The Cell (2009) s01e02 Episode Script
The Chemistry of Life
Have a look at this.
I'm gonna take two living sponges, fresh out of the sea.
And I'm gonna utterly destroy them.
I'm going to reduce this piece of sponge to its individual cells.
Now it's wrapped up in this nylon mesh and this is acting as a kind of a sieve.
So now I'm going to squeeze it through this sieve.
What's left is nothing like a sponge.
A liquid containing cells.
You might think I'd totally killed the sponge.
But, if I leave these individual cells overnight, something really rather astonishing happens.
As the hours pass, the cells start to move.
Slowly they shuffle their way back together.
And, by joining up, they make a new piece of sponge.
Oh, and look at that purple one! I mean, it's such a striking result.
Almost all of the individual cells have gone.
It's as if the cells have acted like individuals with a purpose and they've actually re-aggregated into a piece of sponge tissue.
It's amazing! This experiment was first done over 100 years ago.
And it raised some really enormous questions.
How do cells know what to do? What goes on inside cells? How do these tiny structures make living organisms? If we find the answers to these questions, we'll find out what makes things alive - the secret of life itself.
If you think about it, it's pretty incredible.
Cells are just tiny bags full of molecules.
But how those lifeless molecules bundle together to create life was a fundamental mystery.
So the challenge for the scientists who first began to study the cell was to unravel the chemistry of life.
It was here in Germany, 150 years ago, that scientists set out to tackle the mysteries of the cell.
They'd discovered that plants, animals, people, all living things in fact, are made up of tiny cells.
Doctors began probing the cells of the human body.
Organs and tissues became specimens to be preserved, sliced and put under the microscope.
What they saw, and drew, showed that every organ and tissue is made of different types of cells working together.
And that all cells come from other cells.
New ones are only made when cells split in two.
Somehow, cells must contain the secret of life itself.
But scientists knew nothing about what went on inside these cells.
The problem was that, when doctors and scientists looked down the microscope at cells, what they could see didn't tell them much.
They could see that cells were enclosed by a boundary, a membrane, and there was a dense bit in the middle that they called the nucleus.
This was surrounded by a jelly-like gloopthat they called protoplasm.
But the problem was that these were just blobs within blobs.
They didn't know what the blobs were foror even what they were made of.
The first step towards understanding the working of cells came in the small German town of Tubingen.
It was a centre of scientific excellence.
Europe's first biochemistry lab was established in the local castle.
One of the aims was to find out more about human cells.
And it was here, in 1868, that a keen young scientist, Dr Friedrich Miescher, arrived to take up his first research post.
Miescher's job here at the castle was to study the chemistry of white blood cells.
He decided to look at the large nucleus at the centre of the cell and find out what it was made of.
To do this, he needed two things.
A ready supply of cells, and a way of getting rid of the gloop so he could study the bare nucleus.
Getting hold of white blood cells would normally have been tricky.
But Tubingen was the ideal place.
The region had been at war with Prussia.
Hundreds of injured soldiers with infected wounds lay in the barracks next to the hospital.
Their wounds were oozing copious amounts of pus, which is full of white blood cells.
So, revolting as it sounds, Miescher collected their old bandages so he could scrape off the pus.
Miescher needed something else.
His next stop was the local slaughterhouse, to collect a pig's stomach.
Here it is.
Oh! That's disgusting! 'He was interested in the mucus that lined the stomach.
'This contains an enzyme called pepsin, 'which helps break down and digest food.
' Where's the pepsin? Look here.
This is the pepsin.
This sort of gloopy stuff?Yep.
There's not much of it.
No.
That's all.
And this is what helps digest food in the stomach?Yeah.
Smells like a pig's stomach to me.
'With the pepsin, Miescher now had all he needed for his experiment.
' And this is a delicacy in Tubingen? Yes, you call fill it with bread or you can cut it in stripes, then you cook it and eat it with bread.
Is it tasty?Yes.
I'm not sure about that.
Miescher carried the bandages and the pig's stomach back to the lab.
If he was right, the pepsin would break down the white blood cells.
Then, for the very first time, it would be possible to examine the dense nucleus at the heart of the cell.
Nowadays we do analysis like this using precision equipment.
But of course Miescher didn't have any kit like that so it wasn't easy.
First he had to scrape the pus from the bandages.
Now, this is mayonnaise, but you get the idea.
Then he had to wash the pepsin out of the pig's stomach using an acid.
And mixed it with the pus.
After the enzyme had done its work and digested the cells, only then could he analyse the nucleus on its own.
Now the big question was, what did the nucleus consist of? Miescher spent months analysing its chemistry.
And he found it contained a rather strange molecule.
This molecule was made up of carbon, hydrogen, oxygen and nitrogen.
He knew these elements were found in all living things.
But this molecule contained something extra - phosphorus.
And that made it different.
Very different.
It was an entirely new kind of molecule.
Because he found it in the nucleus, Miescher called it nuclein.
We now know it as DNA.
Intrigued, Miescher repeated his experiment on sperm cells from frogs, carp, bulls and salmon.
Every time he found exactly the same molecule.
Incredibly, some of it has survived.
Here in this test tube is some of the first DNA ever isolated.
It's DNA from salmon sperm that Miescher extracted in the 1870s.
Now, it may not look like much, but this brown powder marks the beginning of a scientific revolution.
Miescher's discovery of DNA was confirmation that there was something special inside the nucleus of cells, a molecule that was common to all life.
But Miescher was way ahead of his time.
His work on the chemistry of the nucleus went unnoticed because scientists still had little idea of what the nucleus was for, or of how cells worked.
It was the warm waters of the Mediterranean that gave them an important breakthrough.
Here, scientists found a ready supply of living cells which they could easily study.
The embryos of the many species of marine life that thrive here.
Which is why the Bay of Naples became the centre of a remarkable scientific community, scientists who were using the abundance of creatures in the sea to study how life is formed.
At the heart of the community was this marine station, built on the shores of Naples.
And in 1888 another young German scientist, Theodor Boveri, arrived here to work on cells.
He'd be studying alongside some of the most eminent scientists of his day.
In fact, the marine station was supported by Charles Darwin himself.
The scientists built a public aquarium to fund their research.
Then, as now, it was a popular attraction.
And it provided a ready supply of cell specimens.
Because fish lay their eggs straight into the water.
Boveri was interested in the fertilisation of eggs.
Once the egg cell is fertilised, it begins to divide.
It creates another cell, and then another, and so a new life is born.
Somehow, when the cells divide, the essence of life is passed from cell to cell.
By the end of the century, with better microscopes and new chemical dyes to stain the cells, embryologists were able to see early dividing cells in more detail than ever before.
And what they saw was incredible.
Have a look at some of these drawings.
Scientists had thought that when the cells divide they simply split down the middle.
But now they began to see that something far more complicated was going on inside the nucleus.
As cells started to divide, discrete objects like little rods would appear inside the nucleus.
These rods seemed to unravel and split in two, migrating to opposite ends of the nucleus.
Then the nucleus would split in half, followed by the cell itself.
Scientists called the rods "chromosomes", meaning coloured bodies, because the chemical dyes they were using gave them a colour.
And they saw that these puzzling chromosomes only appeared in the nucleus when a cell divided.
Now, the obvious question for any scientist looking at something so complex and elaborate iswhy? Why do the cells have to divide in such a curious way? To find the answer, Boveri devised an experiment.
He used a creature found in abundance at the bottom of the bay.
My underwater guide is Dr Ina Arnone.
Ina works at the Naples marine station on the same kind of creature Boveri used - the sea urchin.
The easy part about collecting sea urchins is finding them.
Unlike fish, they just stick to the rocks.
But, without practice, picking them off is harder than you think.
And the spines can really hurt.
There it is, a sea urchin, plucked .
.
plucked from the bottom of the Bay of Naples.
There are thousands of them down there.
You can see why people used these as experimental animals.
The inside of a sea urchin consists almost entirely of its reproductive organs, or gonads.
Oh, this is very good.
Look at the gonads.
How big they are.
And you can recognise this is a male.
Because you see here? These are the gonads and this is theThe white part is the sperm.
Wow.
And, fishermen, they believe this is indeed the the milk of the sea urchin.
Right.
And this is a local delicacy here as well, right?Yes, it is.
Yes.
You wanna try?Of course.
Shall I show you how to do it?Yeah, go on then.
Take this little bit.
It's likeeating the sea.
Let me try.
So I just suck it out? Just suck it out.
HE SLURPS Mmm.
It's pretty salty.
Oh, that's salty, yes! Why have people used these for scientific research? Oh, that's pretty obvious.
They produce billions of eggs and sperm.
'And billions of eggs and sperm, each of them single cells, 'were just what Boveri needed for his experiment.
'Back in the lab, all Boveri had to do was shake the sea urchins.
' Like this! 'This stimulates the sea urchins to spawn.
' So, the orange powdery stuff that's just falling off the bottom, that's the eggs.
Exactly.
They are falling down and you will see them collecting on the bottom.
'Boveri wanted to find out what happened when cells divide.
'So his starting point 'was the moment when the egg is fertilised by a sperm.
' You can see here the nucleus of the egg.
This bit in the middle? Yes, I can focus to show you better.
That's what Boveri used to see under the microscope.
So this is an unfertilised egg.
You can really see the sperm trying to eattheir way into the egg.
Yes.
That's incredible.
Wow! You see the fertilisation envelope.
'Boveri knew that, when an egg is fertilised, 'the nucleus of the egg and sperm combine to form a new nucleus.
'This first cell of the new embryo divides into two.
'Soon, two cells become four.
'Four cells become eight, 16, 32 and so on.
'And, each time a cell divides, the nucleus of the new cell inherits 'an identical copy of all of the chromosomes.
'So Boveri knew the chromosomes must be important.
'But how important?' 'He wondered, if he added extra sperm into the egg, 'would extra chromosomes appear? 'What effect would this have? Would the cellsstill divide normally?' With Ina's fluorescent microscope, we can see what happens.
When extra sperm are added, the whole process of cell division goes off beam.
Clumps of deformed cells of different shapes and sizes appear.
The whitish blobs in the middle are the chromosomes in the nuclei.
But their irregular shape suggests each nucleus has acquired a different amount of chromosomes.
So this one looks very different.
We've got three nuclei here.
But is this one cell or two cells? I can't quite make it out.
Yes.
First of all you can see that there are three nuclei, and not two, as supposed to be at this stage.
But also what you can see is that the nuclear content is different.
So you can see this is much bigger.
This is smaller, this is even smaller.
So this didn't receive the same amount of chromosomes.
So there's different amounts of chromosomes in each bit of the cell? So it's gone wrong.
Exactly.
And this embryo won't develop any further? Well, he will probably do some more division, but it will generate monsters.
A monster.
So it won't develop into a proper sea urchin.
Not at all.
That's what Boveri saw.
Every time he introduced extra sperm into his sea urchin eggs, he got monsters.
Mutant embryos that never got further than a few cells.
So let's just take a moment to think about what a massive discovery Boveri had made.
An embryo would only develop if it had one full set of chromosomes in every cell.
So, every time a cell divided, a new identical set of chromosomes had to be formed in every cell.
Any more or less, and the embryo would die.
So it's suggested that whatever information was in the mysterious chromosomes, it was essential for life.
But what was that information? Boveri had an idea.
The chromosomes for a new life came from the sperm and the egg.
So could the chromosomes be the way in which all the characteristics of sea urchins are passed on when a new life is created? And again and again every time the cells divide.
Boveri spent the next 20 years experimenting on sea urchins.
And he became convinced that chromosomes must contain what he called the "hereditary characters".
In other words, key bits of information that control the characteristics that a creature inherits.
Boveri was predicting the existence of genes.
He was onto something big.
The idea that chromosomes within our cells could be the way that life, and all the traits we inherit, are passed on.
In New York, Boveri's work on chromosomes had caught the attention of a fellow embryologist.
Thomas Hunt Morgan was another veteran of the Naples Marine Station.
But here at Columbia University, he'd moved on from studying sea life.
His creature of choice was Drosophila melanogaster, that's the fruit fly to you and me.
Thanks to Morgan, this tiny insect was to become one of the mighty heroes of biology.
For anyone interested in studying inheritance, the fruit fly has some big advantages.
They're small, cheap, and they breed like, well, flies.
You can get a new generation every ten days.
And they have only four pairs of chromosomes.
Morgan's lab became known as "the fly room".
Now just as we inherit characteristics from our parents so indeed do all creatures, including fruit flies.
Morgan wanted to see if he could see patterns of inheritance in fruit flies and link these patterns to the chromosomes.
Now in nature, fruit flies normally have red eyes.
But one day, Morgan found a male fly with white eyes in his collection.
He decided to crossbreed it with a red-eyed female.
When Morgan bred their offspring, some of the next generation of flies emerged with white eyes.
Morgan noticed that it was only male flies that had inherited white eyes.
None of the females.
He concluded that having white eyes was somehow linked to being male.
Morgan knew that the chromosomes of fruit flies included two which determined gender.
So he deduced that the information for making white eyes had to be carried on the sex chromosomes.
That was his breakthrough.
Morgan had now found evidence that seemed to support what Boveri had predicted, that the characteristics we inherit map to specific parts of the chromosome.
Now the fly room was really buzzing.
The team were soon able to find which parts of the fly's chromosomes accounted for traits like body colour and wing size, as well as eye colour.
And by 1922 they'd drawn up the world's first chromosome map showing the location of 2,000 different traits.
To describe the individual parts of the chromosomes that related to each trait, he used the word "gene".
Nowadays genes are part of our everyday language.
So it's easy to forget just what a huge leap forward this was.
To understand that the way we look and the way we operate might be determined by genes within our cells.
Genes are what families truly share.
They are the biological link between my dad, myself and my son.
Spotting those genetic connections can make family photo albums such fun.
That's you.
That looks like Jakey to me.
Very similar.
You look much more like your mum.
Yeah, I always did.
Where is she? Back in the 1920s, the idea that something within our cells could account for family resemblance was new.
Look at that! Look at those tiger-skin Speedos.
You were on the other side of the camera encouraging me to do something stupid.
Very likely.
Today these genetic links are accepted, but a century ago, this was ground-breaking stuff.
Scientists had peered into the cell nucleus.
They had found chromosomes.
And they had shown that these chromosomes carried information we inherit - genes.
But they still had no idea how.
So here was the new question.
What on earth were genes? What was the chemistry within cells, the molecule, that allowed hereditary information to pass from one cell to another, from generation to generation.
The answer to that would come from two scientists studying not inheritance, but disease.
Fred Griffith and Oswald Avery were both medical researchers working on pneumonia, but on opposite sides of the Atlantic.
They didn't even know each other, but together they would find the next crucial piece of the puzzle of how cells work.
Fred Griffith was working at the Ministry of Health here in London.
He was investigating types of bacteria, single cells that invade the body and reproduce there.
He wanted to find out why some bacteria kill and others don't.
And he stumbled across something rather remarkable.
It all began when he was using laboratory mice to test cocktails of different bacterial strains.
He was looking for a combination that would work as a vaccine to prevent pneumonia.
He started with solutions of two different types of pneumonia bacteria, which I've mocked up in these beakers, one harmless, the other lethal.
And with very basic equipment, he tested his bacteria on the mice.
Unsurprisingly, when he injected the mice with the harmless bacteria, they were fine.
And when he injected them with the lethal bacteria, they died.
Griffith then took the solution of lethal pneumonia bacteria and heated it.
He thought this should kill the bacteria.
And sure enough, when injected, the mice showed no sign of pneumonia.
It was then that Griffith tried something which gave a very surprising result.
When Griffith made a mixture of the lethal, heat-treated bacteria with the harmless bacteria, remember that neither of these had killed the mice on their own, he found that some of the mice died.
When he examined the dead mice, he found deadly bacteria in their blood.
Something very spooky was going on here.
Griffith figured that something in the lethal bacteria had survived.
And whatever it was, it had transformed the harmless bacteria into killer cells.
But what was that something? He never found out.
Griffith had his job to do working on vaccines.
He never realised that he had accidentally found a whopping great clue to what genes are, a clue that would lead to a major breakthrough in our understanding of how cells work.
But his results caught the attention of Oswald Avery, also an expert in pneumonia bacteria.
Avery was determined to find out what it was that had the power to change one type of cell into another.
It would take him nearly a decade, but it would turn out to be a critically important discovery.
At the Rockefeller Institute in New York, Avery and his team were using the latest methods in biochemistry to look inside bacteria.
They knew that bacteria, like all cells, are essentially little bags jammed full of different kinds of molecules.
A chemical soup made of millions of protein molecules, carbohydrates and fatty substances called lipids.
Over nine years they tested every type of molecule in the lethal pneumonia bacteria to find out which molecule was passing on its deadly traits to the harmless bacteria.
Avery decided to work by a process of elimination.
First he removed the carbohydrates and then the lipids, but it wasn't either of them.
Then, he removed all of the proteins but it wasn't them either.
Finally, he turned his attention to a molecule that had seemed like an unlikely candidate.
It was when he started testing DNA, the strange molecule in the nucleus, that Friedrich Miescher had found 75 years earlier, that Avery got a result.
Stripped of their DNA, the power of the lethal bacteria to transform other cells simply vanished.
What Avery had discovered was the molecule that genes are made of.
This was a huge discovery.
It showed that DNA was actually controlling cells.
In order to understand how cells work, indeed, how life works, we would first need to understand DNA.
It became crucial to know exactly what it is and what it's for.
By the late 1940s, the chemistry of the cell was starting to become clearer.
What once had appeared to be indistinct blobs, were now known to contain chromosomes.
These were shown to carry genes.
And now they'd discovered that all genes were made of DNA.
But how did DNA control cells? Scientists thought that they might find the answer in the structure of the molecule.
They needed to work out how DNA was built.
And this quest would turn out to be the most famous story in biology.
It was after the Second World War that the quest began in earnest.
The American nuclear weapons project had involved thousands of physicists who'd delved deep into the atoms at the heart of all matter.
Among them was a British scientist who returned home after the war to take a job at King's College in London.
As part of its postwar rebuilding programme, the college had acquired the latest X-ray imaging techniques to look deep within the cell, and Professor Maurice Wilkins was put in charge.
And here is one of the X-ray generators we are using in this work.
We use X-rays to study the structure of a molecule because an X-ray travels along like this in a wavy kind of way and the length of the waves of the X-rays are about equal to the distance between the atoms in a molecule.
So that when an X-ray strikes the molecule, the waves of the X-rays can squeeze in between the atoms and when they come out the other side their directions are deviated.
And from the deviation of the X-rays we can work out the way in which the atoms are arranged inside the molecule.
The X-rays taken here at King's College were pivotal.
Producing them would be a painstaking job by a brilliant young scientist working with Wilkins.
Her name was Rosalind Franklin.
Franklin was an expert in X-ray imaging.
With her expertise, the college hoped to be the first to find the structure of DNA.
She worked in a new laboratory built in the basement on the rubble of the old college, which had been bombed.
The college authorities were concerned that the X-ray experiments, which used hydrogen, could be dangerous, so they made Franklin and her assistant do their work at night time after the students had gone home.
Franklin used highly concentrated DNA.
One of her skills was in finding just the right amount of moisture to prepare the strands.
It was precision work.
When she stretched out its fibres, she got a single DNA strand, a tenth of a millimetre across.
Here in the lab she took strands of DNA and mounted them inside this specially built camera.
The camera chamber was filled with hydrogen to get the best image.
When the X-rays were switched on, they shone through the DNA, and scattered in different directions, creating an image on a photographic film.
Franklin took over a hundred pictures.
Each one could take up to 90 hours of exposure at close range.
Once the photo was processed, she projected it onto the wall so she could calculate the exact distance between atoms.
It was picture 51 that showed the best image of the mysterious DNA molecule.
This distinctive X shape was the keythat would reveal how DNA is built.
But it was not Franklin's name that came to be associated with the discovery of DNA's structure.
Wilkins was in close touch withscientists from Cambridge, whowere anxious to find the structurebefore American rivals.
Unknown to Franklin, Wilkins gave photo 51 to James Watson, an ambitious young scientist at Cambridge's Cavendish Laboratory.
Having studied the photo, Watson and his collaborator, Francis Crick, had a sudden revelation.
'It would transform them into scientific celebrities 'and put the cell at the centre of world attention.
' This is the Eaglepub here in Cambridge.
According to Watson, on February 28th 1953, Francis Crick strolled into this pub and announced to fellow drinkers, "We have found the secret of life!" Now, if you ask me, this story is a little bit apocryphal, probably embellished with some dramatic licence.
Nevertheless, the sentiment is bang on and shouldn't be understated.
This marks one of the truly great moments in the history of science.
Crick and Watson had workedout the structure of DNA.
And very soon, their double helix model was announced to the world.
The structure of DNA is now themost famous image in all biology.
What Crick and Watson showed is that it's made of two long strands intertwined into two spirals, with sugar and phosphate making up the backbone.
But it's on the inside of the spiral where things get really interesting.
On the inside are fourmolecules - adenine, thymine, cytosine and guanine.
They are known by their letters A,T, C and G.
They're called bases.
What Crick and Watson discovered is that these four basic units pair up millions of times within the double helix andthey pair up in a very specific way.
A always pairs with T and C always pairs with G.
A and T and C and G making up the rungs of the ladder within the double helix.
What Crick and Watson realised is, if you split the twostrands of the DNA apart, you have all the information to maketwo new fresh pieces of DNA.
Every time you have an A, it pairs up with a T.
Every time you have a C, it pairs up with a G.
So when you split them apart, you can replace the missing strand and make up a new double helix.
Twice.
Genius.
'Crick and Watson's discovery 'triggered an explosion in scientific research.
'DNA's structure had revealed thesecret 'of how genes are reproduced every time a cell divides.
' An identical copy of the DNAis passed on from cell to cell.
Incredibly, all the information needed to create life is encoded in this molecule.
So the next big challenge was to crack the code.
Within ten years, scientists had deciphered the codewithin the double helix.
It was the instructions to make the millions of molecules that build our cells.
By then, scientists used electron microscopes to see thecomplex machinery inside the cell.
The electron microscope is an instrument capable of enlarging, of magnifying, of the order of 100,000 times.
Now can we move towards the nucleus? That's fine.
From such minute studies, it ispossible to make models such as the one which is the star of our set.
The half section of the cell with the outer skin removed one million times larger than life.
Professor Swann, perhaps you can orientate us now that we are inside the cell to what Mr Horne was showing us on the electron microscope? Well, I think the first thing to get clear is that you can see very clearly this great tracery oftubes and twigs.
That is the reticulum.
And in middle, of course, the nucleus.
Today's computer graphics show how much more we now know about how the cell works.
Cells use complex machinery to carry out the DNA's instructions and to make the millions of molecules that keep cells, and us, alive.
These are the cells that all living beings are made of.
All of it designed and controlled by DNA.
'And to make a living organism takes a staggering amount of DNA.
'Each human cell has 3.
4billion letters of DNA code.
'To print them on paper has taken 120 volumes.
'But there's a conundrum here.
' If you take any single cell in mybody, whether it's brain or bone or skin, they contain the same instructions, the same DNA, the same genes.
So how do you get from this set ofinstructions to a fully-functional human, containing trillions of highly-specialised cells? Let me show you what I mean.
I'm going to damage my skin by giving myself a burn.
You should not do this at home.
I'm doing it purely in the interests of science.
The burn will destroy some of my skin cells and create a wound.
So here goes.
Ow! Oh, my goodness, that hurt! You can see it's already started to burn the top layer of skin there.
Now we take it for granted that this wound is going to heal, thankfully for me.
But if you think about it, it's a really remarkable process.
And it can only happen because lots of different types of cells get to work to perform highly-specialised functions.
That really hurt! That really hurt quite a lot! Over the next days andweeks, my wound mends itself.
Nerve cells register pain and damage.
White blood cells fight infection.
Red blood cells form the scab.
And crucially, new cells develop and grow and make up layers of young tissue that replace the dead skin cells.
And here's the rub.
'Remember, all the cells in my body share exactly the same DNA, my DNA.
'Yet somehow, all the different kinds of cells 'involved in healing my wound know exactly what they should be doing.
' Four weeks later and my skin is well on its way to healing, although I am going to have a scar.
This process has happened, becauseall the cells involved knew exactly what their function was.
But how did they know that? How do any cellsknow what to do and what they are for? This question continued to puzzlescientists long after they'ddiscovered the structure of DNA.
How could the same DNA make different kinds of cells? The answers would come from some of the freakiest experiments in all biology.
And they would reveal something astonishing about the origins of life itself.
It was here in Switzerland some30 years after Crick and Watson that the first clue was discovered.
And yet again, it camefrom a scientist studying our old friend the fruit fly.
'Professor Walter Gehringis a pioneer of modern biology.
'In the 1980s, his work helpedsolve the mystery 'that remained at the heart of all life.
'How can DNA make all the different types of cell 'needed to build a living being?' Gehring's breakthrough began with something that happens very occasionally in nature.
A mutant fruit fly born with a rare abnormality.
A perfectly formed leg growing out of its head, right where the antennae should be.
The wrong kind of cells in the wrong part of the body.
Spooky! By comparing the genes of thismutant with normal flies, Gehring had been able to isolate the gene thattriggers the growth of a fly's leg.
'Did this gene have anything in common 'with the genes that controlled other parts of the fly's body? 'Gehring and his team got to work analysing 'and comparing the DNA sequences.
' So what you can do is you break this molecule.
You chop it into tiny fragments.
You have to find out where your gene is.
'After months of work, they found the location on the chromosome 'of several very similar genes.
' What we did was to make a huge what we call a restriction map.
And here we have the individual pieces of DNA.
This is the actualdata that you produced? This is the handmade map which we made to map each one of these.
This is actually a piece of history.
This is an historical piece, yes.
'The finished map produced a stunning revelation.
'It showed that all the key parts of the fly's body 'had something in common.
They were controlled 'by a handful of identical genetic switches.
' These switchers turned on other genes in the developing embryo.
And each of these genetic switches controlled one major chunk of the fly's body.
It's been a while since I've done this.
Take out theOh, I need to take out the stopper.
LAUGHTER Good call.
All right, I'll try that again.
'With the help of the mutant, 'Gehring's team had begun to solve the mystery 'of how all the different types of cell in the fly's body 'grow in the right place and at the right time.
' Oh, I miss doing this.
'These genetic switches are called homeobox genes 'and controlwhen other genes are switched on.
' As the fly larva grows, they kick in and lay out the fly's body plan.
Head at one end, tail at the other.
And they start a chain reaction of other genes, to grow a leg, a wing, or an antennae in exactly the right place.
Now scientists wanted to know did other creatures havesimilar genetic switches? 'They began to study other species, 'everything from frogs to mice to humans.
'Species which looked very different.
' And in every species they looked at, they found exactly thesame genetic switches.
The mechanism was the same in wildly different animals.
It was a staggering result.
But the biggest revelation was still to come.
In 1995, a student of Gehring's found the gene in a fruit fly which triggers the formation of eyes.
This gene launches a cascade of 2000other genes that generate all thecells that make up a fly's eye.
This eye gene in the fly looked incredibly similar to thegene that triggers eyes in mammals.
Now here's where it gets really interesting.
Gehring knew that the samegene existed in mice and humans, species whose eyes are completely different to fly eyes.
But a bold idea had taken hold inhis mind and he decided to test it with a bizarre experiment.
He took the mouse eye gene and heput it into a fruit fly embryo.
Dmitri Papadopoulos isshowing me how to insert the gene into the fertilised egg.
OK, so you've got DNA inside the needle and you're injecting it straight into the embryo.
Yes, exactly.
We inject the posterior part of the eggs.
Yes, that's in.
Yeah.
So that's it? 'Nobody knew what would happen.
'Would it kill the developing fly? 'Would it try to make awhole mouse eye in the fly? 'The result was striking.
' The eyes are bright red, so you cannot be mistaken.
If you see something red here, it's is an additional eye.
And they have lots of them.
It's just incredible to look at.
It's got eyes all over its body.
'The eyes grew in several places, because scientists had no way 'of controlling exactly wherethe mouse DNA would end up.
'But the baffling thing is they're not mouse eyes, they're fly eyes.
'The fly cells havebeen able to read the mouse gene 'as though it was their own.
' I can see it's normal eye, but I can also see maybe eight other eyes, including one right on the end of its antennae, which is flicking around.
It's moving around, yeah.
Yeah.
That's quite interesting.
It's like a sensor which moves.
A video camera which moves around and searches.
What we have shown for these antennae eyes is they can see with these eyes.
They can actuallysee?Yes.
Gehring's mutants made headlines around the world.
We came on the front page of the New York Times and they said, "Science outdoes Hollywood.
" It was the time of Spielberg and Jurassic Park.
And so, very wild things were shown on screen.
But the journalist thought that science even outdoes Hollywood at that time.
I completely agree with that.
You look at these things and it's much more impressive.
'But the headlines missed the real significance of Gehring's results.
'If genetic switches are shared across all species, 'everything from fruit flies to humans, 'and if genes can be swapped between species, 'this suggested that all life must have descended 'from one common ancestor, just as Charles Darwin predicted.
' The fact that you used a mouse geneto do that, what does that sayabout the way our DNA is shared? Yeah, it shows that we all are related to one another.
That Darwin was right, that we all share common descent.
'So the story of the cell 'is the story of the evolution of life itself.
'150 years of brilliant science had brought us to this point.
' At the heart of all lifeis one extraordinary molecule - DNA.
A molecule that holds all the information to make everykind of cell that has ever existed.
Understanding the chemistry of life has brought us to the cusp of one of the most exciting scientific experiments of all time.
Now that we know how cells work and how genes work within cells, scientists are about to be able tobuild new cells from scratch, to have them do our bidding.
We are on the brink of doing something that has only happenedonce in the last four billion years - to create new life from its component parts.
To do that, we need to go back to the very beginning of life on Earth to find out how the first cell came about.
In the final programme, I'll reveal how scientists are close to recreating that first cell in the lab.
How they found answers in thetoxic chemistry of the early Earth and in meteorites from space.
And I'll show how unlocking the power of the cell will transform all our lives.
I'm gonna take two living sponges, fresh out of the sea.
And I'm gonna utterly destroy them.
I'm going to reduce this piece of sponge to its individual cells.
Now it's wrapped up in this nylon mesh and this is acting as a kind of a sieve.
So now I'm going to squeeze it through this sieve.
What's left is nothing like a sponge.
A liquid containing cells.
You might think I'd totally killed the sponge.
But, if I leave these individual cells overnight, something really rather astonishing happens.
As the hours pass, the cells start to move.
Slowly they shuffle their way back together.
And, by joining up, they make a new piece of sponge.
Oh, and look at that purple one! I mean, it's such a striking result.
Almost all of the individual cells have gone.
It's as if the cells have acted like individuals with a purpose and they've actually re-aggregated into a piece of sponge tissue.
It's amazing! This experiment was first done over 100 years ago.
And it raised some really enormous questions.
How do cells know what to do? What goes on inside cells? How do these tiny structures make living organisms? If we find the answers to these questions, we'll find out what makes things alive - the secret of life itself.
If you think about it, it's pretty incredible.
Cells are just tiny bags full of molecules.
But how those lifeless molecules bundle together to create life was a fundamental mystery.
So the challenge for the scientists who first began to study the cell was to unravel the chemistry of life.
It was here in Germany, 150 years ago, that scientists set out to tackle the mysteries of the cell.
They'd discovered that plants, animals, people, all living things in fact, are made up of tiny cells.
Doctors began probing the cells of the human body.
Organs and tissues became specimens to be preserved, sliced and put under the microscope.
What they saw, and drew, showed that every organ and tissue is made of different types of cells working together.
And that all cells come from other cells.
New ones are only made when cells split in two.
Somehow, cells must contain the secret of life itself.
But scientists knew nothing about what went on inside these cells.
The problem was that, when doctors and scientists looked down the microscope at cells, what they could see didn't tell them much.
They could see that cells were enclosed by a boundary, a membrane, and there was a dense bit in the middle that they called the nucleus.
This was surrounded by a jelly-like gloopthat they called protoplasm.
But the problem was that these were just blobs within blobs.
They didn't know what the blobs were foror even what they were made of.
The first step towards understanding the working of cells came in the small German town of Tubingen.
It was a centre of scientific excellence.
Europe's first biochemistry lab was established in the local castle.
One of the aims was to find out more about human cells.
And it was here, in 1868, that a keen young scientist, Dr Friedrich Miescher, arrived to take up his first research post.
Miescher's job here at the castle was to study the chemistry of white blood cells.
He decided to look at the large nucleus at the centre of the cell and find out what it was made of.
To do this, he needed two things.
A ready supply of cells, and a way of getting rid of the gloop so he could study the bare nucleus.
Getting hold of white blood cells would normally have been tricky.
But Tubingen was the ideal place.
The region had been at war with Prussia.
Hundreds of injured soldiers with infected wounds lay in the barracks next to the hospital.
Their wounds were oozing copious amounts of pus, which is full of white blood cells.
So, revolting as it sounds, Miescher collected their old bandages so he could scrape off the pus.
Miescher needed something else.
His next stop was the local slaughterhouse, to collect a pig's stomach.
Here it is.
Oh! That's disgusting! 'He was interested in the mucus that lined the stomach.
'This contains an enzyme called pepsin, 'which helps break down and digest food.
' Where's the pepsin? Look here.
This is the pepsin.
This sort of gloopy stuff?Yep.
There's not much of it.
No.
That's all.
And this is what helps digest food in the stomach?Yeah.
Smells like a pig's stomach to me.
'With the pepsin, Miescher now had all he needed for his experiment.
' And this is a delicacy in Tubingen? Yes, you call fill it with bread or you can cut it in stripes, then you cook it and eat it with bread.
Is it tasty?Yes.
I'm not sure about that.
Miescher carried the bandages and the pig's stomach back to the lab.
If he was right, the pepsin would break down the white blood cells.
Then, for the very first time, it would be possible to examine the dense nucleus at the heart of the cell.
Nowadays we do analysis like this using precision equipment.
But of course Miescher didn't have any kit like that so it wasn't easy.
First he had to scrape the pus from the bandages.
Now, this is mayonnaise, but you get the idea.
Then he had to wash the pepsin out of the pig's stomach using an acid.
And mixed it with the pus.
After the enzyme had done its work and digested the cells, only then could he analyse the nucleus on its own.
Now the big question was, what did the nucleus consist of? Miescher spent months analysing its chemistry.
And he found it contained a rather strange molecule.
This molecule was made up of carbon, hydrogen, oxygen and nitrogen.
He knew these elements were found in all living things.
But this molecule contained something extra - phosphorus.
And that made it different.
Very different.
It was an entirely new kind of molecule.
Because he found it in the nucleus, Miescher called it nuclein.
We now know it as DNA.
Intrigued, Miescher repeated his experiment on sperm cells from frogs, carp, bulls and salmon.
Every time he found exactly the same molecule.
Incredibly, some of it has survived.
Here in this test tube is some of the first DNA ever isolated.
It's DNA from salmon sperm that Miescher extracted in the 1870s.
Now, it may not look like much, but this brown powder marks the beginning of a scientific revolution.
Miescher's discovery of DNA was confirmation that there was something special inside the nucleus of cells, a molecule that was common to all life.
But Miescher was way ahead of his time.
His work on the chemistry of the nucleus went unnoticed because scientists still had little idea of what the nucleus was for, or of how cells worked.
It was the warm waters of the Mediterranean that gave them an important breakthrough.
Here, scientists found a ready supply of living cells which they could easily study.
The embryos of the many species of marine life that thrive here.
Which is why the Bay of Naples became the centre of a remarkable scientific community, scientists who were using the abundance of creatures in the sea to study how life is formed.
At the heart of the community was this marine station, built on the shores of Naples.
And in 1888 another young German scientist, Theodor Boveri, arrived here to work on cells.
He'd be studying alongside some of the most eminent scientists of his day.
In fact, the marine station was supported by Charles Darwin himself.
The scientists built a public aquarium to fund their research.
Then, as now, it was a popular attraction.
And it provided a ready supply of cell specimens.
Because fish lay their eggs straight into the water.
Boveri was interested in the fertilisation of eggs.
Once the egg cell is fertilised, it begins to divide.
It creates another cell, and then another, and so a new life is born.
Somehow, when the cells divide, the essence of life is passed from cell to cell.
By the end of the century, with better microscopes and new chemical dyes to stain the cells, embryologists were able to see early dividing cells in more detail than ever before.
And what they saw was incredible.
Have a look at some of these drawings.
Scientists had thought that when the cells divide they simply split down the middle.
But now they began to see that something far more complicated was going on inside the nucleus.
As cells started to divide, discrete objects like little rods would appear inside the nucleus.
These rods seemed to unravel and split in two, migrating to opposite ends of the nucleus.
Then the nucleus would split in half, followed by the cell itself.
Scientists called the rods "chromosomes", meaning coloured bodies, because the chemical dyes they were using gave them a colour.
And they saw that these puzzling chromosomes only appeared in the nucleus when a cell divided.
Now, the obvious question for any scientist looking at something so complex and elaborate iswhy? Why do the cells have to divide in such a curious way? To find the answer, Boveri devised an experiment.
He used a creature found in abundance at the bottom of the bay.
My underwater guide is Dr Ina Arnone.
Ina works at the Naples marine station on the same kind of creature Boveri used - the sea urchin.
The easy part about collecting sea urchins is finding them.
Unlike fish, they just stick to the rocks.
But, without practice, picking them off is harder than you think.
And the spines can really hurt.
There it is, a sea urchin, plucked .
.
plucked from the bottom of the Bay of Naples.
There are thousands of them down there.
You can see why people used these as experimental animals.
The inside of a sea urchin consists almost entirely of its reproductive organs, or gonads.
Oh, this is very good.
Look at the gonads.
How big they are.
And you can recognise this is a male.
Because you see here? These are the gonads and this is theThe white part is the sperm.
Wow.
And, fishermen, they believe this is indeed the the milk of the sea urchin.
Right.
And this is a local delicacy here as well, right?Yes, it is.
Yes.
You wanna try?Of course.
Shall I show you how to do it?Yeah, go on then.
Take this little bit.
It's likeeating the sea.
Let me try.
So I just suck it out? Just suck it out.
HE SLURPS Mmm.
It's pretty salty.
Oh, that's salty, yes! Why have people used these for scientific research? Oh, that's pretty obvious.
They produce billions of eggs and sperm.
'And billions of eggs and sperm, each of them single cells, 'were just what Boveri needed for his experiment.
'Back in the lab, all Boveri had to do was shake the sea urchins.
' Like this! 'This stimulates the sea urchins to spawn.
' So, the orange powdery stuff that's just falling off the bottom, that's the eggs.
Exactly.
They are falling down and you will see them collecting on the bottom.
'Boveri wanted to find out what happened when cells divide.
'So his starting point 'was the moment when the egg is fertilised by a sperm.
' You can see here the nucleus of the egg.
This bit in the middle? Yes, I can focus to show you better.
That's what Boveri used to see under the microscope.
So this is an unfertilised egg.
You can really see the sperm trying to eattheir way into the egg.
Yes.
That's incredible.
Wow! You see the fertilisation envelope.
'Boveri knew that, when an egg is fertilised, 'the nucleus of the egg and sperm combine to form a new nucleus.
'This first cell of the new embryo divides into two.
'Soon, two cells become four.
'Four cells become eight, 16, 32 and so on.
'And, each time a cell divides, the nucleus of the new cell inherits 'an identical copy of all of the chromosomes.
'So Boveri knew the chromosomes must be important.
'But how important?' 'He wondered, if he added extra sperm into the egg, 'would extra chromosomes appear? 'What effect would this have? Would the cellsstill divide normally?' With Ina's fluorescent microscope, we can see what happens.
When extra sperm are added, the whole process of cell division goes off beam.
Clumps of deformed cells of different shapes and sizes appear.
The whitish blobs in the middle are the chromosomes in the nuclei.
But their irregular shape suggests each nucleus has acquired a different amount of chromosomes.
So this one looks very different.
We've got three nuclei here.
But is this one cell or two cells? I can't quite make it out.
Yes.
First of all you can see that there are three nuclei, and not two, as supposed to be at this stage.
But also what you can see is that the nuclear content is different.
So you can see this is much bigger.
This is smaller, this is even smaller.
So this didn't receive the same amount of chromosomes.
So there's different amounts of chromosomes in each bit of the cell? So it's gone wrong.
Exactly.
And this embryo won't develop any further? Well, he will probably do some more division, but it will generate monsters.
A monster.
So it won't develop into a proper sea urchin.
Not at all.
That's what Boveri saw.
Every time he introduced extra sperm into his sea urchin eggs, he got monsters.
Mutant embryos that never got further than a few cells.
So let's just take a moment to think about what a massive discovery Boveri had made.
An embryo would only develop if it had one full set of chromosomes in every cell.
So, every time a cell divided, a new identical set of chromosomes had to be formed in every cell.
Any more or less, and the embryo would die.
So it's suggested that whatever information was in the mysterious chromosomes, it was essential for life.
But what was that information? Boveri had an idea.
The chromosomes for a new life came from the sperm and the egg.
So could the chromosomes be the way in which all the characteristics of sea urchins are passed on when a new life is created? And again and again every time the cells divide.
Boveri spent the next 20 years experimenting on sea urchins.
And he became convinced that chromosomes must contain what he called the "hereditary characters".
In other words, key bits of information that control the characteristics that a creature inherits.
Boveri was predicting the existence of genes.
He was onto something big.
The idea that chromosomes within our cells could be the way that life, and all the traits we inherit, are passed on.
In New York, Boveri's work on chromosomes had caught the attention of a fellow embryologist.
Thomas Hunt Morgan was another veteran of the Naples Marine Station.
But here at Columbia University, he'd moved on from studying sea life.
His creature of choice was Drosophila melanogaster, that's the fruit fly to you and me.
Thanks to Morgan, this tiny insect was to become one of the mighty heroes of biology.
For anyone interested in studying inheritance, the fruit fly has some big advantages.
They're small, cheap, and they breed like, well, flies.
You can get a new generation every ten days.
And they have only four pairs of chromosomes.
Morgan's lab became known as "the fly room".
Now just as we inherit characteristics from our parents so indeed do all creatures, including fruit flies.
Morgan wanted to see if he could see patterns of inheritance in fruit flies and link these patterns to the chromosomes.
Now in nature, fruit flies normally have red eyes.
But one day, Morgan found a male fly with white eyes in his collection.
He decided to crossbreed it with a red-eyed female.
When Morgan bred their offspring, some of the next generation of flies emerged with white eyes.
Morgan noticed that it was only male flies that had inherited white eyes.
None of the females.
He concluded that having white eyes was somehow linked to being male.
Morgan knew that the chromosomes of fruit flies included two which determined gender.
So he deduced that the information for making white eyes had to be carried on the sex chromosomes.
That was his breakthrough.
Morgan had now found evidence that seemed to support what Boveri had predicted, that the characteristics we inherit map to specific parts of the chromosome.
Now the fly room was really buzzing.
The team were soon able to find which parts of the fly's chromosomes accounted for traits like body colour and wing size, as well as eye colour.
And by 1922 they'd drawn up the world's first chromosome map showing the location of 2,000 different traits.
To describe the individual parts of the chromosomes that related to each trait, he used the word "gene".
Nowadays genes are part of our everyday language.
So it's easy to forget just what a huge leap forward this was.
To understand that the way we look and the way we operate might be determined by genes within our cells.
Genes are what families truly share.
They are the biological link between my dad, myself and my son.
Spotting those genetic connections can make family photo albums such fun.
That's you.
That looks like Jakey to me.
Very similar.
You look much more like your mum.
Yeah, I always did.
Where is she? Back in the 1920s, the idea that something within our cells could account for family resemblance was new.
Look at that! Look at those tiger-skin Speedos.
You were on the other side of the camera encouraging me to do something stupid.
Very likely.
Today these genetic links are accepted, but a century ago, this was ground-breaking stuff.
Scientists had peered into the cell nucleus.
They had found chromosomes.
And they had shown that these chromosomes carried information we inherit - genes.
But they still had no idea how.
So here was the new question.
What on earth were genes? What was the chemistry within cells, the molecule, that allowed hereditary information to pass from one cell to another, from generation to generation.
The answer to that would come from two scientists studying not inheritance, but disease.
Fred Griffith and Oswald Avery were both medical researchers working on pneumonia, but on opposite sides of the Atlantic.
They didn't even know each other, but together they would find the next crucial piece of the puzzle of how cells work.
Fred Griffith was working at the Ministry of Health here in London.
He was investigating types of bacteria, single cells that invade the body and reproduce there.
He wanted to find out why some bacteria kill and others don't.
And he stumbled across something rather remarkable.
It all began when he was using laboratory mice to test cocktails of different bacterial strains.
He was looking for a combination that would work as a vaccine to prevent pneumonia.
He started with solutions of two different types of pneumonia bacteria, which I've mocked up in these beakers, one harmless, the other lethal.
And with very basic equipment, he tested his bacteria on the mice.
Unsurprisingly, when he injected the mice with the harmless bacteria, they were fine.
And when he injected them with the lethal bacteria, they died.
Griffith then took the solution of lethal pneumonia bacteria and heated it.
He thought this should kill the bacteria.
And sure enough, when injected, the mice showed no sign of pneumonia.
It was then that Griffith tried something which gave a very surprising result.
When Griffith made a mixture of the lethal, heat-treated bacteria with the harmless bacteria, remember that neither of these had killed the mice on their own, he found that some of the mice died.
When he examined the dead mice, he found deadly bacteria in their blood.
Something very spooky was going on here.
Griffith figured that something in the lethal bacteria had survived.
And whatever it was, it had transformed the harmless bacteria into killer cells.
But what was that something? He never found out.
Griffith had his job to do working on vaccines.
He never realised that he had accidentally found a whopping great clue to what genes are, a clue that would lead to a major breakthrough in our understanding of how cells work.
But his results caught the attention of Oswald Avery, also an expert in pneumonia bacteria.
Avery was determined to find out what it was that had the power to change one type of cell into another.
It would take him nearly a decade, but it would turn out to be a critically important discovery.
At the Rockefeller Institute in New York, Avery and his team were using the latest methods in biochemistry to look inside bacteria.
They knew that bacteria, like all cells, are essentially little bags jammed full of different kinds of molecules.
A chemical soup made of millions of protein molecules, carbohydrates and fatty substances called lipids.
Over nine years they tested every type of molecule in the lethal pneumonia bacteria to find out which molecule was passing on its deadly traits to the harmless bacteria.
Avery decided to work by a process of elimination.
First he removed the carbohydrates and then the lipids, but it wasn't either of them.
Then, he removed all of the proteins but it wasn't them either.
Finally, he turned his attention to a molecule that had seemed like an unlikely candidate.
It was when he started testing DNA, the strange molecule in the nucleus, that Friedrich Miescher had found 75 years earlier, that Avery got a result.
Stripped of their DNA, the power of the lethal bacteria to transform other cells simply vanished.
What Avery had discovered was the molecule that genes are made of.
This was a huge discovery.
It showed that DNA was actually controlling cells.
In order to understand how cells work, indeed, how life works, we would first need to understand DNA.
It became crucial to know exactly what it is and what it's for.
By the late 1940s, the chemistry of the cell was starting to become clearer.
What once had appeared to be indistinct blobs, were now known to contain chromosomes.
These were shown to carry genes.
And now they'd discovered that all genes were made of DNA.
But how did DNA control cells? Scientists thought that they might find the answer in the structure of the molecule.
They needed to work out how DNA was built.
And this quest would turn out to be the most famous story in biology.
It was after the Second World War that the quest began in earnest.
The American nuclear weapons project had involved thousands of physicists who'd delved deep into the atoms at the heart of all matter.
Among them was a British scientist who returned home after the war to take a job at King's College in London.
As part of its postwar rebuilding programme, the college had acquired the latest X-ray imaging techniques to look deep within the cell, and Professor Maurice Wilkins was put in charge.
And here is one of the X-ray generators we are using in this work.
We use X-rays to study the structure of a molecule because an X-ray travels along like this in a wavy kind of way and the length of the waves of the X-rays are about equal to the distance between the atoms in a molecule.
So that when an X-ray strikes the molecule, the waves of the X-rays can squeeze in between the atoms and when they come out the other side their directions are deviated.
And from the deviation of the X-rays we can work out the way in which the atoms are arranged inside the molecule.
The X-rays taken here at King's College were pivotal.
Producing them would be a painstaking job by a brilliant young scientist working with Wilkins.
Her name was Rosalind Franklin.
Franklin was an expert in X-ray imaging.
With her expertise, the college hoped to be the first to find the structure of DNA.
She worked in a new laboratory built in the basement on the rubble of the old college, which had been bombed.
The college authorities were concerned that the X-ray experiments, which used hydrogen, could be dangerous, so they made Franklin and her assistant do their work at night time after the students had gone home.
Franklin used highly concentrated DNA.
One of her skills was in finding just the right amount of moisture to prepare the strands.
It was precision work.
When she stretched out its fibres, she got a single DNA strand, a tenth of a millimetre across.
Here in the lab she took strands of DNA and mounted them inside this specially built camera.
The camera chamber was filled with hydrogen to get the best image.
When the X-rays were switched on, they shone through the DNA, and scattered in different directions, creating an image on a photographic film.
Franklin took over a hundred pictures.
Each one could take up to 90 hours of exposure at close range.
Once the photo was processed, she projected it onto the wall so she could calculate the exact distance between atoms.
It was picture 51 that showed the best image of the mysterious DNA molecule.
This distinctive X shape was the keythat would reveal how DNA is built.
But it was not Franklin's name that came to be associated with the discovery of DNA's structure.
Wilkins was in close touch withscientists from Cambridge, whowere anxious to find the structurebefore American rivals.
Unknown to Franklin, Wilkins gave photo 51 to James Watson, an ambitious young scientist at Cambridge's Cavendish Laboratory.
Having studied the photo, Watson and his collaborator, Francis Crick, had a sudden revelation.
'It would transform them into scientific celebrities 'and put the cell at the centre of world attention.
' This is the Eaglepub here in Cambridge.
According to Watson, on February 28th 1953, Francis Crick strolled into this pub and announced to fellow drinkers, "We have found the secret of life!" Now, if you ask me, this story is a little bit apocryphal, probably embellished with some dramatic licence.
Nevertheless, the sentiment is bang on and shouldn't be understated.
This marks one of the truly great moments in the history of science.
Crick and Watson had workedout the structure of DNA.
And very soon, their double helix model was announced to the world.
The structure of DNA is now themost famous image in all biology.
What Crick and Watson showed is that it's made of two long strands intertwined into two spirals, with sugar and phosphate making up the backbone.
But it's on the inside of the spiral where things get really interesting.
On the inside are fourmolecules - adenine, thymine, cytosine and guanine.
They are known by their letters A,T, C and G.
They're called bases.
What Crick and Watson discovered is that these four basic units pair up millions of times within the double helix andthey pair up in a very specific way.
A always pairs with T and C always pairs with G.
A and T and C and G making up the rungs of the ladder within the double helix.
What Crick and Watson realised is, if you split the twostrands of the DNA apart, you have all the information to maketwo new fresh pieces of DNA.
Every time you have an A, it pairs up with a T.
Every time you have a C, it pairs up with a G.
So when you split them apart, you can replace the missing strand and make up a new double helix.
Twice.
Genius.
'Crick and Watson's discovery 'triggered an explosion in scientific research.
'DNA's structure had revealed thesecret 'of how genes are reproduced every time a cell divides.
' An identical copy of the DNAis passed on from cell to cell.
Incredibly, all the information needed to create life is encoded in this molecule.
So the next big challenge was to crack the code.
Within ten years, scientists had deciphered the codewithin the double helix.
It was the instructions to make the millions of molecules that build our cells.
By then, scientists used electron microscopes to see thecomplex machinery inside the cell.
The electron microscope is an instrument capable of enlarging, of magnifying, of the order of 100,000 times.
Now can we move towards the nucleus? That's fine.
From such minute studies, it ispossible to make models such as the one which is the star of our set.
The half section of the cell with the outer skin removed one million times larger than life.
Professor Swann, perhaps you can orientate us now that we are inside the cell to what Mr Horne was showing us on the electron microscope? Well, I think the first thing to get clear is that you can see very clearly this great tracery oftubes and twigs.
That is the reticulum.
And in middle, of course, the nucleus.
Today's computer graphics show how much more we now know about how the cell works.
Cells use complex machinery to carry out the DNA's instructions and to make the millions of molecules that keep cells, and us, alive.
These are the cells that all living beings are made of.
All of it designed and controlled by DNA.
'And to make a living organism takes a staggering amount of DNA.
'Each human cell has 3.
4billion letters of DNA code.
'To print them on paper has taken 120 volumes.
'But there's a conundrum here.
' If you take any single cell in mybody, whether it's brain or bone or skin, they contain the same instructions, the same DNA, the same genes.
So how do you get from this set ofinstructions to a fully-functional human, containing trillions of highly-specialised cells? Let me show you what I mean.
I'm going to damage my skin by giving myself a burn.
You should not do this at home.
I'm doing it purely in the interests of science.
The burn will destroy some of my skin cells and create a wound.
So here goes.
Ow! Oh, my goodness, that hurt! You can see it's already started to burn the top layer of skin there.
Now we take it for granted that this wound is going to heal, thankfully for me.
But if you think about it, it's a really remarkable process.
And it can only happen because lots of different types of cells get to work to perform highly-specialised functions.
That really hurt! That really hurt quite a lot! Over the next days andweeks, my wound mends itself.
Nerve cells register pain and damage.
White blood cells fight infection.
Red blood cells form the scab.
And crucially, new cells develop and grow and make up layers of young tissue that replace the dead skin cells.
And here's the rub.
'Remember, all the cells in my body share exactly the same DNA, my DNA.
'Yet somehow, all the different kinds of cells 'involved in healing my wound know exactly what they should be doing.
' Four weeks later and my skin is well on its way to healing, although I am going to have a scar.
This process has happened, becauseall the cells involved knew exactly what their function was.
But how did they know that? How do any cellsknow what to do and what they are for? This question continued to puzzlescientists long after they'ddiscovered the structure of DNA.
How could the same DNA make different kinds of cells? The answers would come from some of the freakiest experiments in all biology.
And they would reveal something astonishing about the origins of life itself.
It was here in Switzerland some30 years after Crick and Watson that the first clue was discovered.
And yet again, it camefrom a scientist studying our old friend the fruit fly.
'Professor Walter Gehringis a pioneer of modern biology.
'In the 1980s, his work helpedsolve the mystery 'that remained at the heart of all life.
'How can DNA make all the different types of cell 'needed to build a living being?' Gehring's breakthrough began with something that happens very occasionally in nature.
A mutant fruit fly born with a rare abnormality.
A perfectly formed leg growing out of its head, right where the antennae should be.
The wrong kind of cells in the wrong part of the body.
Spooky! By comparing the genes of thismutant with normal flies, Gehring had been able to isolate the gene thattriggers the growth of a fly's leg.
'Did this gene have anything in common 'with the genes that controlled other parts of the fly's body? 'Gehring and his team got to work analysing 'and comparing the DNA sequences.
' So what you can do is you break this molecule.
You chop it into tiny fragments.
You have to find out where your gene is.
'After months of work, they found the location on the chromosome 'of several very similar genes.
' What we did was to make a huge what we call a restriction map.
And here we have the individual pieces of DNA.
This is the actualdata that you produced? This is the handmade map which we made to map each one of these.
This is actually a piece of history.
This is an historical piece, yes.
'The finished map produced a stunning revelation.
'It showed that all the key parts of the fly's body 'had something in common.
They were controlled 'by a handful of identical genetic switches.
' These switchers turned on other genes in the developing embryo.
And each of these genetic switches controlled one major chunk of the fly's body.
It's been a while since I've done this.
Take out theOh, I need to take out the stopper.
LAUGHTER Good call.
All right, I'll try that again.
'With the help of the mutant, 'Gehring's team had begun to solve the mystery 'of how all the different types of cell in the fly's body 'grow in the right place and at the right time.
' Oh, I miss doing this.
'These genetic switches are called homeobox genes 'and controlwhen other genes are switched on.
' As the fly larva grows, they kick in and lay out the fly's body plan.
Head at one end, tail at the other.
And they start a chain reaction of other genes, to grow a leg, a wing, or an antennae in exactly the right place.
Now scientists wanted to know did other creatures havesimilar genetic switches? 'They began to study other species, 'everything from frogs to mice to humans.
'Species which looked very different.
' And in every species they looked at, they found exactly thesame genetic switches.
The mechanism was the same in wildly different animals.
It was a staggering result.
But the biggest revelation was still to come.
In 1995, a student of Gehring's found the gene in a fruit fly which triggers the formation of eyes.
This gene launches a cascade of 2000other genes that generate all thecells that make up a fly's eye.
This eye gene in the fly looked incredibly similar to thegene that triggers eyes in mammals.
Now here's where it gets really interesting.
Gehring knew that the samegene existed in mice and humans, species whose eyes are completely different to fly eyes.
But a bold idea had taken hold inhis mind and he decided to test it with a bizarre experiment.
He took the mouse eye gene and heput it into a fruit fly embryo.
Dmitri Papadopoulos isshowing me how to insert the gene into the fertilised egg.
OK, so you've got DNA inside the needle and you're injecting it straight into the embryo.
Yes, exactly.
We inject the posterior part of the eggs.
Yes, that's in.
Yeah.
So that's it? 'Nobody knew what would happen.
'Would it kill the developing fly? 'Would it try to make awhole mouse eye in the fly? 'The result was striking.
' The eyes are bright red, so you cannot be mistaken.
If you see something red here, it's is an additional eye.
And they have lots of them.
It's just incredible to look at.
It's got eyes all over its body.
'The eyes grew in several places, because scientists had no way 'of controlling exactly wherethe mouse DNA would end up.
'But the baffling thing is they're not mouse eyes, they're fly eyes.
'The fly cells havebeen able to read the mouse gene 'as though it was their own.
' I can see it's normal eye, but I can also see maybe eight other eyes, including one right on the end of its antennae, which is flicking around.
It's moving around, yeah.
Yeah.
That's quite interesting.
It's like a sensor which moves.
A video camera which moves around and searches.
What we have shown for these antennae eyes is they can see with these eyes.
They can actuallysee?Yes.
Gehring's mutants made headlines around the world.
We came on the front page of the New York Times and they said, "Science outdoes Hollywood.
" It was the time of Spielberg and Jurassic Park.
And so, very wild things were shown on screen.
But the journalist thought that science even outdoes Hollywood at that time.
I completely agree with that.
You look at these things and it's much more impressive.
'But the headlines missed the real significance of Gehring's results.
'If genetic switches are shared across all species, 'everything from fruit flies to humans, 'and if genes can be swapped between species, 'this suggested that all life must have descended 'from one common ancestor, just as Charles Darwin predicted.
' The fact that you used a mouse geneto do that, what does that sayabout the way our DNA is shared? Yeah, it shows that we all are related to one another.
That Darwin was right, that we all share common descent.
'So the story of the cell 'is the story of the evolution of life itself.
'150 years of brilliant science had brought us to this point.
' At the heart of all lifeis one extraordinary molecule - DNA.
A molecule that holds all the information to make everykind of cell that has ever existed.
Understanding the chemistry of life has brought us to the cusp of one of the most exciting scientific experiments of all time.
Now that we know how cells work and how genes work within cells, scientists are about to be able tobuild new cells from scratch, to have them do our bidding.
We are on the brink of doing something that has only happenedonce in the last four billion years - to create new life from its component parts.
To do that, we need to go back to the very beginning of life on Earth to find out how the first cell came about.
In the final programme, I'll reveal how scientists are close to recreating that first cell in the lab.
How they found answers in thetoxic chemistry of the early Earth and in meteorites from space.
And I'll show how unlocking the power of the cell will transform all our lives.