BBC The Cell_2of3_The Chemistry of Life
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00:00Have a look at this.
00:10I'm going to take two living sponges, these are fresh out of the sea, and I'm going to
00:18utterly destroy them.
00:20I'm going to reduce this piece of sponge to its individual cells.
00:26Now it's wrapped up in this nylon mesh and this is acting as a kind of a sieve.
00:34So now I'm going to squeeze it through this sieve.
00:38What's left is nothing like a sponge, a liquid containing cells.
00:45You might think I'd totally killed the sponge, but if I leave these individual cells overnight
00:52something really rather astonishing happens.
01:00As the hours pass, the cells start to move.
01:05Slowly they shuffle their way back together.
01:10And by joining up, they make a new piece of sponge.
01:14Oh, and look at that purple one, I mean it's such a striking result.
01:20Almost all of the individual cells have gone.
01:23It's as if the cells have acted like individuals with a purpose and they've actually re-aggregated
01:30into a piece of sponge tissue, it's amazing.
01:38This experiment was first done over 100 years ago and it raised some really enormous questions.
01:47How do cells know what to do?
01:50What goes on inside cells?
01:54How do these tiny structures make living organisms?
01:59If we find the answers to these questions, we'll find out what makes things alive, the
02:05secret of life itself.
02:21If you think about it, it's pretty incredible.
02:24Cells are just tiny bags full of molecules.
02:29But how those lifeless molecules bundle together to create life was a fundamental mystery.
02:35So the challenge for the scientists who first began to study the cell was to unravel the
02:41chemistry of life.
02:51It was here in Germany, 150 years ago, that scientists set out to tackle the mysteries
02:57of the cell.
03:04They discovered that plants, animals, people, all living things in fact, are made up of
03:10tiny cells.
03:14Doctors began probing the cells of the human body.
03:17Cells and tissues became specimens to be preserved, sliced and put under the microscope.
03:26What they saw and drew showed that every organ and tissue is made of different types of cells
03:32working together.
03:36And that all cells come from other cells.
03:39New ones are only made when cells split in two.
03:44Somehow, cells must contain the secret of life itself.
03:49But scientists knew nothing about what went on inside these cells.
03:55The problem was that when doctors and scientists looked down the microscope at cells, what
04:00they could see didn't tell them much.
04:02They could see that cells were enclosed by a boundary, a membrane, and that there was
04:07a dense bit in the middle that they called the nucleus.
04:10The nucleus was surrounded by a jelly-like gloop that they called protoplasm.
04:15But the problem was that these are just blobs within blobs.
04:18They didn't know what the blobs were for or even what they were made of.
04:27The first step towards understanding the working of cells came in the small German town of
04:32Tübingen.
04:36It was a centre of scientific excellence.
04:40The first biochemistry lab was established in the local castle.
04:45One of the aims was to find out more about human cells.
04:51And it was here, in 1868, that a keen young scientist, Dr Friedrich Miescher, arrived
04:57to take up his first research post.
05:02Miescher's job here at the castle was to study the chemistry of white blood cells.
05:07He decided to look at the large nucleus at the centre of the cell and find out what it
05:11was made of.
05:12To do this, he needed two things, a ready supply of cells and a way of getting rid of
05:17the gloop so he could study the bare nucleus.
05:24Getting hold of white blood cells would normally have been tricky, but Tübingen was the ideal
05:29place.
05:32The region had been at war with Prussia.
05:35Hundreds of injured soldiers with infected wounds lay in the barracks next to the hospital.
05:43Their wounds were oozing copious amounts of pus, which is full of white blood cells.
05:49So, revolting as it sounds, Miescher collected their old bandages so he could scrape off
05:55the pus.
06:00Miescher needed something else.
06:02His next stop was the local slaughterhouse to collect a pig's stomach.
06:07Look here it is.
06:09Oh, it's disgusting.
06:13He was interested in the mucus that lined the stomach.
06:16This contains an enzyme called pepsin, which helps break down and digest food.
06:22Where's the pepsin?
06:23Look here.
06:24This is the pepsin.
06:25Oh, this sort of gloopy stuff.
06:27Yeah.
06:28There's not much of it.
06:29No, that's all.
06:30And this is what digests, helps digest the food in the stomach?
06:33Yeah.
06:34Smells like a pig's stomach to me.
06:36With the pepsin, Miescher now had all he needed for his experiment.
06:42And this is a delicacy in Tübingen?
06:44Yes.
06:45You can fill it with bread or you can cut it in stripes and then you cook it and eat
06:52it with bread.
06:53Is it tasty?
06:54Yes.
06:56I'm not sure about that.
07:04Miescher carried the bandages and the pig's stomach back to the lab.
07:10If he was right, the pepsin would break down the white blood cells.
07:15Then, for the very first time, it would be possible to examine the dense nucleus
07:20at the heart of the cell.
07:23Nowadays, we do analysis like this using precision equipment.
07:27But, of course, Miescher didn't have any kit like that, so it wasn't easy.
07:32First, he had to scrape the pus from the bandages.
07:39Now, this is mayonnaise, but you get the idea.
07:43Then, he had to wash the pepsin out of the pig's stomach using an acid and mixed it
07:51with the pus.
07:53After the enzyme had done its work and digested the cells, only then could he analyse the
07:58nucleus on its own.
08:06Now, the big question was, what did the nucleus consist of?
08:11Miescher spent months analysing its chemistry,
08:14and he found it contained a rather strange molecule.
08:22This molecule was made up of carbon, hydrogen, oxygen and nitrogen.
08:28He knew these elements were found in all living things.
08:34But this molecule contained something extra, phosphorus.
08:38And that made it different.
08:41Very different.
08:43It was an entirely new kind of molecule.
08:46Because he found it in the nucleus, Miescher called it nuclein.
08:50We now know it as DNA.
08:57Intrigued, Miescher examined the nucleus for a long time.
09:02Intrigued, Miescher repeated his experiment on sperm cells from frogs,
09:07carp, bulls and salmon.
09:16Every time, he found exactly the same molecule.
09:23Incredibly, some of it has survived.
09:27Here in this test tube is some of the first DNA ever isolated.
09:32It's DNA from salmon sperm that Miescher extracted in the 1870s.
09:36Now, it may not look like much, but this brown powder
09:40marks the beginning of a scientific revolution.
09:46Miescher's discovery of DNA was confirmation that there was
09:50something special inside the nucleus of cells,
09:53something that was common to all life.
10:00But Miescher was way ahead of his time.
10:03His work on the chemistry of the nucleus went unnoticed
10:07because scientists still had little idea of what the nucleus was for,
10:12or of how cells worked.
10:23Miescher was one of the founders of the Mediterranean
10:26that gave them an important breakthrough.
10:33Here, scientists found a ready supply of living cells
10:36which they could easily study.
10:40The embryos of the many species of marine life that thrive here.
10:47Which is why the Bay of Naples became the centre
10:50of a remarkable scientific community.
10:52Scientists who were using the abundance of creatures in the sea
10:56to study how life is formed.
11:06At the heart of the community was this marine station
11:09built on the shores of Naples.
11:11And in 1888, another young German scientist,
11:15Theodor Boveri, arrived here to work on cells.
11:23He'd be studying alongside some of the most eminent scientists of his day.
11:31In fact, the marine station was supported by Charles Darwin himself.
11:43The scientists built a public aquarium to fund their research.
11:48Then, as now, it was a popular attraction.
11:57And it provided a ready supply of cell specimens.
12:02Because fish lay their eggs straight into the water.
12:09Boveri was interested in the fertilisation of eggs.
12:13Once the egg cell is fertilised,
12:15it begins to divide.
12:17It creates another cell, and then another,
12:20and so a new life is born.
12:24Somehow, when the cells divide,
12:26the essence of life is passed from cell to cell.
12:31By the end of the century, with better microscopes
12:34and new chemical dyes to stain the cells,
12:37embryologists were able to see early dividing cells
12:40in more detail than ever before.
12:42And what they saw was incredible.
12:44Have a look at some of these drawings.
12:48Scientists had thought that when the cells divide,
12:51they simply split down the middle.
12:55But now they began to see that something far more complicated
12:59was going on inside the nucleus.
13:07As cells started to divide,
13:09discrete objects like little rods would appear inside the nucleus.
13:16These rods seemed to unravel and split in two,
13:19migrating to opposite ends of the nucleus.
13:26Then the nucleus would split in half,
13:29followed by the cell itself.
13:32Scientists called the rods chromosomes,
13:35meaning coloured bodies,
13:37because the chemical dyes they were using gave them a colour.
13:43And they saw that these puzzling chromosomes
13:46only appeared in the nucleus of a single cell.
13:51But what about the rest of the cells?
13:53What happened to them?
13:56And they saw that these puzzling chromosomes
13:59only appeared in the nucleus when a cell divided.
14:07Now, the obvious question for any scientist
14:10looking at something so complex and elaborate is, why?
14:14Why do the cells have to divide in such a curious way?
14:19To find the answer, Bavari devised an experiment.
14:30He used a creature found in abundance at the bottom of the bay.
14:36My underwater guide is Dr Ina Arnone.
14:42Ina works at the Naples Marine Station
14:45on the same kind of creature Bavari used, the sea urchin.
14:52The easy part about collecting sea urchins is finding them.
14:56Unlike fish, they just stick to the rocks.
15:02But without practice, picking them off is harder than you think.
15:10And the spines can really hurt.
15:16There it is, a sea urchin.
15:18Plucked...
15:20Plucked from the bottom of a bay of Naples.
15:24There are thousands of them down there.
15:26You can see why people used these as experimental animals.
15:32The inside of a sea urchin consists almost entirely
15:35of its reproductive organs, or gonads.
15:39Oh!
15:41This is very good.
15:43Look, gonads, how big they are.
15:45And you can recognise this is a male.
15:47Because you see here?
15:49These are the gonads and this is the...?
15:51The white part is the sperm.
15:53Wow.
15:55And fishermen, they believe this is indeed the milk of the sea urchin.
15:59Right. And this is a local delicacy here as well, right?
16:02Yes, it is. Yes, it is. Do you want to try?
16:04Of course.
16:06Shall I show you?
16:08It's like eating the sea.
16:10Let me try.
16:14So I just suck it out?
16:16Just suck it out.
16:18Mmm!
16:20It's pretty salty.
16:22Oh, that's salty, yes.
16:24Why have people used these for scientific research?
16:27Oh, that's pretty obvious.
16:29They produce billions of tons of sea urchins a year.
16:32And they produce billions of tons of sea urchins.
16:35Oh, that's pretty obvious.
16:37They produce billions of eggs and billions of sperm.
16:45And billions of eggs and sperm, each of them single cells,
16:49were just what Bavari needed for his experiment.
17:00Back in the lab, all Bavari had to do was simply shake the sea urchins.
17:04Like this.
17:06This stimulates the sea urchins to spawn.
17:10And so the orange powdery stuff that's just falling off the bottom,
17:14that's the eggs?
17:16Exactly. They are falling down
17:18and you will see them collecting on the bottom.
17:25Bavari wanted to find out what happened when cells divide.
17:30So his starting point was the moment
17:32when the egg is fertilised by a sperm.
17:38You can see here the nucleus of the egg.
17:41This bit in the middle, that's the nucleus here?
17:43Yes, I can focus through to show you better.
17:45And that's what Bavari used to see under the microscope.
17:49So this is an unfertilised egg.
17:51You can really actually see the sperm trying to eat their way into the egg.
17:55Yes.
17:56Oh, that's incredible.
17:58Wow.
17:59You see the fertilisation envelope.
18:03Bavari knew that when an egg is fertilised,
18:06the nucleus of the egg and sperm combine to form a new nucleus.
18:12This first cell of the new embryo divides into two.
18:16Soon, two cells become four.
18:19Four cells become eight, 16, 32 and so on.
18:25And each time a cell divides,
18:27the nucleus of the new cell inherits an identical copy
18:31of all of the chromosomes.
18:36So Bavari knew the chromosomes must be important.
18:43But how important?
18:45On the dish.
18:46He wondered if he added extra sperm into the egg,
18:50he wondered if he added extra sperm into the egg,
18:53would extra chromosomes appear?
18:59What effect would this have?
19:01Would the cells still divide normally?
19:11With Ina's fluorescent microscope, we can see what happens.
19:16When extra sperm are added,
19:18the whole process of cell division goes off-beam.
19:22Clumps of deformed cells of different shapes and sizes appear.
19:28The whitish blobs in the middle are the chromosomes in the nuclei,
19:32but their irregular shape suggests each nucleus
19:35has acquired a different amount of chromosomes.
19:40So this one looks very different.
19:42We've got three nuclei here, but is this one cell or two cells?
19:46I can't quite make it out.
19:48Yes. First of all, you can see that there are three nuclei,
19:52and not two, as supposed to be at this stage.
19:55But also what you can see is that the nuclear content is different.
20:01So you can see this is much bigger, this is smaller,
20:04and this is even smaller.
20:06So this didn't receive the same amount of chromosomes.
20:10So there's different amounts of chromosomes in each bit of the cell,
20:14and so it's gone wrong. Exactly.
20:17And this embryo won't develop any further than this?
20:20Well, he will probably do some more division,
20:23but we will generate monsters.
20:25A monster? So it won't develop into a proper sea urchin?
20:29Not at all.
20:34That's what Bavari saw.
20:36Every time he introduced extra sperm into his sea urchin eggs,
20:40he got monsters.
20:43Mutant embryos that never got further than a few cells.
20:51So let's just take a moment to think about
20:54what a massive discovery Bavari had made.
20:57An embryo could only develop
20:59if it had one full set of chromosomes in every single cell.
21:04So every time a cell divided,
21:06a new identical set of chromosomes had to be formed in every cell.
21:12Any more or less, and the embryo would die.
21:16So it suggested that whatever information was contained
21:19within the mysterious chromosomes, it was essential for life.
21:29But what was that information?
21:33Bavari had an idea.
21:35The chromosomes for a new life came from the sperm and the egg.
21:41Could the chromosomes be the way
21:43in which all the characteristics of sea urchins are passed on
21:47when a new life is created?
21:49And again and again, every time the cells divide.
21:55Bavari spent the next 20 years experimenting on sea urchins,
22:00and he became convinced that chromosomes must contain
22:04what he called the hereditary characters.
22:08In other words, key bits of information
22:11that control the characteristics that a creature inherits.
22:15Bavari was predicting the existence of genes.
22:29He was on to something big.
22:32The idea that chromosomes within our cells
22:35could be the way that life and all the traits we inherit are passed on.
23:00In New York, Bavari's work on chromosomes
23:03had caught the attention of a fellow embryologist.
23:10Thomas Hunt Morgan was another veteran of the Naples Marine Station.
23:16But here at Columbia University, he'd moved on from studying sea life.
23:23His creature of choice was Drosophila melanogaster.
23:27That's the fruit fly to you and me.
23:33Thanks to Morgan, this tiny insect
23:36was to become one of the mighty heroes of biology.
23:41For anyone interested in studying inheritance,
23:44the fruit fly has some big advantages.
23:47They're small, cheap, and they breed like, well, flies.
23:53You can get a new generation every ten days.
23:57And they only have four pairs of chromosomes.
24:04Morgan's lab became known as the fly room.
24:13Now, just as we inherit characteristics from our parents,
24:16so indeed do all creatures, including fruit flies.
24:20Morgan wanted to see if he could see patterns of inheritance in fruit flies
24:24and link those patterns to the chromosomes.
24:27Now, in nature, fruit flies normally have red eyes.
24:30But one day, Morgan found a male fly with white eyes in his collection.
24:35He decided to crossbreed it with a red-eyed female.
24:41When Morgan bred their offspring,
24:43some of the next generation of flies emerged with white eyes.
24:49Morgan noticed that it was only male flies that had inherited white eyes,
24:54none of the females.
24:57He concluded that having white eyes was somehow linked to being male.
25:04Morgan knew that the chromosomes of fruit flies included two,
25:08which determined gender.
25:11So he deduced that the information for making white eyes
25:15had to be carried on the sex chromosomes.
25:20That was his breakthrough.
25:23Morgan had now found evidence that seemed to support
25:26what Bovary had predicted,
25:28that the characteristics we inherit mapped to specific parts of the chromosome.
25:36Now, the fly room was really buzzing.
25:41Morgan and his team were soon able to find which parts of the flies' chromosomes
25:46accounted for traits like body colour and wing size,
25:49as well as eye colour.
25:54And by 1922, they'd drawn up the world's first chromosome map,
25:59showing the location of 2,000 different traits.
26:05To describe the individual parts of the chromosomes
26:08that related to each trait, he used the word gene.
26:13Nowadays, genes are part of our everyday language,
26:16so it's easy to forget what a huge leap forward this was,
26:20to understand that the way we look and the way we operate
26:23might be determined by genes within our cells.
26:34Genes are what families truly are.
26:38Genes are what families truly share.
26:41They are the biological link between my dad, myself and my son.
26:48Spotting those genetic connections can make family photo albums such fun.
26:53That's you.
26:55That looks like Jakey to me.
26:57Yes, very, very similar.
26:59You look much more like your mum now.
27:01Yeah, I always did. Yeah, where is she?
27:04Back in the 1920s, the idea that something within our cells
27:08could account for family resemblance was new.
27:12Look at that. Look at those tiger-skin speedos.
27:15That is an awesome pose.
27:17But the thing is that you were on the other side of the camera
27:20probably encouraging me to do something stupid.
27:22Very likely, very likely.
27:24Today, these genetic links are accepted,
27:27but a century ago, this was groundbreaking stuff.
27:31Scientists had peered into the cell nucleus.
27:34They had found chromosomes.
27:36And they had shown that these chromosomes
27:39carried information we inherit, genes.
27:43But they still had no idea how.
27:52So here was the new question.
27:54What on earth were genes?
27:56What was the chemistry within cells?
27:58The molecule that allowed hereditary information
28:01to pass from one cell to another, from generation to generation?
28:10The answer to that would come from two scientists
28:14studying not inheritance, but disease.
28:19Fred Griffith and Oswald Avery were both medical researchers
28:22working on pneumonia, but on opposite sides of the Atlantic.
28:29They didn't even know each other,
28:31but together they would find the next crucial piece of the puzzle
28:35of how cells work.
28:41Fred Griffith was working at the Ministry of Health here in London.
28:48He was investigating types of bacteria,
28:51single cells that invade the body and reproduce there.
28:55He wanted to find out why some bacteria kill and others don't.
28:59And he stumbled across something rather remarkable.
29:07It all began when he was using laboratory mice
29:10to test cocktails of different bacterial strains.
29:16He was looking for a combination
29:18that would work as a vaccine to prevent pneumonia.
29:22He started with solutions of two different types of pneumonia bacteria,
29:26which I've mocked up in these beakers,
29:28one harmless, the other lethal.
29:33And with very basic equipment, he tested his bacteria on the mice.
29:41Unsurprisingly, when he injected the mice with a harmless bacteria,
29:45they were fine.
29:48And when he injected them with the lethal bacteria, they died.
29:58Griffith then took the solution of lethal pneumonia bacteria and heated it.
30:03He thought this should kill the bacteria.
30:07And sure enough, when injected, the bacteria died.
30:11He thought this should kill the bacteria.
30:15And sure enough, when injected, the mice showed no sign of pneumonia.
30:21It was then that Griffith tried something which gave a very surprising result.
30:27When Griffith made a mixture of the lethal heat-treated bacteria
30:32with the harmless bacteria,
30:34remember that neither of these had killed the mice on their own,
30:38he found that some of the mice died.
30:44When he examined the dead mice, he found deadly bacteria in their blood.
30:48Something very spooky was going on here.
30:55Griffith figured that something in the lethal bacteria had survived.
31:01And whatever it was,
31:03it had transformed the harmless bacteria into killer cells.
31:13But what was that something?
31:15He never found out.
31:20Griffith had his job to do, working on vaccines.
31:24He never realised that he'd accidentally found a whopping great clue
31:29to what genes are,
31:31a clue that would lead to a major breakthrough
31:34in our understanding of how cells work.
31:48But his results caught the attention of Oswald Avery,
31:51also an expert in pneumonia bacteria.
31:55Avery was determined to find out what it was
31:58that had the power to change one type of cell into another.
32:02It would take him nearly a decade,
32:04but it would turn out to be a critically important discovery.
32:14At the Rockefeller Institute in New York,
32:17Avery and his team were using the latest methods in biochemistry
32:21to look inside bacteria.
32:25They knew that bacteria, like all cells,
32:28are essentially little bags jammed full of different kinds of molecules.
32:33A chemical soup made of millions of protein molecules,
32:37carbohydrates and fatty substances called lipids.
32:45Over nine years, they'd tested every type of molecule,
32:49in the lethal pneumonia bacteria,
32:51to find out which molecule was passing on its deadly traits
32:55to the harmless bacteria.
33:01Avery decided to work by a process of elimination.
33:05First, he removed the carbohydrates and then the lipids,
33:08but it wasn't either of them.
33:10Then he removed all of the proteins, but it wasn't them.
33:13Finally, he removed all of the proteins,
33:16then he removed all of the proteins, but it wasn't them either.
33:20Finally, he turned his attention to a molecule
33:23that had seemed like an unlikely candidate.
33:30It was when he started testing DNA,
33:33the strange molecule in the nucleus that Friedrich Miescher had found
33:3775 years earlier, that Avery got a result.
33:42Stripped of their DNA,
33:44the power of the lethal bacteria to transform other cells
33:48simply vanished.
33:52What Avery had discovered was the molecule that genes are made of.
34:01This was a huge discovery.
34:04It showed that DNA was actually controlling cells.
34:08In order to understand how cells work, and indeed how life works,
34:12we would first need to understand DNA.
34:15It became crucial to know exactly what it is and what it's for.
34:26By the late 1940s,
34:28the chemistry of the cell was starting to become clearer.
34:33What once had appeared to be indistinct blobs
34:36were now known to contain chromosomes.
34:39These were shown to carry genes.
34:43And now they'd discovered that all genes were made of DNA.
34:50But how did DNA control cells?
34:54Scientists thought that they might find the answer
34:57in the structure of the molecule.
34:59They needed to work out how DNA was built.
35:04And this quest would turn out to be the most famous story in biology.
35:15It was after the Second World War that the quest began in earnest.
35:23The American Nuclear Weapons Project had involved thousands of physicists
35:27who delved deep into the atoms at the heart of all matter.
35:34Among them was a British scientist who returned home after the war
35:38to take a job at King's College in London.
35:42As part of its post-war rebuilding programme,
35:45the college had acquired the latest X-ray imaging techniques
35:49to look deep within the cell,
35:51and Professor Maurice Wilkins was put in charge.
35:54Here is one of the X-ray generators we're using in this work.
36:03We use X-rays to study the structure of a molecule
36:07because an X-ray travels along like this in a wavy kind of way,
36:13and the length of the waves of the X-rays
36:17are about equal to the distance between the atoms in the molecule.
36:22So that when an X-ray strikes the molecule,
36:26the waves of the X-rays can squeeze in between the atoms,
36:30and when they come out the other side, their directions are deviated.
36:34And from the deviation of the X-rays,
36:37we can work out the way in which the atoms are arranged inside the molecule.
36:48The X-rays taken here at King's College were pivotal.
36:51Producing them would be a painstaking job
36:53by a brilliant young scientist working with Wilkins,
36:56and her name was Rosalind Franklin.
37:00Franklin was an expert in X-ray imaging.
37:04With her expertise, the college hoped to be the first to find the structure of DNA.
37:15She worked in a new laboratory built in the basement
37:18on the rubble of the old college which had been bombed.
37:22The college authorities were concerned that the X-ray experiments
37:26which used hydrogen could be dangerous,
37:29so they made Franklin and her assistant do their work at night time
37:33after the students had gone home.
37:41Franklin used highly concentrated DNA.
37:48One of her skills was in finding just the right amount of moisture
37:52to prepare the strands.
37:56It was precision work.
38:00When she stretched out its fibres,
38:02she got a single DNA strand a tenth of a millimetre across.
38:10Here in the lab, she took strands of DNA
38:13and mounted them inside this specially built camera.
38:16The camera chamber was filled with hydrogen to get the very best image.
38:20When the X-rays were switched on, they shone through the DNA
38:23and scattered in different directions,
38:25creating an image on a photographic film.
38:30Here's a close-up.
38:38Franklin took over 100 pictures.
38:41Each one could take up to 90 hours of exposure at close range.
38:49Once the photo was processed, she projected it onto the wall
38:52so she could calculate the exact distance between atoms.
38:59This is a mysterious DNA molecule.
39:07This distinctive X shape was the key that would reveal how DNA is built.
39:13But it was not Franklin's name that came to be associated
39:16with the discovery of DNA's structure.
39:21Wilkins was in close touch with scientists from Cambridge
39:25and was the first to find the structure of DNA before American rivals.
39:31Unknown to Franklin, Wilkins gave Photo 51 to James Watson,
39:36an ambitious young scientist at Cambridge's Cavendish Laboratory.
39:40Having studied the photo, Watson and his collaborator Francis Crick
39:44had a sudden revelation.
39:47It would transform them into scientific celebrities
39:51and put the cell at the centre of world attention.
39:56This is the Eagle Pub here in Cambridge.
39:59According to Watson, on February 28th, 1953,
40:03Francis Crick strolled into this pub
40:06and announced to fellow drinkers,
40:08we have found the secret of life.
40:11Now, if you ask me, this story is a little bit apocryphal,
40:14probably embellished with some dramatic licence.
40:17Nevertheless, the sentiment is bang on and shouldn't be understated.
40:21This marks one of the truly great moments in the history of science.
40:33Crick and Watson had worked out the structure of DNA
40:37and very soon their double helix model was announced to the world.
40:43The structure of DNA is now the most famous image in all biology.
40:49What Crick and Watson showed is that it's made of two long strands
40:53intertwined into two spirals,
40:55with sugar and phosphate making up the backbone.
40:58But it's on the inside of the spiral where things get really interesting.
41:02On the inside are four molecules,
41:05adenine, thymine, cytosine and glycine.
41:09Adenine, thymine, cytosine and guanine.
41:13They're better known by their letters, A, T, C and G.
41:18They're called bases.
41:20What Crick and Watson discovered is that these four basic units
41:24pair up millions of times within the double helix
41:27and they pair up in a very specific way.
41:30A always pairs with T
41:33and C always pairs with G.
41:37A and T and C and G,
41:40making up the rungs of the ladder within the double helix.
41:44What Crick and Watson realised
41:46is if you split the two strands of the DNA apart,
41:49you have all the information to make two new fresh pieces of DNA.
41:53Every time you have an A, it pairs up with a T.
41:56Every time you have a C, it pairs up with a G.
41:59So when you split them apart, you can replace the missing strand
42:03with a new double helix.
42:05Twice. Genius.
42:12Crick and Watson's discovery
42:14triggered an explosion in scientific research.
42:19DNA's structure had revealed the secret of how genes are reproduced
42:23every time a cell divides.
42:26An identical copy of the DNA is passed on from cell to cell.
42:33Incredibly, all the information needed to create life
42:37is encoded in this molecule.
42:44So the next big challenge was to crack the code.
42:48Within ten years, scientists had deciphered the code
42:52within the double helix.
42:56It was the instructions to make the millions of molecules
42:59that build our cells.
43:08By then, scientists used electron microscopes
43:11to see the composition of DNA.
43:13By then, scientists used electron microscopes
43:16to see the complex machinery inside the cell.
43:19The electron microscope is an instrument capable of enlarging,
43:24of magnifying, of the order of 100,000 times.
43:28Now, can we move towards the nucleus?
43:32That's fine.
43:34From such minute studies, it is possible to make models
43:37such as the one which is the star of our set.
43:40The half section of a cell with the outer skin removed,
43:44one million times larger than life.
43:57Professor Swan, perhaps you can orientate us now
44:00that we are inside the cell
44:02to what Mr. Horn was showing us on the electron microscope.
44:06Well, I think the first thing to get clear
44:09is that you can see very clearly
44:11this great tracery of tubes and twigs.
44:15That is the reticulum.
44:18And in the middle, of course, the nucleus.
44:26Today's computer graphics show how much more we now know
44:30about how the cell works.
44:32Cells use complex machinery to carry out the DNA's instructions
44:37and to make the millions of molecules
44:40that keep cells, and us, alive.
44:49These are the cells that all living beings are made of,
44:53all of it designed and controlled by DNA.
44:58And to make a living organism takes a staggering amount of DNA.
45:06Each human cell has 3.4 billion letters of DNA code.
45:11To print them on paper has taken 120 volumes.
45:19But there's a conundrum here.
45:21If you take any single cell in my body,
45:24whether it's brain or bone or skin,
45:27they contain the same instructions, the same DNA, the same genes.
45:32So how do you get from this set of instructions
45:36to a fully functional human
45:38containing trillions of highly specialised cells?
45:45Let me show you what I mean.
45:47I'm going to damage my skin by giving myself a burn.
45:50You should not do this at home.
45:52I'm doing it purely in the interests of science.
45:55The burn is going to destroy some of my skin cells and create a wound.
46:00So here goes.
46:13Ow!
46:15Oh, my goodness!
46:17Ow!
46:19Oh, my goodness, that hurt!
46:23You can see it's already started to burn the top layer of skin there.
46:32We take it for granted that this wound is going to heal, thankfully for me.
46:36But if you think about it, it's a really remarkable process,
46:39and it can only happen because lots of different types of cells
46:42get to work to perform highly specialised functions.
46:46That really hurt. That really hurt quite a lot.
46:54Over the next days and weeks, my wound mends itself.
47:00Nerve cells register pain and damage.
47:05White blood cells fight infection.
47:08Red blood cells form the scab.
47:12And crucially, new cells develop and grow
47:15and make up layers of young tissue that replace the dead skin cells.
47:23And here's the rub.
47:25Remember, all the cells in my body share exactly the same DNA, my DNA.
47:32Yet somehow, all the different kinds of cells involved in healing my wound
47:36know exactly what they should be doing.
47:42Four weeks later, my skin is well on its way to healing,
47:46although I am going to have a scar.
47:48This process has happened because all of the cells involved
47:51knew exactly what their function was.
47:54But how did they know that?
47:56How do any cells know what to do and what they are for?
48:06This question continued to puzzle scientists
48:09long after they'd discovered the structure of DNA.
48:15How could the same DNA make different kinds of cells?
48:28The answers would come from some of the freakiest experiments in all biology.
48:34And they would reveal something astonishing
48:37about the origins of life itself.
48:40It was here in Switzerland, some 30 years after Crickenwatson,
48:44that the first clue was discovered.
48:46And yet again, it came from a scientist studying our old friend,
48:49the fruit fly.
48:56Professor Walter Goering is a pioneer of modern biology.
49:00In the 1980s, his work helped solve the mystery
49:03that remained at the heart of all life.
49:06How can DNA make all the different types of cell
49:10needed to build a living being?
49:19Goering's breakthrough began with something that happens
49:22very occasionally in nature.
49:24A mutant fruit fly, born with a rare abnormality,
49:28a perfectly formed leg growing out of its head,
49:32right where the antenna should be.
49:35The wrong kind of cells in the wrong part of the body.
49:39Spooky.
49:41By comparing the genes of this mutant with normal flies,
49:45Goering had been able to isolate the gene
49:48that triggers the growth of a fly's leg.
49:52Did this gene have anything in common with the genes
49:55that controlled other parts of the fly's body?
49:58Goering and his team got to work analysing
50:01and comparing the DNA sequences.
50:03So what you can do is you split this molecule...
50:06You chop it into tiny fragments.
50:08..you have to find out where your gene is.
50:12After months of work, they found the location of the gene.
50:16What we did was to make a huge, what we call a restriction map.
50:22And here we have the individual pieces of DNA.
50:27This is the actual data that you produced?
50:29This is the handmade map which we made to map each one of these.
50:34But this is actually a piece of history, though.
50:37This is the history of the DNA.
50:39This is the DNA of the fly.
50:43But this is actually a piece of history, though.
50:46This is the historical piece, yes.
50:48The finished map produced a stunning revelation.
50:53It showed that all the key parts of the fly's body had something in common.
50:58They were controlled by a handful of identical genetic switches.
51:05These switches turned on other genes in the developing embryo.
51:12And each of these genetic switches controlled one major chunk of the fly's body.
51:23It's been a while since I've done this.
51:29Let's take out the... Oh, I need to take out the stopper.
51:34Good call. All right, I'll try that again.
51:37With the help of the mutant,
51:39Daring's team had begun to solve the mystery
51:42of how all the different types of cell in the fly's body
51:45grow in the right place and at the right time.
51:49Oh, I miss doing this.
51:52These genetic switches, they're called homeobox genes,
51:56control when other genes are switched on.
52:00As the fly larva grows, they kick in and lay out the fly's body plan,
52:05head at one end, tail at the other.
52:08And they start a chain reaction of other genes
52:11to grow a leg, a wing or an antenna in exactly the right place.
52:18Now scientists wanted to know, did other creatures have similar genetic switches?
52:25They began to study other species, everything from frogs to mice to humans,
52:30species which looked very different.
52:34And in every species they looked at,
52:36they found exactly the same genetic switches.
52:41The mechanism was the same in wildly different animals.
52:46It was a staggering result.
52:50But the biggest revelation was still to come.
52:56In 1995, a student of Daring's found the gene in a fruit fly
53:00which triggers the formation of eyes.
53:03This gene launches a cascade of 2,000 other genes
53:06that generate all the cells that make up a fly's eye.
53:12This eye gene in the fly looked incredibly similar
53:15to the gene that triggers eyes in mammals.
53:19Now here's where it gets really interesting.
53:21Daring knew that the same gene existed in mice and humans,
53:24species whose eyes are completely different.
53:27But a bold idea had taken hold in his mind
53:30and he decided to test it with a bizarre experiment.
53:35He took the mouse eye gene and he put it into a fruit fly embryo.
53:42Dimitri Papadopoulos is showing me how to insert the gene into the fertilised egg.
53:47OK, so you've got DNA inside the needle
53:50and you're injecting it straight into the fertilised egg.
53:53You've got DNA inside the needle
53:56and you're injecting it straight into the embryo.
53:58Yes, exactly.
54:00We inject the posterior part of the eggs.
54:05Yep, that's in.
54:06Yep.
54:07So that's it.
54:10Nobody knew what would happen.
54:12Would it kill the developing fly?
54:14Would it try to make a whole mouse eye in the fly?
54:18The result was striking.
54:23The eyes are bright red, so you cannot be mistaken.
54:27If you see something red here, it's an additional eye.
54:30And they have lots of them.
54:33It's just incredible to look at.
54:36It's got eyes all over its body.
54:39The eyes grew in several places
54:42because scientists had no way of controlling
54:44exactly where the mouse DNA would end up.
54:48But the baffling thing is, they're not mouse eyes.
54:52They're fly eyes.
54:54The fly's cells have been able to read the mouse gene
54:57as though it was their own.
55:01I can see its normal eye, but I can also see maybe eight other eyes,
55:06including one right on the end of its antenna,
55:10which is flicking around.
55:12It's moving around, yeah.
55:14Yeah.
55:15That's quite interesting.
55:17It's like a sensor which moves,
55:19a video camera which moves around and searches.
55:23What we have shown for these antennal eyes,
55:26they can see with these eyes.
55:28They can actually see with these eyes?
55:30They can see, yeah.
55:33Gehring's mutants made headlines around the world.
55:39We came on the front page of the New York Times
55:42and they said, science outdoes Hollywood.
55:46It was the time of Spielberg and Jurassic Park,
55:51and so very wild things were shown on screen.
55:55But the journalists thought that science
55:58even outdoes Hollywood at that time.
56:00Well, I completely agree with that.
56:02You look at these things and it's much more impressive.
56:06But the headlines missed the real significance of Gehring's results.
56:13If genetic switches are shared across all species,
56:17everything from fruit flies to humans,
56:20and if genes can be swapped between species,
56:23this suggested that all life must have descended
56:26from one common ancestor, just as Charles Darwin predicted.
56:32The fact that you used a mouse gene to do that,
56:36what does that say about the way our DNA is shared?
56:40It shows that we all are related to one another,
56:44that Darwin was right, that we share common descent.
56:54So the story of the cell is the story of the evolution of life itself.
57:02150 years of brilliant science had brought us to this point.
57:07At the heart of all life is one extraordinary molecule, DNA.
57:15A molecule that holds all the information
57:18to make every kind of cell that has ever existed.
57:23Understanding the chemistry of life has brought us to the cusp
57:27of one of the most exciting scientific experiments of all time.
57:32Now that we know how cells work and how genes work within cells,
57:36scientists are about to be able to build new cells from scratch,
57:40to have them do our bidding.
57:42We are on the brink of doing something that has only happened once
57:45in the last four billion years,
57:48to create new life from its component parts.
57:51And to do that, we need to go back to the very beginning of life on Earth,
57:55to find out how the first cell came about.
58:00In the final programme, I'll reveal how scientists are close
58:04to recreating that first cell in the lab.
58:08How they found answers in the toxic chemistry of the early Earth
58:12and in meteorites from space.
58:18And I'll show how unlocking the power of the cell
58:21will transform all our lives.
58:30And the final part of Cell is here on BBC4 in a few moments.
58:34Stay with us.