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- Herausgeber: David Fickling Books
- Kategorie: Wissenschaft und neue Technologien
- Sprache: Englisch
- Veröffentlichungsjahr: 2023
Biology affects every aspect of our lives, but its marvels can often seem mysterious. Here, at last, is an enjoyable read that will help you make sense of it all.From the origins of life to the structure of modern ecosystems, follow the story of life on Earth, stopping along the way to understand key developments and how they have shaped our planet.Lindsay Turnbull teaches biology at the University of Oxford, and here she has written the perfect accompaniment to those hard-to-read textbooks. This book is indispensable both for students of biology and anyone curious about how life works.
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For Rowan
Contents
Physics is often described as the science of the twentieth century, but biology has staked a bold claim to be the science of the twenty-first. Every day we are bombarded with new and important biological findings, from new vaccines for deadly viruses to strange new species lurking in hitherto unexplored places. Of course, the physicists haven’t yet thrown in the towel. They continue to vie for public attention by enticing us with exciting new projects, and most recently they have turned their attentions to our neighbouring planet, Mars.
NASA’s Perseverance rover is a robotic vehicle that landed on Mars in 2021 to trundle around its surface, collecting samples and setting them aside for future human visitors to inspect. The mission is a spectacular feat of human ingenuity and the scientists at NASA are rightly proud of their achievements. But the stated goal of the mission is unmistakeably biological – to look for signs of ancient past life on Mars’s dusty surface – because today, its thin atmosphere and lack of liquid water mean that the red planet is undoubtedly a dead planet.
Personally, I’m happy to give Mars a miss. It’s not that Mars isn’t beautiful in its austere way, nor that it doesn’t have some attractions, like the largest volcano in our solar system. But Mars, like so many of us humans, is utterly eclipsed by its gorgeous, stunning sibling. Why would you want to go to Mars when you can live on its shining sister – Earth?
Earth is unmistakeably a living planet. Suspended in the blackness of space, oceans of deep-blue water hold glowing green continents in their liquid embrace. The Earth’s atmosphere is thick – and rich in oxygen gas – quite unlike the atmosphere of every other dull and lifeless rock that’s scattered around our solar system. And it teems with unimaginable wonders.
Earth is currently home to at least eight million species of animals and plants – the products of four-and-a-half-billion years of evolution – and all earthlings have free access to at least part of this bounty. We can gasp at the aerobatics of a passing swift, or shudder at the scuttling arthropods that rush out from underneath the nearest rock. Even a drop of pond water contains a twirling, whirling frenzy of micro-organisms, which any microscope can reveal.
We ourselves are just one example of evolution’s creative frenzy. Humans 2have undoubtedly been highly successful, spreading around the globe and reaching every continent. But we don’t live quietly alongside other species – instead, we have transformed the planet, removing entire ecosystems and replacing them with others that more closely serve our needs. Indeed, so profound is our impact, that many now believe our planet may not support us for much longer.
Today, many children worry deeply about the planet-scale mess that they stand to inherit. If they are to tackle the challenges ahead, then a good grasp of biology is essential; but this is a daunting prospect. Biology is an enormous subject that grows every day, and the problems that biologists are expected to solve keep mounting: we need better antibiotics; we must prevent the emergence of the next pandemic; and all the time, species are disappearing, as the diversity of life on Earth comes under pressure from a growing human population that demands more every day.
I certainly sympathize with those children. I teach students at the University of Oxford, and they too worry about their future. They often feel overwhelmed by the immensity of biology, and it’s my job to try to make it manageable. Studying the school curriculum and looking at other sources of readily available information led me to conclude that there are two intertwined problems with teaching and learning biology today. The first problem is that biology does, indeed, continue to grow at an alarming rate. Biologists begin with an idea and then further investigations add more knowledge and the original idea might start to fracture into several sub-ideas, each with their own supporting evidence. In the end, this continued growth makes it difficult to teach any biological topic, as it’s extremely hard to know what is essential and what is simply nice to know.
The second problem is the tendency to serve up biology in rather large indigestible chunks. Even the best textbooks continue to lay biology out in a rather dull way and don’t attempt to turn it into an enjoyable read. It’s the student’s job to simply learn the information, and there isn’t any real context or story to help the reader along.
This is strange because the history of life on our planet is the most incredible story. It begins with a molten rock being bombarded by meteorites and it ends with what you see around you today: a teeming world of species that interact with each other 3and their surroundings. Between that distant hot rock and the present day, millions of living things have sprung into being, and although most have since vanished, we can learn something new from each and every one of them.
The story of life on Earth provides the perfect backdrop for the important biological concepts that we all need to know, and I have used that story to structure this book. You’ll be glad to know that I don’t give equal space to each period of the Earth’s history – indeed this would be a recipe for a very dull book – as for very long periods we honestly don’t really know what was happening. It also doesn’t follow a slavish chronology – my goal is to tell the story in the way that makes it easiest to understand, so animals get two chapters before plants get to muscle in and tell their story.
Despite my best efforts, many episodes in the story of life are still somewhat controversial. There are also many things that we simply don’t know. I believe that the best way to deal with this issue is to be honest, in the hope that this might inspire some readers to fill these gaps by becoming biologists themselves. So, I hope that you will find these gaps reassuring – there’s still plenty for budding biologists to find out!
Finally, when writing about science, a decision has to be made about the scientists themselves, and mostly I decided to leave them out. I accept that science is done by real people and obviously they deserve appropriate credit, but mentioning them all means introducing yet more names to a subject that is already full to bursting with new terminology. To deal with this particular problem, there is a glossary at the back of this book and any technical word written in italics, like cell nucleus, can be found there, together with a brief definition. The book also contains illustrations. These have been developed in conjunction with my fantastic colleague, Cécile Girardin, and are simpler than those found in most text books. They are not a replacement for a text-book diagram and we have allowed ourselves a certain artistic licence when we think it helps to make a tricky concept clearer (a ribosome is not really a stout man in braces!).
In writing this book, I relied on the expertise of many incredible colleagues at the University of Oxford, who shared their knowledge with the relish and 4eagerness that typifies most biologists. Of course, I must take the blame for any errors. As I have already explained, new discoveries are made every day, but I still believe that many of the core concepts in this book have stood the test of time and are unlikely to change dramatically. So, if each biological topic can be thought of as a delicious dish, then future biologists might tinker slightly with the ingredients, but I doubt that they will entirely change the recipe.
So, now, let’s begin with the fundamental unit of all life on Earth – the cell. These tiny entities form the building blocks of larger creatures, but most of the cells on Earth live alone – quietly passing on their information to the next generation and turning long-evolved plans for world domination into action. Cells might be small but don’t let their size fool you. These tiny titans are the ultimate life form and if cell biology were a delicious dish, then it would be the equivalent of the best cake you’ve ever eaten.
Every life form on our planet is made from cells. They are the fundamental unit of life, and for most of Earth’s history, cells lived alone and did not join forces to build larger beings. But today, our planet is populated by bodies of all shapes and sizes. Each one is a collaboration between enormous numbers of cells that work together seamlessly, so it’s unfortunate when their collective efforts are undermined by cells that don’t properly play their part.
Each morning, Sara sits in the window of her house and watches the world go by, and like most of us, she is oblivious to the internal workings of her body. But Sara’s world is a difficult one. She suffers from a condition called cystic fibrosis and must endure hours of physiotherapy to clear deep-seated mucus from her lungs. Yet, even with this help, she has spent long periods of her short life in hospital, receiving treatment for bacterial infections that threaten her very existence.
Inside Sara’s lungs, we can begin to find out what has gone wrong. Thick sticky mucus has accumulated in the tiny air passages, allowing bacteria to thrive and so making Sara ill. This problem has arisen because some of the cells within her body are malfunctioning. A human body is made from around 37 trillion cells, and most of us are lucky enough that those cells carry out their assigned functions most of the time. So, why are some of Sara’s cells causing her so much harm?
To answer this question, we need to understand how cells know what it is they are supposed to be doing. Studying cells means peering into their interiors, but cells are so small that they can’t generally be seen with the naked eye. Fortunately, since the invention of the microscope, scientists have gradually found out more and more about them, revealing orderly interiors sculpted from even tinier molecules. Their minuscule size can deceive us into thinking that individually they are dull and somewhat lifeless – perhaps similar to a tiny Lego brick – but nothing could be further from the truth.
Far below our range of vision is a world of mind-boggling complexity. A cell is a tiny hive of ceaseless activity – more akin to Willy Wonka’s chocolate factory than a lifeless piece of plastic. If we could win a golden ticket to visit this factory, we would see workers hammering out new tools and spare parts at an extraordinary rate and being bombarded by messages flying out from head office with instructions 7to make and repair essential components; and if we stayed long enough, we might witness the most momentous time in the life of any cell – when it pulls itself apart to become two identical descendants.
Many of us learn about cells for the first time at school, and it’s common to draw pictures of ‘typical’ animal and plant cells. These cells are generally large, and the diagrams highlight a few prominent features that are visible under a light microscope: an outer cell membrane that separates the cell’s contents from the world outside; a cell nucleus that acts like a head office; and a watery cytoplasm that acts like the factory floor, where the business of the cell is mostly carried out. However, there are many other types of cells on our planet, including bacterial cells that far outnumber animals and plants, and these cells look deceptively simpler – for example, they don’t have a cell nucleus – which might delude us into thinking that they are fundamentally different. But if we focus on what cells do, rather than on what cells look like, then we might draw a different type of diagram to highlight the handful of crucial features that all cells share, and most of these are central to processing the information that lies at the heart of every cell.
Fundamentals of a Cell
8All cells, whether animal, plant or bacteria, have to follow instructions to ensure that the cell runs smoothly, and their instruction manual is called a genome. A genome is generally too small to see, even with a light microscope, but that doesn’t make it any less valuable. The importance of carefully written instructions is clear to many of us when we buy things like flat-pack furniture that require some assembly. If the finished object is to look like the one shown on the box, then the pieces must be correctly assembled, and the instructions show the buyer how to do this. In a cell, the genome acts in the same way – providing precise instructions for constructing everything that the cell needs using tiny building blocks that the cell either imports or makes from scratch.
Of course, someone needs to read the instructions and build the finished products. To perform this role, cells are filled with miniaturized workers called ribosomes, and if we compare the cell to Willy Wonka’s chocolate factory, then these are the Oompa-Loompas. Ribosomes are inexplicably missing from many of the diagrams drawn at school, but cells would grind to a halt without these indefatigable workers.
Surprisingly, perhaps, ribosomes aren’t allowed direct access to the genome. Instead, messages are sent out that specify precisely what needs to be made. Each cell might make hundreds or thousands of different pieces of equipment and the ribosomes are capable of making any of these, as long as they receive the right instructions. And only when it has the right equipment can the cell perform its proper function.
So, the genome provides detailed instructions to the ribosomes, and they build all of the machinery that the cell needs. This transfer of information from genome to ribosomes is central to the operation of all cells, but they don’t just process information so that they can run their own lives, cells also pass information on to the next generation. Sara, like every multicellular being on Earth, began her life as a single cell. To create the 37 trillion cells that she now consists of, this first cell had to divide, again and again, producing vast numbers of descendants to take up every role in Sara’s body. But before a cell divides, it must copy the all-important 9genome, so that each of its descendants, often called daughter cells, can properly manage their own affairs.
These two acts – passing on information to the next generation of cells and translating that information into action – are the most fundamental things that cells do, and they are carried out by every cell on Earth. This information processing is so important that we need to understand it in more detail. Only by doing so can we get to grips with how organisms truly work, how things go wrong and, crucially, how the first cells on our planet came into being.
Written in a simplified language that no human would recognize, the genome contains the instructions for building every machine and spare part that the cell could possibly need. Laid out on an enormous scroll, the genome is kept by different cells in different places. In bacteria it simply floats around, while in the larger cells, like those from which we and other complex beings are made, the genome is kept apart within the cell nucleus, although its function is the same.
The instructions within the genome are spelled out using DNA, an information molecule, whose sole purpose is to store information and keep it safe. Like most of the large molecules inside cells, long strands of DNA are formed by joining together smaller building blocks just as we could make a necklace by stringing together glass beads. The building blocks of DNA are called nucleotides and there are four of them: adenine, cytosine, guanine and thymine. They are denoted by their four initial letters – A, C, G and T – which are used to spell out each instruction. Different organisms need different instructions, depending on whether or not they have legs, wings or leaves, and so the genome of each organism is unique.
We can begin to appreciate the enormous complexity of living things by noting that the genomes possessed by even the simplest organisms are massive. Building and running a bacterium requires a genome that clocks in at around one million DNA letters, a worm needs one hundred times that, while the genomes of more complex creatures, like sharks, pigeons or horses, contain at least one billion letters and usually more. Indeed, a genome contains so much information that only 10a miracle of coiling and packaging allows it to squeeze inside the cell.
The Genome is Written in DNA Letters
Instructions are sent out from the genome by a second information molecule called RNA. Strands of RNA are made by stringing together building blocks that are very similar to the ones used to construct DNA strands, but they have their own nucleotide alphabet: A, C, G and U: adenine, cytosine, guanine and uracil. So, given the similarity between the two information molecules, we need to understand why the cell needs both.
RNA strands are short, consisting of a few thousand letters at most. They are perfect for delivering simple instructions, but wouldn’t be much use for storing the billions of letters needed to encode the genome of a horse or a shark. But, DNA has a trick up its sleeve. A strand of DNA letters is always bonded to a second, complementary strand and the two coil around each other to form a structure rather like a spiral staircase, with the letters hidden deep inside. Known as a double helix, this arrangement is very robust and means that the cell can keep 11adding more and more letters to the DNA molecule without it falling apart.
The double helix of DNA allows enormous genomes containing billions of letters to remain intact for the hours, days, weeks, months or even years that some cells survive. Indeed, without this miracle-molecule, complex animals and plants with massive genomes simply couldn’t have evolved. Once the cell dies, DNA slowly degrades, but it’s stable enough to allow us to read the sequence of letters inside the dried-up genomes of long-dead plants, animals and even people – so by digging up mummies from their tombs, we can learn more about ancient Egyptians, but we won’t be able to resurrect dinosaurs (whatever the makers of Jurassic Park may claim).
While the cell is alive, DNA can’t just sit around in splendid isolation – if the cell is going to make things, then its instructions must be put to use. If the cell needs a particular piece of machinery or a spare part, then the double helix is prised apart. An individual instruction within the genome is called a gene, and by exposing the sequence of DNA letters for the gene required, RNA messengers can faithfully copy the gene’s code into their own alphabet and carry it away. But only the industrious ribosomes know how to decode the message and turn it into a piece of viable kit.
Most of the objects that humans knowingly interact with are large, with sizes ranging from a few centimetres to a few metres, so cells are too small for most of us to notice. An amoeba is about the largest free-living cell out there and 10 of them lined up side by side would fit into one millimetre, while for the typical cells inside a human body, around fifty to one hundred of them could probably fit into the same space. Bacterial cells are smaller again, so fitting one thousand or so into our millimetre wouldn’t be too hard. But whichever cell we choose, its internal parts and machinery are very small indeed, which has dramatic effects on how things work.
The world we inhabit – filled with objects measured in centimetres and metres – is dominated by gravity. Earth is massive, so it attracts other large objects and keeps them rooted to one spot. Gravity dictates that our factories are laid out on a flat surface, where machines stay in place and people walk around – hence the factory floor – but the components of a cell are far too small to feel gravity’s pull. 12Instead, the inside of a cell is more like a factory inside the international space station, where everything is weightless and things float around. Within the crowded cell, tiny molecules often bump into each other, and while most of these collisions simply result in them bouncing off each other again, if two molecules are the right shape, then they will stick together and something more interesting might happen.
The RNA messages floating out of the genome are hoping to bump into a ribosome – one of the cell’s key workers. Their job is to capture the RNA messages and use the information to build something useful, and with up to 10 million of them within a single cell, bumping into one shouldn’t be too hard. In terms of scale, they are to the cell what individual people are to a city like London. A ribosome is so tiny that no regular microscope will ever reveal one, but more advanced techniques have shown that, unlike city dwellers, they resemble tiny snowmen with fat bodies and large heads, and the gap between body and head is just the right size and shape to trap the RNA message.
The job of a ribosome is to build proteins. Proteins play a multitude of roles within cells. Some are structural – forming scaffolds to support the cell – while others act as signals so the cell can communicate with the world beyond its outer membrane; but the biggest class of proteins are enzymes – molecular machines that form the equivalent of the cell’s toolbox. Advanced microscopy has revealed that proteins can fashion an extraordinary array of tools and machinery, including tiny locks with perfectly fitting keys, channels through the membrane that only allow selected traffic to enter, and even the blades of molecular turbines that allow the cell to generate the energy it needs. To play all these roles effectively, proteins have to be built in a bewildering variety of shapes and sizes. But how does a single type of molecule manage such extraordinary flexibility?
Like the information molecules, a protein is made by sticking together smaller building blocks to form a long chain, but this time the building blocks are amino acids rather than nucleotides. The flexibility of proteins lies in the amino acids, because while the four letters in a DNA strand are rather similar, there are 20 possible amino acids to choose from, each with unique chemical and physical properties. Amino acids carry different electrical charges (positive, negative or neutral), bond to different 13substances, and some, like valine, hate water, while others, like arginine, love it.
Once the amino acids are strung together, the chain seems to take on something of a life of its own. The water-hating amino acids pull themselves towards the middle of the protein, while the water-loving ones are happy to be on the outside. Meanwhile, amino acids in different parts of the chain are repelled or attracted to each other by their varying electrical charges, and all this jostling means that the chains can fold and twist themselves into practically any shape we can think of. And because each protein contains a different sequence of amino acids, the shape of each protein is unique.
The shape of the protein is determined by the sequence of amino acids, so the ribosomes have to ‘know’ exactly which amino acids to join together, as otherwise the key won’t fit the lock, the wrong molecules will pile up in the channel, and the turbine blades won’t spin. But they don’t have to trust to luck. This crucial information is encoded in the genome and delivered by the RNA messengers. Once trapped by a ribosome, the message simply has to be translated.
Protein Folding
14The messages flying out from the genome are written in RNA-speak, an unusual language in which all words are exactly three letters long. Each three-letter word specifies a single amino acid, so correct translation allows the ribosome to join amino acids together in exactly the right sequence. The ribosome begins by locking onto the message and finding the three-letter word AUG, which means ‘start’. It then keeps moving – three letters at a time – to discover which of the 20 different amino acids comes next. If the next three letters are GUA, then the ribosome adds an amino acid called valine, but if the next three letters are GGA, then it adds an amino acid called glycine instead.
Ribosomes can find the right amino acid because each one is attached to a three-letter RNA tag. The ribosome just has to make sure that the tag on the amino acid complements the three-letter word on the RNA message – and if it does, then it’s the right one to add next. Any number of amino acids can be added to the chain, although a typical protein in a human body contains between 350 and 400, but eventually, the ribosome encounters a word meaning ‘stop’, at which point it will detach itself from the message and the protein chain floats free. On release, the finished protein spontaneously folds into its three-dimensional shape, and if the sequence was right, then this shape allows the protein to perform its proper function.
One of the most astonishing revelations of twentieth-century biology is that RNA-speak is a truly universal language, understood by all. Whether the cells are embedded in the legs of a galloping horse or basking in the petals of an unfolding sunflower, they all know that GGA spells glycine – and it’s not just animal and plant cells. In the heart of deep-sea vents, billions of bacterial cells living inside the guts of giant tube-worms are united in their certainty that GGA spells glycine.
RNA-speak first emerged around 3.8 billion years ago and many of its speakers haven’t spoken to each other since, but the three-letter words for all 20 amino acids are written in exactly the same way – with almost no exceptions – in every cell on Earth. Contrast this uniformity with human language, which emerged around 100,000 years ago and has already diverged into at least 6,500 modern forms. People can 15change their language quite easily because the consequences of doing so are unlikely to be severe, but if a cell tried to change RNA-speak, then every protein would be affected – and it’s spectacularly unlikely that at least one of those changes wouldn’t bring disaster. So, despite trillions of opportunities to evolve a new language, no cell has ever done so.
A Ribosome at Work
16The one-way flow of information within cells – from genome via RNA messenger to protein – is called the central dogma of molecular biology. It is a universal system adopted by all cellular life and is one way to define what cells are: they are factories that process information and use it to build ‘stuff’ (formally called matter). But cells do more than just process information during their own lifetimes – they also pass information on to their descendants, and to do this, the genome must be copied.
The life of any cell is finite, and eventually it will either die or pull itself apart to produce two identical descendants. For single-celled organisms, the two daughter cells then separate and lead independent lives, but in complex beings, like humans or horses, the two cells stay together and keep dividing again and again. These divisions generate the enormous numbers of cells that are needed to fashion a complex being: a small leaf captures sunlight with around 100,000 cells; a human heart beats with the aid of two billion; and an adult human is kept walking and talking by 37 trillion. But all these ambitious building projects started in the same way – with a single cell that divided in two.
Producing two cells out of one is the sort of everyday miracle that life performs so effortlessly, we barely notice how remarkable it is. But before the cell divides, the genome must be copied, as otherwise the daughter cells will be lost and lifeless. To reveal the hidden letters, the DNA helix is untwisted and the two strands prised apart, which are then used as templates to build an identical copy using molecular copying machines that are built from enzymes.
Once pulled apart, each of the two strands can be used as a template to recreate the complementary strand that is now missing. This works smoothly because each 17DNA letter will only pair up with one of the four letters on offer. For example, the letter A will only pair up with the letter T, so when the copying machine meets the letter A, it knows that a letter T is required on the new complementary strand that it is building. In turn, T will only pair with A, C will only pair with G and G with C. So, by working away and adding new letters, the copying machine produces two new identical double-stranded DNA molecules.
When faced with a three-billion-letter genome, a single copying machine in a typical animal cell would need around eight hundred hours to finish the job if it started at the beginning and continued all the way to the end. To avoid such an impractical wait, an army of machines starts in multiple different places at the same time, and so can finish copying a three-billion-letter genome in around one hour – about the time it would take 1,000 crack typists to copy out the complete works of Shakespeare.
DNA Replication
19Inside multicellular beings, the copying process doesn’t stop once adult size is reached. Within bodies, cells need to be continually replaced and each new cell needs a copy of the genome. In complex organisms, like humans, the amount of copying needed to generate enough cells for a lifetime is truly astronomical. By the time we reach 40 years old, it’s estimated that our bodies have produced a light-year of DNA (9 trillion kilometres) – enough to extend well beyond the outer reaches of our solar system, although not quite enough to get us to the next star.
A genome can be copied again and again, giving it a life span far beyond that of individual cells or organisms. Indeed, our bodies are just disposable shells and easily discarded. Only information is truly immortal, and because new cells can only arise from old ones, the transmission of information between generations is crucial to life as we know it.
The molecular machines that copy DNA are fantastically good at their job, so the genome handed to every daughter cell should be identical. But in truth, the copying machinery isn’t perfect. Although it has built-in proofreading, it sometimes makes mistakes, and these mistakes can have devastating consequences for the daughter cells that inherit them.
It’s time to return to Sara and examine the cause of her illness. Sara suffers from cystic fibrosis, which mainly affects the lungs, but how do Sara’s lungs differ from those of non-sufferers?
In non-sufferers, the cells that line the air passages in the lungs make a very large protein, called the CFTR protein. This is inserted into the cell’s outer membrane where it forms a channel allowing charged particles, called ions, to enter and leave the cell. With ions flowing freely, the cells are able to secrete thin mucus that performs its intended function of trapping any bacteria that enter the airways, which are then swept away by the tiny hairs that cover the cell’s surface.
In Sara’s lungs, these channels appear to be missing. Without them, ions can’t flow freely in and out of her cells, so they can’t secrete mucus properly either. The thick sticky mucus – which is all her cells manage to produce – also traps bacteria, but 20it can’t be swept away, leaving the bacteria to build up to dangerous levels. So, why are these crucial channels missing?
Zooming inside her cells, we see that messages to build the CFTR protein are certainly flying out of her genome and being trapped and translated by ribosomes. But something must have gone wrong because the CFTR protein they are making is one amino acid short. It should contain 1480 amino acids, but, in Sara’s cells, the 508th amino acid is missing, and this is catastrophic for the protein’s final shape – it simply won’t form an acceptable channel, and so it is rejected and its amino acid parts recycled.
The fault does not appear to lie with the ribosomes, as they are successfully making other proteins, so something must be wrong with the message itself. In fact, the message sent to the ribosomes is too short because three crucial letters are missing from the relevant part of Sara’s genome. At some point, three tiny letters were accidentally deleted from the genome of the founding cell of Sara’s body, and because all the cells in her body are clones, they have all inherited the same mistake.
Although Sara has the benefit of various drugs to ease her symptoms, a cure would require editing the genome within each of her cells to insert the missing letters in exactly the right place. Such technology, called gene editing, is developing rapidly, and it may be that sufferers of cystic fibrosis in the future can benefit from totally new kinds of genetic treatment. But until this technology is perfected, Sara must rely on more traditional methods to manage her condition.
Cystic fibrosis is one example of a genetic disorder. Humans suffer from thousands of genetic disorders, some incredibly rare and others more common, and while some have only mild effects, others can be life-changing. Regardless of their severity, all genetic disorders have the same cause: a change to the genome that alters one of the RNA messages sent out to the ribosomes. Of course, it might be better if the ribosomes noticed the mistake, but unfortunately, in contrast to the dedicated Oompa-Loompas who worked in Willy Wonka’s chocolate factory, ribosomes are nothing more than mindless machines. On receipt of a faulty message, ribosomes don’t ask questions, but churn out the altered protein, unaware of any potential problems. The consequences range from mild to serious to utterly catastrophic, and there’s 21absolutely nothing that the cell – or the body to which it belongs – can do about it. The change to the genome that causes cystic fibrosis is an example of a mutation, where DNA letters are missing, added or simply swapped around. In films, mutations are usually caused by mad scientists and experiments in their laboratories, and there are certainly some chemicals, called mutagens, that damage DNA. But the vast majority of mutations have a more humdrum origin: they are simply mistakes made by the cell’s own copying machinery.
Mutations in the genome alter the RNA messages flying out to the ribosomes, and the bigger the mutation, the more likely it is to have dramatic effects. But the size of the change isn’t the only important factor. The unique nature of RNA-speak means that even swapping one DNA letter for another can have very different impacts on the cell – and the body to which it belongs – depending on exactly where the change takes place.
Each three-letter word in the RNA message spells out a single amino acid and all cells use the same language. The three-letter word GGA spells out glycine, but glycine has three alternative spellings: GGC, GGG and GGU – all equally good – and the three alternatives are also recognized by all cells everywhere.
Alternative spellings of the same amino acid mean that some mutations are neutral. If GGA mutates into GGC then the protein chain remains exactly the same, because both words spell out glycine; but if GGA mutates into GCA then the meaning of the word has changed and glycine will be replaced by a different amino acid – in this case alanine. Even so, the change might not affect the function of the protein, if its shape stays the same, but swapping just a single amino acid can cause a change in shape large enough to give rise to problems.
For some people, a sudden burst of exercise can leave them in severe pain for days or even weeks. The pain is caused by misshapen red blood cells getting stuck in the tiny vessels that deliver oxygen to the farthest reaches of the body. Normal red blood cells are squishy, allowing them to squeeze easily through narrow spaces, but sufferers of a genetic disorder called sickle cell disease build red blood cells that are just too rigid.
Sickle cell disease is caused, not by the loss of letters, but by a change to a single 22letter of the genome within the instruction (or gene) to make an oxygen-carrying protein called haemoglobin. Red blood cells are stuffed full of haemoglobin, and if the protein is the wrong shape, then the cells are too. The mutation changes the three-letter word GAG to GTG, and when the ribosomes encounter this word during the building of the protein, they use the amino acid valine instead of the usual glutamic acid. This single change is enough to transform the shape of the protein and with it the crucial red blood cells on which our bodies depend.
The central dogma means that all cells are slaves to their genomes. They can only process the information they have been given – there is no way for cells to rewrite their genomes or for ribosomes to leave feedback on the quality of the proteins they build. Mindlessly engaged in turning written instructions into three-dimensional objects, ribosomes are wonderful machines – but if the instructions are faulty, they aren’t interested in our complaints.
The Effect of Mutation
23Harmful mutations might be so severe that a cell or body is lost before its genome can be passed on, but for those cells or bodies that manage to reproduce, information flows forward into the next generation. So, if each new cell requires an existing cell to bring it into being, then all cells must have an unbroken line of ancestors that stretch back to the dawn of life on Earth. But if we follow different lines back through time, do they converge on the same ancestor?
The cell defines life on Earth and the defining features of cells reveal something undeniable about their origins. Cells share an extraordinary amount in common: they have a genome encoded by DNA using the same four letters; they send out instructions via RNA messengers that are written in RNA-speak; and these are decoded by near-identical machines called ribosomes that all speak the same language. Only one conclusion is possible – all life on Earth today is related, so there must be a founding cell from which we can all claim descent. Although there may have been other types of life in the past, they are not here now and we have no evidence for their existence. But amazing though this seems, it raises an even more mind-boggling question: we might know how a new life starts on Earth today, but how on earth did life itself get started?
Attempts to unravel the mysteries of life’s origin began in the 1950s by focusing on the simple building blocks, like amino acids, from which larger molecules, like proteins, are made. Animal cells rely on their diet to obtain most of the building blocks they need, but the very first cells had to be much more self-sufficient. The early Earth only contained very simple molecules, like carbon dioxide and small amounts of methane, a natural gas, which we now burn to generate heat. So, how can cellular life have started from such unpromising beginnings?
The first serious attempt to solve this mystery took place in 1953 when a mixture of the very simple molecules thought to be present on the early Earth were repeatedly zapped with electricity to imitate lightning in the early Earth’s atmosphere. To the world’s astonishment, this unlikely attempt at primeval cookery yielded several different amino acids within the first week, so it seemed that it was easy to 24conjure up the ingredients for life. But, hopes were dashed when it turned out that the first guesses at the chemistry of the early Earth might have been some way off the mark, and attempts to repeat the experiment under more realistic conditions were rather less successful.
25Just when it seemed that the building blocks of life might resist all attempts at earthly conjuring, the cosmos came to our rescue. The early Earth was bombarded with meteorites and these are often loaded with the kind of building blocks that life needs – so their arrival might have kick-started life on our planet. Of course, this makes it quite likely that other planets in other systems have also received the same starter culture, so perhaps there’s good reason to hope – or fear – that other life is out there.
Others believe that meteorites are a red herring – arguing that any extra-terrestrial building blocks would quickly have been used up – so is there somewhere on Earth where building blocks are continually manufactured? Perhaps the answer is not in space but closer to home, in the depths of the oceans. In 1977 marine scientists discovered strange new habitats on the ocean floor where seawater was interacting with molten rock deep within the crust in volcanically active areas. This interaction produces deep-sea vents, where hot chemically-rich fluid bubbles up, forming black or white columns of streaming chemicals in the water, called ‘smokers’, that teem with life. These chemical brews are now prime contenders for the site of life’s origin as they could be a natural source of amino acids – a key building block for early cells. But, while fascinating, the source of the building blocks isn’t the greatest challenge faced by those who want to understand the origins of life.
To work out how the first cells arose, we need to solve the puzzle of the central dogma, which goes something like this. A cell relies on machinery built from proteins to carry out essential tasks – but it can’t build these proteins without instructions. The instructions are provided by the information molecules – DNA, which stores the instructions and RNA, which carries them to the ribosomes for translation – but the instructions are useless without the machines to put these instructions into action. This tightly woven sequence leaves us with a classic chicken and egg conundrum, so which came first: the message or the machine? 26
To unravel the origins of the cell’s deeply intertwined core biology, a bunch of assorted theories, some wild, some plausible, have been advanced over the decades. None has yielded an entirely satisfactory answer, and in 2019 a $10 million prize-fund was founded by the Royal Society in London for anyone who could finally solve it. The origin of the first cell may forever be shrouded in mystery – after all, it happened so long ago that it’s rather like peering down the wrong end of a deeply cracked and clouded telescope at a star buried in a galaxy thousands of light years away; but that hasn’t stopped us getting gradually closer.
It seems likely that the central dogma, which assigns different roles to different molecules, probably evolved from a simpler system where one molecule played all roles, but which one? DNA is chemically lifeless and it’s impossible to imagine it doing anything other than simply quietly storing information. But RNA is quite different.
One of the shared features of all cells are the indefatigable ribosomes. These unsung heroes are unique among the cell’s machinery in being constructed from both RNA and protein. Indeed, the active part of the ribosome – which can join amino acids together – is made from RNA, whereas nearly all other chemical activity within cells is carried out by enzymes (made from protein, not RNA).
The ability of RNA to carry out chemical reactions, while simultaneously storing information, gave rise to the idea that there was once an ‘RNA world’ in which RNA multi-tasked. Indeed, short strands of RNA can copy themselves without the help of enzymes, allowing information to be passed on. The theory goes that once a self-sustaining RNA world had developed, DNA took over the role of information storage and proteins became the masters of chemical activity – leaving RNA relegated to its current roles as ribosome and messenger.
Supporters of the RNA world point to one last remaining scrap of evidence. In 2020 a new disease called Covid swept the world, causing widespread lockdowns and disruption. The disease was caused by a virus – an agent that arose from living things – but like the black riders that galloped out of Mordor in The Lord of the Rings, is itself neither living nor dead.
Viruses are simply genomes wrapped in a protective layer. They contain information to build themselves but not the cellular machinery to turn those instructions into 27anything useful. Alone, they are nothing, and this impotence exposes why the message and the machine are so intimately connected in all cellular life. But viruses don’t need their own machinery because they can enter cells and hijack their ribosomes, causing them to churn out viral proteins, including enzymes that copy viral genomes and package them up into new virus particles. Eventually, the cell bursts, releasing hundreds of new viruses into the world, each of which can go on to infect a new cell.
A Virus
28Viral genomes are intriguing because not all are made from DNA. Indeed, the virus that causes Covid has an RNA genome, and can perhaps trace its ancestry all the way back to the RNA world. If true, it means that viruses were present at the dawn of life, and perhaps even played a key role in getting cellular life up and running. Cells can only transmit information to their descendants, but by penetrating cells and moving information molecules around, viruses might have unwittingly swapped pieces of genome between different types of cells, and so produced new and exciting combinations.
The idea of an RNA world certainly holds many attractions, but not all scientists are convinced. Despite herculean efforts, longer strands of RNA have never been found to successfully copy themselves without the help of enzymes. Other scientists are working on theories that bypass the RNA world entirely. Perhaps life’s origins will never be entirely clear and this is what makes it so fascinating. Competing theories go in and out of fashion and scientists fight to defend their favourites. What is clear is that much more remains to be done and that new evidence will continue to trickle out, as the cracked and clouded telescope gradually reveals long-hidden secrets from the dawn of life.
Tiny fossils from ancient hydrothermal vents reveal that the first cells were probably up and running by around 3.8 billion years ago, and they eventually gave rise to all the living things that have ever walked, crawled or rooted themselves upon our planet. But how do we get from single cells to prancing ponies and towering trees?
All life is defined by the information it carries, so this must have changed over the millennia. Mutations can generate difference, but most, like Sara’s, are harmful, as cells and organisms are well-oiled machines and random changes are unlikely to be of any benefit. But just occasionally, a change to the genome results in a protein that 29functions rather better than the old one. Perhaps the key is now a slightly better fit to the lock or the turbine blades spin more smoothly – and such a change makes the cell or organism even better attuned to the world around it. But mutations occur in individuals, so how does a change to one end up being adopted by all?
To see how mutations can shape entire species, we need to look at an extraordinary force – one that can supersize dinosaurs or allow birds to take flight. Natural selection is a somewhat dull term for the ultimate power on our planet – one that elevates some and spells doom for others. But it’s sometimes surprising who the winners and losers are.
In 1819 in a woodland in Northern England, a moth shrugs off the shackles of its underground cocoon and crawls up the trunk of the nearest tree. Called a peppered moth, it has spent the winter sheltering below ground and must now extend two pairs of newly formed wings in preparation for its first flight. In this respect, as in nearly all others, it is no different from the other peppered moths emerging in the woods around it – but there is one crucial exception. This moth is a mutant, and instead of owning pale speckled wings like almost all the other members of its species, it has beautiful sooty-black ones. Given that most mutations are harmful, we might prophesy doom for this new arrival, but in the decades to come, naturalists will watch in awe as this moth and its descendants become wildly successful. But how?
At the start of the nineteenth century, the Industrial Revolution in Britain was well underway. Victorian engineers had worked out how to burn coal to heat water to produce steam to drive newly invented machines, so they could produce things cheaper and faster than ever before. Industrial development was greatest in the north of England and coal-powered industries flourished there. But coal is a dirty fuel.
Burning coal produces clouds of black soot, and the tiny particles settle out onto factories, homes, lungs and even trees. Worse, coal contains impurities, like sulphur – and when sulphur burns, it forms the acid gas sulphur dioxide – highly toxic to many of the crusty-looking grey-green lichens (pronounced: like-uns) that grow on tree trunks. In the space of a few decades, this deadly combination of soot and sulphur dioxide transformed the trees near English industrial towns from columns of speckled grey-green into pillars of purest black.
For a pale peppered moth sitting on a tree in nineteenth-century industrial England this transformation was disastrous. For thousands of years, the speckled wings of the pale peppered moths had allowed them to perch unseen on the light-coloured bark and encrusting lichens, but on the newly blackened tree trunks, the pale speckled moths stuck out like sore thumbs. The birds of Northern England did not let this opportunity go to waste. Moths make a good meal – and if birds can see them, they will eat them. So, was the peppered moth at risk of extinction?
Salvation lay in the mutant moth, whose sooty-black wings provided near-perfect camouflage against the newly converted tree trunks. Passing birds barely gave the 32black moth a second glance, so it was much more likely to survive and lay eggs than its speckled cousins. Its offspring inherited the black wings and so, before long, the woods of Northern England were filled with black peppered moths, while the original pale moths were almost impossible to find. It might have been a rarity in 1819, but by the middle of the twentieth century, the black moth had become the new normal.
The Peppered Moth
The story of the peppered moth reveals that species are not set in stone – they can evolve as the typical genome changes over time. Change begins with a lucky mutation in a single individual but it spreads through a group because those that carry it are more successful and have more offspring than those that don’t. This almost ludicrously simple process might seem an unlikely way to generate the incredible diversity of life that we see around us, but it forms the core of the most important theory in biology: the theory of evolution by natural selection
