BBC The Cell_1of3_The Hidden Kingdom
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00:00What is life and where does it come from?
00:27These are questions that have puzzled human minds for thousands of years, and yet it's
00:32only in the last couple of centuries that we've come to discover what life is actually
00:36made of.
00:37Take me, for example.
00:39How is it that I'm alive?
00:41I can show you what I consist of, the chemicals that make up a standard issue human.
00:47You need 18 kilos of carbon, a small canister of nitrogen, 50 kilos of water, enough phosphorus
00:55to make 2,000 matches, the same amount of iron as a small nail, and around 20 other
01:01elements.
01:02Chemically, the two sides are identical.
01:08But biologically, we're completely different.
01:10Obviously, I'm alive, and the difference is that these exact same chemicals are organised
01:17into cells.
01:2060,000 billion tiny, incredibly complex structures that make up my body.
01:27Quite simply, we are cells.
01:34Every time we breathe, we move, we think, cells do the work for us.
01:42Like all biologists, the more I find out about them, the more they amaze me.
01:48The idea that all living creatures, from amoebas to humans, are made up of cells is
01:54the cornerstone of biology.
01:57It's the theory of everything.
02:00Yet the story of how we came to understand the cell is rarely told.
02:06It's a fantastic voyage, delving deeper and deeper into an almost magical, unseen world.
02:12It's about nothing less than unlocking the mysteries of life itself.
02:16And for me, the story of the cell is the most powerful story in science.
02:33My starting point is September 1674, and the Royal Society of London.
02:43A mysterious satchel arrived at this club for gentlemen scientists.
02:47It had taken five days to get here from Holland, across the North Sea by ship, and then by
02:52horseback rider.
02:55The package came from a man who'd built the world's most powerful microscope, a microscope
03:00which revealed a hidden kingdom nobody had seen before.
03:07The secretary of the Royal Society opened the satchel.
03:11In it, there was a long letter in Dutch, with a description of something truly extraordinary.
03:17Tiny animals that pirouetted and swam like eels.
03:21And so small, according to the author, that you could fit a million of them on a single
03:25grain of sand.
03:28So let's have a look.
03:29These are the letters.
03:30You can see the date, 1674, at the top, written in Dutch.
03:34I don't speak Dutch, so I can't understand that.
03:36There's the signature, the Sender Antonie van Leeuwenhoek.
03:40And the drawings came in later letters.
03:42You can see these crazy, tiny creatures.
03:45This one here, he's got a little dotted line to indicate the movement.
03:48There he is, spinning round.
03:52So picture the scene.
03:54These guys at the Royal Society, these stuffy old scientists, never seen anything like this
03:58before.
03:59And yet, suddenly, this letter comes through from Holland, with these totally alien creatures.
04:05Not only looking really weird, but also so small that they couldn't even see them.
04:10It must have been just completely amazing.
04:12Did they even believe that these were real?
04:16The fellows of the Royal Society did have their own microscopes.
04:20The device had been around since about 1600.
04:23But they'd never seen the tiny animals van Leeuwenhoek claimed to have found.
04:29Quite frankly, they suspected this unknown Dutchman must be crazy.
04:47Antonie van Leeuwenhoek came from the market town of Delft.
04:51He wasn't a scientist at all.
04:53In fact, he was a linen merchant.
04:59Scientists like van Leeuwenhoek inspected their cloth with magnifying glasses.
05:03And Holland had pioneered their manufacture.
05:07They're still used today.
05:10Here, look, this, that's maybe nice to show.
05:16This is a 17th century napkin.
05:18Shall I show you how big they were in those days?
05:20This is actually from the 17th century?
05:22This is not a replica?
05:23No, this is a real 17th century napkin, eh?
05:27Look.
05:28That's huge.
05:29Yes, that was huge.
05:30Were they particularly messy eaters in the 17th century?
05:33Yes, we think so.
05:34But they're not.
05:35Look.
05:36That's like a tablecloth.
05:37Yes.
05:38But it's only a napkin.
05:40They didn't tuck it in?
05:41Sometimes.
05:42Like that?
05:43But you had to put it on your lap, of course.
05:44I'm sorry.
05:45I'm being slightly disrespectful for a 300-year-old piece of cloth.
05:50And how do you look at the quality of the cloth?
05:53Well, when I want to look at the quality quite good, then I use a loop and I look through
06:00it.
06:01And look, this is a very old loop.
06:03So this is a loop, which is the same word in English, it's like what watchmakers use,
06:08but basically it's a magnifying glass.
06:10Okay, magnifying glass, yeah.
06:12And you can look through it, and when you look through it, you can count the threads,
06:16you can see the threads from the napkin quite good.
06:19Can I have a go?
06:20Yes, you can have a look at the quality.
06:23So you pull it up, and then it comes into focus, and there you go, there you can see
06:28every single thread, every single stitch, it's amazing.
06:33You can really see the pattern.
06:36This is basically exactly the same technique that Van Leeuwenhoek would have done in the
06:4017th century.
06:41Yes.
06:42Yes.
06:43Van Leeuwenhoek became obsessed with lenses, a sort of a lens geek.
06:52He turned out to be the best lens maker there was.
06:56He used delicately crafted lenses like these in his own unique viewing machine.
07:04This is a replica of Van Leeuwenhoek's microscope.
07:06Look how simple it is.
07:08It's just a piece of brass, and it's got one tiny hole with a lens in it, which is maybe
07:12a millimetre across.
07:15Yet this is the gadget that transformed the way we see the world.
07:23A tiny lens, yet more powerful than any other.
07:30Van Leeuwenhoek knew that it's the curvature of a lens that bends the light passing through
07:35it, so making the object being observed, here it's a flea, appear larger.
07:41And because Van Leeuwenhoek was a master craftsman, he could curve the lens more than
07:46anybody else, almost to the point it was spherical.
07:50This allowed him to magnify objects up to 500 times.
08:00No one would make a more powerful microscope for over a century.
08:07So he now had the technology, but what did he look at?
08:12He went from linen, to fleas, to the sting of a bumblebee, in fact pretty much anything
08:17he could get his hands on.
08:19And one of the things he looked at was water.
08:22He'd noticed that in a lake near Delft, the water changed colour with the seasons, and
08:28he figured that there might be something in the water that he could discover.
08:38Many of the fundamental breakthroughs of science seem so simple, so absurdly simple, but we
08:44shouldn't forget that until Van Leeuwenhoek, no one had the curiosity to find out what
08:49might be lurking in the water.
08:56He raced home to take a closer look with his microscope.
09:03The man who's going to help me study the water is Hans Loncker.
09:08He keeps the spirit of Van Leeuwenhoek alive by making replicas of his microscopes.
09:13To grind a lens, Hans needs no special glass, just a shard from an old jam jar will do.
09:28The only way to get enough curvature in the lens is to make it tiny.
09:37This was Van Leeuwenhoek's secret, and it requires great skill and patience.
09:43Van Leeuwenhoek built a staggering 247 microscopes, a new one every couple of months for over
09:4950 years, and told nobody how he made them.
09:54He's placed a drop of my lake water onto a slide that slots into the device.
10:01With a bit of luck, I'll be able to see what Van Leeuwenhoek saw.
10:06Now I've looked down a fair few microscopes in my time, and this is nothing like anything
10:11I've used before.
10:13It's fiendishly difficult to use, so I've got hands with me just in case I can't see
10:16a thing.
10:17So what do I actually do?
10:19Where am I looking?
10:21At the wrong side, you must look through this hole, a very tiny hole, and there's a lens
10:28in it, and through the lens you see the sample that is put between the glass.
10:38So if I hold it up to the light, like this.
10:40Close to your eyes.
10:44And I can see, I can see green.
10:48There is a focusing knob.
10:50There's a focus?
10:51Yes, there is a focusing knob.
10:54This might be made...
10:55So I can move it actually away from my eye.
10:58This one, this is the focusing knob.
11:01It's so simple, and it works so well.
11:04Yeah, that works, that really works, it's now in focus.
11:09Oh wow!
11:10Oh my god, you can actually see moving creatures.
11:14Yes.
11:16Oh god, that's incredible.
11:17There's a tiny, tiny bug in there, which is scooting around, which I guess is a protozoa.
11:31That's astonishing.
11:36I know this story, but I didn't think this was what I was going to actually see.
11:43It's just like looking down a modern microscope in fact, even though it's completely different
11:47to use.
11:50Van Leeuwenhoek gushed with delight too, writing,
11:54This was to me, among all the marvels that I have discovered in nature, the most marvellous
11:59of all.
12:01No greater pleasure has yet come to my eye than these spectacles of so many thousands
12:06of living creatures in a small drop of water, moving among one another.
12:15And so in the 17th century, when people were discovering Australia and astronomers were
12:19exploring the heavens, so Van Leeuwenhoek was peering into a new microscopic universe.
12:33The full meaning of what he saw in that universe, seen here down a modern microscope, escaped
12:38Van Leeuwenhoek.
12:40He assumed he was seeing miniaturised versions of everyday animals, with beating hearts and
12:45contracting muscles, just like their larger counterparts.
12:49He called them animalcules.
12:56Little did he know, it wasn't just a question of scale.
13:02Van Leeuwenhoek's discovery was the beginning of a scientific revolution.
13:06He had seen new forms of life.
13:09We now know he was looking at microscopic plants and single-celled animals such as amoeba.
13:15This Dutch draper was the very first person to see individual living cells.
13:24This revelation could easily have been lost to science, because Van Leeuwenhoek was an
13:28obscure linen merchant working on his own.
13:32He himself was afraid of being ignored, and whinged,
13:36''I suffer many contradictions, and oft times hear it said that I do but tell fairy tales
13:42about the little animals.''
13:46He sent his notes off to the wise gentlemen of London, more in desperation than hope.
13:59And Charles II had granted the Royal Society its charter in 1662, with the motto, ''Take
14:06nobody's word for it.''
14:09The fellows were pretty sceptical of Van Leeuwenhoek's claims.
14:15Even so, they turned to one of their most famous members, our very own Robert Hooke.
14:19He was the go-to guy when you had very small things to investigate.
14:23A decade earlier, he'd spent several years looking down his own microscope to see what
14:27he could find.
14:33Hooke had written one of the most important books in early biology, important not just
14:38for what he saw, but for how he described it.
14:44So this is it?
14:45This is Micrographia?
14:46This is the Micrographia, yes.
14:47This is the first edition, as it would have been seen by fellows of the Royal Society
14:52in 1660.
14:53The title page is here, Micrographia, or some physiological descriptions of minute
14:59bodies made by magnifying glasses.
15:02So he calls them magnifying glasses rather than microscopes at this stage?
15:06That's right, and really this was the first book of microscopy.
15:10So you can see why there was a slight uncertainty about terms.
15:15He was doing it for the first time, effectively.
15:18So at the time, this is near the beginning of the Royal Society's...
15:22My goodness, let's have a look at this dedication.
15:25To the King!
15:26God, that's a big font, isn't it?
15:28That's real deference there.
15:30It is, and very great deference.
15:33We do here most humbly lay the small present at your Majesty's royal feet.
15:39Now that Hooke was a famously cantankerous man, and he annoyed a lot of his contemporaries,
15:44did he not?
15:45Is this sincere?
15:46This sounds a little bit sarcastic to me.
15:48I think it is.
15:49It's formulaic.
15:50I want to see some of the specimens.
15:53Mm, sure.
15:54Oh, wow.
15:55That's the head of a fly, so you get the compound eyes there.
15:58That's incredible.
15:59This is a 17th-century drawing.
16:01I mean, it looks exactly like a modern electron micrograph.
16:05Yeah, and this is the first real view that a general audience had of this kind of world
16:11of the very small.
16:13The drawings alone make this book special, but it's the language Hooke uses when he turns
16:18his microscope on cork that makes it a landmark in science.
16:23In looking at cork, he then coined the word cell.
16:28So here's the sentence right here.
16:30Partitions of those pores were near as thin in proportion to their pores as those thin
16:35films of wax in a honeycomb which enclose and constitute the hexangular...
16:40Is that hexangular?
16:42Hexangular.
16:43Hexangular.
16:44Hexangular cells.
16:45Cells.
16:46Are to theirs.
16:47Next, in these pores, or cells, were not very deep, but consisted of a great many little
16:53boxes.
16:54So this is it.
16:55This is the moment where he writes the word cells to describe what he's looking at, the
16:59individual units that make up a cork structure.
17:03That's right, and self-contained units is what he's saying from the description.
17:07It's incredible.
17:08I mean, this is a real piece of history.
17:10This is the moment where the biggest field in biology was born.
17:15It's a genuine first, yes.
17:19We now know that Hooke was indeed looking at the basic building blocks of plants, cells.
17:26But back in 1664, Hooke thought he was seeing something very different, narrow channels
17:31or pipes that carried sap up and down the plant.
17:38Nowhere in Micrographia does he mention the living animalcules Van Leeuwenhoek had described.
17:44Hooke had never seen them.
17:47So imagine his irritation when the letters from Delft arrived over a decade later.
17:53With a bruised ego, he dusted off his own microscope, a very different design from that
17:58of Van Leeuwenhoek's, larger but less powerful.
18:05Trying to copy his work, Hooke took samples from the River Thames, brought them back,
18:10looked at them under the microscope, and he saw nothing, absolutely nothing.
18:15Here are his notes, and his comment speaks volumes about the time in which he was working.
18:20I concluded, therefore, that either my microscope was not so good as the one he made use of
18:25or that Holland might be more proper for the production of such little creatures than England.
18:35Hooke might have jacked it in at this point, but they're only found in Holland.
18:39But that wasn't his style.
18:41Hour after hour, day after day, he stuck with it.
18:45He tried to cram more light into his microscope.
18:47He ramped up the magnification, and then, within a fortnight, Hooke finally saw them
18:53for the first time.
18:56Van Leeuwenhoek had been right all along.
18:58The tiny animals were the real deal.
19:02Now, the stuffy fellows of the Royal Society did get excited,
19:07though, like Van Leeuwenhoek, none of them really knew what they were.
19:13What they did realise for the very first time was that there was quite literally
19:18more to life than meets the eye,
19:20a whole kingdom of minuscule creatures whose existence they'd never imagined.
19:25It was a shocking revelation.
19:27The natural world was, quite simply, not as it had seemed.
19:36In 1680, the Royal Society made Van Leeuwenhoek a fellow
19:41and formally declared him the discoverer of the little animals.
19:46This is his certificate.
19:49And here he is, looking justifiably smug.
19:58He was the most famous man of Holland, and royalty would visit him at his home.
20:04The Russian Tsar, Peter the Great, and Anne, the new Queen of England,
20:09couldn't resist a peep through his amazing viewing machine.
20:17But Van Leeuwenhoek didn't rest on his laurels.
20:19He decided to turn his microscope on himself
20:22and stepped even further into the hidden kingdom.
20:28He scraped the gunk off his teeth
20:31and found a whole new family of animalcules.
20:36Now we know them as bacterial plaque, the cause of tooth decay.
20:46And in a drop of his own blood,
20:48he was astonished to see tiny red round things floating around.
20:52He described them as globules.
20:55We call them red blood cells.
20:59He didn't dare tell Queen Anne about his secretive research on human sperm.
21:04He used his own semen, acquired, he was keen to stress,
21:08not by sinfully defiling himself,
21:10but as a natural by-product of conjugal coitus.
21:14To be honest, I can't make that same claim.
21:17Now, it's embarrassing enough talking about this in the 21st century.
21:21Imagine what it was like in the 17th.
21:26But, you know, there they are, tiny little Adams,
21:30swimming along, they look kind of like tadpoles.
21:35In his own semen, Van Leeuwenhoek would have seen the same thing,
21:39thousands of tiny little animalcules,
21:42powering along with whiplash-like tails.
21:45He was the very first person to see a human sperm.
21:51Another great discovery.
21:53Van Leeuwenhoek had made the earliest link
21:55between the microscopic wriggling creatures and the creation of new life.
22:02Modern scientists are familiar with the idea
22:04that each sperm is an individual cell.
22:07And at the moment of fertilisation,
22:09the sperm combines with a much bigger cell, the egg.
22:13This fusion of cells is the starting point for a new life.
22:20But Van Leeuwenhoek had no idea of all of this,
22:23trapped in a 17th-century mindset.
22:26He believed that the sperm contained a tiny man
22:30that, once inside the womb,
22:32He believed that the sperm contained a tiny man
22:35that, once inside the womb,
22:40He never saw him, but others drew fantastical pictures like this one.
22:45The imagination of the microscope pioneers
22:48had run beyond their technology.
22:55It's easy to forget where scientists like Van Leeuwenhoek
22:58and Hooke were coming from.
23:00The creation of new life was still very mysterious at this time.
23:04Many philosophers believe that life originated by spontaneous generation,
23:09the idea that creatures could somehow spring forth from inanimate matter.
23:14So crocodiles came from rotting logs
23:16and bumblebees came from the carcasses of bulls.
23:19Now, this stuff sounds completely nuts to our modern ears,
23:23but it's an idea that lasted a surprisingly long time.
23:27Spontaneous generation was to prove a persistent obstacle
23:31to the advance of cell biology,
23:33and it wasn't just a crazy fringe idea.
23:36Mainstream scientists lapped it up.
23:39Take Jean-Baptiste Van Helmont,
23:42a 17th-century Flemish aristocrat
23:44who did important early work on the chemistry of gases.
23:48But Van Helmont also wanted to prove
23:50that mice arose spontaneously from sweat and grains of wheat.
23:56And this is his protocol for making a mouse.
24:00If a foul shirt be pressed within the mouth of a vessel wherein wheat is,
24:06within a few days, to it 21,
24:09a ferment being drawn from the shirt
24:12and changed by the odour of the grain,
24:15the wheat transchangeth into mice.
24:18As they say, take nobody's word for it.
24:21Take nobody's word for it.
24:23Here is our vessel, and here is some wheat.
24:29And here is the crucial extra ingredient, my stinky shirt.
24:35And here's one I prepared earlier, to it 21 days earlier.
24:41So let's see if we've made any mice.
24:43Let's see.
24:51Well, what a surprise, there are no mice.
24:55Now, we're not 100% sure that Van Helmont ever actually did this experiment,
25:00just like I've done.
25:02But if he did, then the only sensible explanation
25:05is that the mice snuck in to have a bit of a snack.
25:08Mice have a habit of doing that.
25:10But whatever the truth is,
25:12nobody believed enough that he actually wrote the protocol down.
25:18Thanks to Van Helmont,
25:20spontaneous generation was the received wisdom of the day.
25:23Because of this, nobody made the connection
25:26between what Robert Hooke and Antony van Leeuwenhoek
25:29had seen down their microscopes and the origin of life.
25:36No-one yet suspected that the new discoveries
25:39in microscopes, the strange and wonderful animalcules and globules,
25:43were essentially the same thing, and that all life was made of them.
25:49For over 100 years, the study of cells was trapped in medieval thinking.
25:55It would need pioneers with the vision and the technology
25:59to dive deeper into the world of the cell
26:02before minds could be opened.
26:10The Royal Botanic Gardens, Kew, the early 19th century.
26:17The deadlock is coming to an end.
26:19The science of cell biology is about to be revitalised.
26:26And in order to understand how that happened,
26:28we need to return to plants.
26:30Since Robert Hooke's work with cork,
26:33botanists had been eagerly tearing up plants
26:36to study their anatomy.
26:38And what they'd slowly discovered
26:40was that plants had some kind of a structure that was made of cells.
26:46Every plant they looked at had them.
26:49These cells were turning out to be much more prevalent
26:52than anyone had realised.
26:54But what did they do?
26:56What were they for?
27:00A Scottish botanist, Robert Brown,
27:03decided to peer into the heart of the plant cell,
27:06and there he'd reveal something as important
27:09as the discovery of the cell itself.
27:15Brown had been the ship's naturalist on an expedition to Australia.
27:19He was no slouch, and he returned to Britain in 1805
27:23with over 3,000 exotic species,
27:26including previously undiscovered orchids.
27:30He studied the collection for many years.
27:36Now, the orchid was a lucky choice as it happened,
27:39because it has cells which are larger than other plants.
27:43If it weren't for this,
27:45it's unlikely that Brown would have discovered what he did.
27:48Now, I'm going to try and see what was so important
27:51using Brown's own discovery of the cell.
27:54Hi, David.
27:56So, this is the actual microscope?
27:59This is Robert Brown's microscope from the Linnaean Society of London,
28:02and it was the one that he used to bring to Kew
28:05when he was working on our living collections.
28:07And so this is actually where he did this work?
28:10Yes, this is where he did this work.
28:12So, this is the actual microscope?
28:14Yes, this is the actual microscope.
28:16So, this is where he did this work?
28:18Yes, this is where he did this work.
28:21And so this is actually where he did this work?
28:24Not on this exact spot, but here at Kew,
28:26which has been a major collection of plants for over 250 years.
28:30And why was he looking specifically at orchids?
28:33Well, he was interested in their sex life, basically.
28:37And so he was interested to look at pollen grains
28:40and how they actually got to the eggs.
28:42And so he was investigating this through this microscope.
28:45And so he would get pieces of the flowers, get the pollen out,
28:49but he was also interested in the other parts of the plants as well.
28:52So he would mount them on something a bit like this
28:54and under this single lens.
28:56Can I have a look? Yes, of course.
29:00Can I move this? It looks very fragile.
29:02I'd rather you didn't move it. OK.
29:04This instrument is a travelling microscope,
29:07which he used to come in a handsome cab,
29:09and this thing was all folded up in a box.
29:11And with great difficulty, we put it back together again,
29:14and it is a very delicate one now.
29:17Brown noticed a distinctive shape within each cell.
29:21It was a turning point in science.
29:24He called it the nucleus.
29:28Wow, so you really can see every cell.
29:32So it's like a... I can see a sort of honeycomb structure,
29:35and in many of the cells, there's a very solid, dark blob in the middle,
29:40which I presume is the nucleus.
29:42Yes, I mean, the point that Robert Brown made
29:44was that each cell actually had a nucleus.
29:46That was his pioneering discovery.
29:49Other people had said they'd seen it,
29:51but he was the first to describe it properly,
29:53give it the name, the nucleus, and show how ubiquitous it was.
29:57And after he'd seen the nucleus for the first time,
30:00what was his interpretation of what he was looking at?
30:03Well, obviously he didn't understand the role of the nucleus
30:06as we would understand it today,
30:08but the important thing was he said,
30:10these are in all cells,
30:12because he started looking at other plants and other plants
30:15and other plants and other plants,
30:17and then he found that they were everywhere.
30:19And therefore the idea that each cell has one nucleus
30:22comes from his work, 1830.
30:28The identification of the nucleus
30:30wasn't Robert Brown's only contribution to science.
30:33He's much better known for his role in physics,
30:36where he was looking at the movement of particles within pollen grains,
30:39what we now call Brownian motion.
30:42100 years later, a chap called Albert Einstein
30:45would use Brownian motion to prove the existence of the atom.
30:49So Brown has a unique position in the history of science
30:52as having made major contributions to atomic theory and to cell theory,
30:57the smallest units of matter and the smallest units of life.
31:01Respect!
31:05Brown's observation would one day allow us to understand
31:08how cells work.
31:10Since then, we've discovered the nucleus is the control centre
31:14that runs each cell.
31:16Not only that, but within it
31:18are the instructions to make every cell in an organism.
31:26In 1831, though, just knowing that the nucleus was there
31:29was the breakthrough.
31:31Its presence in cells would be the clue
31:33to show that the cell might be universal to all living things.
31:39Though no-one yet could suggest something so radical.
31:45Before biology could progress any further,
31:48scientists had to build a much more powerful microscope.
31:52But they'd reached a technological impasse.
31:55Now, it was an Englishman, Joseph Jackson Lister,
31:59who rose to the challenge.
32:01He was a wealthy wine merchant
32:03but had been long obsessed with microscopes.
32:06At the time, he set about designing one
32:08that would be superior to all others.
32:14Lister figured that he needed two lenses,
32:17unlike the single-lens microscopes of van Leeuwenhoek and Brown.
32:25Using two lenses had been tried many times before.
32:28It boosted magnification,
32:30but it also boosted some of the problems inherent in all lenses.
32:34The most vexing of these was an effect known as colour blurring.
32:40You can get a feel for what this looks like
32:42by fiddling with the lens on the camera.
32:45This weird coloured halo around the edge of the light,
32:49that's what I'm talking about.
32:55Lister's genius was to discover
32:57that there was one specific distance between two lenses
33:01and that colour blurring and other focusing problems were minimised.
33:06In 1830, after several years of hard graft,
33:09experimenting with different types of lenses,
33:12testing out various prototypes,
33:14Lister revealed his new design of microscope.
33:19For the first time since van Leeuwenhoek,
33:22there were the means and the know-how
33:24to build ever more powerful microscopes.
33:27This amateur scientist had made a breakthrough
33:30when he rendered the single lens microscope obsolete.
33:34Now biologists had the tool that allowed them to go deeper and deeper
33:39inside the world of the cell.
33:46The stage was set,
33:48but what was still lacking were the scientists with the imagination
33:52to see cells for what they really were.
33:57And here in Berlin, one young and ambitious man
33:59was about to break the impasse.
34:01Theodore Schwann.
34:03The two strands of biology, animal and vegetable,
34:06were about to come together.
34:13At the time, Berlin was the European centre for anatomy
34:17and the university the magnet for the most brilliant biologists around.
34:30Theodore Schwann was keen to make a name for himself
34:34and took a position at the prestigious Anatomical Museum.
34:40Be warned, though, it's not for the faint-hearted.
34:48A guidebook comments,
34:50boys will be admitted only in the company of their fathers or teachers,
34:54and of the female sex, only midwives will be granted admission.
34:58The visitor's attention is called mainly to the wealth of nerve preparations,
35:02a long array of monstrous births and about 500 animal skeletons.
35:16The field of anatomy was in chaos.
35:19Nobody really knew what animals or humans were made of.
35:23Researchers believed that they were built of many different structures,
35:27granules, fibres, tubes, globules and bladders,
35:31and none of them seemed any more important than the others.
35:38Animal studies were seriously lagging behind botany
35:41and this was because their cells are so much harder to see.
35:45So the scientists didn't really realise there were any cells there at all
35:49and this was fuelling the notion that somehow animal tissue
35:53was fundamentally different from that of plants.
35:58But Schwann used innovative ways to stain his animal tissue.
36:04And he had one of the new Lister-style microscopes.
36:09He kept finding the same type of globular structure
36:12in all the different samples.
36:17We know that Schwann was looking at cells,
36:20but at the time, researchers used different terms
36:23to describe what they were seeing.
36:25Kornchen, Kugelchen and Zellen.
36:30The penny hadn't dropped that they were looking at the same thing
36:34and without this connection, they couldn't make the intellectual leap
36:37that cells were common to all life forms.
36:47That was all to change one day in October 1837.
36:51Over a meal, Schwann was chatting about his work to a fellow scientist,
36:55a guy called Matthias Schleiden.
36:57Now, Schleiden had also been studying cells,
37:00but he'd been looking at plants.
37:05Schleiden talked passionately with Schwann about his investigation
37:09into the make-up of dozens of different plants,
37:12from grasses to tulips.
37:15In turn, Schwann revealed his work on the nerves of the edible plants.
37:21He called them the edible frog.
37:23Could such very different things, tulips and frogs,
37:27be built of the same microscopic structure?
37:30It seemed unlikely in the extreme.
37:33The popular perception of scientific discovery
37:36is that there's a sudden brainwave and you leap out of the bath,
37:40everything becomes clear and you run down the street in a buff.
37:43The sad truth is a little more disappointing.
37:46Many scientists toil away grinding out small incremental advances.
37:53However, Schwann and Schleiden's meeting was a classic eureka moment.
37:58Up to this point, neither knew of the other's research.
38:02But both scientists had been using the nucleus
38:05as the way to identify their building blocks.
38:10This is a typical plant cell.
38:12It has a well-defined cell wall and a single nucleus.
38:15And this is a typical animal cell.
38:17It has a soft boundary, which is difficult to make out,
38:20but a cell membrane all the same.
38:22It also has a single nucleus.
38:24By comparing the two, the scientists knew
38:27that they were looking at essentially the same thing.
38:30They were both cells.
38:34Everything they'd observed was built of cells.
38:37Schleiden's flowering plants and grasses,
38:40Schwann's frog and other animal samples.
38:43Now they realised that wherever there was life, there were cells.
38:47I believe this is one of the three great concepts in biology.
38:52It's right up there with Charles Darwin's theory of evolution
38:55and the discovery of the structure of DNA.
38:58Schwann and Schleiden had uncovered an idea
39:01that united all life on Earth.
39:04This meal was where biology changed forever.
39:09Animals and plants, humans and amoebas,
39:13they were all made of the same building block, cells.
39:19In Schwann's book, he explained how cells were self-sufficient units
39:24that could work together to make up a much larger organism,
39:28a cooperative of cells.
39:32Schwann and Schleiden went down in history
39:36as the founders of cell theory.
39:45At least that's the conventional view.
39:48The truth is a bit more complicated and a bit more interesting, I think.
39:52You see, Schwann and Schleiden got half of their theory completely wrong
39:57and their error sent biology down a blind alley for more than a decade.
40:01Their mistake was about where new cells actually come from.
40:15The two Germans believed that new cells formed spontaneously
40:19and grew up like crystals from a tiny speck of nucleus material.
40:24They claimed to have seen this under the microscope.
40:27It was almost as if new cells had come out of nowhere.
40:31Now, if you're thinking this sounds familiar from earlier in the story,
40:35you're absolutely spot on.
40:37You see, this idea of cell formation was uncannily similar
40:41to the theory of spontaneous generation.
40:45By this time, biologists had dismissed the idea
40:48that larger animals could spring out of inanimate matter,
40:51but could it happen with new cells and new microbes?
40:56Spontaneous generation seemed to be the medieval idea that would never die.
41:07Paris, 1860.
41:10The French version of the Royal Society announced a competition
41:14to settle the question of spontaneous generation once and for all.
41:18They had an agenda.
41:20They knew this theory was holding up the advance of biology.
41:25The award? A cool 2,500 francs.
41:30One young French scientist was determined to win the prize.
41:34You'd probably come across his name pretty much every day
41:37without even realising it.
41:39Louis Pasteur is much better known for his work sterilising milk.
41:42We call it pasteurisation.
41:45But in the 1860s, he was a young scientist struggling for credibility
41:50and probably short of a franc or two.
41:53He was convinced that spontaneous generation was a load of medieval bunkum.
42:01Pasteur set out to disprove the idea and win the competition.
42:07Spontaneous generation was a hot topic.
42:10Researchers had spent years studying microbes in the laboratory,
42:14or rather, inside glass flasks.
42:18They'd fill a flask with nutrient broth,
42:21and they'd put in foods that encouraged growth
42:24but was itself sterile, devoid of life.
42:28And then they waited to see what happened.
42:34It all turned into a bizarre battle of the flasks.
42:41Now, the spontaneous generation crowd believed that
42:44as long as there was a nice airflow to get things going,
42:47that life would suddenly spring out of nowhere,
42:50and lo and behold, after a couple of weeks, the solution went cloudy.
42:55And when they looked at it under the microscope...
42:59..it was teeming with microbes.
43:01Life, they claimed, had spontaneously generated.
43:06Pasteur didn't buy it.
43:08He suspected that the microbes came in from the outside,
43:11on dust particles, and set up home in the flask.
43:15And as they multiplied, the flask went cloudy.
43:19But how to prove it?
43:24Pasteur knew he had to design a new type of flask
43:27that let air in, but at the same time,
43:30kept out the surrounding dust and microbes.
43:33A seemingly impossible challenge.
43:38Wow, what sort of temperature is that?
43:40It's hot. It's 2,000 degrees.
43:42How many? 2,000 degrees.
43:50Nice.
43:56That's amazing, as simple as that.
44:02I'm going to hold it while the glass sets.
44:07That is amazing. That is really skilful.
44:10And then we wait for it to cool, and I'll cut that off there
44:13and gently flame the end so that it's not sharp.
44:16And the next stage will be to fill it.
44:18I'm really impressed with that. Well done, Ray. That was amazing.
44:26This was Pasteur's ingenious solution, a swan neck.
44:30Now, it may not look like much,
44:32but this simple design changed the course of science.
44:35Have a look. The air can get in through here,
44:38but the microbes get stuck in the bottom of the curve.
44:40So the broth inside should remain sterile,
44:43and clear and free of microbes.
44:48Yet the spontaneous generation folk were still convinced
44:51that even with the swan neck, new life would form of its own accord.
44:55Who was right?
45:00To find out, Pasteur set up two flasks,
45:03one with the swan neck and one with the neck open to dust particles.
45:07Now, we recreated the experiment a couple of weeks ago.
45:10Here are the two flasks with the broth in them.
45:12This one is Pasteur's with the swan neck,
45:14and you can see that the broth is perfectly clear.
45:19This one's the open-neck flask, which is very cloudy, full of bacteria.
45:24Pasteur had won the competition,
45:27and he proudly declared,
45:29never again will I be able to use the swan neck again.
45:33He had won the competition, and he proudly declared,
45:36never again will the doctrine of spontaneous generation
45:40recover from the mortal blow struck by this simple experiment.
45:46Pasteur made a tidy sum.
45:48He'd shown that new microbes must have drifted in on the breeze.
45:53And he'd sounded the death knell for spontaneous generation.
45:57It couldn't account for new mice, new microbes or new cells.
46:02But it did.
46:19It seems incredible to me that an idea like spontaneous generation
46:23could have lasted as long as it did.
46:26By the 19th century, the world had changed beyond recognition,
46:30and the changes were being driven by science and engineering.
46:34The Industrial Revolution was in full swing.
46:38People now believed in machines and scientific laws,
46:42in cause and effect,
46:44so when the next generation of scientists wanted to find out
46:47where new cells really came from,
46:50they wanted a functional explanation
46:52that didn't rely on cells simply springing forth from inanimate matter.
47:00The quest had started even before Pasteur's killer experiment,
47:05in Berlin, the birthplace of cell theory.
47:08And it was here that two friends had been searching
47:11for a new explanation for the origin of cells.
47:20Robert Remak was a Polish Jew,
47:23while his friend Rudolf Virchow was a politically astute German.
47:28One man would do all the key research,
47:31but the other would take all the credit.
47:34See if you can work out which is which.
47:36Robert Remak is not one of the best-known names in the history of science,
47:40but for me, he's a genuine hero for our story.
47:48Remak was Jewish, so attaining the professorship he deserved
47:52was always going to be an uphill struggle.
47:55He was forced to do his research in a dingy attic apartment.
48:04Despite these obstacles,
48:06Remak set out to discover how new cells originated.
48:10He realised his best hope was to look in a place
48:13where he'd be guaranteed to see lots of cells forming.
48:18Professor Redis has helped us recreate Remak's experiment from the 1840s.
48:25The chick embryo was the animal model of choice for embryology at the time,
48:31because eggs are very easy to get, they're very inexpensive,
48:36and also the embryo is accessible.
48:39That means you can now take some scissors,
48:43and cut a hole here on top.
48:48Oh, and there it is.
48:50The embryo floats on top.
48:52We're going to cut a blood vessel now and collect a little bit of blood.
48:57So I have a glass pipette here, and I'm going to suck a drop of blood.
49:05Here you can actually see that there is red fluid in the pipette,
49:11it contains blood cells, red blood cells,
49:14and I'm putting them on a glass here.
49:18And to see them better, we put a cover slip on top,
49:22so that we can look at it under the microscope.
49:25Here you go.
49:27Now let's have a look.
49:33I take the microscope here, which is of the type that Remak
49:37may have used, it's a really old one.
49:40I have to adjust the light source with the mirror here.
49:43Not the type of scope that you're used to using.
49:46Well, the scopes we're using are a bit more modern now.
49:49You can actually look with both eyes.
49:51I will have to close one eye and look through here.
49:54And what you can see actually is many, many blood cells.
49:58They're still floating around a little bit because the fluid is moving.
50:02They are round, most of them.
50:05But occasionally I see a cell in division, which is not round,
50:10but which has...
50:14I don't know the technical terms in English.
50:17There is some invagination of the cell membrane.
50:20That is the same word, invagination.
50:22Yeah.
50:23So it begins to split into two like that.
50:25Right.
50:26So it invaginates at both sides.
50:28Yes.
50:29That means cells separating from each other in this state
50:33which takes a long time.
50:35So you cannot see the whole process because it takes several hours.
50:39But you see snapshots of this process.
50:41Have a look.
50:49So it's not actually obvious.
50:51He must have been very persistent to see the individual stages
50:55from one cell as it begins to sort of fold in on itself
50:59and then divides into two cells.
51:01He must have done this experiment a lot of times.
51:03He must have used hundreds of eggs, actually.
51:06And what's amazing is that what caught his attention
51:09were the few cells, the very few cells that were in division.
51:12They may have easily been missed by some other researchers
51:15who may have thought that these few cells in division
51:18are some artefacts under the microscope.
51:21But he focused on them and systematically studied them.
51:24And these stages in division
51:27are actually those that he depicted in his publication.
51:30You look at the surroundings that Riemack was working in,
51:34which is a sort of dusty old attic.
51:36It's amazing that he came up with the results that he did.
51:39Well, that shows you that sometimes the instruments themselves
51:43do not advance science, but the thinking of people and having new ideas
51:48is more important than good equipment sometimes.
51:51And so Riemack is a true pioneer.
51:53I would say he is one of the heroes in science, in cell biology,
51:59because he really persisted on this idea
52:02and supported it by very well-founded observations.
52:09Riemack couldn't wait to tell his old buddy Virchow about the research.
52:13Virchow was now a professor of anatomy.
52:16But you know what? He wasn't bowled over.
52:19He thought Riemack's research was interesting,
52:22but believed that this cell division was a rare event
52:25and only applied to the red blood cells of developing chicks.
52:29Big deal. Hardly a major breakthrough.
52:41Ever the diligent scientist, Riemack went off to look for more evidence,
52:46to find out if this process occurred in other cells, in other animals.
52:52To show this, he did something that kids have been doing for centuries.
52:56He went out and he got some frog spawn.
52:59With frog spawn, he could show how a single fertilised cell
53:03could turn into an embryo.
53:05If he was right, then at every stage of development,
53:08he should see cells dividing to become various tissues,
53:12not just red blood cells, but into heart, muscle, bone, into a whole frog.
53:19By now, scientists knew that the development of an organism
53:22began when an egg and a sperm combined.
53:25But they were hazy as to what happened afterwards.
53:31Riemack witnessed the very first cell division,
53:34just after the egg was fertilised.
53:39And, seen here through a modern microscope, subsequent divisions.
53:44Two cells became four. Four became eight. Eight became 16.
53:52Cell division was the key.
53:58And over time, these cells formed all the different tissues of the embryo
54:03and eventually the frog itself.
54:07Riemack had founded the field of embryology
54:11Riemack had founded the field of embryology.
54:14That's how you get from one single fertilised egg cell
54:17into a fully functional animal made of trillions of cells.
54:21He considered his work on frogs to be the keystone of his theory.
54:28And what a theory.
54:30Riemack had shown that cell division was how all new cells form
54:34and that it was a universal phenomenon across all nature
54:39and that cells were only born from other cells.
54:45For over a decade,
54:47Virchow had been unconvinced by Riemack's research,
54:50but it slowly dawned on him that his friend might actually be right.
54:59In 1855, Professor Virchow made a spectacular U-turn.
55:03In a widely read medical textbook,
55:05he took all of Riemack's work on cell division
55:08and he simply claimed it as his own.
55:11Because he was the big man, the big professor,
55:13people stood up and they took notice.
55:16He even came up with his own catchy Latin phrase to summarise it.
55:20Omnis Cellula, A Cellula.
55:22All cells from other cells.
55:27Not surprisingly, the two fell out.
55:30I'm sorry to say that Virchow was, and still is,
55:33celebrated in every textbook.
55:37And Riemack, the man who came up with the theory,
55:40just a footnote in the history of science.
55:46Yet out of this betrayal,
55:48one of the most powerful ideas in biology was revealed to the world.
55:52It is a truly profound concept
55:55because it means that all life on Earth
55:58must have begun with a single cell.
56:02And all life on Earth shares a family tree.
56:05Cell theory had come of age.
56:13On the brink of the 20th century,
56:15scientists had a pretty modern understanding
56:17of the importance of the cell.
56:19They'd come a long way since those squiggly drawings of tiny creatures
56:23that had so puzzled the fellows of the Royal Society.
56:26Now they knew that all life was made of cells,
56:29from plankton to people,
56:31and that cells could only come from other cells.
56:35Thousands of years of ignorance and superstition had been swept away.
56:40And yet, as they looked closer into the world of the cell,
56:43they realised that there were some really big questions
56:46that remained unanswered.
56:50Why are cells essential to life?
56:53What's going on inside?
56:55To find out, scientists would have to embark on a new endeavour
56:58and peer deeper within the cell.
57:01And what they were about to discover
57:03would turn out to be more complex, more extraordinary
57:06and more powerful than they could have possibly imagined.
57:17Stay right where you are, part two of Cell is coming right up.
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