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The Hidden Life of the Cell
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00:01It takes 120 trillion cells to make a human.
00:07They are the fundamental units of life.
00:11Making up our brain, muscles, organs, every part of us.
00:21In the last decade, scientists have been able to witness what once seemed impossible.
00:26The world inside a human cell.
00:35When I was a student, the idea that we could burrow deep inside a living cell was unthinkable.
00:43Recent advances have made it so scientists can see inside cells like never before.
00:49We can see the parts of single cells and how they work together.
00:54The more we learn about the universe, the simpler it seems.
00:58But the cell isn't like that.
01:00The more we find out, the more complicated things get.
01:05But these beautiful worlds are also on the front line of the longest war in history.
01:11This is a battle that goes back into the depths of time.
01:15To a time when the Earth was dominated by single cells and viruses.
01:19Every day, our cells confront these ancient virus enemies.
01:23Tiny, ruthless machines that kill to reproduce.
01:27There is this whole mechanism inside cells that are taking out viruses that previously we just didn't know was there.
01:33It is a four billion year old struggle that has changed the course of our evolution.
01:40This battle of these viruses against yourselves, this amazing epic science fiction movie, it's going on inside your body all
01:49the time.
01:49And you don't even know it.
02:16Cells are the basic building blocks of living tissue.
02:21And the smallest units of what makes us human.
02:27And yet, beneath the surface of every one, lies a world stranger than any in science fiction.
02:42A world in which a billion microscopic machines all play their part.
02:47Working in concert through every second of our life.
02:53Every one of us is made of 120 trillion cells.
02:57And every one of those cells is different.
02:59But they contain the same instructions.
03:01Cells are a bit like babies.
03:03When they're born, they all look the same.
03:04But they change very quickly.
03:06In different countries, they learn to speak different languages.
03:09And our bodies like that, some cells speak heart and some cells speak liver.
03:16The workers of this incredible world are proteins, chains of complex chemicals, that can lock together to transform into spectacular
03:27machines.
03:30Others work to create incredible structures, like the internal skeleton that holds the cell together.
03:37These great trusses are constantly adjusting to stresses and strains.
03:43Building and rebuilding to give the cell its shape and strength.
03:51Then there are the motor proteins, haulage workers, that use the cell's skeleton as highways to deliver food, chemicals and
03:58the essential building materials of life to wherever they are needed.
04:06They are just one of the astonishing micromachines that keep this bustling community healthy.
04:13Scientists are asked all the time, how do things in a cell know how to get where they're supposed to
04:17go?
04:17To do their job.
04:19And for sure cells are very chaotic and things are bumping into each other and most of that's just random.
04:24But enough things get where they're supposed to go that the entire system works.
04:31And powering all this activity are the cell's power stations.
04:38Inside these free-floating structures called mitochondria, turbines spin at over a thousand times per minute.
04:49Recharging billions of tiny chemical batteries.
05:00Everything we do, every heartbeat, every movement, every thought, is powered by the batteries charged by these cellular power stations.
05:26And everything in this world works to a master plan.
05:33And the plan is protected deep in the heart of every cell.
05:38The nucleus is the vault containing the instruction manual for life.
05:46DNA.
05:52DNA is a chain of chemicals organized into genes.
05:58Each gene holds the instructions to build a specific protein.
06:04The double helix contains over 20,000 instructions that tell our cells what to make and when.
06:12How to organize not just our cells, but our entire bodies.
06:19The double helix has become the icon of the 21st century.
06:23And it's pretty amazing stuff.
06:25There's six feet of DNA in every cell of the body.
06:28And if all those bits were set out in a straight line, they'd reach to the moon and back thousands
06:34of times.
06:45But this crucial chain of chemicals would be useless without an army of microscopic machines that endlessly travel its length,
06:53repairing it and transcribing it.
06:56Turning the DNA into instructions that the cell can understand.
07:08Once a gene has been copied, the instructions are carried outside the nucleus.
07:16Here, mobile factories read them and turn them into proteins.
07:28Up to two million different kinds.
07:32Each with its own specific shape and purpose.
07:44And little goes to waste in the cell.
07:48Used and faulty proteins are tagged for recycling.
07:55Then chewed apart by powerful roving shredders called proteasomes, reducing them to tiny building blocks for new proteins.
08:06But each cell is also part of a wider neighborhood of cells.
08:11All continually communicating with each other.
08:15Fragments of shredded proteins are constantly transported to the surface.
08:22Here, they are presented for inspection.
08:28To be monitored by the guardians of our body's immune system.
08:35Our white blood cells.
08:43These roving soldiers check the protein fragments for signs of damage or infection.
08:56And for the moment, everything is in order.
09:13And for the moment, everything is in order.
09:23Every single human cell contains this world of breathtaking complexity.
09:29Organized by the nuclear machines at its heart.
09:32Ceaselessly working from instructions written down in our DNA.
09:49But our cells are under constant attack.
09:53And this cell is about to face an ancient enemy.
09:58In an encounter that starts with an event so commonplace.
10:06You seldom even notice it.
10:13Every day, our bodies are constantly bombarded by these invisible critters, bacteria and viruses.
10:19But we have our skin.
10:20It's our first line of defense that keeps them out.
10:24But we have Achilles heels.
10:25We have openings to the outside world.
10:28Our mouths, our noses.
10:29We touch things.
10:30We rub our lips.
10:31We rub our eyes or wipe our nose.
10:33They can get in.
10:35And once they're in, they're in.
10:50Inhaled from a sneeze, an alien army is being carried into our body.
10:57A million invaders, hell-bent on destruction.
11:15This is one of our most common enemies.
11:19The adenovirus.
11:26It's a masterpiece of design.
11:30And each one has a single aim.
11:40To breach a cell's defenses.
11:44And reach the nucleus.
11:48Once inside, any one of these viruses can take control of the cell.
11:55And reproduce 10,000 times over.
12:00The result could be anything.
12:03From the common cold.
12:04To pneumonia.
12:06Even death.
12:14But our bodies are prepared.
12:28As the viruses approach the cell.
12:31They are met by a cloud of resistance.
12:39Antibodies.
12:40Y-shaped proteins that identify alien intruders.
12:45The virus.
12:46Patrol the space between our cells.
12:49Looking for viruses.
12:54Recognizing the invader, they lock to the viruses' armor plating.
13:00Shackling them together.
13:01Shackling them together.
13:01Making the viruses easy meat for the white blood cells that feed on alien invaders like these.
13:07Antibodies and white blood cells form the front line of our immune system.
13:13The immune system is certainly amazing.
13:16And it actually evolved to see invading microbes and get rid of them.
13:20But that's just one part of your body's defenses.
13:22Our DNA encodes all these other features that help us to fight against virus at every single step.
13:39Despite the body's early immune response, hundreds of thousands of viruses make it through to our cell.
13:50But at the surface, they face their next obstacle.
14:08The cell's membrane, or skin.
14:13The surface of the cell is an amazingly complicated place.
14:16There are hundreds, maybe thousands, of receptor proteins sticking out of the cell.
14:21And they all have a unique function to play.
14:23Some of them would be just transporting information from outside the cell into the cell.
14:27Other receptors can bring whole cargos in.
14:34The surface of each cell is a living barrier.
14:38Teeming with security proteins that constantly monitor molecules as they enter and leave.
14:51Small molecules like water and oxygen can simply seep through the membrane.
15:03Larger molecules like sugar are allowed entry through specialised pumps.
15:10But the largest deliveries require a special key before they are allowed into the cell.
15:18These protein keys are recognised by teams of mobile sentries that continually roam the surface.
15:29This sophisticated system is designed to keep harmful molecules out of the cell.
15:35But over billions of years of evolution, the adenovirus has evolved its very own key.
15:43Etched into the end of these projecting fibres.
15:50Antibodies still cling to some of these fibres, blocking many of the counterfeit keys.
15:55Antibodies.
15:56But not all.
15:58One by one, sentries all over the cell's surface are fooled.
16:09And the virus army quietly slips inside.
16:15And before you go into the dead.
16:16In this ancient battle for the cell, it's round two to the virus.
16:29so how far back does it go this cat and mouse game this battle between cells and viruses every
16:37indication suggests it goes right back to the origins of life on earth wherever life started
16:43very early on there was a divergence two different strategies that life followed one of them was to
16:49become more complex to become cells to become ultimately organisms like ourselves the other
16:54way was to remain simple to become viruses and to exploit those cells to their own ends to replicate
17:01themselves beneath the surface the cell prepares to receive the deadly invaders fooled into thinking
17:17that the virus is an important nutrient special proteins slot together to form a spherical mold
17:29they pinch out a bubble of cellular membrane wrapping the virus inside
17:38finally a separate protein pinches the bubble free delivering the virus into the cells interior
17:50unwittingly the cell has just taken a large step towards its own downfall
18:05every single member of this invading virus army has the weaponry to ultimately destroy this cell
18:13its protein shell is a multi-layered cloak of deception which is still more surprises in store
18:21and at its heart it carries a tiny string of DNA its ultimate weapon it's a masterpiece of evolution
18:30and design and yet scientists still can't decide if it's actually alive or dead the level of large
18:38animals like ourselves the difference between living things and non-living things is very obvious come
18:44down a level though to cells and it becomes a bit more ambiguous for our own cells of course you
18:51can
18:51still tell immediately that they're alive come down another level though to the virus and it's no longer
18:57obviously alive they don't look alive yet they behave perhaps as if they are they behave with a sense of
19:05purpose a virus isn't strictly alive it can't make more of itself on its own it only can replicate if
19:15it
19:15uses parts that it hijacks from a cell but the cell still has a formidable array of defenses to keep
19:25these killing
19:25machines at bay
19:32every delivery that the cell receives is taken to a sorting station called an endosome
19:41endosomes process incoming supplies and decide where inside the cell they will be delivered
19:49the first step of the process is to break them down
19:56the virus army is about to be digested
20:02the walls of the sorting stations are fitted with specialized protein pumps
20:11the pumps draw in special atoms turning the inside of the endosome into an acid bath
20:25the acid breaks down large nutrients into smaller molecules that are easier for the cell to transport and use
20:35and as the acid eats away at the virus's outer shell it begins to break apart
20:44this should spell disaster for the adenovirus
20:50but the acid is part of its escape plan
20:54the virus fibers are the first to break away
21:00but their disintegration releases a special protein hidden inside the virus
21:08that targets the wall of the sorting station
21:14tearing the membrane apart and setting the virus free
21:26the virus
21:26but not every virus escapes
21:29many still carry antibodies locked to their surface
21:33their primary job was to alert the immune system to intruders
21:37but their firm grip now ties the shell together
21:42the fibers cannot break free and the escape protein stays trapped inside the shell
21:52countless viruses are eaten away before they can escape
22:04but enough are released
22:07now there is nothing between these viruses and the nucleus of the cell
22:11their ultimate goal
22:15yet although they are just five micrometers from their target
22:21most might as well be a million miles away
22:35for ninety percent of the army
22:38the invasion will end here
22:41floating helplessly beneath the surface
23:04and they have no way of utilizing the energy generated by the cells floating power stations
23:12the mitochondria
23:32inside each mitochondrion the food we eat
23:36and the air we breathe drives thousands of turbines
23:39that continually recharge billions of tiny batteries
23:45but what is even more extraordinary is that scientists believe that mitochondria were once
23:50simple cells themselves
23:53then one was swallowed by another cell
23:56firing one of the greatest leaps in evolution
24:00complex life
24:03to be complex at all you must have all this machinery all these proteins encoded by genes and to support
24:10all
24:10of that requires a tremendous amount of energy
24:13all complex life share a single common ancestor and that ancestor arose just once in four billion
24:21years of life on earth for two to three billion years it was bacteria and nothing else and then this
24:26complex cell arose
24:28one simple cell got inside another simple cell it's a very rare event in itself and once it happened
24:34it transforms the energetic possibilities of life
24:38and without that energy evolution could never have produced the astonishing diversity of life
24:44that we see around us without that energy we wouldn't see plants and animals we wouldn't see ourselves
24:50the world would be an almost sterile desert
25:07throughout each cell hundreds of mitochondria feed energy to power the network of proteins that make us the
25:14complex creatures that we are
25:22the virus has evolved into a model of efficiency but the simplicity of its design makes it useless without
25:30the machinery of complex life
25:35but just beneath the surface large numbers of motor proteins molecular haulage workers
25:41a weight nutrients processed for delivery by the endosomes
26:01and in this billion year arms race
26:05the virus has evolved the precise mechanism to attach to the cell's motor proteins
26:23now it can use the energy of the mitochondria
26:30the virus the virus is on its way
26:38it has hijacked the cell's own transport system
26:42and is being carried towards the nucleus and its ultimate prize the dna machines it needs
26:48to take control of the cell
26:58these microscopic motorized legs are a wonder of the natural world
27:04slowed down to one-thirtieth of their normal speed their movement is clearly visible
27:08but at their actual speed over 100 steps a second they would appear a blur
27:29but speed isn't everything cells are densely packed and their internal highways are littered with obstacles
27:41and these motor proteins can only move in one direction
27:45and these motor proteins can only move in one direction
28:16but scientists have recently discovered the virus locks on to a second motor protein
28:32and this one is built to move in the opposite direction
28:36and this one is built to move in the opposite direction
28:52together the two motor proteins can navigate around almost any obstacles
29:01and once again the invader benefits
29:22the virus is on the move again
29:29and it leads an army of hundreds
29:36so
29:59it's been almost an hour since the adenovirus first attacked the cell
30:06the nucleus is just one more hour away until recently scientists thought that
30:14once the viral army was on the march nothing could stop it but then they found that the cell
30:20has its own internal immune system there is this whole mechanism inside cells that are taking out
30:28viruses that previously we just didn't know was there and I remember the day on which we published
30:33the paper about it I woke up to hear it being announced on the national radio and then went
30:38into a shop to pick up the newspapers to discover it was on the front page
31:18dotted along the cells highway system a special protein searches for anything carrying antibodies
31:25from the surface the clever thing about this protein is it uses systems that the cell already
31:31has in place once it's stuck to the antibody it sends signals to a cellular machine called the
31:37proteasome and the proteasome plays a role of recycling proteins in the cell so it gets brought
31:42along to the virus and it destroys the virus breaking down all its parts into tiny fragments once attached
31:50the defense protein initiates a chain reaction attracting specialized tagging proteins together they mark the
31:59virus for destruction
32:10then it's only a matter of time
32:16before the recyclers arrive
32:27they rip the virus to shreds
32:41they rip the virus and they form the virus and the attacks on the chain reaction, so we can see
32:43that they have anèsze重ね
32:43up there they're flying up
32:45there they're flying up
32:52there they're flying up
32:58there
33:01Somewhere inside your body, this battle is raging right now.
33:15The discovery of Trin21 provides potentially new ways of making therapeutics to fight viruses.
33:21And one way this could work is if we could find ways for encouraging the immune system to make more
33:25Trin21.
33:26So as soon as that virus enters into the cell, the Trin21 is ready to recognise the antibodies and destroy
33:31the virus.
33:43By working together, the defence proteins and recycling shredders can destroy an army of viruses in just a few hours.
34:11But it only takes a single virus to take control of an entire cell, spreading infection throughout the body.
34:23With no antibodies attached, this virus has evaded the cell's shredders.
34:39Nothing now stands between it and its target.
34:56The virus is now just one thousandth of a millimetre from the nucleus.
35:05But if it is to achieve its ultimate goal, it first has to get inside.
35:13Compared to the cell, the virus is tiny.
35:16But really they are just different versions of the same machine.
35:20And its only job is to copy itself.
35:22But the virus needs to take advantage of our cell mechanism for its own selfish ends.
35:30At the heart of every cell lies the nucleus.
35:34And it is a world all of its own.
35:42Its surface is made of the same molecules as the cell membrane.
35:48But entry into this world is governed by completely different gateways.
35:55Across the surface, protein arms search for molecules to draw inside nuclear pores.
36:05Through these gateways, billions of chemical messages and instructions pass between the DNA and the cell.
36:15But only if they are recognised by the protein arms.
36:24But once again, the viral shell carries a counterfeit pass.
36:33The arms lock on, but the virus is too large to be ferried inside.
36:44Thinking that they have hit an obstruction,
36:48the motor proteins shunt the virus into reverse.
37:16Pulled in two directions.
37:18Pulled in two directions.
37:22The virus is ripped apart.
37:24The virus is ripped apart.
37:32But what looks like a catastrophe for the virus is, in fact, its masterstroke.
37:57Now, the single strand of DNA it held inside is carried through the pore, and into the cell's control centre.
38:27Inside the human cell nucleus, there are about 23,000 genes.
38:31They culled for thousands and thousands of biochemical pathways.
38:35The virus has just got 40, but with those 40, it can do remarkable things.
38:42It's so tiny.
38:44Just a piece of DNA, a couple of proteins to make its shell, and yet it can take over and
38:49wreak havoc in a huge human cell.
38:53It's brilliant.
39:05The adenovirus has proven itself a master of deception.
39:11Continually exploiting the cell's processes to further its own deadly aims.
39:17But its greatest trick is yet to come.
39:26The cell's DNA machines have no way of telling the difference between its own DNA and the DNA of the
39:33virus.
39:37Blindly, they set about converting its deadly code into thousands of instructions for the cell to act upon.
39:53Blueprints for the cell's own destruction.
40:26But the machines that turn the blueprints into proteins lie outside the nucleus.
40:36Out in the main body of the cell, the instructions are met by a squadron of mobile protein factories called
40:43ribosomes.
40:47The ribosomes precisely follow the instruction and start to construct viral proteins.
40:53Each is carefully folded into a specific shape with a unique job to do.
40:58These large cellular machines, ribosomes, are absolutely fundamental to life.
41:03And very similar forms of them are found in every type of living cell on the planet.
41:07They read the genetic information and they decode it, bringing in the building blocks that make up proteins,
41:12and sticking them together to make these functional molecules that are going to work inside the living cell.
41:27Only these functional molecules are the kit of parts needed to build an enemy army.
41:55But the army will not be built out here.
42:07The raw material for the new army is drawn back inside the nucleus.
42:16Ready for construction.
42:32With its mission reaching its climax, the virus turns its attention to the cell's DNA,
42:38halting any process it doesn't need.
42:44The virus has taken complete control.
42:55And yet the cell still has a small window of opportunity.
43:01Before all normal activity stops, it has just enough time to send a message to the outside world.
43:26This parcel contains fragments of the viral army.
43:36The parcel merges with the cell membrane, and the enemy fragments are pushed to the surface.
43:42Flags warning of the invasion that has taken place.
43:50If patrolling white blood cells spot the distress signal,
43:55they will destroy the cell along with the entire alien army inside.
44:00If not, the infection will spread from cell to cell to cell.
44:16After just one day of occupation, the virus has complete control over the cell.
44:22With routine maintenance halted, the cell has started to decay.
44:28And all activity is now focused on building the brand new viral army inside the nucleus.
44:44The new army self-assembles.
44:51How do viruses know how to invade our cells, how to break an end to the nucleus itself?
44:56We know that viruses and cells co-evolved together over long periods of time, but it's more than that.
45:03We're actually surprisingly closely related.
45:06It turns out that the viruses that attack us are actually made from bits and pieces of our own cells.
45:12As our cells were evolving, as the nucleus itself was first coming to be,
45:16so these viruses were cobbled together from bits and pieces,
45:20and they can attack our nucleus because they're made of the same stuff.
45:26Already built into its surface are the binding sites for the cell's motorized legs.
45:36Fibres snap into place, arming each virus with the keys to enter other cells.
45:46But these shells are harmless without its instructions.
46:03The final component is loaded.
46:06Identical copies of the virus's deadly DNA.
46:15Carried by powerful motors, long strands of DNA are fed into every single virus.
46:41All this is the result of one single virus
46:46getting through our cells' defences.
46:55It's been two days since the virus entered the body, and the nucleus, once the centre
47:01of cellular organisation, now harbours an army of 10,000 deadly viruses.
47:20But before it can begin its conquest, it has to overcome two barriers. The army is trapped
47:27inside the tough nuclear membrane, held at the centre of the cell itself. And then there
47:35is the skin of the cell itself. The protein factories outside the nucleus are instructed
47:43to build viral saboteurs.
47:54The first are released into the decaying cell and target its cytoskeleton. The effects
48:05are cataclysmic. Without support, the cell starts to collapse.
48:23Now, the virus turns its attention to the nuclear membrane.
48:33A second protein is released.
48:39Called the adenovirus death protein, it burrows into the membrane and weakens it.
49:01The nucleus can no longer contain the bulging army.
49:30Beyond the nucleus, the cell is a wasteland.
49:42Unrecognisable from the harmonious, buzzing community of just 48 hours ago.
49:55The cell is now completely helpless to stop the virus army from flooding into surrounding tissue, attacking
50:07neighbouring cells and spreading infection throughout the body.
50:20The battle for this cell is over.
50:37But the war has only just begun.
50:55While the virus has been busy inside the cell, our antibodies have adapted and now come back
51:01in force carrying new receptors, tailor-made to lock on to the escaping army.
51:09Yet even in these numbers, they cannot stop every virus.
51:16But they are not alone.
51:20The cell's dying message to the outside world was not in vain.
51:24Giant white blood cells flock to the stricken cell to devour the escaping hordes.
51:30They too are learning how to tackle this particular invader.
51:35Once the virus has been detected by the immune system, there's a heightened level of security inside your body.
51:41And one of the results of this is that the cells that make antibodies and make the right antibody for
51:45that virus will make lots of copies of themselves.
51:48And then they will start pumping out up to 5,000 antibodies per second to flood your bloodstream, the spaces
51:54between your cells.
51:55Since viruses emerge from dying cells, they can get tagged by antibodies and then destroyed by white blood cells.
52:02Taking no chances, white blood cells engulf nearby cells that may have been infected.
52:13Meanwhile, surrounding healthy cells make the ultimate sacrifice, destroying themselves to stop the spread of the virus.
52:25It is only at this stage that we become aware of the battle taking place inside us.
52:31Increasing blood flow brings more white blood cells to the battleground, causing our nasal tissue to become inflamed.
52:38What we feel as a blocked nose is in fact the clearest sign of a viral onslaught.
52:45Once you've had an infection, one cell that makes the right antibody for that infection will be kept inside your
52:51bone marrow
52:52for the rest of your life, that if you ever get another infection with the same virus, the immune system
52:57already knows how to respond.
52:58It knows what antibody to make and it can respond very quickly and stop you getting sick.
53:06Working together, the body's immune system finally prevents the viral infection from spreading.
53:13It's one more battle in an unending war.
53:18The struggle between viruses and ourselves is evolution, but it's co-evolution.
53:25Both sides have to change.
53:27It's a bit like an arms race.
53:29One party gets better weapons, the other party has to match them.
53:36Even though the individual cells are fighting this epic battle against the viruses, remember you have trillions of cells.
53:43And so even if one cell loses its war, most of the time the organism wins and we get better.
54:03The war is over.
54:07For now.
54:17Although many cells have been lost, there are many more healthy cells waiting to replace them.
54:30And at the heart of each one lies an identical copy of our DNA.
54:41Inherited from our parents and their parents over countless generations, our DNA connects us to a family tree
54:48that stretches back over three billion years to the very first cell.
54:55A cell that existed long before humans, long before mammals, long before the dinosaurs.
55:03It's a lineage that connects us to every living creature and plant on Earth.
55:08We are all descended from a single prehistoric ancestor.
55:13A cell containing the single strand of DNA that started it all.
55:21But the virus is as old as we are.
55:24It has evolved alongside us, forcing us to adapt, to change or die in a deadly game of cat and
55:31mouse.
55:36This eternal arms race has driven our evolution and made us both stronger.
55:46We wouldn't be what we are today were it not for this battle with our ancient enemy.
55:55The story of the cell is a story of innovation and change.
55:58And because viruses continuously force cells to change, they actually aid their adaptation to different environments.
56:07And for that reason, they've also helped shape us.
56:11They've made us who we are.
56:20Every minute of every day, this battle with the virus rages within seven billion of us.
56:32Though we are rarely aware of it, we fight each other.
56:37Change each other.
56:39Change each other.
56:40Improve each other.
56:49Uncovering the truth about our ancestors here on BBC HD this week.
56:53A groundbreaking prehistoric autopsy gets underway tomorrow at nine.
57:11Plus, the Electro-Christians live our synagogue.
57:12The
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