The Cell (2009) s01e01 Episode Script
The Hidden Kingdom
What is life and where does it come from? These are questions that have puzzled human minds for thousands of years.
And yet it's only in the last couple of centuries that we've come to discover what life is actually made of.
Take me, for example.
How is it that I'm alive? I can show you what I consist of, the chemicals that make up a standard-issue human.
RUTHERFORD: You need 18 kilos of carbon, a small canister of nitrogen, 50 kilos of water, enough phosphorus to make 2,000 matches, the same amount of iron as a small nail, and around 20 other elements.
Chemically, the two sides are identical.
But biologically, we're completely different.
Obviously, I'm alive, and the difference is that these exact same chemicals are organised into cells.
RUTHERFORD: 60,000 billion tiny, incredibly complex structures that make up my body.
Quite simply, we are cells.
RUTHERFORD: Every time we breathe, we move, we think, cells do the work for us.
Like all biologists, the more I find out about them, the more they amaze me.
The idea that all living creatures, from amoebas to humans, are made up of cells is the cornerstone of biology.
It's the theory of everything.
Yet the story of how we came to understand the cell is rarely told.
It's a fantastic voyage, delving deeper and deeper into an almost magical unseen world.
It's about nothing less than unlocking the mysteries of life itself.
And, for me, the story of the cell is the most powerful story in science.
RUTHERFORD: My starting point is September, 1674 and the Royal Society of London.
A mysterious satchel arrived at this club for gentleman scientists.
It had taken five days to get here from Holland, across the North Sea by ship and then by horseback rider.
The package came from a man who'd built the world's most powerful microscope, a microscope which revealed a hidden kingdom nobody had seen before.
The secretary of the Royal Society opened the satchel.
In it, there was a long letter in Dutch with a description of something truly extraordinary, tiny animals that pirouetted and swam like eels, and so small, according to the author, that you could fit a million of them on a single grain of sand.
So let's have a look.
These are the letters.
You can see the date, 1674, at the top.
It's written in Dutch.
I don't speak Dutch so I can't understand that.
There's the signature, the sender Antoni van Leeuwenhoek.
And the drawings came in later letters.
You can see these crazy, tiny creatures.
This one here, he's got a little dotted line to indicate the movement.
There he is, spinning round.
So, picture the scene.
These guys at the Royal Society, these stuffy, old scientists, had never seen anything like this before and yet, suddenly, this letter comes through from Holland with these totally alien creatures, not only looking really weird, but, also, so small that they couldn't even see them.
It must have just been completely amazing.
Did they even believe that these were real? The fellows of the Royal Society did have their own microscopes.
The device had been around since about 1600, but they'd never seen the tiny animals van Leeuwenhoek claimed to have found.
Quite frankly, they suspected this unknown Dutchman must be crazy.
Antoni van Leeuwenhoek came from the market town of Delft.
He wasn't a scientist at all.
In fact, he was a linen merchant.
Drapers like van Leeuwenhoek inspected their cloth with magnifying glasses and Holland had pioneered their manufacture.
They're still used today.
Here, look, this That may be nice to show.
This is a 17th-century napkin.
Shall I show you how big they were in those days? This is actually from the 17th century? This is not a replica? No, this is a real 17th-century napkin.
- Look.
- It's huge! Yes.
That was huge.
Were they particularly messy eaters in the 17th century? Yes, we think so.
- But they're not Look, this big.
- It's like a tablecloth.
(LAUGHING) Yes.
But it's only a napkin.
What? They didn't tuck it in Sometimes.
But you had to put it on your lap, of course.
I'm sorry.
I'm being slightly disrespectful for a 300-year-old piece of cloth.
And how do you look at the quality of the cloth? Well, when I want to look the quality quite good, then I use a loupe.
And I look through it.
And, look, this is a very old loupe.
- So this is a loupe - This is a loupe.
Which is the same word in English, it's like what watchmakers use, but basically it's a magnifying glass.
Okay, magnifying glass, yeah.
And you can look through it, and when you look through it, you can count the threads, you can see the threads from the napkin quite good.
Can I have a go? Yes, you can have a look at the quality.
Thank you.
So, you pull it up and then it comes into focus and there you go.
There you can see every single Every single thread, every single stitch, it's amazing.
You can really see the pattern.
This is basically exactly the same technique that van Leeuwenhoek would have done in the 17th century.
Yes.
Yes.
RUTHERFORD: Van Leeuwenhoek became obsessed with lenses, a sort of a lens geek.
(BELL TOLLING) He turned out to be the best lens maker there was.
He used delicately crafted lenses like these in his own unique viewing machine.
This is a replica of van Leeuwenhoek's microscope.
Look how simple it is.
It's just a piece of brass and it's got one tiny hole with the lens in it, which is maybe a millimetre across.
Yet this is the gadget that transformed the way we see the world.
A tiny lens, yet more powerful than any other.
Van Leeuwenhoek knew that it's the curvature of a lens that bends the light passing through it, so making the object being observed, here it's a flea, appear larger.
And because van Leeuwenhoek was a master craftsmen he could curve the lens more than anybody else, almost to the point it was spherical.
This allowed him to magnify objects up to 500 times.
No one would make a more powerful microscope for over a century.
So he now had the technology, but what did he look at? He went from linen to fleas to the sting of a bumblebee.
In fact, pretty much anything he could get his hands on.
And one of the things he looked at was water.
He'd noticed that in a lake near Delft, the water changed colour with the seasons and he figured that there might be something in the water that he could discover.
Many of the fundamental breakthroughs of science seem so simple, so absurdly simple.
But we shouldn't forget that, until van Leeuwenhoek, no one had the curiosity to find out what might be lurking in the water.
He raced home to take a closer look with his microscope.
The man who's going to help me study the water is Hans Loncke.
He keeps the spirit of van Leeuwenhoek alive by making replicas of his microscopes.
To grind a lens, Hans needs no special glass, just a shard from an old jam jar will do.
The only way to get enough curvature in the lens is to make it tiny.
This was van Leeuwenhoek's secret and it requires great skill and patience.
Van Leeuwenhoek built a staggering 247 microscopes, a new one every couple of months for over 50 years, and told nobody how he made them.
We've placed a drop of my lake water onto a slide that slots into the device.
With a bit of luck I'll be able to see what van Leeuwenhoek saw.
Now I've looked down a fair few microscopes in my time and this is nothing like anything I've used before.
It's fiendishly difficult to use so I've got Hans with me just in case I can't see a thing.
So what do I actually do? Where am I looking? - Uh, the wrong side.
- Mmm-hmm.
- You must look through this hole.
- Yeah.
A very tiny hole.
- And there's a lens in it.
- Yes.
And the lens, through the lens you see, - uh, the - The sample.
The sample that is put between the glass.
So if I hold it up to the light, like this Close to your eyes.
And I can see I can see green.
- There is a focusing knob.
- There's a focus? Yes, there is a focusing knob.
This might be made So you can move it, actually, away from my eye.
- This one, this is the focus.
- Let me try that.
It's so simple and it works so well.
Yeah, that works, that really works.
It's now in focus.
Oh, wow.
Oh, my God, you can actually see moving creatures.
LONCKE: Yes.
RUTHERFORD: Oh, God, that's incredible.
(CHUCKLING) There's a tiny, tiny bug in there, which is scooting around, which I guess is a protozoa.
That's astonishing.
I know this story, but I didn't think this was what I was going to actually see.
It's just like looking down a modern microscope, in fact, even though it's completely different to use.
Van Leeuwenhoek gushed with delight, too, writing, "This was, to me, among all the marvels that I have discovered in nature, "the most marvellous of all.
"No greater pleasure has yet come to my eye "than these spectacles of so many thousands of living creatures "in a small drop of water moving among one another.
" And so, in the 17th century, when people were discovering Australia and astronomers were exploring the heavens, so van Leeuwenhoek was peering into a new microscopic universe.
The full meaning of what he saw in that universe, seen here down a modern microscope, escaped van Leeuwenhoek.
He assumed he was seeing miniaturised versions of everyday animals with beating hearts and contracting muscles, just like their larger counterparts.
He called them "animalcules".
Little did he know, it wasn't just a question of scale.
Van Leeuwenhoek's discovery was the beginning of a scientific revolution.
He had seen new forms of life.
We now know he was looking at microscopic plants and single-celled animals such as amoeba.
This Dutch draper was the very first person to see individual living cells.
This revelation could easily have been lost to science because van Leeuwenhoek was an obscure linen merchant working on his own.
He himself was afraid of being ignored, and whinged, "I suffer many contradictions and oft-times hear it said "that I do but tell fairytales about the little animals.
" He sent his notes off to the wise gentlemen of London, more in desperation than hope.
King Charles II had granted the Royal Society its charter in 1662 with the motto, "Take nobody's word for it.
" The fellows were pretty sceptical of van Leeuwenhoek's claims.
Even so, they turned to one of their most famous members, our very own Robert Hooke.
He was the "go to guy" when you had very small things to investigate.
A decade earlier, he'd spent several years looking down his own microscope to see what he could find.
Hooke had written one of the most important books in early biology, important not just for what he saw, but for how he described it.
So this is it.
This is Micrographia.
This is the Micrographia, yes.
This is the first edition, as it would have been seen by Fellows of the Royal Society in the 1660s.
The title page is here.
"Micrographia, or some Physiological Descriptions of Minute Bodies "Made By Magnifying Glasses.
" So he calls them magnifying glasses rather than microscopes at this stage.
That's right, and really this was the first book of microscopy, so you can see why there was a slight uncertainty about terms.
He was doing it for the first time, effectively.
RUTHERFORD: So, at the time, this is near the beginning of the Royal Society's My goodness, let's have a look at this dedication.
"To the King.
" God, that is That's a big font, isn't it? That's real deference there.
It is.
"In very great deference, we do here most humbly "lay this small present at Your Majesty's royal feet.
" Now, Hooke was a famously cantankerous man and he annoyed a lot of his contemporaries, did he not? Is this sincere? This sounds a little bit sarcastic to me.
I think it is.
It's formulaic.
I want to see some of the specimens Mmm, sure.
- There's the head of a fly - Oh, wow.
- So you get the compound eyes there.
- That's incredible.
This is a 17th-century drawing.
I mean, it looks exactly like a modern electron micrograph.
Yeah, and this is the first real view that a general audience had of this kind of world of the very small.
RUTHERFORD: The drawings alone make this book special.
But it's the language Hooke uses when he turns his microscope on cork that makes it a landmark in science.
In looking at cork, he then coined the word "cell".
So here's the sentence right here.
"Partitions of those pores were near as thin in proportion to their pores "as those thin films of wax in a honeycomb "which enclose and constitute the hexangular" - Hexangular? Is that hexangular? - Sexangular.
"Sexangular cells are to theirs.
"Next, these pores or cells were not very deep "but consisted of a great many little boxes.
" So this is it, this is the moment where he writes the word "cells" to describe what he's looking at, the individual units that make up a cork structure.
That's right, and self-contained units is what he's saying from the description.
It's incredible.
I mean, this a real piece of history.
This is the moment where the biggest field in biology was born.
It's a genuine first.
Yes.
RUTHERFORD: We now know that Hooke was indeed looking at the basic building blocks of plants, cells.
But, back in 1664, Hooke thought he was seeing something very different, narrow channels or pipes that carried sap up and down the plant.
And nowhere in Micrographia does he mention the living animalcules van Leeuwenhoek had described.
Hooke had never seen them.
So imagine his irritation when the letters from Delft arrived over a decade later.
With a bruised ego, he dusted off his own microscope, a very different design from that of van Leeuwenhoek's, larger but less powerful.
Trying to copy his work, Hooke took samples from the River Thames, brought them back, looked at them under the microscope and he saw nothing, absolutely nothing.
Here are his notes.
And his comment speaks volumes about the time in which he was working.
"I concluded, therefore, that either my microscope "was not so good as the one that he made use of, "or that Holland might be more proper "for the production of such little creatures than England.
" Hooke might have jacked it in at this point.
"Bah, they're only found in Holland.
" But that wasn't his style.
Hour after hour, day after day, he stuck with it.
He tried to cram more light into his microscope.
He ramped up the magnification.
And then, within a fortnight, Hooke finally saw them for the first time.
Van Leeuwenhoek had been right all along.
The tiny animals were the real deal.
Now the stuffy fellows of the Royal Society did get excited, though, like van Leeuwenhoek, none of them really knew what they were.
What they did realise for the very first time was that there was, quite literally, more to life than meets the eye, a whole kingdom of miniscule creatures whose existence they'd never imagined.
It was a shocking revelation.
The natural world was quite simply not as it had seemed.
In 1680, the Royal Society made van Leeuwenhoek a Fellow and formally declared him the discoverer of the little animals.
This is his certificate and here he is looking justifiably smug.
He was the most famous man of Holland and royalty would visit him at his home.
The Russian Tsar, Peter the Great, and Anne, the new Queen of England, couldn't resist a peep through his amazing viewing machine.
But van Leuwenhoek didn't rest on his laurels.
He decided to turn his microscope on himself and stepped even further into the hidden kingdom.
He scraped the gunk off his teeth and found a whole new family of animalcules.
Now we know them as bacterial plaque, the cause of tooth decay.
And in a drop of his own blood, he was astonished to see tiny, red, round things floating around.
He described them as globules.
We call them red blood cells.
He didn't dare tell Queen Anne about his secretive research on human sperm.
He used his own semen, acquired, he was keen to stress, not by sinfully defiling himself, but as a natural by-product of conjugal coitus.
To be honest, I can't make that same claim.
Now, it's embarrassing enough talking about this in the 21 st century, imagine what it was like in the 17th.
But, you know, there they are, tiny little Adams swimming along.
They look kind of like tadpoles.
In his own semen, van Leeuwenhoek would have seen the same thing, thousands of tiny little animalcules powering along with whiplash-like tails.
He was the very first person to see a human sperm.
Another great discovery.
Van Leeuwenhoek had made the earliest link between the microscopic, wriggling creatures and the creation of new life.
Modern scientists are familiar with the idea that each sperm is an individual cell.
And, at the moment of fertilisation, the sperm combines with a much bigger cell, the egg.
This fusion of cells is the starting point for a new life.
But van Leeuwenhoek had no idea of all this, trapped in a 17th-century mindset.
He believed that the sperm contained a tiny man that, once inside the womb, grew into a baby.
He never saw him, but others drew fantastical pictures, like this one.
The imagination of the microscope pioneers had run beyond their technology.
It's easy to forget where scientists like van Leeuwenhoek and Hooke were coming from.
The creation of new life was still very mysterious at this time.
Many philosophers believed that life originated by spontaneous generation, the idea that creatures could somehow spring forth from inanimate matter.
So crocodiles came from rotting logs and bumblebees came from the carcasses of bulls.
Now, this stuff sounds completely nuts to our modern ears, but it's an idea that lasted a surprisingly long time.
Spontaneous generation was to prove a persistent obstacle to the advance of cell biology.
And it wasn't just a crazy fringe idea.
Mainstream scientists lapped it up.
Take Jean Baptist van Helmont, a 17th-century Flemish aristocrat who did important early work on the chemistry of gases.
But van Helmont also wanted to prove that mice arose spontaneously from sweat and grains of wheat.
And this is his protocol for making a mouse.
"If a foul shirt be pressed within the mouth of a vessel wherein wheat is, "within a few days (to wit, 21) A ferment being drawn from the shirt "and changed by the odour of the grain, the wheat transchangeth into mice.
" As they say, "Take nobody's word for it.
" Here is our vessel and here is some wheat.
And here is the crucial extra ingredient, my stinky shirt.
And here's one I prepared earlier, to wit 21 days earlier.
So let's see if we've made any mice.
Well, what a surprise, there are no mice.
Now, we're not 100% sure that van Helmont ever actually did this experiment, just like I've done, but if he did, then the only sensible explanation is that the mice snuck in to have a bit of a snack.
Mice have a habit of doing that.
But whatever the truth is, van Helmont believed enough that he actually wrote the protocol down.
Thanks to Van Helmont, spontaneous generation was the received wisdom of the day.
Because of this, nobody made the connection between what Robert Hooke and Antoni van Leeuwenhoek had seen down their microscopes and the origin of life.
No one yet suspected that the new discoveries revealed by the microscopes, the strange and wonderful animalcules and globules, were essentially the same thing, and that all life was made of them.
For over 100 years the study of cells was trapped in medieval thinking.
It would need pioneers with the vision and the technology to dive deeper into the world of the cell before minds could be opened.
The Royal Botanic Gardens, Kew, the early 19th century.
The deadlock is coming to an end.
The science of cell biology is about to be revitalised.
And in order to understand how that happened, we need to return to plants.
Since Robert Hooke's work with cork, botanists had been eagerly tearing up plants to study their anatomy.
And what they'd slowly discovered was that plants had some kind of a structure that was made of cells.
Every plant they looked at had them.
These cells were turning out to be much more prevalent than anyone had realised.
But what did they do? What were they for? A Scottish botanist, Robert Brown, decided to peer into the heart of the plant cell.
And there, he'd reveal something as important as the discovery of the cell itself.
Brown had been the ship's naturalist on an expedition to Australia.
He was no slouch and he returned to Britain in 1805 with over 3,000 exotic species, including previously undiscovered orchids.
He studied the collection for many years.
Now, the orchid was a lucky choice, as it happened, because it has cells which are larger than other plants.
If it weren't for this, it's unlikely that Brown would have discovered what he did.
Now, I'm going to try and see what was so important using Brown's own microscope.
Hi, David.
So, this is the actual microscope? This is Robert Brown's microscope from the Linnaean Society of London and it was the one that he used to bring to Kew when he was working on our living collections.
And so this is actually where he did his work? Not in this exact spot, but here at Kew, which has been a major collection of plants for over 250 years.
And why was he looking specifically at orchids? Well, he was interested in their sex life, basically.
And so he was interested to look at pollen grains and how they actually got to the eggs.
And so he was investigating this through this microscope.
So he'd get pieces of the flowers, get the pollen out, but he was also interested in the other parts of the plants, as well.
So he would mount them on something a bit like this and under this single lens.
- Can I have a look? - Yes, of course.
Can I move this? It looks very fragile.
- I'd rather you didn't move it.
- Okay.
This instrument is a travelling microscope, which He used to come in a hansom cab and this thing was all folded up in a box, and, with great difficulty, we put it back together again, and it is a very delicate one now.
RUTHERFORD: Brown noticed a distinctive shape within each cell.
It was a turning point in science.
He called it the nucleus.
Wow, so you really can see every cell.
So it's like a I can see a sort of honeycomb structure and in many of the cells there's a very solid, dark blob in the middle, which I presume is the nucleus.
Yes.
I mean, the point that Robert Brown made was that each cell, actually, had a nucleus.
That was his pioneering discovery.
Other people had said they'd seen it, but he was the first to describe it properly, give it the name "the nucleus" and show how ubiquitous it was.
And after he'd seen the nucleus for the first time, what was his interpretation of what he was looking at? Well, obviously, he didn't understand the role of the nucleus as we would understand it today.
But the important thing was that he said, these are in all cells.
Because he started looking at other plants and other plants and other plants.
And then he found that they were everywhere.
And therefore the idea that each cell has one nucleus comes from his work, 1830.
The identification of the nucleus wasn't Robert Brown's only contribution to science.
He's much better known for his role in physics, where he was looking at the movement of particles within pollen grains, what we now call Brownian motion.
A hundred years later, a chap called Albert Einstein would use Brownian motion to prove the existence of the atom.
So Brown has a unique position in the history of science as having made major contributions to atomic theory and to cell theory, the smallest units of matter and the smallest units of life.
Respect! Brown's observation would one day allow us to understand how cells work.
Since then, we've discovered the nucleus is the control centre that runs each cell.
Not only that, but within it are the instructions to make every cell in an organism.
In 1831 though, just knowing that the nucleus was there was the breakthrough.
Its presence in cells would be the clue to show that the cell might be universal to all living things, though no one yet could suggest something so radical.
Before biology could progress any further, scientists had to build a much more powerful microscope.
But they'd reached a technological impasse.
Now, it was an Englishman, Joseph Jackson Lister, who rose to the challenge.
He was a wealthy wine merchant, but had been long obsessed with microscopes.
So in his spare time, he set about designing one that would be superior to all others.
Lister figured that he needed two lenses, unlike the single-lens microscopes of van Leeuwenhoek and Brown.
Using two lenses had been tried many times before.
It boosted magnification, but it also boosted some of the problems inherent in all lenses.
The most vexing of these was an effect known as colour blurring.
You can get a feel for what this looks like by fiddling with the lens on the camera.
This weird coloured halo around the edge of the light, that's what I'm talking about.
Lister's genius was to discover that there was one specific distance between two lenses where colour blurring and other focusing problems were minimised.
In 1830, after several years of hard graft, experimenting with different types of lenses, testing out various prototypes, Lister revealed his new design of microscope.
For the first time since van Leeuwenhoek, there were the means and the know-how to build ever more powerful microscopes.
This amateur scientist had made a breakthrough that rendered the single-lens microscope obsolete.
Now biologists had the tool that allowed them to go deeper and deeper inside the world of the cell.
The stage was set.
But what was still lacking were the scientists with the imagination to see cells for what they really were.
And here in Berlin, one young and ambitious man was about to break the impasse, Theodor Schwann.
The two strands of biology, animal and vegetable, were about to come together.
At the time, Berlin was the European centre for anatomy, and the university the magnet for the most brilliant biologists around.
Theodore Schwann was keen to make a name for himself and took a position at the prestigious anatomical museum.
Be warned, though.
It's not for the fainthearted.
The guidebook comments, "Boys will be admitted only in the company of their fathers or teachers, "and of the female sex, only midwives will be granted admission.
"The visitor's attention is called "mainly to the wealth of nerve preparations, "a long array of monstrous births and about 500 animal skeletons.
" The field of anatomy was in chaos.
Nobody really knew what animals or humans were made of.
Researchers believed that they were built of many different structures, granules, fibres, tubes, globules and bladders.
And none of them seemed any more important than the others.
Animal studies were seriously lagging behind botany.
And this was because the cells are so much harder to see.
So the scientists didn't really realise there were any cells there at all.
And this was fuelling the notion that somehow animal tissue was fundamentally different from that of plants.
But Schwann used innovative ways to stain his animal tissue.
And he had one of the new Lister-style microscopes.
He kept finding the same type of globular structure in all the different samples.
We know that Schwann was looking at cells, but, at the time, researchers used different terms to describe what they were seeing, "KÃrnchen, Kügelchen and Zellen".
The penny hadn't dropped that they were looking at the same thing.
And without this connection, they couldn't make the intellectual leap that cells were common to all life forms.
That was all to change one day in October, 1837.
Over a meal, Schwann was chatting about his work to a fellow scientist, a guy called Mathias Schleiden.
Now, Schleiden had also been studying cells, but he'd been looking at plants.
Schleiden talked passionately with Schwann about his investigation into the make-up of dozens of different plants, from grasses to tulips.
In turn, Schwann revealed his work on the nerves of the edible frog.
Could such very different things, tulips and frogs, be built of the same microscopic structure? It seemed unlikely in the extreme.
The popular perception of scientific discovery is that there's a sudden brainwave and you leap out of the bath, everything becomes clear and you run down the street in the buff.
The sad truth is a little more disappointing.
Most scientists toil away, grinding out small, incremental advances.
However, Schwann and Schleiden's meeting was a classic eureka moment.
Up to this point, neither knew of the other's research, but both scientists had been using the nucleus as the way to identify their building blocks.
This is a typical plant cell.
It has a well defined cell wall and a single nucleus.
And this is a typical animal cell.
It has a soft boundary, which is difficult to make out, but a cell membrane, all the same.
It also has a single nucleus.
By comparing the two, the scientists knew that they were looking at essentially the same thing.
They were both cells.
Everything they'd observed was built of cells, Schleiden's flowering plants and grasses, Schwann's frog and other animal samples.
Now they realised that wherever there was life, there were cells.
I believe this is one of the three great concepts in biology.
It's right up there with Charles Darwin's theory of evolution and the discovery of the structure of DNA.
Schwann and Schleiden had uncovered an idea that united all life on Earth.
This meal was where biology changed forever.
Animals and plants, humans and amoebas, they were all made of the same building block, cells.
In Schwann's book, he explained how cells were self-sufficient units that could work together to make up a much larger organism, a "cooperative of cells".
Schwann and Schleiden went down in history as the founders of cell theory.
At least, that's the conventional view.
The truth is a bit more complicated and a bit more interesting, I think.
You see, Schwann and Schleiden got half of their theory completely wrong and their error sent biology down a blind alley for more than a decade.
Their mistake was about where new cells actually come from.
The two Germans believed that new cells formed spontaneously and grew up like crystals from a tiny speck of nucleus material.
They claimed to have seen this under the microscope.
It was almost as if new cells had come out of nowhere.
Now, if you're thinking this sounds familiar from earlier in the story, you're absolutely spot on.
You see, this idea of cell formation was uncannily similar to the theory of spontaneous generation.
By this time, biologists had dismissed the idea that larger animals could spring out of inanimate matter.
But could it happen with new cells and new microbes? Spontaneous generation seemed to be the medieval idea that would never die.
Paris, 1860.
The French version of the Royal Society announced a competition to settle the question of spontaneous generation once and for all.
They had an agenda.
They knew this theory was holding up the advance of biology.
The award, a cool 2,500 francs.
One young French scientist was determined to win the prize.
You probably come across his name pretty much every day without even realising it.
Louis Pasteur is much better known for his work sterilising milk, we call it "pasteurisation", but in the 1860s, he was a young scientist struggling for credibility and probably short of a franc or two.
He was convinced that spontaneous generation was a load of medieval bunkum.
Pasteur set out to disprove the idea and win the competition.
Spontaneous generation was a hot topic.
Researchers had spent years studying microbes in the laboratory, or rather, inside glass flasks.
They'd fill a flask with nutrient broth, a mixture of sugars and foods that encourage growth, but was itself sterile, devoid of life.
And then they waited to see what happened.
It all turned into a bizarre battle of the flasks.
Now, the spontaneous generation crowd believed that, as long as there was a nice air flow to get things going, that life would suddenly spring out of nowhere.
And lo and behold, after a couple of weeks, the solution went cloudy.
And when they looked at it under the microscope, it was teeming with microbes.
Life, they claimed, had spontaneously generated.
Pasteur didn't buy it.
He suspected that the microbes came in from the outside, on dust particles, and set up home in the flask.
And as they multiplied the flask went cloudy.
But how to prove it? Pasteur knew he had to design a new type of flask that let air in, but at the same time kept out the surrounding dust and microbes.
A seemingly impossible challenge.
What sort of temperature is that? That looks hot.
- 2,000 degrees.
- How many? - 2,000.
- 2,000 degrees! Approximately.
RUTHERFORD: Nice! That's amazing, as simple as that.
I've got to hold it while the glass sets.
That is amazing.
That's really skilful.
And then we wait for it to cool and I'll cut that off there and gently flame the end so that it's not sharp, uh, and the next stage will be to fill it.
I'm really impressed with that.
Well done, Ray.
That was amazing.
Thank you.
This was Pasteur's ingenious solution, a swan neck.
Now, it may not look like much, but this simple design changed the course of science.
Have a look.
The air can get in through here, but the microbes get stuck in the bottom of the curve.
So the broth inside should remain sterile and clear and free of microbes.
Yet the spontaneous generation folk were still convinced that even with the swan neck new life would form of its own accord.
Who was right? To find out, Pasteur set up two flasks, one with the swan neck and one with a neck open to dust particles.
Now, we recreated the experiment a couple of weeks ago.
Here are the two flasks with the broth in them.
This one is Pasteur's, with the swan neck, and you can see that the broth is perfectly clear.
This one's the open-necked flask, which is very cloudy, full of bacteria.
Pasteur had won the competition and he proudly declared, "Never again will the doctrine of spontaneous generation recover "from the mortal blow struck by this simple experiment.
" Pasteur made a tidy sum.
He'd shown that new microbes must have drifted in on the breeze.
And he'd sounded the death knell for spontaneous generation.
It couldn't account for new mice, new microbes or new cells.
So what did? It seems incredible to me that an idea like spontaneous generation could have lasted as long as it did.
By the 19th century, the world had changed beyond recognition and those changes were being driven by science and engineering.
The Industrial Revolution was in full swing.
People now believed in machines and scientific laws, in cause and effect.
So when the next generation of scientists wanted to find out where new cells really came from, they wanted a functional explanation that didn't rely on cells simply springing forth from inanimate matter.
The quest had started even before Pasteur's killer experiment, in Berlin, the birthplace of cell theory.
And it was here that two friends had been searching for a new explanation for the origin of cells.
Robert Remak was a Polish Jew, while his friend, Rudolf Virchow, was a politically astute German.
One man would do all the key research, but the other would take all the credit.
See if you can work out which is which.
Robert Remak is not one of the best known names in the history of science, but for me, he's a genuine hero for our story.
Remak was Jewish, so attaining the professorship he deserved was always going to be an uphill struggle.
He was forced to do his research in a dingy attic apartment.
Despite these obstacles, Remak set out to discover how new cells originated.
He realised his best hope was to look in a place where he'd be guaranteed to see lots of cells forming.
Professor Redies has helped us recreate Remak's experiment from the 1840s.
The chick embryo was the animal model of choice for embryology at the time because eggs are very easy to get, they were very inexpensive, and also the embryo is accessible.
That means you can now take some scissors and cut a hole here on top.
Oh, and there it is.
- The embryo floats on top.
- Okey-dokey.
And we're going to cut a blood vessel now and collect a little bit of blood.
So I have a glass pipette here and I'm going to suck a drop of blood.
- Now, here you can actually see - Yep.
That there is red fluid in the pipette.
It contains blood cells, red blood cells, and I'm putting them on a glass here.
And to see them better, we put a cover slip on top, so that we can look at it under the microscope.
There you go.
Now let's have a look.
I take the microscope here, which is of the type that Remak may have used.
It's a really old one.
I have to adjust the light source with the mirror here.
Not the type of scope that you're used to using.
Well, the scopes we are using are a bit more modern now.
- You can actually look with both eyes.
- Mmm-hmm.
I will have to close one eye and look through here.
And what you can see, actually, is many, many blood cells.
They're still floating around a little bit because the fluid is moving.
They are round, most of them, but, occasionally I see a cell in division, which is not round, but which has, uh The It is Oh, I don't know the technical terms in English.
Uh, there is some invagination of the cell wall.
- That is the same word, "invagination".
- Yeah? So it begins to split into two like that - Right.
- So it invaginates at both sides.
Yes.
That means cells separating from each other in this stage, which takes a long time, so you cannot see the whole process because it takes several hours, but you see snapshots of this process.
Have a look.
So it's not actually obvious.
He must have been very persistent to see the individual stages from one cell as it begins to sort of fold in on itself and then divides into two cells.
He must have done this experiment a lot of times.
He must have used hundreds of eggs actually.
And what's amazing is that what caught his attention were the few cells, the very few cells, that were in division.
They may have easily been missed by some other researchers who may have thought that these few cells in division are some artefacts under the microscope, but he focused on them and systematically studied them and these stages in division are actually those that he depicted in his publication.
You look at the surroundings that Remak was working in, which is a sort of dusty, old attic, it's amazing that he came up with the results that he did.
That shows you that sometimes the instruments themselves do not advance science, but the thinking of people and, um, having new ideas is more important than good equipment sometimes.
And so Remak is a true pioneer.
I would say he is one of the heroes in science, in cell biology, uh, because he really persisted on this idea and supported it by very well-founded observations.
RUTHERFORD: Remak couldn't wait to tell his old buddy Virchow about the research.
Virchow was now a professor of anatomy.
But you know what? He wasn't bowled over.
He thought Remak's research was interesting but believed that this "cell division" was a rare event and only applied to the red blood cells of developing chicks.
Big deal.
Hardly a major breakthrough.
Ever the diligent scientist, Remak went off to look for more evidence, to find out if this process occurred in other cells, in other animals.
To show this, he did something that kids have been doing for centuries.
He went out and he got some frog spawn.
With frog spawn, he could show how a single fertilised cell could turn into an embryo.
If he was right, then at every stage of development, he should see cells dividing to become various tissues, not just red blood cells, but into heart, muscle, bone, into a whole frog.
By now, scientists knew that the development of an organism began when an egg and a sperm combined.
But they were hazy as to what happened afterwards.
Remak witnessed the very first cell division just after the egg was fertilised, and, seen here through a modern microscope, subsequent divisions.
Two cells became four.
Four became eight, eight became sixteen.
Cell division was the key.
And, over time, these cells formed all the different tissues of the embryo and, eventually, the frog itself.
Remak had founded the field of embryology.
That's how you get from one single fertilised egg cell into a fully functional animal made of trillions of cells.
He considered his work on frogs to be the keystone of his theory.
And what a theory.
Remak had shown that cell division was how all new cells form and that it was a universal phenomenon across all nature and that cells were only born from other cells.
For over a decade, Virchow had been unconvinced by Remak's research, but it slowly dawned on him that his friend might actually be right.
In 1855, Professor Virchow made a spectacular U-turn.
In a widely-read medical textbook, he took all of Remak's work on cell division and he simply claimed it as his own.
Because he was the big man, the big professor, people stood up and they took notice.
He even came up with his own catchy Latin phrase to summarise it.
"Omnis cellula e cellula.
" All cells from other cells.
Not surprisingly, the two fell out.
I'm sorry to say that Virchow was, and still is, celebrated in every textbook, and Remak, the man who came up with the theory, just a footnote in the history of science.
Yet out of this betrayal, one of the most powerful ideas in biology was revealed to the world.
It is a truly profound concept because it means that all life on Earth must have begun with a single cell and all life on Earth shares a family tree.
Cell theory had come of age.
On the brink of the 20th century, scientists had a pretty modern understanding of the importance of the cell.
They'd come a long way since those squiggly drawings of tiny creatures that had so puzzled the fellows of the Royal Society.
Now they knew that all life was made of cells, from plankton to people, and that cells could only come from other cells.
Thousands of years of ignorance and superstition had been swept away.
And yet, as they looked closer into the world of the cell, they realised that there were some really big questions that remained unanswered.
Why are cells essential to life? What's going on inside? To find out, scientists would have to embark on a new endeavour and peer deeper within the cell.
And what they were about to discover would turn out to be more complex, more extraordinary and more powerful than they could have possibly imagined.
And yet it's only in the last couple of centuries that we've come to discover what life is actually made of.
Take me, for example.
How is it that I'm alive? I can show you what I consist of, the chemicals that make up a standard-issue human.
RUTHERFORD: You need 18 kilos of carbon, a small canister of nitrogen, 50 kilos of water, enough phosphorus to make 2,000 matches, the same amount of iron as a small nail, and around 20 other elements.
Chemically, the two sides are identical.
But biologically, we're completely different.
Obviously, I'm alive, and the difference is that these exact same chemicals are organised into cells.
RUTHERFORD: 60,000 billion tiny, incredibly complex structures that make up my body.
Quite simply, we are cells.
RUTHERFORD: Every time we breathe, we move, we think, cells do the work for us.
Like all biologists, the more I find out about them, the more they amaze me.
The idea that all living creatures, from amoebas to humans, are made up of cells is the cornerstone of biology.
It's the theory of everything.
Yet the story of how we came to understand the cell is rarely told.
It's a fantastic voyage, delving deeper and deeper into an almost magical unseen world.
It's about nothing less than unlocking the mysteries of life itself.
And, for me, the story of the cell is the most powerful story in science.
RUTHERFORD: My starting point is September, 1674 and the Royal Society of London.
A mysterious satchel arrived at this club for gentleman scientists.
It had taken five days to get here from Holland, across the North Sea by ship and then by horseback rider.
The package came from a man who'd built the world's most powerful microscope, a microscope which revealed a hidden kingdom nobody had seen before.
The secretary of the Royal Society opened the satchel.
In it, there was a long letter in Dutch with a description of something truly extraordinary, tiny animals that pirouetted and swam like eels, and so small, according to the author, that you could fit a million of them on a single grain of sand.
So let's have a look.
These are the letters.
You can see the date, 1674, at the top.
It's written in Dutch.
I don't speak Dutch so I can't understand that.
There's the signature, the sender Antoni van Leeuwenhoek.
And the drawings came in later letters.
You can see these crazy, tiny creatures.
This one here, he's got a little dotted line to indicate the movement.
There he is, spinning round.
So, picture the scene.
These guys at the Royal Society, these stuffy, old scientists, had never seen anything like this before and yet, suddenly, this letter comes through from Holland with these totally alien creatures, not only looking really weird, but, also, so small that they couldn't even see them.
It must have just been completely amazing.
Did they even believe that these were real? The fellows of the Royal Society did have their own microscopes.
The device had been around since about 1600, but they'd never seen the tiny animals van Leeuwenhoek claimed to have found.
Quite frankly, they suspected this unknown Dutchman must be crazy.
Antoni van Leeuwenhoek came from the market town of Delft.
He wasn't a scientist at all.
In fact, he was a linen merchant.
Drapers like van Leeuwenhoek inspected their cloth with magnifying glasses and Holland had pioneered their manufacture.
They're still used today.
Here, look, this That may be nice to show.
This is a 17th-century napkin.
Shall I show you how big they were in those days? This is actually from the 17th century? This is not a replica? No, this is a real 17th-century napkin.
- Look.
- It's huge! Yes.
That was huge.
Were they particularly messy eaters in the 17th century? Yes, we think so.
- But they're not Look, this big.
- It's like a tablecloth.
(LAUGHING) Yes.
But it's only a napkin.
What? They didn't tuck it in Sometimes.
But you had to put it on your lap, of course.
I'm sorry.
I'm being slightly disrespectful for a 300-year-old piece of cloth.
And how do you look at the quality of the cloth? Well, when I want to look the quality quite good, then I use a loupe.
And I look through it.
And, look, this is a very old loupe.
- So this is a loupe - This is a loupe.
Which is the same word in English, it's like what watchmakers use, but basically it's a magnifying glass.
Okay, magnifying glass, yeah.
And you can look through it, and when you look through it, you can count the threads, you can see the threads from the napkin quite good.
Can I have a go? Yes, you can have a look at the quality.
Thank you.
So, you pull it up and then it comes into focus and there you go.
There you can see every single Every single thread, every single stitch, it's amazing.
You can really see the pattern.
This is basically exactly the same technique that van Leeuwenhoek would have done in the 17th century.
Yes.
Yes.
RUTHERFORD: Van Leeuwenhoek became obsessed with lenses, a sort of a lens geek.
(BELL TOLLING) He turned out to be the best lens maker there was.
He used delicately crafted lenses like these in his own unique viewing machine.
This is a replica of van Leeuwenhoek's microscope.
Look how simple it is.
It's just a piece of brass and it's got one tiny hole with the lens in it, which is maybe a millimetre across.
Yet this is the gadget that transformed the way we see the world.
A tiny lens, yet more powerful than any other.
Van Leeuwenhoek knew that it's the curvature of a lens that bends the light passing through it, so making the object being observed, here it's a flea, appear larger.
And because van Leeuwenhoek was a master craftsmen he could curve the lens more than anybody else, almost to the point it was spherical.
This allowed him to magnify objects up to 500 times.
No one would make a more powerful microscope for over a century.
So he now had the technology, but what did he look at? He went from linen to fleas to the sting of a bumblebee.
In fact, pretty much anything he could get his hands on.
And one of the things he looked at was water.
He'd noticed that in a lake near Delft, the water changed colour with the seasons and he figured that there might be something in the water that he could discover.
Many of the fundamental breakthroughs of science seem so simple, so absurdly simple.
But we shouldn't forget that, until van Leeuwenhoek, no one had the curiosity to find out what might be lurking in the water.
He raced home to take a closer look with his microscope.
The man who's going to help me study the water is Hans Loncke.
He keeps the spirit of van Leeuwenhoek alive by making replicas of his microscopes.
To grind a lens, Hans needs no special glass, just a shard from an old jam jar will do.
The only way to get enough curvature in the lens is to make it tiny.
This was van Leeuwenhoek's secret and it requires great skill and patience.
Van Leeuwenhoek built a staggering 247 microscopes, a new one every couple of months for over 50 years, and told nobody how he made them.
We've placed a drop of my lake water onto a slide that slots into the device.
With a bit of luck I'll be able to see what van Leeuwenhoek saw.
Now I've looked down a fair few microscopes in my time and this is nothing like anything I've used before.
It's fiendishly difficult to use so I've got Hans with me just in case I can't see a thing.
So what do I actually do? Where am I looking? - Uh, the wrong side.
- Mmm-hmm.
- You must look through this hole.
- Yeah.
A very tiny hole.
- And there's a lens in it.
- Yes.
And the lens, through the lens you see, - uh, the - The sample.
The sample that is put between the glass.
So if I hold it up to the light, like this Close to your eyes.
And I can see I can see green.
- There is a focusing knob.
- There's a focus? Yes, there is a focusing knob.
This might be made So you can move it, actually, away from my eye.
- This one, this is the focus.
- Let me try that.
It's so simple and it works so well.
Yeah, that works, that really works.
It's now in focus.
Oh, wow.
Oh, my God, you can actually see moving creatures.
LONCKE: Yes.
RUTHERFORD: Oh, God, that's incredible.
(CHUCKLING) There's a tiny, tiny bug in there, which is scooting around, which I guess is a protozoa.
That's astonishing.
I know this story, but I didn't think this was what I was going to actually see.
It's just like looking down a modern microscope, in fact, even though it's completely different to use.
Van Leeuwenhoek gushed with delight, too, writing, "This was, to me, among all the marvels that I have discovered in nature, "the most marvellous of all.
"No greater pleasure has yet come to my eye "than these spectacles of so many thousands of living creatures "in a small drop of water moving among one another.
" And so, in the 17th century, when people were discovering Australia and astronomers were exploring the heavens, so van Leeuwenhoek was peering into a new microscopic universe.
The full meaning of what he saw in that universe, seen here down a modern microscope, escaped van Leeuwenhoek.
He assumed he was seeing miniaturised versions of everyday animals with beating hearts and contracting muscles, just like their larger counterparts.
He called them "animalcules".
Little did he know, it wasn't just a question of scale.
Van Leeuwenhoek's discovery was the beginning of a scientific revolution.
He had seen new forms of life.
We now know he was looking at microscopic plants and single-celled animals such as amoeba.
This Dutch draper was the very first person to see individual living cells.
This revelation could easily have been lost to science because van Leeuwenhoek was an obscure linen merchant working on his own.
He himself was afraid of being ignored, and whinged, "I suffer many contradictions and oft-times hear it said "that I do but tell fairytales about the little animals.
" He sent his notes off to the wise gentlemen of London, more in desperation than hope.
King Charles II had granted the Royal Society its charter in 1662 with the motto, "Take nobody's word for it.
" The fellows were pretty sceptical of van Leeuwenhoek's claims.
Even so, they turned to one of their most famous members, our very own Robert Hooke.
He was the "go to guy" when you had very small things to investigate.
A decade earlier, he'd spent several years looking down his own microscope to see what he could find.
Hooke had written one of the most important books in early biology, important not just for what he saw, but for how he described it.
So this is it.
This is Micrographia.
This is the Micrographia, yes.
This is the first edition, as it would have been seen by Fellows of the Royal Society in the 1660s.
The title page is here.
"Micrographia, or some Physiological Descriptions of Minute Bodies "Made By Magnifying Glasses.
" So he calls them magnifying glasses rather than microscopes at this stage.
That's right, and really this was the first book of microscopy, so you can see why there was a slight uncertainty about terms.
He was doing it for the first time, effectively.
RUTHERFORD: So, at the time, this is near the beginning of the Royal Society's My goodness, let's have a look at this dedication.
"To the King.
" God, that is That's a big font, isn't it? That's real deference there.
It is.
"In very great deference, we do here most humbly "lay this small present at Your Majesty's royal feet.
" Now, Hooke was a famously cantankerous man and he annoyed a lot of his contemporaries, did he not? Is this sincere? This sounds a little bit sarcastic to me.
I think it is.
It's formulaic.
I want to see some of the specimens Mmm, sure.
- There's the head of a fly - Oh, wow.
- So you get the compound eyes there.
- That's incredible.
This is a 17th-century drawing.
I mean, it looks exactly like a modern electron micrograph.
Yeah, and this is the first real view that a general audience had of this kind of world of the very small.
RUTHERFORD: The drawings alone make this book special.
But it's the language Hooke uses when he turns his microscope on cork that makes it a landmark in science.
In looking at cork, he then coined the word "cell".
So here's the sentence right here.
"Partitions of those pores were near as thin in proportion to their pores "as those thin films of wax in a honeycomb "which enclose and constitute the hexangular" - Hexangular? Is that hexangular? - Sexangular.
"Sexangular cells are to theirs.
"Next, these pores or cells were not very deep "but consisted of a great many little boxes.
" So this is it, this is the moment where he writes the word "cells" to describe what he's looking at, the individual units that make up a cork structure.
That's right, and self-contained units is what he's saying from the description.
It's incredible.
I mean, this a real piece of history.
This is the moment where the biggest field in biology was born.
It's a genuine first.
Yes.
RUTHERFORD: We now know that Hooke was indeed looking at the basic building blocks of plants, cells.
But, back in 1664, Hooke thought he was seeing something very different, narrow channels or pipes that carried sap up and down the plant.
And nowhere in Micrographia does he mention the living animalcules van Leeuwenhoek had described.
Hooke had never seen them.
So imagine his irritation when the letters from Delft arrived over a decade later.
With a bruised ego, he dusted off his own microscope, a very different design from that of van Leeuwenhoek's, larger but less powerful.
Trying to copy his work, Hooke took samples from the River Thames, brought them back, looked at them under the microscope and he saw nothing, absolutely nothing.
Here are his notes.
And his comment speaks volumes about the time in which he was working.
"I concluded, therefore, that either my microscope "was not so good as the one that he made use of, "or that Holland might be more proper "for the production of such little creatures than England.
" Hooke might have jacked it in at this point.
"Bah, they're only found in Holland.
" But that wasn't his style.
Hour after hour, day after day, he stuck with it.
He tried to cram more light into his microscope.
He ramped up the magnification.
And then, within a fortnight, Hooke finally saw them for the first time.
Van Leeuwenhoek had been right all along.
The tiny animals were the real deal.
Now the stuffy fellows of the Royal Society did get excited, though, like van Leeuwenhoek, none of them really knew what they were.
What they did realise for the very first time was that there was, quite literally, more to life than meets the eye, a whole kingdom of miniscule creatures whose existence they'd never imagined.
It was a shocking revelation.
The natural world was quite simply not as it had seemed.
In 1680, the Royal Society made van Leeuwenhoek a Fellow and formally declared him the discoverer of the little animals.
This is his certificate and here he is looking justifiably smug.
He was the most famous man of Holland and royalty would visit him at his home.
The Russian Tsar, Peter the Great, and Anne, the new Queen of England, couldn't resist a peep through his amazing viewing machine.
But van Leuwenhoek didn't rest on his laurels.
He decided to turn his microscope on himself and stepped even further into the hidden kingdom.
He scraped the gunk off his teeth and found a whole new family of animalcules.
Now we know them as bacterial plaque, the cause of tooth decay.
And in a drop of his own blood, he was astonished to see tiny, red, round things floating around.
He described them as globules.
We call them red blood cells.
He didn't dare tell Queen Anne about his secretive research on human sperm.
He used his own semen, acquired, he was keen to stress, not by sinfully defiling himself, but as a natural by-product of conjugal coitus.
To be honest, I can't make that same claim.
Now, it's embarrassing enough talking about this in the 21 st century, imagine what it was like in the 17th.
But, you know, there they are, tiny little Adams swimming along.
They look kind of like tadpoles.
In his own semen, van Leeuwenhoek would have seen the same thing, thousands of tiny little animalcules powering along with whiplash-like tails.
He was the very first person to see a human sperm.
Another great discovery.
Van Leeuwenhoek had made the earliest link between the microscopic, wriggling creatures and the creation of new life.
Modern scientists are familiar with the idea that each sperm is an individual cell.
And, at the moment of fertilisation, the sperm combines with a much bigger cell, the egg.
This fusion of cells is the starting point for a new life.
But van Leeuwenhoek had no idea of all this, trapped in a 17th-century mindset.
He believed that the sperm contained a tiny man that, once inside the womb, grew into a baby.
He never saw him, but others drew fantastical pictures, like this one.
The imagination of the microscope pioneers had run beyond their technology.
It's easy to forget where scientists like van Leeuwenhoek and Hooke were coming from.
The creation of new life was still very mysterious at this time.
Many philosophers believed that life originated by spontaneous generation, the idea that creatures could somehow spring forth from inanimate matter.
So crocodiles came from rotting logs and bumblebees came from the carcasses of bulls.
Now, this stuff sounds completely nuts to our modern ears, but it's an idea that lasted a surprisingly long time.
Spontaneous generation was to prove a persistent obstacle to the advance of cell biology.
And it wasn't just a crazy fringe idea.
Mainstream scientists lapped it up.
Take Jean Baptist van Helmont, a 17th-century Flemish aristocrat who did important early work on the chemistry of gases.
But van Helmont also wanted to prove that mice arose spontaneously from sweat and grains of wheat.
And this is his protocol for making a mouse.
"If a foul shirt be pressed within the mouth of a vessel wherein wheat is, "within a few days (to wit, 21) A ferment being drawn from the shirt "and changed by the odour of the grain, the wheat transchangeth into mice.
" As they say, "Take nobody's word for it.
" Here is our vessel and here is some wheat.
And here is the crucial extra ingredient, my stinky shirt.
And here's one I prepared earlier, to wit 21 days earlier.
So let's see if we've made any mice.
Well, what a surprise, there are no mice.
Now, we're not 100% sure that van Helmont ever actually did this experiment, just like I've done, but if he did, then the only sensible explanation is that the mice snuck in to have a bit of a snack.
Mice have a habit of doing that.
But whatever the truth is, van Helmont believed enough that he actually wrote the protocol down.
Thanks to Van Helmont, spontaneous generation was the received wisdom of the day.
Because of this, nobody made the connection between what Robert Hooke and Antoni van Leeuwenhoek had seen down their microscopes and the origin of life.
No one yet suspected that the new discoveries revealed by the microscopes, the strange and wonderful animalcules and globules, were essentially the same thing, and that all life was made of them.
For over 100 years the study of cells was trapped in medieval thinking.
It would need pioneers with the vision and the technology to dive deeper into the world of the cell before minds could be opened.
The Royal Botanic Gardens, Kew, the early 19th century.
The deadlock is coming to an end.
The science of cell biology is about to be revitalised.
And in order to understand how that happened, we need to return to plants.
Since Robert Hooke's work with cork, botanists had been eagerly tearing up plants to study their anatomy.
And what they'd slowly discovered was that plants had some kind of a structure that was made of cells.
Every plant they looked at had them.
These cells were turning out to be much more prevalent than anyone had realised.
But what did they do? What were they for? A Scottish botanist, Robert Brown, decided to peer into the heart of the plant cell.
And there, he'd reveal something as important as the discovery of the cell itself.
Brown had been the ship's naturalist on an expedition to Australia.
He was no slouch and he returned to Britain in 1805 with over 3,000 exotic species, including previously undiscovered orchids.
He studied the collection for many years.
Now, the orchid was a lucky choice, as it happened, because it has cells which are larger than other plants.
If it weren't for this, it's unlikely that Brown would have discovered what he did.
Now, I'm going to try and see what was so important using Brown's own microscope.
Hi, David.
So, this is the actual microscope? This is Robert Brown's microscope from the Linnaean Society of London and it was the one that he used to bring to Kew when he was working on our living collections.
And so this is actually where he did his work? Not in this exact spot, but here at Kew, which has been a major collection of plants for over 250 years.
And why was he looking specifically at orchids? Well, he was interested in their sex life, basically.
And so he was interested to look at pollen grains and how they actually got to the eggs.
And so he was investigating this through this microscope.
So he'd get pieces of the flowers, get the pollen out, but he was also interested in the other parts of the plants, as well.
So he would mount them on something a bit like this and under this single lens.
- Can I have a look? - Yes, of course.
Can I move this? It looks very fragile.
- I'd rather you didn't move it.
- Okay.
This instrument is a travelling microscope, which He used to come in a hansom cab and this thing was all folded up in a box, and, with great difficulty, we put it back together again, and it is a very delicate one now.
RUTHERFORD: Brown noticed a distinctive shape within each cell.
It was a turning point in science.
He called it the nucleus.
Wow, so you really can see every cell.
So it's like a I can see a sort of honeycomb structure and in many of the cells there's a very solid, dark blob in the middle, which I presume is the nucleus.
Yes.
I mean, the point that Robert Brown made was that each cell, actually, had a nucleus.
That was his pioneering discovery.
Other people had said they'd seen it, but he was the first to describe it properly, give it the name "the nucleus" and show how ubiquitous it was.
And after he'd seen the nucleus for the first time, what was his interpretation of what he was looking at? Well, obviously, he didn't understand the role of the nucleus as we would understand it today.
But the important thing was that he said, these are in all cells.
Because he started looking at other plants and other plants and other plants.
And then he found that they were everywhere.
And therefore the idea that each cell has one nucleus comes from his work, 1830.
The identification of the nucleus wasn't Robert Brown's only contribution to science.
He's much better known for his role in physics, where he was looking at the movement of particles within pollen grains, what we now call Brownian motion.
A hundred years later, a chap called Albert Einstein would use Brownian motion to prove the existence of the atom.
So Brown has a unique position in the history of science as having made major contributions to atomic theory and to cell theory, the smallest units of matter and the smallest units of life.
Respect! Brown's observation would one day allow us to understand how cells work.
Since then, we've discovered the nucleus is the control centre that runs each cell.
Not only that, but within it are the instructions to make every cell in an organism.
In 1831 though, just knowing that the nucleus was there was the breakthrough.
Its presence in cells would be the clue to show that the cell might be universal to all living things, though no one yet could suggest something so radical.
Before biology could progress any further, scientists had to build a much more powerful microscope.
But they'd reached a technological impasse.
Now, it was an Englishman, Joseph Jackson Lister, who rose to the challenge.
He was a wealthy wine merchant, but had been long obsessed with microscopes.
So in his spare time, he set about designing one that would be superior to all others.
Lister figured that he needed two lenses, unlike the single-lens microscopes of van Leeuwenhoek and Brown.
Using two lenses had been tried many times before.
It boosted magnification, but it also boosted some of the problems inherent in all lenses.
The most vexing of these was an effect known as colour blurring.
You can get a feel for what this looks like by fiddling with the lens on the camera.
This weird coloured halo around the edge of the light, that's what I'm talking about.
Lister's genius was to discover that there was one specific distance between two lenses where colour blurring and other focusing problems were minimised.
In 1830, after several years of hard graft, experimenting with different types of lenses, testing out various prototypes, Lister revealed his new design of microscope.
For the first time since van Leeuwenhoek, there were the means and the know-how to build ever more powerful microscopes.
This amateur scientist had made a breakthrough that rendered the single-lens microscope obsolete.
Now biologists had the tool that allowed them to go deeper and deeper inside the world of the cell.
The stage was set.
But what was still lacking were the scientists with the imagination to see cells for what they really were.
And here in Berlin, one young and ambitious man was about to break the impasse, Theodor Schwann.
The two strands of biology, animal and vegetable, were about to come together.
At the time, Berlin was the European centre for anatomy, and the university the magnet for the most brilliant biologists around.
Theodore Schwann was keen to make a name for himself and took a position at the prestigious anatomical museum.
Be warned, though.
It's not for the fainthearted.
The guidebook comments, "Boys will be admitted only in the company of their fathers or teachers, "and of the female sex, only midwives will be granted admission.
"The visitor's attention is called "mainly to the wealth of nerve preparations, "a long array of monstrous births and about 500 animal skeletons.
" The field of anatomy was in chaos.
Nobody really knew what animals or humans were made of.
Researchers believed that they were built of many different structures, granules, fibres, tubes, globules and bladders.
And none of them seemed any more important than the others.
Animal studies were seriously lagging behind botany.
And this was because the cells are so much harder to see.
So the scientists didn't really realise there were any cells there at all.
And this was fuelling the notion that somehow animal tissue was fundamentally different from that of plants.
But Schwann used innovative ways to stain his animal tissue.
And he had one of the new Lister-style microscopes.
He kept finding the same type of globular structure in all the different samples.
We know that Schwann was looking at cells, but, at the time, researchers used different terms to describe what they were seeing, "KÃrnchen, Kügelchen and Zellen".
The penny hadn't dropped that they were looking at the same thing.
And without this connection, they couldn't make the intellectual leap that cells were common to all life forms.
That was all to change one day in October, 1837.
Over a meal, Schwann was chatting about his work to a fellow scientist, a guy called Mathias Schleiden.
Now, Schleiden had also been studying cells, but he'd been looking at plants.
Schleiden talked passionately with Schwann about his investigation into the make-up of dozens of different plants, from grasses to tulips.
In turn, Schwann revealed his work on the nerves of the edible frog.
Could such very different things, tulips and frogs, be built of the same microscopic structure? It seemed unlikely in the extreme.
The popular perception of scientific discovery is that there's a sudden brainwave and you leap out of the bath, everything becomes clear and you run down the street in the buff.
The sad truth is a little more disappointing.
Most scientists toil away, grinding out small, incremental advances.
However, Schwann and Schleiden's meeting was a classic eureka moment.
Up to this point, neither knew of the other's research, but both scientists had been using the nucleus as the way to identify their building blocks.
This is a typical plant cell.
It has a well defined cell wall and a single nucleus.
And this is a typical animal cell.
It has a soft boundary, which is difficult to make out, but a cell membrane, all the same.
It also has a single nucleus.
By comparing the two, the scientists knew that they were looking at essentially the same thing.
They were both cells.
Everything they'd observed was built of cells, Schleiden's flowering plants and grasses, Schwann's frog and other animal samples.
Now they realised that wherever there was life, there were cells.
I believe this is one of the three great concepts in biology.
It's right up there with Charles Darwin's theory of evolution and the discovery of the structure of DNA.
Schwann and Schleiden had uncovered an idea that united all life on Earth.
This meal was where biology changed forever.
Animals and plants, humans and amoebas, they were all made of the same building block, cells.
In Schwann's book, he explained how cells were self-sufficient units that could work together to make up a much larger organism, a "cooperative of cells".
Schwann and Schleiden went down in history as the founders of cell theory.
At least, that's the conventional view.
The truth is a bit more complicated and a bit more interesting, I think.
You see, Schwann and Schleiden got half of their theory completely wrong and their error sent biology down a blind alley for more than a decade.
Their mistake was about where new cells actually come from.
The two Germans believed that new cells formed spontaneously and grew up like crystals from a tiny speck of nucleus material.
They claimed to have seen this under the microscope.
It was almost as if new cells had come out of nowhere.
Now, if you're thinking this sounds familiar from earlier in the story, you're absolutely spot on.
You see, this idea of cell formation was uncannily similar to the theory of spontaneous generation.
By this time, biologists had dismissed the idea that larger animals could spring out of inanimate matter.
But could it happen with new cells and new microbes? Spontaneous generation seemed to be the medieval idea that would never die.
Paris, 1860.
The French version of the Royal Society announced a competition to settle the question of spontaneous generation once and for all.
They had an agenda.
They knew this theory was holding up the advance of biology.
The award, a cool 2,500 francs.
One young French scientist was determined to win the prize.
You probably come across his name pretty much every day without even realising it.
Louis Pasteur is much better known for his work sterilising milk, we call it "pasteurisation", but in the 1860s, he was a young scientist struggling for credibility and probably short of a franc or two.
He was convinced that spontaneous generation was a load of medieval bunkum.
Pasteur set out to disprove the idea and win the competition.
Spontaneous generation was a hot topic.
Researchers had spent years studying microbes in the laboratory, or rather, inside glass flasks.
They'd fill a flask with nutrient broth, a mixture of sugars and foods that encourage growth, but was itself sterile, devoid of life.
And then they waited to see what happened.
It all turned into a bizarre battle of the flasks.
Now, the spontaneous generation crowd believed that, as long as there was a nice air flow to get things going, that life would suddenly spring out of nowhere.
And lo and behold, after a couple of weeks, the solution went cloudy.
And when they looked at it under the microscope, it was teeming with microbes.
Life, they claimed, had spontaneously generated.
Pasteur didn't buy it.
He suspected that the microbes came in from the outside, on dust particles, and set up home in the flask.
And as they multiplied the flask went cloudy.
But how to prove it? Pasteur knew he had to design a new type of flask that let air in, but at the same time kept out the surrounding dust and microbes.
A seemingly impossible challenge.
What sort of temperature is that? That looks hot.
- 2,000 degrees.
- How many? - 2,000.
- 2,000 degrees! Approximately.
RUTHERFORD: Nice! That's amazing, as simple as that.
I've got to hold it while the glass sets.
That is amazing.
That's really skilful.
And then we wait for it to cool and I'll cut that off there and gently flame the end so that it's not sharp, uh, and the next stage will be to fill it.
I'm really impressed with that.
Well done, Ray.
That was amazing.
Thank you.
This was Pasteur's ingenious solution, a swan neck.
Now, it may not look like much, but this simple design changed the course of science.
Have a look.
The air can get in through here, but the microbes get stuck in the bottom of the curve.
So the broth inside should remain sterile and clear and free of microbes.
Yet the spontaneous generation folk were still convinced that even with the swan neck new life would form of its own accord.
Who was right? To find out, Pasteur set up two flasks, one with the swan neck and one with a neck open to dust particles.
Now, we recreated the experiment a couple of weeks ago.
Here are the two flasks with the broth in them.
This one is Pasteur's, with the swan neck, and you can see that the broth is perfectly clear.
This one's the open-necked flask, which is very cloudy, full of bacteria.
Pasteur had won the competition and he proudly declared, "Never again will the doctrine of spontaneous generation recover "from the mortal blow struck by this simple experiment.
" Pasteur made a tidy sum.
He'd shown that new microbes must have drifted in on the breeze.
And he'd sounded the death knell for spontaneous generation.
It couldn't account for new mice, new microbes or new cells.
So what did? It seems incredible to me that an idea like spontaneous generation could have lasted as long as it did.
By the 19th century, the world had changed beyond recognition and those changes were being driven by science and engineering.
The Industrial Revolution was in full swing.
People now believed in machines and scientific laws, in cause and effect.
So when the next generation of scientists wanted to find out where new cells really came from, they wanted a functional explanation that didn't rely on cells simply springing forth from inanimate matter.
The quest had started even before Pasteur's killer experiment, in Berlin, the birthplace of cell theory.
And it was here that two friends had been searching for a new explanation for the origin of cells.
Robert Remak was a Polish Jew, while his friend, Rudolf Virchow, was a politically astute German.
One man would do all the key research, but the other would take all the credit.
See if you can work out which is which.
Robert Remak is not one of the best known names in the history of science, but for me, he's a genuine hero for our story.
Remak was Jewish, so attaining the professorship he deserved was always going to be an uphill struggle.
He was forced to do his research in a dingy attic apartment.
Despite these obstacles, Remak set out to discover how new cells originated.
He realised his best hope was to look in a place where he'd be guaranteed to see lots of cells forming.
Professor Redies has helped us recreate Remak's experiment from the 1840s.
The chick embryo was the animal model of choice for embryology at the time because eggs are very easy to get, they were very inexpensive, and also the embryo is accessible.
That means you can now take some scissors and cut a hole here on top.
Oh, and there it is.
- The embryo floats on top.
- Okey-dokey.
And we're going to cut a blood vessel now and collect a little bit of blood.
So I have a glass pipette here and I'm going to suck a drop of blood.
- Now, here you can actually see - Yep.
That there is red fluid in the pipette.
It contains blood cells, red blood cells, and I'm putting them on a glass here.
And to see them better, we put a cover slip on top, so that we can look at it under the microscope.
There you go.
Now let's have a look.
I take the microscope here, which is of the type that Remak may have used.
It's a really old one.
I have to adjust the light source with the mirror here.
Not the type of scope that you're used to using.
Well, the scopes we are using are a bit more modern now.
- You can actually look with both eyes.
- Mmm-hmm.
I will have to close one eye and look through here.
And what you can see, actually, is many, many blood cells.
They're still floating around a little bit because the fluid is moving.
They are round, most of them, but, occasionally I see a cell in division, which is not round, but which has, uh The It is Oh, I don't know the technical terms in English.
Uh, there is some invagination of the cell wall.
- That is the same word, "invagination".
- Yeah? So it begins to split into two like that - Right.
- So it invaginates at both sides.
Yes.
That means cells separating from each other in this stage, which takes a long time, so you cannot see the whole process because it takes several hours, but you see snapshots of this process.
Have a look.
So it's not actually obvious.
He must have been very persistent to see the individual stages from one cell as it begins to sort of fold in on itself and then divides into two cells.
He must have done this experiment a lot of times.
He must have used hundreds of eggs actually.
And what's amazing is that what caught his attention were the few cells, the very few cells, that were in division.
They may have easily been missed by some other researchers who may have thought that these few cells in division are some artefacts under the microscope, but he focused on them and systematically studied them and these stages in division are actually those that he depicted in his publication.
You look at the surroundings that Remak was working in, which is a sort of dusty, old attic, it's amazing that he came up with the results that he did.
That shows you that sometimes the instruments themselves do not advance science, but the thinking of people and, um, having new ideas is more important than good equipment sometimes.
And so Remak is a true pioneer.
I would say he is one of the heroes in science, in cell biology, uh, because he really persisted on this idea and supported it by very well-founded observations.
RUTHERFORD: Remak couldn't wait to tell his old buddy Virchow about the research.
Virchow was now a professor of anatomy.
But you know what? He wasn't bowled over.
He thought Remak's research was interesting but believed that this "cell division" was a rare event and only applied to the red blood cells of developing chicks.
Big deal.
Hardly a major breakthrough.
Ever the diligent scientist, Remak went off to look for more evidence, to find out if this process occurred in other cells, in other animals.
To show this, he did something that kids have been doing for centuries.
He went out and he got some frog spawn.
With frog spawn, he could show how a single fertilised cell could turn into an embryo.
If he was right, then at every stage of development, he should see cells dividing to become various tissues, not just red blood cells, but into heart, muscle, bone, into a whole frog.
By now, scientists knew that the development of an organism began when an egg and a sperm combined.
But they were hazy as to what happened afterwards.
Remak witnessed the very first cell division just after the egg was fertilised, and, seen here through a modern microscope, subsequent divisions.
Two cells became four.
Four became eight, eight became sixteen.
Cell division was the key.
And, over time, these cells formed all the different tissues of the embryo and, eventually, the frog itself.
Remak had founded the field of embryology.
That's how you get from one single fertilised egg cell into a fully functional animal made of trillions of cells.
He considered his work on frogs to be the keystone of his theory.
And what a theory.
Remak had shown that cell division was how all new cells form and that it was a universal phenomenon across all nature and that cells were only born from other cells.
For over a decade, Virchow had been unconvinced by Remak's research, but it slowly dawned on him that his friend might actually be right.
In 1855, Professor Virchow made a spectacular U-turn.
In a widely-read medical textbook, he took all of Remak's work on cell division and he simply claimed it as his own.
Because he was the big man, the big professor, people stood up and they took notice.
He even came up with his own catchy Latin phrase to summarise it.
"Omnis cellula e cellula.
" All cells from other cells.
Not surprisingly, the two fell out.
I'm sorry to say that Virchow was, and still is, celebrated in every textbook, and Remak, the man who came up with the theory, just a footnote in the history of science.
Yet out of this betrayal, one of the most powerful ideas in biology was revealed to the world.
It is a truly profound concept because it means that all life on Earth must have begun with a single cell and all life on Earth shares a family tree.
Cell theory had come of age.
On the brink of the 20th century, scientists had a pretty modern understanding of the importance of the cell.
They'd come a long way since those squiggly drawings of tiny creatures that had so puzzled the fellows of the Royal Society.
Now they knew that all life was made of cells, from plankton to people, and that cells could only come from other cells.
Thousands of years of ignorance and superstition had been swept away.
And yet, as they looked closer into the world of the cell, they realised that there were some really big questions that remained unanswered.
Why are cells essential to life? What's going on inside? To find out, scientists would have to embark on a new endeavour and peer deeper within the cell.
And what they were about to discover would turn out to be more complex, more extraordinary and more powerful than they could have possibly imagined.