BBC The Cell_3of3_The Spark of Life
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00:00I'm about to look back to some of the earliest evidence of life on Earth.
00:14Evidence trapped inside rocks from our planet's ancient past.
00:21A time long before the dinosaurs.
00:29Even before the first creatures appeared in the oceans, over 500 million years ago.
00:39They are fossilised cells.
00:45These cells are a staggering 1 billion years old.
00:54It's now believed that all life on Earth emerged from one single primordial cell, perhaps
01:00not dissimilar to one of these.
01:03Ever since, the spark of life has passed from cell to cell in a perfect unbroken chain.
01:10With life adapting and evolving into the millions of species on our planet today.
01:19Every single one of them can trace its origins back to that first cell.
01:26But now we're on the brink of something truly profound.
01:29We may be about to create living cells from scratch.
01:33If we succeed, it'll be the first life form on Earth that hasn't evolved from that original
01:39cell.
01:40It'll be the second genesis.
01:59In all the billions of years that this planet has existed, only once did a cell survive
02:06to evolve into every living thing we have today.
02:14That's quite a thought.
02:17All life on Earth came from just one cell.
02:23So how are scientists going to create life in the lab when nature only ever achieved
02:30this once?
02:41I've come to San Francisco to show you why the cell could become the most powerful tool
02:46on the planet.
02:51Building cells in the lab sounds like science fiction, but scientists can already alter
02:56the cells that nature has made.
02:59They can take cells that have evolved over billions of years and manipulate them in unbelievable
03:06ways.
03:07Dr. Stephen Del Cadare leads a team of scientists who have started with a bacterial cell and
03:14re-engineered its inner workings.
03:19We've basically remodelled the cell.
03:22We've taken a naturally occurring bacteria, E. coli, and we've souped it up.
03:27We are taking this microbe, the chassis of this organism, and it's analogous to building
03:32a monster truck.
03:33So we start with a small little truck with this bacteria and we're going to pull off
03:38the original wheels and we're going to put in some big wheels.
03:44Steve and his team have added new genetic components to the bacteria's ancient DNA.
04:01When they take this cell with its modified DNA and feed it sugar, the result is awesome.
04:09Just want to get to it.
04:10I want to see them.
04:11We've got to get to a good place on the slide where...
04:16That, so stop, stop, stop there.
04:17This round thing is a blob of pure diesel oil.
04:22So these things here are the bacteria.
04:24You can sort of see the rod shape.
04:26There you go.
04:27Yeah, yeah, right, there's one there.
04:29They're in the midst of, or just finished, converting renewable sugar to secreted ultra
04:35clean diesel.
04:36It's an oil product.
04:37You feed sugar to these modified bacteria cells and they give you diesel oil.
04:43That big blob there is simply oil.
04:46That's our ultra clean diesel product.
04:48It is a finished product fuel.
04:51We have to separate it, wash it a little bit, and it's ready to go.
04:55Yeah, I mean, you're really, really blasé about this, but that is completely nuts.
04:59You know, you've got these, you've got microbes producing diesel.
05:04You're really excited about it, don't...
05:07We've been working really hard on this.
05:09I think the microbes have been working harder.
05:16This is revolutionary stuff.
05:19And Steve and his team have set up a test refinery where these manipulated bacteria
05:25are now producing not just a few drops of oil, but gallons of it.
05:33And this is what you end up with.
05:35In this case, pure diesel.
05:38Just in case you think this is a hoax, watch this.
05:52Look at that.
05:54Diesel power.
05:56Sensational.
05:57Just a couple of days ago, that was just bacteria.
06:00Now it's running a diesel generator.
06:05That is the power of the cell.
06:08Diesel power.
06:13What's happening here is a glimpse of what cells could do for us in the future.
06:18As living machines, they have enormous powers.
06:22Up to now, we've only been able to manipulate naturally occurring cells.
06:28But how much further could we go if we could actually create life,
06:32if we could build new cells from scratch?
06:35To do that, we'd have to solve a fundamental mystery.
06:39What gives a cell its spark of life?
06:42What turns lifeless chemicals into a living thing?
06:46The obvious starting point is to try to understand
06:50how life on Earth began in the first place.
06:56So I'm beginning with a man who, in 1859, published a theory
07:00that addressed the question of how life evolved.
07:06Charles Darwin.
07:08Were these in Darwin's books that he owned?
07:10Yeah.
07:11OK.
07:13And I've been given unprecedented access to his private library.
07:17God, now this is an important book.
07:19Am I allowed to touch these?
07:22I feel like I can't touch these things.
07:28This is The Origin of Species, the book in which Charles Darwin
07:32outlines the theory of evolution by natural selection.
07:36But this copy is unique.
07:39This is the first copy of the first edition,
07:41the one that the publisher sent to Darwin himself,
07:45hot off the press.
07:47Now, on page 484, there's a remarkable passage
07:51which gives an insight into what Darwin himself
07:55thought about the origins of life.
07:58All the organic beings which have ever lived on this Earth
08:02have descended from some one primary species.
08:06All the organisms which have ever lived on this Earth
08:09have descended from some one primordial form
08:12into which life was first breathed.
08:15Now, this doesn't simply say that we humans have evolved
08:19from an ape-like ancestor.
08:21No, it goes much further than that.
08:23It suggested that all living things, from insects to elephants,
08:27from a hyacinth to a human,
08:30have evolved from one single common ancestor.
08:33This is the Bible's account of creation.
08:41At the time, Darwin didn't propose a scientific explanation
08:45for what created this original life form.
08:52His notion that life was breathed into the primordial common ancestor
08:57left room for the creator.
09:00Yet Darwin's origin of species
09:03introduced one of the most important thoughts in science,
09:07that all life on Earth sprung from one single organism.
09:18But to know what that organism would have been,
09:21you have to turn to the other big idea around in Darwin's day.
09:26It was the theory that cells form the basis of all living things.
09:32When it was first proposed in the 1830s,
09:35this was a shocking revelation.
09:41From man to flowers to frogs,
09:44it showed we're all made up of the same building blocks.
09:49By the time Darwin published his work on evolution,
09:53cell theory was the new bedrock of biology.
09:57And crucially, scientists had shown that new cells are born
10:01only when existing cells divide.
10:05All living cells are descended from other cells.
10:13So in just two decades in the 19th century,
10:16scientists had come up with the two biggest ideas in biology,
10:20cell theory and evolution.
10:22And if you put the two together, there can only be one conclusion,
10:27that all life on Earth began with one single cell.
10:35Darwin himself never connected the two theories in such a direct way.
10:40But what he did do, just 11 years after publishing The Origin of Species,
10:45was make an unholy attempt to explain how life may have begun.
10:51He expressed this thought in a private letter
10:54to his botanist friend Joseph Hooker.
10:57And this time, there was no mention of the creator.
11:05And this is it. It's incredible.
11:07I've studied Darwin for many years,
11:09but this is the first time I've ever seen one of his letters
11:12penned by his own hand.
11:14And I've got to tell you that his handwriting is appalling.
11:17But just listen to what he says.
11:19If we could conceive of some warm little pond
11:22with all sorts of ammonia and phosphoric salts,
11:25light, heat, electricity, etc., present,
11:29that a protein compound was chemically formed,
11:32ready to undergo still more complex changes.
11:36So Darwin had done a complete U-turn.
11:39No sign of the creator.
11:41He was now suggesting that life on Earth began with chemistry.
11:47No wonder he stopped going to church.
11:56Darwin had seeded an important thought.
11:59He'd suggested that with the right cocktail of ingredients,
12:02the chemicals of life could have emerged spontaneously.
12:07But how on Earth, and where on Earth that could have happened,
12:11was a mystery.
12:14The answer wouldn't be proposed until the 1920s
12:18by a rather unlikely duo.
12:23One half was Russian biochemist Alexander Oparin.
12:28The second was the renowned British scientist John Haldane.
12:33Although the men had never met,
12:35they both came up with almost identical theories
12:38about the conditions in which the first cells came to life.
12:44There would have been very little oxygen in the atmosphere.
12:48Instead, a mixture of other gases.
12:52Hydrogen, methane and ammonia.
12:57These would have combined with the waters of the oceans
13:01to form a chemical brew which Haldane christened the prebiotic soup.
13:07This soup would have been exposed
13:09to the scorching ultraviolet rays from the sun,
13:13which kick-started all manner of chemical reactions within it.
13:19Simple compounds reacted together,
13:22evolving into more complex molecules.
13:25Eventually, they formed a system that could feed, reproduce and evolve.
13:31The first cells.
13:37This picture of the early origins of life
13:40became known as the Oparin-Haldane hypothesis.
13:46In its day, the idea that life could emerge
13:49in such a hostile and toxic environment
13:52seemed kind of daft,
13:54but nowadays it's not quite so.
13:56Here at Mono Lake in California,
13:58the conditions are not dissimilar
14:00to how we imagine they might have been on the early Earth.
14:05There's almost no oxygen in the water
14:08and it's warm and bubbling with sulphurous gases.
14:12If you taste it...
14:17..it's absolutely revolting.
14:20It's like you're in a cave.
14:23It's absolutely revolting.
14:26More than three times the salt that we find in the sea.
14:29And it's highly alkali, like window cleaner.
14:33And yet life still abounds here.
14:36In this sample, there are millions of single-celled organisms
14:40that flourish in these extreme conditions.
14:45Yet, even without this knowledge,
14:48Oparin and Haldane had taken Darwin's notion
14:51of a warm little pond
14:53and developed it into a scientific theory.
14:57One that proposed the chemical ingredients
15:00that may have led to the first cells.
15:04What was missing was the experimental evidence
15:07to back their case.
15:09That was the discovery of a chemical compound
15:13That would come almost 30 years later from a most unlikely source.
15:28America, 1952.
15:31The University of Chicago.
15:34The can-do post-war optimism had rubbed off
15:37on a 22-year-old graduate student in the chemistry department.
15:42His name was Stanley Miller.
15:45And for one so young, he was about to do something remarkable.
15:55Miller was intrigued by Oparin and Haldane's theory,
15:59so he designed an experiment to test it in the lab.
16:03His plan was to have a stab
16:05at reproducing the conditions of the early Earth
16:08to see if anything related to life would form.
16:13It sounded so far-fetched
16:15that Miller's professor gave him just six months to produce a result.
16:19Rather shorter than the millions of years the Earth had taken.
16:27Now, this is the actual kit that Stanley Miller built.
16:31This lower sphere is filled with boiling water
16:34and that represents the early oceans of the Earth.
16:37And compared to the experiment,
16:39this top sphere was filled with gases
16:42that represented the atmosphere of the primordial Earth.
16:45That's methane, ammonia and hydrogen.
16:48And these two probes are introducing an electrical spark
16:52and that simulated the violent, lightning-rich atmosphere
16:55of the early Earth, like this.
17:02Now, I can't do this experiment for real
17:05because it's highly dangerous.
17:07Unless you flush out all of the air in the system,
17:10the whole kit might explode.
17:13Plus, this electrical grid is live at 10,000 volts,
17:18so I really mustn't touch it.
17:24Just two days into his experiment,
17:27Miller noticed that the water had turned pale yellow.
17:31After just a week, the flask was coated in an oily brown scum.
17:38Something weird was definitely happening in his primordial soup.
17:43But what was it?
17:46Using a technique called paper chromatography,
17:49Miller analysed the contents of the flask.
17:52And this is a copy of the actual results.
17:55Now, it may not look like much,
17:57but to Miller it was absolutely sensational
18:00because each one of these blobs is the chemical signature
18:04of a molecule called an amino acid.
18:11And amino acids are essential molecules to all life.
18:15No wonder Miller got so excited.
18:20Amino acids are the building blocks
18:22that join up to form larger, complex molecules called proteins,
18:27molecules inside all cells.
18:31Some proteins you may have heard of.
18:34The haemoglobin found inside our blood cells is a protein.
18:39Its job is to pick up oxygen molecules and carry them round our body.
18:49Antibodies are proteins.
18:53They're dispatched by our immune cells to attack foreign invaders.
19:00And hair and nails get their structure from keratin.
19:04That's a protein too.
19:10There are literally thousands of weird and wonderful types of protein,
19:14frantically busy carrying out all the activities that make cells alive.
19:23And all of these different proteins can be made
19:26by combining just 20 different amino acids.
19:33So when Stanley Miller found five amino acids in his primordial soup,
19:38it was pretty shocking stuff.
19:41He'd shown experimentally how some of the crucial ingredients
19:45of the cell could have formed on the early Earth.
19:49When the results were published in 1953,
19:52Stanley Miller instantly became a celebrity,
19:55with some newspapers rather extravagantly reporting
19:58that he'd created life in the lab, all very Frankenstein.
20:02But many believed we were close to achieving
20:05what was thought to be impossible, understanding the origin of life.
20:13After the success of his early experiments,
20:16Miller continued his research here at the University of California,
20:20on San Diego's Pacific Beach.
20:27And though he died in 2007, his work is still yielding surprises.
20:34Hi, Geoffrey. Hello. Nice to meet you. Adam. Nice to see you.
20:39Professor Geoffrey Bader, who was taught by Miller,
20:42has stumbled across evidence that the original experiments
20:45were even more successful than Miller realised.
20:49So, Geoffrey, I understand you've made a really pretty amazing discovery
20:53in the last couple of years.
20:55Right. Yeah, it turns out that I inherited everything
20:58that was in Stanley's laboratory,
21:01and we went in and we found an old cardboard box,
21:05and then inside it were...
21:07Geoffrey's discovered the sealed vials containing residues
21:10from Miller's original experiments nearly 60 years ago.
21:14This is actually them? This is actually them.
21:17This is Stanley's writing. Oh, that's so cool.
21:20So he used methane, ammonia, hydrogen, water and a spark.
21:24And a spark. Yeah. Nothing more precise than that.
21:28And then you look at these and you see that each one of these little vials
21:32has a little tiny amount of residue in there.
21:35I mean, that's a real piece of history there.
21:37It really is, and so we were just dumbstruck when we had these.
21:42This is the classic experiment,
21:44but what I was really intrigued by is this little box here.
21:48This box came from a different experiment.
21:51These vials are from a variation on Miller's original experiment,
21:55and its focus was volcanoes.
21:59This time, Miller had modified his equipment
22:02to simulate the effect of hot lava on volcanoes.
22:06To simulate the effect of hot volcanic gases on early Earth.
22:16He never fully published the results, but with today's technology,
22:20Professor Bader has been able to re-examine these historic residues.
22:25In where? In this tiny little hole here? Yeah.
22:28You're going to have steady hands to do this.
22:31This is quite an honour.
22:33I'm injecting one of the original samples into this analysis machine.
22:39This is the part of his research Miller never got to see.
22:43OK? Yeah.
22:45OK, there's the results, and you can see... That's amazing!
22:49..each one of these peaks here are a different amino acid.
22:53This very large peak here is one that he could not identify.
22:57This is alpha-aminobutyric acid. You can see it's huge.
23:01Every single one of these spikes on the graph represents an amino acid
23:05that you've found in one of the old samples.
23:08We've got one, two, three, four, five, six, seven, eight here.
23:11How many have you found in all of your analysis?
23:14Over 20. I think close to 25.
23:17Actually, there's more there that we just stopped at 25,
23:22but there's probably another 30 or 40 in there, a very low amount.
23:26So he found five. He found five.
23:29And you rediscovered the samples 50 years later... Yeah.
23:32..and you found five times more. Yeah, at least five times more.
23:36So you knew Stanley Miller.
23:38What do you think he would have thought of this new analysis?
23:41I think he would have been thrilled to realise
23:43that this experiment was even more successful than he imagined.
23:48What Stanley Miller's experiment did was demonstrate
23:52how many of the amino acids vital to all living things
23:56could have been present in the Earth's primordial soup.
24:02Although Miller's discovery was a staggering revelation,
24:05it was still a long way from actually creating life.
24:09It was a long way from creating life.
24:12To even make a single protein molecule,
24:14like the ones you find in a living cell,
24:16you have to string together a whole chain of amino acids
24:20in a very specific order.
24:23So how do cells do it?
24:27In Britain, James Watson and Francis Crick
24:30were about to make a huge discovery.
24:35One that would provide the key to how life was created.
24:40One that would provide the key
24:42to how cells assemble amino acids to make proteins.
24:48DNA. It stands for deoxyribonucleic acid.
24:53This is the stuff of life.
24:56In 1953, James Watson and Francis Crick
25:00famously discovered its double helix structure.
25:04That's just one year after Stanley Miller's experiment.
25:08It's an exquisite architecture.
25:11All along the inside of the two strands
25:14are four molecules that we call bases, and they pair up.
25:19These are the chemical letters that form the genetic code.
25:23A, T, C and G.
25:26And this gives DNA the ability to carry information.
25:31Nothing like this had ever been found in nature before.
25:39But Crick and Watson's discovery didn't yet explain
25:42how the information stored in DNA's chemical letters
25:46translated into life.
25:49This would come from Crick alone.
25:52In 1958, he published a theory
25:55that would end up underpinning all of biology.
26:01It also explained how cells
26:03can do what Stanley Miller's experiment hadn't.
26:07Join up amino acids to make proteins.
26:18To understand it, let me take you inside a cell's nucleus.
26:25Crick proposed that the information inside DNA
26:29was in fact a precise set of instructions.
26:32Instructions which specify the exact order
26:35to join up amino acids to make the proteins in our cells.
26:44The way the cell carries out these instructions is spectacular.
26:50Each time the cell needs to make a particular protein,
26:54the instructions are copied from part of the DNA strand
26:58to a new molecule called RNA.
27:03The RNA carries the instructions for building the protein
27:07out of the cell nucleus,
27:09heading for this structure, called a ribosome.
27:15This is basically the cell's protein factory.
27:20As the ribosome works its way along the RNA strand,
27:24it reads the instructions,
27:26and these tell it which amino acids to join together
27:29and in which order to make the specific protein.
27:37There it is, a protein.
27:42And just think, the cell builds proteins
27:45thousands of times a minute to stay alive.
27:50It may sound pretty complex and elaborate,
27:53but this very same process,
27:55DNA makes RNA makes protein,
27:58is at the heart of every living cell on Earth,
28:02from bacteria to insects, from plankton to people.
28:06It's so quintessential to life
28:09that it's become known as the central dogma.
28:15And the discovery of this process at the heart of all life
28:19opened up vast new possibilities.
28:23By the 1970s, geneticists could isolate individual genes,
28:28that's specific stretches of DNA,
28:31to find out what proteins they made.
28:36And it wasn't long before scientists spotted
28:39the massive potential of this new knowledge.
28:44Now they could attempt to change the inner workings of the cell
28:48to take control of life itself.
28:53At the cutting edge was a young scientist, Herbert Boyer,
28:58soon to be the first biotech millionaire.
29:03Working with a team in California,
29:05Boyer was the first to take a gene from a human cell
29:09and insert it into the DNA of a bacterial cell.
29:14This technique is known as gene splicing,
29:17and it's opened up a whole new chapter
29:20in our quest to harness the power of the cell,
29:23as this experiment will demonstrate.
29:28I'm taking a gene from a jellyfish,
29:31the one that makes it glow green in nature.
29:35And I'm splicing it into the DNA of some yeast cells.
29:41Now, in this tube, I've got the jellyfish DNA,
29:45and in this tube, I've got some yeast cells suspended in a solution.
29:49I'm simply going to add the DNA to the yeast cells.
29:56Now, I'm going to take a gene from a jellyfish,
30:00the one that makes it glow green in nature.
30:05Using some clever biochemistry pioneered by Boyer,
30:08I'm inserting the jellyfish DNA into the DNA of yeast cells.
30:17I'm going to give that a little mix-up.
30:20If it works, when the yeast cells are grown overnight
30:24on a plate of sugary jelly,
30:26they'll divide and pass on the genetic alteration
30:29to millions of offspring.
30:35These cells are called transgenic.
30:38They contain the DNA of more than one species.
30:44And when you look at them under a microscope,
30:47you can see how gene splicing gave us the power to control cells.
30:57Now, the yeast cells have been growing for 24 hours now.
31:00There should be millions of them.
31:02I'll put them on a slide and under this rather fancy microscope,
31:06and we should see something pretty awesome.
31:11And not something yeast cells have ever done in nature.
31:21And there they are.
31:23So every single yeast cell is now glowing bright green.
31:27The jellyfish gene is now working inside the yeast cells
31:31to produce a green fluorescent protein,
31:34which normally is only found in nature in the jellyfish.
31:38You have to admit, that is pretty damn cool.
31:44What Herbert Boyer did was use this technique
31:47to insert the human gene that makes the protein insulin into bacteria.
31:54Remarkably, the bacteria started to produce human insulin
31:58in large amounts.
32:02MUSIC
32:07Insulin that could be used to treat people with diabetes.
32:13Boyer's company, Genentech, launched a new industry, biotechnology.
32:19An industry based on the astonishing fact
32:22that DNA is interchangeable between all cells.
32:26Boyer and his colleagues had given us a vital tool
32:30to begin to control the cell.
32:35And it's giving us a profound insight into our past.
32:38If DNA is at the heart of every cell,
32:41and every cell can read the DNA of every other cell,
32:45then there can only be one conclusion.
32:47We're all fundamentally made of the same stuff.
32:51And this is the smoking gun, the indisputable evidence
32:54that Charles Darwin's predictions were bang on.
32:57All life must have originated from a single common ancestral cell.
33:12For the scientists trying to discover
33:14how the chemistry on early Earth gave rise to that cell,
33:19DNA presented them with a new problem.
33:23So how did something as complex as DNA
33:27come into existence in the first place?
33:30Well, to answer that, some people turned to God,
33:34believing that DNA is so exquisite
33:37it shows the hand of some kind of intelligent design.
33:41Others turned to the stars.
33:44And here at Imperial College in London,
33:47a surprising discovery has provided a clue to the origins of DNA.
33:54At the end of this corridor,
33:56pioneers in a field called astrobiology
33:59have spent years analysing rocks older than planet Earth itself.
34:06These are meteorites,
34:08some of which are more than 4.6 billion years old.
34:14One of the lead astrobiologists is Dr Zeta Martens.
34:18She looks for evidence of life beyond the confines of Earth
34:22by searching for particular molecules
34:24buried inside rocks from outer space.
34:29Hi, Zeta. How are you doing?
34:31I'm good.
34:33So what is it about meteorites that is interesting,
34:36that can tell us about the origin of life?
34:38We know that specific samples of meteorites,
34:42like the ones I have here,
34:45they're about 4.6 billion years old.
34:49They're as old as the formation of our early solar system.
34:53This is 4.6 billion years old?
34:56Yes.
34:58It's just... It's amazing.
35:00It's exciting to hold these samples in your hands.
35:03And that hasn't changed in close to 5 billion years?
35:07No.
35:08When you first start looking at this, it looks like a rock,
35:11but you are finding stuff in here.
35:14Yes, we're finding organic molecules,
35:16extraterrestrial organic molecules
35:18that may have been important for the origin of life in our planet,
35:22and that's why it's so exciting.
35:24So what you're saying is that up in space,
35:26which we think of as a big vacuum,
35:28actually there's masses of chemistry just going on,
35:31which is actually creating the building blocks for cells.
35:34Exactly. We think the space is an empty place, but it's not.
35:38It's bubbling with chemical reactions.
35:41Right, with activity. Exactly.
35:43In 2003, Zeta got hold of one particular sample
35:48whose molecules would reveal something special.
35:52It was from a meteorite that had fallen to Earth in 1969
35:56near the Australian town of Murchison.
35:59It was dated to be nearly as old as our solar system.
36:11Thanks to new technology,
36:13Zeta's now able to analyse the molecules in a way
36:16that would have been impossible before.
36:19Zeta's now able to analyse the molecules inside the rock,
36:23and she's going to show me why this particular meteorite
36:26has made such an impact.
36:28Now, this is precious stuff, right?
36:30It is precious.
36:31So usually we only have access to milligrams of meteorite sample,
36:35so you have to be really careful and not mess up what you're doing.
36:39Yeah, I can feel a sneeze coming on.
36:41You might want to hold that away. No, I'm going to run away.
36:45It's essential that I don't accidentally ruin the evidence.
36:53So, the meteorite is sealed inside a glass tube
36:57to prevent contamination from DNA and other molecules on Earth.
37:02Once dissolved in solution,
37:04the sample can then be analysed by a machine
37:07capable of detecting the molecules that make up the genetic code.
37:12OK, Zeta, you've analysed the meteorite sample
37:16using this pretty awesome machine.
37:18Show me what you find.
37:21So, what you find is something like this.
37:24This represents one of the bases of our genetic code.
37:29So this is a sort of signature for one of the letters
37:33that makes up the genetic code for all life.
37:37Exactly.
37:38And this comes out of a 4.5 billion-year-old meteorite.
37:41Exactly. This is present in the Murchison meteorite.
37:47It must have been mind-blowing to see that for the first time.
37:50Exactly. It was a very exciting and amazing moment, actually.
37:54I mean, conceptually, that's just out of this world.
37:57Well, literally out of this world. It is out of this world.
38:00Because what you're talking about is something
38:02which is absolutely inherent to life, to every single cell on Earth,
38:06and it existed before the Earth even existed.
38:10We finally have proven that components of our genetic code
38:14were in fact extraterrestrial and were present in a meteorite sample.
38:22The young Earth was bombarded by meteorites for millions of years.
38:30So this is definitely a plausible explanation
38:33of how the molecules that make up DNA and RNA may have appeared on Earth.
38:45Combined with Stanley Miller's experiments,
38:47we now have some of the essential molecules of life
38:51present on the early planet.
38:53The amino acids to build proteins...
38:57..and molecules of the genetic code.
39:04So the big question is,
39:06how did all these separate molecules come together
39:09inside a kind of bag or membrane
39:12so they could make the leap to become living cells?
39:20If we could do all this in the lab,
39:23we would discover the secret of what makes cells alive.
39:28It would be the second Genesis.
39:37And if I had to place a bet on who was going to get there first,
39:41I'd put my money here, Harvard University.
39:45They've even got a special department, the Origin of Life Initiative.
39:51And their starting point is something fundamentally different.
39:55Their starting point is something fundamental to all cells,
39:59the membrane.
40:01That's the bag or boundary that contains
40:03all of those clever little chemicals like DNA and proteins.
40:07Without the membrane to hold them all together,
40:10life would never have begun in the first place.
40:19Hi, Jack.
40:21The lead scientist is Professor Jack Szostak.
40:24With his new device, he can show how the first cell membranes
40:28could have formed four billion years ago.
40:33How much of this field is...guesswork?
40:38I mean, it feels like a lot of it is intelligent guesswork,
40:42but you've not got a lot of evidence to go on.
40:45Well, we can't go back and see what happened, right?
40:48So we just have to come up with ideas
40:50that kind of make sense, that are reasonable.
40:53We don't have any step-by-step way of going from, you know,
40:57really simple starting materials up to cells.
41:00So we're just trying to fill in the gaps with reasonable ideas.
41:07Cells construct their own membranes each time they divide.
41:12But how could the first cell membrane form
41:15without the machinery of a cell to make it?
41:19Jack's homed in on a molecule called a fatty acid,
41:23a simpler form of the molecules that make up today's cell membranes.
41:28There's evidence that these fatty acids
41:31could have been around on the early Earth.
41:34But could they have formed the first cell membranes?
41:37Jack's talking me through what he's discovered.
41:41So we have some dried-down fatty acids in here.
41:44So you can unclip that.
41:48Inside this flask is a sample of fatty acid molecules
41:52stained with a red dye.
41:54If you add liquid to them to represent the water on early Earth,
41:59the fatty acids do something unexpected.
42:06So I'm going to put the lid on and shake it up.
42:09Shake it up.
42:13Yeah, give it a good shake.
42:15OK, is it looking cloudy? Yeah, yeah, it is. It's gone cloudy.
42:19Now, when the sample goes cloudy,
42:21it might not look that revealing to the naked eye.
42:27You need to look at it through a microscope.
42:30It's only then that you can step back four billion years.
42:35Oh, wow, look at that.
42:39So they've just self-assembled into...
42:41They just self-assemble, yeah.
42:44Natural forces of attraction have caused the fatty acid molecules
42:48to group together spontaneously to form simple membrane-like structures.
42:57Jack calls them protocells.
43:01So, I mean, it looks like a cell.
43:03It's what we think a primitive cell membrane would be like.
43:08And Jack's protocells didn't just look like living cells,
43:12they kind of behaved like them too.
43:15They could do something that resembled primitive feeding.
43:19Watch what happens after we've added extra fatty acids.
43:26This single protocell absorbs the extra molecules,
43:30stretching out to form one long string-like bag.
43:34But it's still one membrane.
43:38Oh, no, look at that.
43:40And it's at this point that Jack and his team had an idea.
43:48OK, so give them a few puffs of air.
43:50From here? Yeah. Like that? Yeah.
43:54To simulate the effects of wind and waves on the primordial Earth,
43:58they tried blasting the elongated protocells
44:01with a jet of compressed air.
44:05Just direct it toward the slide.
44:07There. Oh.
44:09And when you do this, Jack's protocells show
44:12one of the most fundamental characteristics of life.
44:16A little bit of division at the end there.
44:18Oh, yeah. It's breaking up, it's breaking up.
44:20With a little help...
44:23..they did it.
44:25With a little help...
44:28..they divide.
44:30That's amazing. So it's gone into one, two, three, four, five,
44:33six different smaller...
44:35There's still part of the filament left.
44:38If you don't know what you're looking at,
44:40this kind of looks bizarre and there's nothing much there,
44:44but if you do, it's actually quite stunning.
44:47It's very much like cell division,
44:49a very simple form of cell division.
44:51I'm deeply impressed.
44:56But these protocells are not alive.
44:59They lack many of the vital characteristics of life.
45:03They have no DNA, and without it,
45:06they're not able to take on new functions and evolve.
45:11Making that happen is Jack's next goal.
45:14If he succeeds, he will have done in the lab
45:17what nature did four billion years ago,
45:20create life from lifeless chemicals.
45:26And we'll be closer to understanding
45:28how our single most distant ancestor,
45:31the first primordial cell, may have formed.
45:38But there's an even more ambitious goal for science.
45:42Not just creating primitive cells,
45:45but building cells more like the ones that make up our world today.
45:49Cells with highly sophisticated inner machinery.
45:54Billions of years of evolution have turned them
45:57into extraordinary living nanomachines,
46:00far more complex than anything humans have ever designed.
46:07To build this type of cell,
46:09scientists are taking on a radical way of thinking,
46:12approaching the cell like an engineering project.
46:19This is where biology meets engineering,
46:22and a new branch of science has been invented.
46:27It's called synthetic biology,
46:29and if you haven't heard of it yet, trust me, you soon will.
46:33Because SynBio, as it's known,
46:35is beginning to use the cell's components as a kind of toolbox
46:39to radically re-engineer existing cells.
46:42And its holy grail is to find a way to build new man-made cells.
46:47It'll be the first time a new life form has been created from scratch.
46:52These will be cells with bespoke components,
46:55programmed by us to do our bidding.
46:58Anything from cleaning our teeth to seeking out and destroying cancer.
47:03And once again, it's here at Harvard
47:05that one man has taken the first steps.
47:11His name is George Church, professor of genetics at Harvard.
47:15He's also advisor to more than a dozen biotech companies.
47:19This guy is one seriously smart cookie.
47:24Keeping you busy, aren't we?
47:26We're always busy, George.
47:30By the age of nine, Church had built his first computer.
47:34Decades later, ever the technical whiz,
47:37he's using computers and genetics
47:39to analyse some of the thousands of components of living cells
47:43and discover exactly what they do.
47:58He's identified 151 essential components,
48:02which he believes are the minimum you need to create a living cell.
48:09In essence, what Church and his team think they've done
48:12is designed a blueprint for life itself.
48:18Well, George, we've been on a long trip to get to this point,
48:21but this is definitely the most complicated diagram I've seen.
48:26I don't even know where to start.
48:28What are we actually looking at here?
48:30So, thousands of scientists over decades
48:35have, by taking apart the cell into its pieces
48:39and showing how each one of them works,
48:41sort of a reductionist approach,
48:43have accumulated this information.
48:46But all we're doing is we're now reversing that process
48:49and taking all that knowledge and turning it into something
48:52where we can make a factory
48:54that's based on all that prior knowledge.
48:56And it's nice to get it on one page
48:58where you can actually see the shape of these things
49:00just the same way you would a motor or something.
49:03You take things apart and you put it back together.
49:06Do you think about them in terms of car parts?
49:08We do. I mean, we're trying to make practical systems that help society.
49:13And since we now know what their structures look like
49:17and we know which ones we need to do which tasks,
49:20it is very appealing to think of it as we can engineer each part
49:25and we can engineer the whole system.
49:27If they don't have the properties you want, you can redesign it
49:30and you can evolve it in the lab
49:32and you can make them better for your purposes.
49:36Hang on a second. Just listen again to what George said.
49:40We can engineer each part and we can engineer the whole system.
49:43If they don't have the properties you want, you can redesign it
49:46and you can evolve it in the lab
49:48and you can make them better for your purposes.
49:51When George says engineer the whole system,
49:54that's his geek speak for build a new life form in the lab.
49:59I'm in awe.
50:05But to build this synthetic cell in the lab,
50:08there's one essential component George knew he'd have to crack.
50:16The ribosome.
50:18The cell's protein factory.
50:21The bit that reads the instructions written in the DNA code
50:25and actually builds the protein molecules that make cells alive.
50:31It's nature's most exquisite nanomachine.
50:37More and more indication this is the key component of life.
50:41It's one of the most ancient components.
50:44It's one of the most conserved, meaning it's one of the only things
50:47that's present in all types of living things.
50:50And so you just keep coming back to this. This is the key part.
50:56Put simply, no ribosome, no life.
50:59So it'll be a crucial component of any synthetic cell.
51:03Trouble is, it's a staggering feat of natural engineering.
51:08It has 57 parts that rotate, grab and shift,
51:12together made of almost a million atoms.
51:15So how could you possibly make one in the lab?
51:18You can't build a ribosome like a model aeroplane.
51:22We're talking about a molecule so small
51:24that you could fit tens of thousands of them on the tip of a sharpened pencil.
51:29Tweezers don't come that small.
51:32So we have to return to the way that nature does it,
51:35and our old friend DNA.
51:39Now, of course, DNA contains the instructions
51:42to build the ribosomes within cells.
51:44So George has used DNA to do it for him in the lab.
51:48And today I'm going to build a ribosome myself.
51:52Brace yourselves.
51:55First, you need the strand of DNA with the right instructions.
52:01This clever machine here can make it synthetically.
52:04I simply have to enter the right letters of the genetic code
52:08and it assembles the DNA molecule by molecule.
52:11Magic.
52:18That's the easy bit.
52:20Now we have to put together the exact mixture of molecules
52:23the DNA needs to make a ribosome.
52:26To create this has taken decades of work
52:29by George and thousands of other scientists.
52:35So this is the DNA that we've just synthesised.
52:38So how do I do it?
52:39Just pick up the pipette and add the predetermined volume.
52:43Simple as that.
52:45All I have to do, with a little supervision from George,
52:48is the last stage in this remarkable process.
52:52Add the DNA to George's ribosome mixture.
52:56I'm now just one step away from creating a synthetic ribosome,
53:01one that hasn't been created by a cell.
53:04This lab is the only place this has been achieved
53:08during the entire history of life on Earth,
53:11and it's certainly never been filmed before.
53:14Right, so that's 1.25 microlitres of ribosome DNA
53:21and that's going into this mix
53:23which contains everything else to make a ribosome, right?
53:27That's right.
53:28So basically I'm taking the instructions
53:30to finish making the ribosome and adding them to the rest of the mix.
53:33The synthetic DNA will make the ribosome.
53:36OK, that's it. It's done.
53:38So it doesn't look like much.
53:40It looks like about 15 microlitres of a colourless liquid,
53:44but actually what's in here
53:46is all of the ingredients to make a synthetic ribosome,
53:50which is the piece of machinery that is going to translate
53:53the code of DNA into actual working proteins,
53:56and all I have to do now is put it in the incubator
53:59and cook it for half an hour.
54:0230 minutes later, George seems pretty confident
54:06we've built fully functioning ribosomes.
54:09But I want to see for myself.
54:11I want to see if they're actually working.
54:14Can our man-made ribosomes make proteins
54:17like their counterparts in nature?
54:19George has got an ingenious way to show that they can.
54:24He's given our synthetic ribosomes a stretch of firefly DNA.
54:28Normally, this bit of DNA tells the ribosomes inside the firefly cells
54:33to make a protein that glows in the dark.
54:38If my man-made ribosomes are working,
54:41then it should also read the firefly's DNA
54:44and make the same protein.
54:46But if it's not working,
54:48then it should also read the firefly's DNA
54:51and make the same protein.
54:53In short, my colourless liquid should start to glow green.
55:02Switch off the lights, please.
55:06No way! That's amazing!
55:09My goodness, that is just shocking.
55:12I mean, this is groundbreaking stuff.
55:14I mean, this is a synthetic ribosome in action, actually doing its job.
55:18Right.
55:20Oh, that's... that's... that's off the hook.
55:23For me, as a scientist, this is just awesome.
55:28So this is one of the key steps to making a synthetic cell.
55:34You've produced a working synthetic ribosome
55:37which actually translates the DNA code into a working protein,
55:42just like it does in a real cell.
55:44How long is it going to be before you're going to make
55:47the rest of the components to make a living cell?
55:49Probably about a year.
55:51A year. A year from going from this tube, which is glowing,
55:54to making effectively what is a synthetic life form.
55:57Right. It's only about 100 extra components,
55:59so we can make those all at once.
56:01You must be pretty excited.
56:03I mean, you're on the threshold of something enormous.
56:05How does that make you feel?
56:07Well, it hasn't happened yet.
56:09I feel very happy once it happens.
56:16We've just built one of the most complicated
56:19and vital components of all living cells.
56:24Something that has been present in nature for billions of years.
56:29And we've done it in an afternoon.
56:34If George Church is right that he will soon be able to build
56:38the first man-made cell,
56:40then we will have reached one of the most important moments in history.
56:45The second genesis.
56:56This is where four centuries
56:58of extraordinary scientific achievement has brought us.
57:03From the time when scientists first peered through their blurry lenses
57:08and puzzled at the mysteries of cells...
57:14..to a moment when we can turn our knowledge
57:16of their innermost secrets to benefit humanity.
57:25This is a future that no doubt will present challenges.
57:30But it's a future I believe we should embrace.
57:35This ability to create living cells
57:38is kick-starting the next scientific revolution
57:41and it'll affect every aspect of our lives,
57:44from fuel to food to medicine.
57:47It'll even question our definition of what life is.
57:51The implications and the benefits for humankind are simply breathtaking.
58:00And there's more from the BBC's Darwin season
58:03with Charles Darwin and the Tree of Life.
58:06David Attenborough's personal insights
58:08on the father of evolutionary theory
58:10is right here on BBC4 on Thursday at nine.
58:29.