go to do their job?

And for sure cells are very chaotic and things are bumping

into each other and most of that's just random.

But enough things get where they're supposed to go

that the entire system works.

And powering all this activity are the cell's power stations.

Inside these free-floating structures called mitochondria,

turbines spin at over 1,000 times per minute...

..recharging billions of tiny chemical batteries.

Everything we do, every heartbeat,

every movement, every thought,

is powered by the batteries charged by these cellular power stations.

And everything in this world works to a master plan.

And the plan is protected deep in the heart of every cell.

The nucleus is the vault containing the instruction manual for life.

DNA.

DNA is a chain of chemicals, organised into genes.

Each gene holds the instructions to build a specific protein.

The double helix contains over 20,000 instructions

that tell our cells what to make and when,

how to organise not just our cells, but our entire bodies.

The double helix has become the icon of the 21st century,

and it's pretty amazing stuff.

There's six feet of DNA in every cell of the body.

And if all of those bits were set out in a straight line,

they'd reach to the moon and back thousands of times.

But this crucial chain of chemicals would be useless

without an army of microscopic machines that endlessly travel its length,

repairing it and transcribing it,

turning the DNA into instructions that the cell can understand.

Once a gene has been copied,

the instructions are carried outside the nucleus.

Here, mobile factories read them and turn them into proteins.

Up to two million different kinds,

each with its own specific shape and purpose.

And little goes to waste in the cell.

Used and faulty proteins are tagged for recycling...

..then chewed apart by powerful roving shredders called proteasomes,

reducing them to tiny building blocks for new proteins.

But each cell is also part of a wider neighbourhood of cells,

all continually communicating with each other.

Fragments of shredded proteins are constantly transported to the surface.

Here, they are presented for inspection...

..to be monitored by the guardians of our body's immune system...

..our white blood cells.

These roving soldiers check the protein fragments for signs

of damage or infection.

And for the moment, everything is in order.

Every single human cell contains

this world of breathtaking complexity,

organised by the nuclear machines at its heart,

ceaselessly working from instructions written down in our DNA.

But our cells are under constant attack,

and this cell is about to face an ancient enemy...

..in an encounter that starts with an event so commonplace...

..you seldom even notice it.

Every day our bodies are constantly bombarded

by these invisible critters,

bacteria and viruses. But we have our skin,

it's our first line of defence that keeps them out.

But we have Achilles heels - we have openings to the outside world,

our mouths, our noses, we touch things, we rub our lips,

we rub our eyes or wipe our nose. They can get in.

And once they're in, they're in.

Inhaled from a sneeze,

an alien army is being carried into our body.

A million invaders, hellbent on destruction.

This is one of our most common enemies - the adenovirus.

It's a masterpiece of design,

and each one has a single aim...

..to breach a cell's defences...

..and reach the nucleus.

Once inside, any one of these viruses can take control of the cell...

..and reproduce 10,000 times over.

The result could be anything,

from the common cold to pneumonia - even death.

But our bodies are prepared.

As the viruses approach the cell,

they are met by a cloud of resistance.

Antibodies, Y-shaped proteins that identify alien intruders

patrol the space between our cells,

looking for viruses.

Recognising the invader, they lock to the virus's armour plating,

shackling them together, making the viruses easy meat

for the white blood cells that feed on alien invaders like these.

Antibodies and white blood cells form the front line

of our immune system.

The immune system is certainly amazing,

and it actually evolved to see invading microbes

and get rid of them. But that's just one part of your body's defences.

Our DNA encodes all these other features that help us

to fight against virus at every single step.

Despite the body's early immune response...

..hundreds of thousands of viruses make it through to our cell.

But at the surface, they face their next obstacle...

..the cell's membrane, or skin.

The surface of the cell is an amazingly complicated place.

There are hundreds, maybe thousands of receptor proteins

sticking out of the cell and they all have a unique function to play.

Some of them will be just transporting information

from outside of the cell into the cell.

Other receptors can bring whole cargoes in.

The surface of each cell is a living barrier,

teeming with security proteins that constantly monitor molecules

as they enter and leave.

Small molecules like water

and oxygen can simply seep through the membrane.

Larger molecules, like sugar,

are allowed entry through specialised pumps.

But the largest deliveries require a special key

before they are allowed into the cell.

These protein keys are recognised by teams of mobile sentries

that continually roam the surface.

This sophisticated system is designed to keep harmful molecules

out of the cell.

But over billions of years of evolution,

the adenovirus has evolved its very own key,

etched into the end of these projecting fibres.

Antibodies still cling to the some of these fibres,

blocking many of the counterfeit keys - but not all.

One by one, sentries all over the cell's surface are fooled.

And the virus army quietly slips inside.

In this ancient battle for the cell, it's round two to the virus.

So, how far back does it go, this cat and mouse game,

this battle between cells and viruses?

Every indication suggests it goes right back

to the origins of life on Earth.

Wherever life started, very early on there was a divergence,

two different strategies that life followed.

One of them was to become more complex, to become cells,

to become, ultimately, organisms like ourselves.

The other way was to remain simple - to become viruses,

and to exploit those cells to their own ends, to replicate themselves.

Beneath the surface,

the cell prepares to receive the deadly invaders.

Fooled into thinking that the virus is an important nutrient,

special proteins slot together to form a spherical mould.

They pinch out a bubble of cellular membrane,

wrapping the virus inside.

Finally, a separate protein pinches the bubble free,

delivering the virus into the cell's interior.

Unwittingly, the cell has just taken a large step

towards to its own downfall.

Every single member of this invading virus army

has the weaponry to ultimately destroy this cell.

Its protein shell is a multi-layered cloak of deception,

which has still more surprises in store.

And at its heart, it carries a tiny string of DNA,

its ultimate weapon.

It's a masterpiece of evolution and design.

And yet scientists still can't decide

if it's actually alive or dead.

At the level of large animals like ourselves,

the difference between living things and non-living things

is very obvious.

Come down a level, though, to cells, and it becomes a bit more ambiguous.

For our own cells, of course, you can still tell immediately

that they are alive. Come down another level, though, to the virus,

and it's no longer obviously alive. They don't look alive.

Yet they behave perhaps as if they are.

They behave with a sense of purpose.

A virus isn't strictly alive,

it can't make more of itself on its own.

It only can replicate if it uses parts that it hijacks from a cell.

But the cell still has a formidable array of defences

to keep these killing machines at bay.

Every delivery that the cell receives is taken

to a sorting station, called an endosome.

Endosomes process incoming supplies and decide where

inside the cell they will be delivered.

The first step of the process is to break them down.

The virus army is about to be digested.

The walls of the sorting stations are fitted

with specialised protein pumps.

The pumps draw in special atoms,

turning the inside of the endosome into an acid bath.

The acid breaks down large nutrients into smaller molecules

that are easier for the cell to transport and use.

And as the acid eats away at the virus's outer shell,

it begins to break apart.

This should spell disaster for the adenovirus.

But the acid is part of its escape plan.

The virus fibres are the first to break away.

But their disintegration releases a special protein

hidden inside the virus...

..that targets the wall of the sorting station...

..tearing the membrane apart and setting the virus free.

But not every virus escapes.

Many still carry antibodies locked to their surface.

Their primary job was to alert the immune system to intruders,

but their firm grip now ties the shell together.

The fibres cannot break free,

and the escape protein stays trapped inside the shell.

Countless viruses are eaten away before they can escape.

But enough are released.

Now there is nothing between these viruses

and the nucleus of the cell - their ultimate goal.

Yet although they are just five micrometres from their target...

..most might as well be a million miles away.

For 90% of the army, the invasion will end here,

floating helplessly beneath the surface.

Although they are surrounded by the constant bustle of cellular activity,

the inert invaders have no way of moving themselves.

And they have no way of utilising the energy generated

by the cells' floating power stations...

..the mitochondria.

Inside each mitochondrion, the food we eat and the air we breathe

drives thousands of turbines that continually recharge billions

of tiny batteries.

But what is even more extraordinary

is that scientists believe that mitochondria were once simple cells themselves.

Then they one was swallowed by another cell,

firing one of the greatest leaps in evolution -

complex life.

To be complex at all, you must have all this machinery,

all these proteins encoded by genes.

And to support all of that requires a tremendous amount of energy.

All complex life share a single common ancestor,

and that ancestor arose just once in four billion years

of life on Earth.

For two to three billion years it was bacteria and nothing else,

and then this complex cell arose.

One simple cell got inside another simple cell,

it's a very rare event in itself.

And once this happened, it transforms the energetic possibilities of life.

Without that energy, evolution could never have produced

the astonishing diversity of life that we see around us.

Without that energy, we wouldn't see plants and animals,

we wouldn't see ourselves. The world would be an almost sterile desert.

Throughout each cell, hundreds of mitochondria feed energy to power

the network of protein that make us the complex creatures that we are.

The virus has evolved into a model of efficiency.

But the simplicity of its design makes it useless

without the machinery of complex life.

But just beneath the surface, large numbers of motor proteins,

molecular haulage workers,

await nutrients processed for delivery by the endosomes.

And in this billion-year arms race...

..the virus has evolved the precise mechanism

to attach to the cell's motor proteins.

Now it can use the energy of the mitochondria.

The virus is on its way.

It has hijacked the cell's own transport system,

and is being carried towards the nucleus and its ultimate prize,

the DNA machines it needs to take control of the cell.

These microscopic motorised legs are a wonder of the natural world.

Slowed down to one-thirtieth of their normal speed,

their movement is clearly visible.

But at their actual speed, over 100 steps a second,

they would appear a blur.

But speed isn't everything.

Cells are densely packed,

and their internal highways are littered with obstacles.

And these motor proteins can only move in one direction.

For this virus, it seems to be the end of the road.

But scientists have recently discovered the virus locks on

to a second motor protein.

And this one is built to move in the opposite direction.

Together, the two motor proteins can navigate

around almost any obstacles.

And once again, the invader benefits.

The virus is on the move again.

And it leads an army of hundreds.

It's been almost an hour since the adenovirus first attacked the cell.

The nucleus is just one more hour away.

Until recently, scientists thought that once the viral army

was on the march, nothing could stop it.

But then they found that the cell has its own internal immune system.

There is this whole mechanism inside cells that are taking out viruses

that previously we just didn't know was there.

And I remember the day we published the paper about it,

I woke up to hear it being announced on the national radio

and then went into a shop to pick up the newspapers

to discover it was on the front page.

Dotted along the cell's highway system,

a special protein searches for anything carrying antibodies

from the surface.

The clever thing about this protein is it uses systems

that the cell already has in place.

Once it's stuck to the antibody,

it sends signals to a cellular machine called the proteasome.

And the proteasome plays the role of recycling proteins in the cell.

It gets brought along to the virus and it destroys the virus,

breaking down all its parts into tiny fragments.

Once attached, the defence protein initiates a chain reaction,

attracting specialised tagging proteins.

Together, they mark the virus for destruction.

Then it's only a matter of time...

..before the recyclers arrive.

They rip the virus to shreds.

Somewhere inside your body, this battle is raging right now.

The discovery of TRIM21 provides potentially new ways

of making therapeutics to fight viruses,

and one way this could work is if we find ways of encouraging the immune system to make more TRIM21.

So as soon as that virus enters into the cell, the TRIM21 is ready

to recognise the antibodies and destroy the virus.

By working together, the defence proteins and recycling shredders

can destroy an army of viruses in just a few hours.

But it only takes a single virus to take control of an entire cell...

..spreading infection throughout the body.

With no antibodies attached,

this virus has evaded the cell's shredders.

Nothing now stands between it and its target.

The virus is now just one thousandth of a millimetre from the nucleus.

But if it is to achieve its ultimate goal, it first has to get inside.

Compared to the cell, the virus is tiny.

But really they're just different versions of the same machine,

and its only job is to copy itself.

But the virus needs to take advantage of our cell mechanism

for its own selfish ends.

At the heart of every cell lies the nucleus,

and it is a world all of its own.

Its surface is made of the same molecules as the cell membrane.

But entry into this world is governed by completely different gateways.

Across the surface,

protein arms search for molecules to draw inside nuclear pores.

Through these gateways, billions of chemical messages

and instructions pass between the DNA and the cell.

But only if they are recognised by the protein arms.

But once again, the viral shell carries a counterfeit pass.

The arms lock on, but the virus is too large to be ferried inside.

Thinking that they have hit an obstruction...

..the motor proteins shunt the virus into reverse.

Pulled in two directions...

..the virus is ripped apart.

But what looks like a catastrophe for the virus is, in fact, its masterstroke.

Now the single strand of DNA it held inside is carried through the pore,

and into the cell's control centre.

Inside the human cell nucleus there are about 23,000 genes.

They code for thousands and thousands of biochemical pathways.

The virus has just got 40,

but with those 40 it can do remarkable things.

It's so tiny, just a piece of DNA,

a couple of proteins to make its shell, and yet it can take over

and wreak havoc in a huge human cell.

It's brilliant.

The adenovirus has proven itself a master of deception...

..continually exploiting the cell's processes to further its own deadly aims.

But its greatest trick is yet to come.

The cell's DNA machines have no way of telling the difference

between its own DNA and the DNA of the virus.

Blindly, they set about converting its deadly code

into thousands of instructions for the cell to act upon...

..blueprints for the cell's own destruction.

But the machines that turn the blueprints into proteins

lie outside the nucleus.

Out in the main body of the cell, the instructions are met

by a squadron of mobile protein factories, called ribosomes.

The ribosomes precisely follow the instruction

and start to construct viral proteins.

Each is carefully folded into a specific shape,

with a unique job to do.

These large cellular machines, ribosomes, are absolutely fundamental

to life, and very similar forms of them are found in every type

of living cell on the planet.

They read the genetic information and they decode it,

bringing in the building blocks that make up proteins

and sticking them together to make these functional molecules

that are going to work inside the living cell.

Only these functional molecules

are the kit of parts needed to build an enemy army.

But the army will not be built out here.

The raw material for the new army is drawn back inside the nucleus...

..ready for construction.

With its mission reaching its climax,

the virus turns its attention to the cell's DNA,

halting any process it doesn't need.

The virus has taken complete control.

And yet the cell still has a small window of opportunity.

Before all normal activity stops,

it has just enough time to send a message to the outside world.

This parcel contains fragments of the viral army.

The parcel merges with the cell membrane,

and the enemy fragments are pushed to the surface,

flags warning of the invasion that has taken place.

If patrolling white blood cells spot the distress signal...

..they will destroy the cell, along with the entire alien army inside.

If not, the infection will spread from cell to cell, to cell.

After just one day of occupation,

the virus has complete control over the cell.

With routine maintenance halted, the cell has started to decay.

And all activity is now focused on building the brand new viral army

inside the nucleus.

The new army self-assembles.

How do viruses know how to invade our cells, how to break

and enter the nucleus itself?

We know that viruses and cells co-evolved together over long periods of time, but it's more than that.

We're actually surprisingly closely related.

It turns out that the viruses that attack us

are actually made from bits and pieces of our own cells.

As our cells were evolving,

as our nucleus itself was first coming to be,

so these viruses were cobbled together from bits and pieces,

and they can attack our nucleus

because they're made of the same stuff.

Already built into its surface are the binding sites

for the cell's motorised legs.

Fibres snap into place,

arming each virus with the keys to enter other cells.

But these shells are harmless without its instructions.

The final component is loaded - identical copies

of the virus's deadly DNA.

Carried by powerful motors,

long strands of DNA are fed into every single virus.

All this is the result of one single virus

getting through our cell's defences.

It's been two days since the virus entered the body,

and the nucleus, once the centre of cellular organisation,

now harbours an army of 10,000 deadly viruses.

But before it can begin its conquest,

it has to overcome two barriers.

The army is trapped inside the tough nuclear membrane,

held at the centre of the cell itself.

And then there is the skin of the cell itself.

The protein factories outside the nucleus are instructed

to build viral saboteurs.

The first are released into the decaying cell

and target its cytoskeleton.

The effects are cataclysmic.

Without support...

the cell starts to collapse.

Now the virus turns its attention to the nuclear membrane.

A second protein is released.

Called the Adenovirus Death Protein, it burrows into the membrane...

..and weakens it.

The nucleus can no longer contain the bulging army.

Beyond the nucleus, the cell is a wasteland...

..unrecognisable from the harmonious, buzzing community

of just 48 hours ago.

The cell is now completely helpless to stop the virus army

from flooding into surrounding tissue...

..attacking neighbouring cells

and spreading infection throughout the body.

The battle for this cell is over.

But the war has only just begun.

While the virus has been busy inside the cell,

our antibodies have adapted and now come back in force,

carrying new receptors, tailor-made to lock onto the escaping army.

Yet even in these numbers, they cannot stop every virus.

But they are not alone.

The cell's dying message to the outside world was not in vain.

Giant white blood cells flock to the stricken cell

to devour the escaping hordes.

They too are learning how to tackle this particular invader.

Once the virus has been detected by the immune system,

there's a heightened level of security inside your body,

and one of the results of this is that the cells that make antibodies,

and make the right antibody for that virus,

will make lots of copies of themselves,

and then they will start pumping out up to 5,000 antibodies per second

to flood your bloodstream, the spaces between your cells,

so as the viruses emerge from dying cells,

they can get tagged by antibodies, then destroyed by white blood cells.

Taking no chances,

white blood cells engulf nearby cells that may have been infected.

Meanwhile, surrounding healthy cells make the ultimate sacrifice,

destroying themselves to stop the spread of the virus.

It is only at this stage that we become aware of the battle

taking place inside us.

Increasing blood flow brings more white blood cells to the battleground,

causing our nasal tissue to become inflamed.

What we feel is a blocked nose is, in fact, the clearest sign

of a viral onslaught.

Once you've had an infection,

one cell, that makes the antibody for that infection, will be kept

inside your bone marrow for the rest of your life.

So that if you ever get another infection with the same virus,

the immune system already knows how to respond,

it knows what antibody to make and it can respond very quickly and stop you getting sick.

Working together, the body's immune system finally prevents

the viral infection from spreading.

It's one more battle in an unending war.

The struggle between viruses and ourselves is evolution,

but it's co-evolution - both sides have to change.

It's a bit like an arms race - one party gets better weapons,

the other party has to match them.

Even though the individual cells are fighting this epic battle

against viruses, remember, you have trillions of cells.

And so even if one cell loses its war, most of the time the organism wins and we get better.

The war is over.

For now.

Although many cells have been lost,

there are many more healthy cells waiting to replace them.

And at the heart of each one lies an identical copy of our DNA.

Inherited from our parents,

and their parents over countless generations,

our DNA connects us to a family tree that stretches back

over three billion years, to the very first cell...

..a cell that existed long before humans, long before mammals,

long before the dinosaurs.

It's a lineage that connects us to every living creature and plant on Earth.

We are all descended from a single prehistoric ancestor,

a cell containing the single strand of DNA that started it all.

But the virus is as old as we are.

It has evolved alongside us, forcing us to adapt,

to change or die in a deadly game of cat and mouse.

This eternal arms race has driven our evolution

and made us both stronger.

We wouldn't be what we are today were it not for this battle

with our ancient enemy.

The story of the cell is a story of innovation and change,

and because viruses continuously force cells to change,

they actually aid their adaptation to different environments.

And for that reason they've also helped shape us,

they've made us who we are.

Every minute of every day,

this battle with the virus rages within seven billion of us.

Though we are rarely aware of it, we fight each other,

change each other,

improve each other.

Subtitles by Red Bee Media Ltd