The Science of Discworld III - Darwin's Watch tsod-3

by Terry Pratchett

  The big question in this area, asked many times and largely ignored, has always been: if introns (which occupy all but one-twentieth of a typical protein-coding gene) have no biological function, why are they there? It is easy to dismiss them as relics of some dim evolutionary past, no longer useful, lying around because natural selection can't get rid of things that are harmless. Even so, we can still wonder whether introns are present because they do have some useful function, one that we haven't yet worked out. And it's starting to look as if that may be the case.

  For a start, introns are not that ancient. It now seems that they became incorporated into the human genome relatively recently. They are probably related to mobile genetic elements known as group II introns, which are a `parasitic' form of DNA that can invade host genomes and then remove themselves when the DNA is expressed as RNA. Moreover, they now seem to have a role as 'signals' in the regulation of genetic processes. An intron may be relatively short, compared to the long protein-coding sequences that arise when the introns are snipped out, but a short signal has advantages and can do quite a lot. In effect, the introns may be genetic 'txt msgs' in the mobile phone of life. Short, cheap, and very effective. An RNA-based `code', running parallel to the DNA double helix, can affect the activity of the cell very directly. An RNA sequence can act as a very specific, well-defined signal, directing RNA molecules to their targets in RNA or DNA.

  The evidence for the existence of such a signalling system is reasonable, but not yet undeniable. If such a system does exist, it clearly has the potential to resolve many biological mysteries. A big puzzle about the human genome is that its 34,000 genes manage to encode over 100,000 proteins. Clearly `one gene one protein' doesn't work. A hidden RNA signalling system could make one gene produce several proteins, depending on what the accompanying RNA signal specified. Another puzzle is the complexity of eukaryotes, especially the Cambrian explosion of 525 million years ago, when the range of terrestrial body-plans suddenly diversified out of all recognition; indeed, was more diverse than it is now. Perhaps the hypothetical RNA signalling system started to take off at that time. And it's widely known that the human and chimpanzee genomes are surprisingly similar (though the degree of similarity seems not to be 98 per cent as widely quoted even a few years ago). If our RNA signals are significantly different, that would be one way to explain why humans don't greatly resemble chimps.

  At any rate, it very much looks as if all that `junk' DNA in your genome is not junk at all. On the contrary, it may be a crucial part of what makes you human.

  This lesson is driven home by those business associates of parasitic wasps, the symbiotic polydnaviruses, sneakily buried inside the wasps' own DNA. There is a message there about human evolution, and it's a very strange one.

  Genome-sequencing may have been oversold as the answer to human diseases, but it's very good basic science. The activities of the sequencers have revealed that wasps are not the only organisms to have bits of viral DNA hanging around in their genomes. In fact, most creatures do, humans included. The human genome even contains one complete viral genome, and only one, called ERV-3 (Endogenous RetroVirus). This may seem an evolutionary oddity, a bit of `junk DNA' that really is junk ... but, actually, without it none of us would be here. It plays the absolutely crucial role of preventing rejection of the foetus by the mother. Mother's immune system `ought to' recognise the tissue of a developing baby as `foreign', and trigger actions that will get rid of it. By `ought to' here we mean that this is what the immune system normally does for tissue that is not the mother's own.

  Apparently, the ERV-3 protein closely resembles another one called p15E, which is part of a widespread defence system used by viruses to stop their hosts killing them off. The p15E protein stops lymphocytes, a key type of cell in the immune system, from responding to antigens, molecules that reveal the virus's foreign nature. At some stage during mammalian evolution, this defence system was stolen from the viruses and used to stop the female placenta responding to antigens that reveal the foreign nature of the foetus's father. Perhaps on the principle of being hung for a sheep as well as for a lamb, the human genome decided to go the whole hog[50] and steal the entire retroviral genome.

  When evolution carried out the theft, however, it did not just dump its booty into the human DNA sequence unchanged. It threw in a couple of introns, too, splitting ERV-3 into several separate pieces. It's complete, but not connected. No matter: enzymes can easily snip out the introns when that bit of DNA is turned into protein. But no one knows why the introns are there. They might be an accidental intrusion. Or - pursuing the RNA interference idea - they might be much more significant. Those introns might be an important part of the genetic regulatory system, `text messages' that let the placenta use ERV-3 without running the risk of setting the corresponding virus loose.

  At any rate, whatever the introns are for, warm-bloodedness is not the only trick that mammalian evolution managed to find and exploit.

  It also indulged in wholesale theft of a virus's genome, to stop mother's immune system booting out baby because it `smelled' of father. And we also get another lesson that DNA isn't selfish. ERV-3 is present in the human genome, but not because it's a bit of junk that gets copied along with everything else and has remained because it does no harm. It's there because, in a very real sense, humans could not survive - could not even reproduce - without it.

  21. NOUGAT SURPRISE

  THE ACTIVITY IN THE GREAT HALL was slowing down now. All along the rainbow lines of time, the nodes were closed. Or shut, or denoded, Rincewind thought. Whatever you did with nodes, anyway.

  There was a little cheer as the last glowing wizard symbol faded away, and a roar from outside as three wizards and a lot of tentacles landed in the fountain. Rincewind had been surprised about that, and then dismayed. Since it did not have his name on it, this meant that Ridcully had something worse in mind.

  `Looks like I'm not needed now,' he said hopefully, just in case.

  'Haha, professor, what a card you are and no mistake,' said the lobster next to him. `The Archchancellor was very definite that we was to keep you here no matter what you said.'

  `But I wasn't running away!'

  `No, you was only inspecting the wall with the loose bricks in it,' said the lobster[51]. `We quite understand. Lucky for you we caught you before you dropped over into the alley, eh? Could've done yerself a mischief.'

  Rincewind sighed. The lobsters were always hard to outrun. They hunted in packs, appeared to share a common brain, and many years of harrying erring students had given them a malignant street cunning that verged on the supernatural.

  Some of the senior wizards swept in ... There was an argument going on between Ridcully and the Dean.

  `I don't see why I shouldn't.'

  `Because you get too excited in the presence of combat, Dean. You run around making silly "hut, hut" noises,' said Ridcully. `Remember why we had to stop those paintball afternoons? You didn't seem to be able to get the hang of the term "people on my side".'

  `Yes, but this is-'

  `It took us a week to get the Senior Wrangler looking halfway suitable for polite company - Ah, Rincewind. Still with us, I see. Good man. Very well, Mr Stibbons: report!'

  Ponder coughed.

  `Hex confirms that, er, that our recent activities may have left camiloops between our word and Roundworld, Sir. That is to say, residual connections that may be used deliberately or inadvertently from either side. Magic doors, in fact, drifting without anchor. These will evaporate within a matter of days. Um ...'

  `I don't want to hear "um", Mr Stibbons. "Um" is not a word we entertain here.'

  `Well, the fact is that since the camiloops are spread over centuries, the Auditors may very well have been in Roundworld for some time. We have no way of knowing for how long. Hex, um, sorry, does report some circumstantial evidence that humans are dimly aware of their malign meddling, albeit at a very mundane level as evidenced by the findings of a researcher calle
d Murphy. Roundworld would be difficult for them. They would be bewildered. Things would not work the way they expect. They are not flexible thinkers.'

  `They were able to mess around with Mr Darwin's voyage!'

  `By doing lots of small and rather stupid things at great effort, sir. They don't react well to adversity. They get petulant. From what Professor Rincewind tells us, many hundreds of them have to combine to perform even a simple physical action.'

  He stood back and indicated some items laid out on a dining table.

  `There is some evidence that Auditors, being embodiments of physical laws, find it hard to deal with nonsensical or contradictory instructions. Therefore, I have prepared these.'

  He flourished something that looked like a table-tennis bat. On it were printed the words: `Do Not Read This Sign.'

  `That works, does it?' said the Dean, doubtfully.

  `It's said to put their minds into a fugue state, Dean. They feel confused and alone, and evaporate instantly. Being alone means having a sense of self, and any Auditor that develops an individuality is said to die instantly.'

  `And the catapult bows?' What are they for?' said the Archchancellor, slapping the Dean's hand off one of them.

  `In addition, it is possible that a collective of Auditors with sufficient presence in the material world may develop crude physical senses, and so I have adapted some catapult bows to fire a mixture of intense, er, stimuli. Old references suggest chilli, essence of Wahoonie or Blissberry blossoms, but modern thinking inclines to Higgs & Meakins Luxury Assortment.'

  `Chocolate?' said Ridcully.

  `They don't like it, sir.'

  `But those things can live in empty space and inside stars, man!'

  `Where chocolate is significantly absent, sir,' said Ponder, patiently. `They keep away from it. Also, it comes handily packed. They particularly don't like the Strawberry Whirl.'

  Ridcully picked up a bow, pointed it at a wizard, and fired. There was a distant `ow!'

  'Hmm. Spreads nicely on impact,' he said. `Well done, Mr Stibbons. I'm impressed. You are in charge.'

  The Dean bridled at this. `I protest! I am the Dean, when all is said and done!'

  `Oh, all right, Dean, you can come! But, and I want to make myself absolutely clear, you are not to point anything at anything unless I give you a clear instruction, understood?'

  `Yes, Mustrum,' said the Dean meekly.

  `Furthermore, you will not, at any point, wave your weapon in the air and shout "choc and load". Is that clear? I say that because I can practically see the silly words forming in your head!'

  `That's a vile calumny!' the Dean shouted.

  `I hope so. Stibbons, wait here with the proctors and see no harm comes to Mr Darwin. Hex, you know where to send us. Invisibly, if you please!'

  While Charles Darwin was sitting in a blue haze in Unseen University, a slightly younger Charles Darwin was staring out at the rain, noting idly that the rain sounded a little like whispering.

  A drawback of invisibility is that no one can see you; it is in fact the main drawback if there is a group of you -

  `- that was my foot!'

  `Who is that?'

  `Look where you're going!'

  `And what help will that be?'

  `Keep it down, you fellows! He'll hear you!'

  At which point, the wall in the corner dissolved and brilliant light shone through. Beetles of all sizes and colours poured into the study in a shimmering torrent.

  A figure that the wizards recognised stepped though the hole and looked around him with an air of amiable bewilderment. He had a slightly lopsided circlet of leaves on his head, and glowed with the light of deity.

  `Mr Darwin?' he said, as the figure in the corner turned and stared. `I understand you are studying evolution and are currently perplexed?' 'Look behind him!' Ridcully whispered.

  The unseen wizards stared into the flickering hole. There was sand, and sea in the distance, a suggestion of moving shadows ...

  `After me,' Ridcully hissed, as an astonished Darwin dropped to his knees. `Let's get them ...'

  The wizards poured through the camiloop, while behind them an elderly voice said: `Of course, selection is, ahaha, anything but natural. Take, for example, a species of parasitic wasp ...'

  The sand boiled. Sometimes handfuls of it fountained into the air. One invisible person can move with stealth and speed. Half a dozen invisible people are an accident waiting to happen again and again.

  `This is not being our finest hour,' said the voice of Ridcully. `Every time I start to stand up someone else treads on me! Can't Hex sort this out?'

  `We're back in the real world,' said the invisible Dean. `Hex's power isn't so strong here. It'll take him some time to find us. Would you mind getting off my leg. Thank you so very much.'

  `That's not me, I'm over here. I don't see why it's a problem. We were in another world, after all!'

  `Roundworld is right inside the High Energy Magic Building,' said the Lecturer in Recent Runes. `We're thousands of miles way, I suspect. Could I possibly suggest we all endeavour to crawl away in different directions? If you, Dean, head for that little bush with the red flowers, and Rincewind - where's Rincewind?'

  `Here,' said a muffled voice from under the sand.

  `Sorry ... you head for that rock there. ..'

  By degrees, with only the occasional curse, the wizards were able to get to their unseen feet.

  `This is Mono Island, I recognise that mountain,' said Ridcully. `Look out for-'

  `Why didn't we just bop him on the head?' said the Dean. `Just a tap on the noggin? Then we could have dragged him back here, end of problem.'

  `But it's quantum,' said Rincewind. `We have to deal with what's happened. If we stop it happening before it happens, the other things we've. ..' he hesitated. `Look, it's quantum. Believe me, I'd prefer it the other way.'

  `Anyway, you can't just bop gods on the head,' said Ridcully, now a faint outline against the distant ocean. `It doesn't usually work and it causes talk. The other gods would be bound to hear about it, too.'

  `So? None of them like him. They exiled him here after he invented the hermit elephant!' said the Dean, who was also fading into view.

  `It's the look of the thing,' said Ridcully. `They don't want to encourage deicide. Besides, look up there ...'

  `Oh dear,' said Rincewind. `Auditors ...'

  A grey cloud was rolling down the mountain. As it neared, it contracted upon itself, growing darker.

  `They've learned things,' said Ridcully. `They've never done that before. Oh, well ... Rincewind, first line of defence, if you please. And hurry!'

  Rincewind, who'd always operated on the assumption that if you carried a weapon you were giving the enemy something extra to hit you with, held up a placard. It read: GO AWAY.

  `Stibbons says it should work,' said Ridcully, uncertainly.

  The Auditors drew closer, merging until, now, only half a dozen were left. They were dark, and full of menace.

  `Ah, they probably aren't the reading sort, then,' said Ridcully. `Gentlemen, it's chocolate time ...'

  It had to be said that the most of the wizards were not natural aimers. A spell went where you wanted it to go. You just had to wave in the general direction. They'd never learned to be serious about pointing.

  Some shots went home. When several hit an Auditor it let out a thin scream and began to break up into its component robes, which then evaporated. But one, slightly larger than the others, zigged and zagged through the tumbling chocolates. Auditors did learn here ... and the wizards were running out of chocolate.

  `Hold it,' said the Dean, pointing his bow.

  The shape stopped.

  `Ah,' said the Dean, happily. 'Ha, I expect you are wondering, eh, I expect you are wondering, indeed, if I have any chocolate left? And as a matter of fact I'm no-'

  `No,' said the Auditor, drifting forward.

  `What? Pardon?'

  `I am not wondering if you have any cho
colate left,' said the dark apparition. `You have none left. The Higgs & Meakins Luxury Assortment comprises two each of: Walnut Whips, Strawberry Whirls, Caramel Bars, Violet Creams, Coffee Creams, Cherry Whips and Walnut Clusters and one each of Almond Delight, Vanilla Cup, Peach Cream, Coffee Fondue and Lemon Extravaganza.'

  The Dean smiled the smile of a man whose Hogswatches had come all at once. He raised the bow.

  `Then be so kind as to say good day to the Nougat Surprise!'

  There was a twang. The sweet flew. For a moment the Auditor wavered, and the wizards held their breath. Then, with the slightest of whimpers, it faded into nothing.

  `Everyone forgets the Nougat Surprise,' said the Dean, turning to the other wizards. `I suppose it's because it's so irredeemably awful.'

  There was nothing but the sound of the sea for a few seconds. Then:

  `Er ... well done, Dean,' said Ridcully.

  `Thank you, Archchancellor.'

  `A little too showy, nevertheless. I mean, you didn't have to chat to the thing.'

  `I wasn't in fact sure if I had used the nougat,' said the Dean, still smiling. Quite an effort would be needed to wipe that smile away, Ridcully knew, and so he gave up.

  'Good show, all the same,' he mumbled, and then raised his voice.

  'If you can hear me, Hex ... back to the Great Hall, please.'

  Nothing happened. An important part of transferring matter across the world is the moving of an equivalent mass the other way. This can take a while.

  Then an oak table, three chairs and two spoons crashed into the beach. A moment later, the wizards vanished.

  22. FORGET THE FACTS

  IT'S THEORIES THAT MATTER.

  Discworld does not have science as such. But it does have a variety of systems of causality, ranging from human intentions ('I'll just go out for a drink in the Mended Drum') to magical spells to a generalised narrativium that keeps local and general history close to the lines of `story'. Roundworld does have science, but it's difficult to discover the extent to which it determines, modifies, affects people's actions - technology does, of course, but does science? Science does affect what we do, what we think, but it doesn't change what we do and think because so much of our basic knowledge is simply accepted scientific `fact'.