Why are we told always to finish a course of antibiotics?

Most of us have at one time or another been prescribed a course of antibiotics by our GP. But how many of us heed the instruction to complete the course – to continue taking the tablets or capsules until none remain? Very often, our strict adherence to the prescription fades in line with our symptoms: the prescription may last for, say, seven days, but we’re often feeling much better after just two or three. So why bother continuing to take the antibiotic? After all, if we’re feeling better, the antibiotic has done its job, right? Well, you may think so. But, in fact, stopping a course of antibiotics early can have potentially lethal consequences. How can that be?

To answer this question, we must travel inside our body to mingle with the bacteria the antibiotics have been prescribed to kill. At face value, all the bacteria in a given population might seem identical. But look a little deeper, and you’ll see subtle differences. And one difference is the way in which they respond to a given antibiotic.

I described in a previous post how antibiotics are designed selectively to attack bacteria rather than causing harm to our own cells, which must necessarily get exposed to the antibiotic as it travels through our body in search for the alien intruder within. But different bacteria, even from within the same population, may respond differently to a particular dose of antibiotic. The ‘weak’ ones may be susceptible to a relatively low dose – they may be killed after just a few days of exposure to the antibiotic; by contrast, others may be much more resilient, and will still be alive after a few days of treatment.

The important point here is that the population as a whole is made up of bacteria exhibiting a range of tolerances – at one end of spectrum, a few real weaklings; at the other, a few really resilient ones. And, in between, we find many average, run-of-the-mill individuals, who can hold out against the antibiotic for so long – but not for very long. (I saw the same kind of distribution within a population when we grew some tomato plants this summer: some were noticeably short, some were unusually tall, but a majority hovered somewhere in between.)

But what’s causing this difference in tolerance? I mentioned in a previous post that each time a genome is copied there’s a chance a mutation (an error) will creep in to one of the genes making up that genome. Well, every time a bacterium reproduces it has to make a copy of its genome to pass on to its offspring – and, every time, there’s a chance an error will creep in. The chances are that the variation in tolerance to antibiotics that we witness in this population of bacteria is due to slight variations in their genomes; it could be that our resilient individuals show this resilience because they picked up mutations not present in their weak or average cousins.

Now, let’s return to our bacterial infection and imagine that we’ve started to take a course of antibiotics. It takes just a day or two to kill the real weaklings. And, in three or four days, even the Mr Averages will start to feel the proverbial heat. At this point, the population as a whole will have gone into noticeable decline, and we may start to feel much better as the number of alien invaders reduces.

But what has actually happened by the three or four day stage? The population as a whole may have shrunk in size – we’ll have rid ourselves of the few real weaklings and the larger number of Mr Averages – but we’ll be left with the few hangers-on at the other end of the spectrum, the real bruisers.

Before we started taking the antibiotics, the antibiotic-resilient bacteria (our ‘bruisers’) were fighting for a share of the available food with all the other members of the population. (It’s important to note that, when I talk of ‘weak’ or ‘resilient’ individuals I’m only referring to their tolerance level to antibiotics, not their ability to scavenge for food, and other aspects of survival in an antibiotic-free world.) In essence, the bruisers were being kept in check by everyone else – they remained in the minority because the whole population, including the weaklings and the Mr Averages, was growing at about the same rate. Now, three or four days in, the bruisers suddenly find themselves with much less competition for food. Imagine going to the buffet table at a wedding with 200 guests, all of whom are vying for a slice of the pie (quite literally), versus going to the same-sized buffet table with the same amount of food at a wedding attended by just 20 guests. At which wedding are you most likely to be able to fill your proverbial boots?

Now let’s consider what happens after day three or four, once the supply of antibiotic has stopped. At this point, remember, there are just a relatively small number of antibiotic-resilient bacteria left, but no weak or average ones. When the resilient bacteria suddenly find themselves the guests at an unexpected banquet – with competition for food gone – they do what bacteria do best: they reproduce. And without the previous competition for food, they can do so rapidly. So, we’ve suddenly gone from a mixed population in which the majority didn’t take kindly to antibiotics and only a few were the bruisers, to one in which virtually everyone is unusually tolerant to antibiotics. And this is where the real danger can lurk.

I mentioned above that the resilient bacteria may exhibit their resilience because they have accumulated more errors in their genomes than their weak or average cousins as successive generations have reproduced. As this resilient population now continues to thrive, it risks accumulating even more errors. And one of those errors could be what it takes to tip the balance from the bacterium being highly-tolerant of the antibiotic to it being completely resistant. You don’t need to be a medical expert to realise that complete resistance to an antibiotic is a really bad thing. If a bacterium has overwhelmed our immune system, and we don’t have an antibiotic to act as a back-up defence system, we have no weapons left to fight with.

If we carry on taking our antibiotics as prescribed, the story ends quite differently: even the resilient bacteria lose the will to live in the end. But we have to keep up the pressure by finishing the course of antibiotics. That way, any resilient individuals don’t get to dominate, and we reduce the risk of one of them picking up a mutation that makes them virtually invincible – but which is potentially lethal for us. In future, you know what you need to do…

What happens when our immune system doesn’t work as it should?

I consider myself lucky: I don’t wait for the onset of summer with trepidation, knowing that it will bring days of itchy eyes and sneezing. For others, though, the blossoming of our natural world through spring and summer is less a time for marvelling at the wonders of nature, and more a time for an annual battle with hay fever. But why do some people have to suffer such afflictions while others don’t? What’s going on?

As I’ve mentioned in earlier posts, our immune system protects us from attack from potentially dangerous alien invaders in our surroundings. But sometimes even the best systems can go awry, as hay fever demonstrates so clearly.

The symptoms of hay fever – the itchy eyes and runny noses – are a consequence of the reaction of our bodies to pollen in the air. On the one hand, pollen is an alien invader (after all, it’s not a natural part of our body), so you might think it’s a valid target for attack by our immune system. However, it’s a harmless intruder, whose presence won’t actually cause any damage if left alone. So, in fact, there is no real benefit to be had from our bodies mounting an attack against it. Indeed, this is why, for many people, no attack is mounted. (It’s a bit like having both a neighbour’s cat and a poisonous snake wandering into your garden: the cat might not belong there, but at least it won’t do much harm. You’d struggle to feel the same about the snake. It’s a question of knowing which battles are worth fighting.) For others, though, the lack of danger posed by the intruding pollen isn’t recognised by their immune system, and the familiar response I’ve noted above is triggered.

Hay fever is an example of an allergy – the inappropriate response by our body to something that isn’t actually a threat. This inappropriate response takes the form of our immune system over-producing a particular type of antibody – but it is the knock-on effect of this antibody over-production that we really notice. As I mentioned in a previous post, antibodies can summon other parts of our immune system into action. When we suffer an allergic reaction, the overabundant antibodies sound a call-to-arms that triggers inflammation – localised swelling as the white blood cells of our immune system rush in to mount an attack on the perceived intruder. 

Sometimes this over-sensitive response is little more than an annoyance, as in the case of hay fever (though I should note that it’s a significant annoyance for hay fever sufferers); other times, an over-sensitive response can be life-threatening, as in the case of asthma, where the network of tiny tubes that form our lungs swell up, making breathing very difficult. 

It’s not just invaders from outside that can trigger an inappropriate response by our immune system, however. Sometimes, our immune system can turn inwards and start to attack components of our own body, wrongly considering them to be a threat. Such a response is called an autoimmune response. For example, rheumatoid arthritis – the painful swelling and degeneration of our joints – is caused by the white blood cells of our immune system attacking the cells in our joints, as if they were dangerous intruder cells. 

Similarly, a certain type of diabetes, in which an individual’s body fails to control the level of sugar in their blood, is also associated with the misbehaviour of our immune system; in this instance, the immune system attacks a certain type of cell found in the pancreas, the part of the body that manufactures insulin. Insulin is a chemical ‘messenger’, which travels round the body, controlling how much sugar is taken up from our bloodstream. When the pancreas is damaged by attack from our immune system, its production of insulin is impeded and, with it, the vital control of our blood sugar levels.

So what causes our immune system to malfunction in these ways? While we don’t yet understand enough to have all the answers, allergies, in particular, seem to stem from the way the immune system is ‘trained’. It may seem odd to say that the immune system needs to be ‘trained’. After all, our heart doesn’t need to ‘learn’ to pump blood; our skin and nails aren’t educated in the art of growth. But our immune system does need to learn – and one way is for it to be exposed to germs and the like during childhood. Increasingly, however, this isn’t happening. 

As a child, growing up in a relatively rural part of the UK, I spent much of my time outdoors, playing in the garden, or tramping over local fields, and getting exposed to plenty of old-fashioned dirt in the process. Now, however, children spend much of their time in dirt-free zones, slumped in front of the TV, or huddled round games consoles. And this clean living comes at a price: we are seeing a significant increase in the incidence of asthma in countries of the Western world, where children are growing up in increasingly germ-free surroundings. It seems possible that, by being exposed to too sterile an environment, our immune system may not be encountering a sufficient number of potential threats to learn how properly to differentiate between harmful and harmless, and risks becoming overly-sensitive to things that are, in fact, harmless. (This is a possibility set out in the so-called ‘hygiene hypothesis’ – but is something that remains a hypothesis, rather than an irrefutable fact.)

There are also lots of questions around how our immune system fails to ignore ‘self’ – that is, why our immune system wrongly turns against the cells and tissues of our own body. Early in life, our immune system is ‘trained’ to ignore self: those white blood cells (the B cells and T cells that I mentioned in my last post) that recognise self are eliminated. But, for reasons that are still being explored, this process of education clearly isn’t quite enough. Sometimes it seems that the information stored in a person’s genes makes them susceptible to autoimmune diseases; in other cases, environmental factors such as certain bacterial and viral infections seem to be a contributory factor.

Whatever the answers prove to be, it remains the case that we would live in constant peril if we had no immune system at all, as by those with severe combined immunodeficiency (SCID). These individuals have such severe defects associated with their T cells and B cells that they can only survive, without treatment, if kept in a completely germ-free environment, as so heart-wrenchingly demonstrated by the case of David Vetter, whose childhood spent living in a plastic, sterile bubble led him being known to the world as the ‘bubble boy’. The rest of us have a lot to thank our immune systems for – even if they don’t behave quite as intended 100% of the time.

How are bacteria and viruses different?

In my last post I discussed how our bodies protect us from the threat of attack from our surroundings. Two of these threats take the form of bacteria and viruses. But is there any major difference between these two invaders? In short, yes – and we’ll explore what this difference is during the rest of this post.

Let’s start by thinking about bacteria, and how they differ from the cells from which our bodies are made. By contrast with the sprawling metropolis of cells that form our body, a bacterium (we talk of a single bacterium, but many bacteria) is just a single cell. And unlike the cells of our body, which rely on each other for survival, a bacterium is a self-contained living entity. Inside that single cell is all the machinery needed for the bacterium to survive, along with that all-important element of life: a genome; the genome contains all the information needed to instruct the formation of a new bacterium, allowing the continuation of life. A bacterium feeds, grows, reproduces and dies, mirroring our own existence, but at the level of a single cell. However, bacterial cells have distinct differences from other cells, the cells of our bodies included. For example, the building materials used to construct a bacterial cell wall are quite different from the materials that encapsulate each of our cells. These differences are important, as we’ll see a little later.

So what of a virus? In short, a virus is nothing more than a neatly-packaged instruction manual. A bacterium contains its own instruction manual – its genome – but also all the molecular machinery needed to read and make use of that instruction manual: it can use its genome to maintain its own existence (and does so very effectively). By contrast, a virus simply contains a set of instructions – its own genome – but none of the machinery to bring those instructions to life. So how does it survive? Well, in the absence of its own set of molecular machinery, it steals a set from elsewhere – namely, from a living organism like us. When a virus infects us, it hijacks the molecular machinery found in each of our cells; this machinery stops reading the information stored in our own genome, and starts to read the viral genome instead.

When a viral genome is ‘read’ by a cell, two things happen: the cell makes more copies of the viral genome, and more packaging to wrap it in. The virus is basically hijacking a living cell and using the cell as a photocopier to generate multiple copies of itself. So why is this such a problem? In some cases, it isn’t: some viruses infect us without there being any adverse effects – and, indeed, without us ever being aware that the infection has happened. Others, however, are much less forgiving. In some instances, once the hijacked cell has made copies of the viral genome and new packaging to wrap it in, the cell bursts, releasing its newly-built viral cargo, but also killing the cell in the process.

By contrast with viruses, bacteria seem almost to be tame, and certainly don’t hijack our cells to drive forward their existence in the same ruthless way that some viruses do. Indeed, some bacteria are entirely harmless to humans: we have 1.5 kilos of bacteria in our gut alone, which carry out a range of useful functions. Other bacteria are less accommodating, however, and release toxins, substances that our bodies find poisonous. It is these toxins that cause our bodies to react in ways we associate with ‘being ill’ – for example, the bouts of diarrhoea and vomiting that we could all live without.

So how do we defend ourselves against these particularly harmful invaders? The key issue for our own wellbeing is that we want to eliminate the alien intruders without damaging our own cells. A bottle of bleach might well do serious damage to some invading bacteria, but it would do just as much damage to our own cells too. Not an ideal solution. The problem is compounded when it comes to viruses: the ideal solution would be to switch off their means of reproducing – but as that means of reproducing is us – our own cells – we’re left having to find other solutions. The key is to find a way of discriminating between ‘them’ and ‘us’. So what options are there?

I mentioned earlier how bacteria are encased by cell walls that are made from different building materials than those that are used to build our own cells. This is just the kind of difference that can be exploited to our benefit. Some antibiotics – naturally-occurring or man-made chemicals that destroy bacteria – can selectively target and destroy bacterial cell walls (having much the same effect as a sledgehammer on a brick wall) while leaving our own cells intact.

Viruses are somewhat trickier beasts to overcome; as I mention above, if we were to target the machinery they use to reproduce, we’d be targeting our own cells. Instead, we need to find ways of stopping the virus getting into the cell in the first place. Typically, the first step in a virus attacking a cell is its attachment to the outside of that cell. If we can prevent the virus from clinging on to the cell surface, we can stop it from subsequently getting inside to wreak its usual havoc. And this is exactly what some vaccines do: they stimulate the production of antibodies, which essentially act as cellular bodyguards, getting in the way of the virus and its intended target.

We don’t have antibiotics and vaccines to protect us against infection by all bacteria and viruses, but only those that have the potential to do us particular harm, and which could overwhelm our immune system before it had chance to respond. Other bacteria and viruses – the ones that cause us merely some annoyance and discomfort (such as the viruses that cause the common cold) – are removed through the protective action of our immune system, as explained in my previous post.

The eagle-eyed amongst you will have noted an important point above: antibiotics and vaccines attack bacteria and viruses in different ways. This is why there’s no point taking antibiotics to treat a viral infection: the antibiotic just won’t work; they’re designed to do a completely different job. You wouldn’t eat a peppermint and expect it to relieve a headache; equally, you shouldn’t take an antibiotic and expect it to cure a viral infection. So, your GP diagnoses you with a viral infection, don’t think they’re neglecting you if they don’t immediately write you a prescription for an antibiotic; to do so will be of no benefit to you at all. In fact, taking antibiotics unnecessarily can do more harm than good, as I’ll explain in a future post. 

How does our immune system work?

Each day of our lives is a battle for survival against an army of invaders so vast in size that it outnumbers the human population hugely. Yet, despite its vastness, this army is an invisible threat, each individual so small that it cannot be seen with the naked eye. These are the microbes – among them the bacteria and viruses – that surround us every day, and could in one way or another kill us were it not for our immune system, an ingenious defence mechanism that protects us from these invisible foes.

Our immune system is a multi-layered operation, much like the fortifications mounted to protect medieval castles. Our first line of defence – the equivalent of a castle moat – is our skin, a physical barrier that separates the hordes of microbes in our environment from the cells of our bodies that lie beneath. However, our skin does not keep us sealed off completely from our surroundings; indeed, some gaps in our defences are essential for our survival. And two gaps are very obvious: our nose and mouth. 

Every minute of every day we inhale air deep into our lungs. But along with the oxygen molecules we so desperately need come other less desirable particles, including viruses and fungal spores. Fortunately, we have another barrier in place to prevent these less desirable particles getting where we don’t want them. The lining of our lungs is covered by a layer of mucus, which traps many of these particles. Under this layer of mucus lie millions of tiny finger-like protrusions that bend from side-to-side, generating a Mexican wave-like movement that wafts this detritus-laden mucus up and out of our lungs, to be expelled (to put it as delicately as I can) every time we cough up phlegm or blow our noses.

Our requirement for food also leaves us exposed to the threat of invasion, this time via our digestive system. Once again, though, we are primed to defend ourselves. The inside of our stomach isn’t the most hospitable of places: it is highly acidic – perfect for aiding the digestion of food, but not a great place for many bacteria to set up home.

Despite the best efforts of these first lines of defence, however, the most determined invaders succeed in their mission and infect us. But this isn’t the end of the fight as far as our bodies are concerned: when our outer defences are breached a whole army of cells are in place to protect us. These cells are our white blood cells. 

The white blood cells operate as two separate battalions. One battalion is on the constant look-out for any general signs of trouble. In this respect, it acts a bit like a bouncer in a nightclub, who is primed to respond quickly and decisively to any one of a number of general ‘alarm’ signals - be it signs of a scuffle on the dance floor, or signs of inebriation from a late-night reveller. Whenever the alarm is raised inside the body, our first battalion is called to arms, and responds equally quickly and decisively, often simply by ‘eating’ whatever intruder first raised the alarm. 

This approach lacks what one might call any refinement: it is a fairly indiscriminate one-size-fits-all strategy. By contrast, the second battalion acts in a much more specific way, more akin to a group of snipers, each waiting for their particular target. This second battalion has two regiments – the B cells and T cells: B cells police the areas of the body outside of individual cells, including the blood; by contrast, T cells monitor the inside of cells. So how is the specificity of this second battalion achieved?

To answer this question, let’s focus on the B cell. B cells produce special Y-shaped molecules called antibodies. An antibody is like one half of a two-piece jigsaw: its specific shape allows it to recognise – and bind to – something with a complementary shape (just like neighbouring pieces of  a jigsaw fit together because their shapes are complementary). In the case of antibodies, however, the other piece of the jigsaw is a foreign object, such as a bacterium. The binding of an antibody to a foreign particle is one of the general alarm signals that call our first battalion to arms. So, the two battalions of white blood cell work together, with the second ‘sniper’ battalion often helping to focus the activity of the first on a particular invader.

Of central importance to the operation of our immune system is the fact that each B cell produces a uniquely-shaped antibody. Consequently, each antibody will recognize something different. This is important when we consider that our bodies face many different sources of danger, including many thousands of different microbes: we need lots of different antibodies to recognise them all. 

When we get infected by a specific type of bacteria, however, our bodies won’t be facing just one or two cells, but a whole army. We need lots of antibody to tag all of these invaders for destruction – but there’s no way we can always keep in circulation enough B cells to produce all the antibodies we need to destroy all the different microbes we might ever encounter. Instead, our immune system has a clever way of ensuring that large numbers of a particular antibody are only produced when actually needed. So how does this happen?

B cells circulate throughout our bodies in a continual surveillance mission, waiting until they encounter a foreign particle that can bind to their particular antibody (which, at this point in time, is protruding from the B cell like a probe). As soon as recognition happens, the B cell rapidly proliferates, stimulating the production of many copies of its particular antibody, which is now available in sufficient quantities to ‘tag’ many members of the invading army. This rapid proliferation is the reason why it feels like our ‘glands are up’ when we’re fighting infection: these ‘glands’ are our lymph nodes, specific areas around our bodies where B cells accumulate while they undergo proliferation; this accumulation occurs to such an extent that the lymph nodes actually swell.

The ingenuity of our immune system doesn’t end with the way it can detect many different foreign particles: it ‘remembers’ if it has encountered a particular invader before, and responds all the more rapidly (and effectively) if it encounters the same invader again. This memory is exploited by various vaccines, which ‘trick’ the immune system into thinking it is being attacked by a fully-fledged threat (when, in fact, it isn’t). When the body is subsequently exposed to the real threat, however, our immune system can mount a full-scale attack on the invader much more quickly than it could have done if encountering the invader for the first time. Indeed, the priming of our immune system by vaccines is essential to defend us against particularly nasty invaders, which could kill us if the immune system hadn’t already been primed.

This post leaves a number of questions unanswered. For example, is there a difference between bacteria and viruses, and what does this mean for how we defend ourselves against them? We’ll explore these questions in my next post.

How do organisms evolve?

The world around us has been in a state of constant change for millions of years: mountains have been thrust skywards as the plates that make up the Earth’s surface crash against each other; huge glaciers have sculpted valleys into the landscape; arid deserts have replaced fertile grasslands as rain patterns have changed. But the living organisms that populate this world are just as dynamic: as environments have changed, so too has the plethora of creatures inhabiting them. But how do creatures change to keep step with the world in which they live? The answer lies in the process of evolution.

Many organisms are uniquely suited to their environment: polar bears have layers of fur and fat to insulate them from the bitter Arctic cold; camels have hooves with broad leathery pads to enable them to walk on desert sand. These so-called adaptations – characteristics that tailor a creature to its environment – do not develop overnight: a giraffe that is moved to a savannah with unusually tall trees won’t suddenly grow a longer neck to be able to reach the far-away leaves. Instead, adaptations develop over many generations. This process of gradual change to make you better suited to your environment is called what’s called evolution.

So how does this change actually happen? In previous posts I’ve explored how the information in our genomes acts as the recipe for the cells, tissues and organs from which we’re constructed. If we are somehow changing to suit our environment, then our genes must be changing too. But there isn’t some mysterious process through which our genes ‘know’ how to change: if an organism finds its environment turning cold, its genome won’t magically change so that it now includes a new recipe for the growth of extra fur to keep it warm. Instead, the raw ‘fuel’ for genetic change is an entirely random process: the process of gene mutation.

In my last post, I considered how gene mutation alters the DNA sequence of a gene, and so alters the information stored by that gene. If you change a recipe when cooking, the end product will be different. And so it is with our genome: if the information stored in our genome – the recipe for our existence – changes, then we must change in some way too. 

I mentioned above how the process of mutation is random. A mutation may be introduced when an incorrect DNA ‘letter’ is inserted into a growing chain as a chromosome is being copied: instead of manufacturing a stretch of DNA with the sequence ATTGCCT, an error may occur at the second position, to give AATGCCT. But it’s just as likely that an error could have been introduced at the sixth position instead of the second, with ATTGCCT becoming ATTGCGT. Such mutations are entirely down to chance.

And this is where we encounter something of a paradox. Though the mutations that occur in our genes to fuel the process of evolution do so at random, evolution itself is anything but random. So how can we reconcile this seeming conflict?

To answer this question, let’s imagine a population of sheep, all of whom have a woolly coat of similar thickness. Quite by chance, a gene in one of the sheep in the population picks up a mutation so that offspring of that sheep develop a slightly thicker coat. However, the thick-coated sheep is in a minority: most of the population carry the normal, non-mutated gene, and so have coats of normal thickness. Now, the sheep population live in a fairly temperate environment in which a slightly thicker or slightly thinner coat makes little difference to an individual’s chance of survival. So, it’s just as likely that our thick-coated sheep will reproduce – and pass on its mutated gene to the next generation – as it is that the normal-coated sheep will reproduce, and pass on their non-mutated gene. When we look at the population as a whole, we don’t see any real change, as the balance between normal-coated and thick-coated sheep is staying firmly tipped towards coats of a normal thickness. 

However, over a period of years, the climate grows chilly. As this change occurs, the thick-coated sheep – a minority in the population as a whole – find themselves at a distinct advantage. Their thicker coats keep them warmer than their thinner-coated cousins, who find themselves increasingly susceptible to cold-induced disease; in other words, in the population as a whole, the thick-coated sheep have a greater chance of survival. Vitally, this increased chance of survival makes it more likely that they, rather than the thinner-coated sheep, will pass their genes on to the next generation. And so we see the prevalence of the mutated ‘thick coat’ gene increasing as time goes on, and see a greater proportion of the sheep population sporting thicker coats. 

Over time, what started out as a little quirk – a thicker woolly coat – goes from being an anomaly to being the norm, a defining characteristic of a species. When this happens – when a change becomes pervasive – the species is said to have evolved.

Charles Darwin is famed for introducing the world to the process of evolution in his book On the Origin of Species by Natural Selection; what we have seen here is the process of natural selection in action: in a population with different coat thicknesses, environmental conditions are favouring those sheep with the thicker coat. As a consequence, it is more likely that their genes are passed on to the next generation. We’re seeing a random event – the mutation that generated the ‘thick coat’ version of the gene – having a non-random consequence, all thanks to environmental pressures.

This exploration of evolution shows how life is driven by an elegant interplay between the recipe for our existence – our genomes – and the environment in which we live. In biological terms, nothing much happens in a single lifetime: it seems almost as unchanging as a single frame in a film. It is only by playing the film of life through many frames, over many generations, that the real beauty of this interplay is revealed.

What is a gene mutation?

In my last three posts I’ve introduced you to the world of biological information, taking you from the storage of biological information in libraries called genomes, which house information in individual books called chromosomes (themselves divided into chapters called genes), to the way the cell makes use of that stored information to manufacture the molecular machines called proteins.

But what happens when the storage of information goes wrong? If we’re reading a recipe and that recipe contains a mistake, chances are that the end-result of our culinary endeavour won’t end up as it should. And so it is at the level of cells. If the information the cell is using is somehow wrong, the end result will also be wrong – sometimes with catastrophic results.

I’ve mentioned in previous posts how biological information is captured by the sequence of the building block ‘letters’ from which DNA is constructed. The sequence of letters is ultimately deciphered by a molecular machine called the ribosome, which reads the sequence of letters in sets of three, and uses each trio to determine which amino acid – the building block of proteins – should be used next in its mission to construct a particular protein. It should come as no surprise that, if the recipe for the protein is changed – if the sequence of DNA ‘letters’ is altered – the protein that is manufactured will probably contain errors as a result. And if a protein contains errors, it won’t be able to function correctly, just as flat-packed furniture will end up being decidedly wobbly if you construct it from the wrong parts.

Imagine a snippet of DNA has the sequence GGTGCTAAG. The ribosome would ‘read’ this sequence, and would use it as the recipe for building a chain of three amino acids: Glycine-Alanine-Lysine. Now imagine that we alter just one letter in our original sequence so that it becomes GGTCCTAAG. All we’ve done is swap a G for a C at the fourth position in the DNA sequence. However, this change is sufficient to affect the composition of the protein that is produced when the sequence is deciphered: the ribosome will now build a chain with the composition Glycine-Proline-Lysine. 

Surely such a small change won’t actually cause significant problems in a cell, though. Right? Wrong. Amazingly (and perhaps unnervingly) the tiniest error can have really quite significant consequences.

Let’s take just one example. Sickle cell anaemia is a condition that affects the red blood cells of humans.  Red blood cells fulfil the essential role of transporting oxygen from our lungs to all the living cells of our body: they continually circulate through our arteries and veins, shuttling oxygen from one place to another. A healthy red blood cell looks a bit like a ring doughnut (though it doesn’t actually have a hole right through the middle); by contrast, the red blood cells of individuals with sickle cell anaemia become warped into crescent-like shapes (like a sickle, the grass-cutting tool, after which the disease is named). These sickle cells no longer pass freely through our arteries and veins. Instead, they tend to get entangled with each other. As a result, the flow of oxygen round the body is impeded, and the individual afflicted with the disease can suffer breathlessness, dizziness, and sudden pain throughout the body as a result.

So what has this to do with changes in the sequence of a gene? Almost unbelievably, this debilitating disease is caused by just a single error in the sequence of a particular gene. The gene in question (one particular ‘chapter’ in one of our chromosomes, the genetic ‘books’ that make up our genome ‘library’) is constructed from a total of 625 building block letters. Yet, a change in just one of those letters – from the letter A to T – results in the amino acid valine being added in place of the amino acid glutamic acid at a particular point in the protein haemoglobin - the part of the red blood cell to which oxygen actually attaches - as it is constructed from the recipe that the gene spells out. This change is all that’s needed to affect the structure of the haemoglobin, which, in turn, affects the shape of the red blood cell in which it is found, causing it to adopt the distorted sickle shape.

Why do such errors happen in the first place? In short, because cells have to make copies of their genomes – and no process of copying is completely error-free. Almost every cell in our body must possess a full library of biological information – a complete copy of our genome. So, every time a cell divides to produce two daughter cells (when our skin cells divide to repair a cut or graze, or the cells of our stomach lining are replenished, for example) it must first make a copy of its genome so that each daughter cell ends up with a full genome. But as the cell copies its genome – literally letter by letter – mistakes creep in. (If you were to re-type this post without using the delete key as you typed, how many errors do you think there would be in the end result? I’m writing this on a laptop that’s just a few months old, and I can already see that the delete key is the most worn key on the keyboard!) These mistakes are what we call mutations.

Fortunately for us, however, the introduction of errors during the genome-copying process is a rare event: the cells of our bodies do a truly remarkable job of keeping things error-free. Indeed, they copy DNA with an accuracy of 99.999% - this means that only one error is introduced for every 100,000 letters that are copied. That’s no mean feat - and is thanks to a particular molecular ‘editor’ that proof-reads the DNA as it is being copied, spotting errors and correcting them as it reads.

Hiccups in the copying of DNA by our cells are not the only cause of gene mutations: various environmental factors can cause them too. The most prevalent of these is ultra-violet light, a natural component of sunlight – but a component that can cause unwanted changes in the chemical structure of DNA when it comes into contact with our cells. The effect of ultra-violet light on our DNA is the reason why we’re encouraged to wear sunscreens when we’re out basking in the sun: you might think a tan will make you look healthy, but the cost might be the creation of an error in the DNA of some of your skin cells that triggers the formation of a skin tumour. Is that a price worth paying for a few weeks of looking bronzed?

Despite this, gene mutation itself isn’t necessarily a bad thing. Indeed, if mutations weren’t to occur, we’d not see around us the remarkable diversity of life that we do. For gene mutation is the molecular ‘fuel’ for the process of evolution, as I’ll explore in a future post.