Kitabı oku: «Secrets of the Human Body»

CONTENTS

COVER

TITLE PAGE

COPYRIGHT

PRAISE

DEDICATION

INTRODUCTION: SECRETS

GROW

LEARN

SURVIVE

FUTURE

PICTURE SECTION

INDEX

ACKNOWLEDGEMENTS

ABOUT THE AUTHOR

ABOUT THE PUBLISHER

INTRODUCTION: SECRETS

The human body is in the business of keeping secrets. This was never more apparent to me than in the dissection room in my first year at medical school. The cohort of students was divided up into groups of six and we each had our own cadaver, the euphemism used for dead human body. Looking back, there was a great deal of secrecy about the whole endeavour: we were not allowed to know our bodies’ names or their life story (though peculiarly we were later allowed to attend their funeral if we wished). We were not allowed to take photographs. Only medical students and staff were allowed into the room, no backstage tours for curious friends. We were meant to be respectful, which generally we were, although the atmosphere was cheerful. We were not really exploring uncharted territory, after all there isn’t much anatomy left to be discovered, at least not any that I was likely to find with my scalpel and forceps. We were more like a little gang of tourists trying to get to know a new town with the help of a guide book and tour guide, in the form of our instructor Professor Hall-Craggs. And yet we were uncovering secrets: we had views of our cadavers that few people had ever seen before. How many people in your lifetime will see you stark naked? Ten? Maybe twenty? OK, maybe more depending on your job and physique, but most of us keep most of our physical bodies concealed most of the time. For many of us it was our first experience with the intimacy with which we would later have to examine living bodies (I can really only speak for myself, not my classmates, but I had seen very few naked people at age 18). And how many people have seen the inside of your body, with its various anatomical irregularities? Probably none? Perhaps a surgeon? When cutting open a body, whether alive or dead, you get a sense of seeing into a place that no one has seen before, of being privy to a secret.

My group found that our cadaver’s false teeth had been left in and that they had a name engraved on them, I suppose to avoid mix-ups, which must be a concern when surrounded by older contemporaries later in life. It was a shock to think what else we didn’t know about this previously anonymous man. Likewise finding his tattoos. Reminders of the secrets that were kept from us.

We got used to the smell (of chemicals, particularly formalin – not rot or decay) and to the cold slippery texture of the bodies like kelp on a beach in winter. We also got used to the squeamishness that I think we all felt with the gristle and stomach contents and vast quantities of congealed fat. I remember Professor Hall-Craggs running his hands through his hair in exasperation at my continued failure to identify the various parts of the brachial plexus. He had been dissecting all morning and his hands were covered in bits of human, and so a large globule of human fat lodged in his hair, along with a decent amount of formalin and other small bits and pieces. I was amazed and impressed by his comfort with the material of these dead people who had so generously let us cut them up. I thought that my reluctance to really get stuck in and to leave the room at the end of each session with little parts of human in my hair probably accounted for much of my ignorance. I am sure I was right. You can’t be squeamish and be a good student of the human body.

We got used to the strange sight of naked humans among clothed ones day after day. Medicine involves asking people to take their clothes off, to expose their bodies at different points. We do our best to preserve patients’ modesty but if you want to know what’s going on with a person’s body, you need to see it. We were taught two rules of thumb. If you want to examine someone’s abdomen (tummy), you had better expose them ‘nipples to knees’ lest you miss the chest or thigh manifestations of some abdominal pathology. The other rule was ‘if you don’t put your finger in it you’ll put your foot in it’. Meaning that we were not to shy away from rectal exams. It is frequently difficult, undignified and uncomfortable to reveal the secrets of any particular person’s body. The early anatomy classes with our cadavers did a great deal to get us all used to the intimacy needed to examine and diagnose a person.

What I never got used to was the vast complexity of human anatomy. I passed my exams like everyone else. I even went on to teach anatomy at Cambridge for a term. But the sense of how hard it must have been for my predecessors to make the original anatomical discoveries stayed with me. I was doing what they, the early anatomists, had done: cutting up dead bodies. But those plastic models in the doctor’s office? It doesn’t look like that at all. It’s a confusing jumble of tubes and sinews. The question for me has stopped being ‘how is the body put together?’ and is now ‘why is it put together that way?’

The early anatomists – the important Italians, for example: Eustachius, Vesalius, Malpighi – had to dissect, observe and catalogue with no knowledge of what the liver did or what a nerve was for. It is hard to imagine a contemporary equivalent. Perhaps mapping the outer reaches of the Solar System? Though the astrophysicists do not face either the smell of decomposition or illegality of obtaining scientific material that the anatomists did. They were in a very real sense uncovering secrets. Secrets that the church did not want them to know, that many older doctors did not want them to know and that the bodies themselves did not want them to know. No one in Renaissance Italy left their body to medical science.

When I want to feel better about my inability to tell one part of the body from another, I think of Leonardo da Vinci. Possibly the greatest draughtsman that ever lived and one of the greatest minds. A phenomenal observer of the human body in every way. And yet, he never entirely figured out how the heart and circulation worked. This is probably the only human organ whose function you can understand from simple macroscopic inspection. It still works after death to some extent: if you go to the butcher’s shop and buy a beef heart and fill it with water from the tap, it will still pump blood in the right direction if you squeeze it. But even the great da Vinci could not quite work out the order of valves and chambers such is the stringy, fleshy complexity of it.

Andreas Vesalius (1514–64). De humani corporis fabrica libri septum. The last section of the Fabrica is devoted to the brain. Here, the dura mater has been peeled away, exposing the brain with its thin membrane and vessels. Vesalius drew such exquisite charts for his students that he became famous enough that the judges of Padua ensured a steady supply of cadavers from the gallows.

Learning anatomy with the cadavers was a geography lesson: the rivers and mountains of the body all labelled and connected. It was a vast quantity of information. In the foot there are 26 bones. Taken out of the foot and held in the hand, they look like pebbles on a beach: they do not have a particularly discernible function. And yet assembled, you can see that they sit together the way that a stone bridge holds together: in your foot you have a keystone, the navicular bone. A miraculous example of biological engineering. I felt like I had acquired a lot of secret knowledge that first year, and all in Greek and Latin, so it felt doubly secret. I had begun to speak a language that my non-medical friends could not. And if you can draw the chambers of the heart and the valves and label the flow correctly, as most GCSE biology students can, then you’re doing better than the smartest man in seventeenth-century Florence. In studying anatomy you feel like you are approaching a complete catalogue of the secrets of the human body: after all, if you know every road and house and place of interest in London, then you know London right? Of course not. There are other kinds of knowledge that are far more secret.

Doctors are in the business of keeping secrets. We keep them about our patients. All the details of a medical consultation, no matter how mundane, are confidential except in very unusual circumstances. Patients rarely confess to murder or plan to deliberately spread their deadly diseases so, although these potential dilemmas are popular among medical students determined to imagine that their careers will be difficult in exciting ways, the secret-keeping pretty much boils down to not talking about what you heard. Why is this so important? Because knowledge makes us vulnerable in many ways. Secrets must be kept not because they are illicit or shameful but because they can be exploited. Your business competitors, employers, insurers, bank and maybe even relatives are all in a position to exploit knowledge about your body: your fertility, your risk of future illness, your health fears and the limits of your abilities. Medical confidentiality isn’t just about privacy, shame or discretion. It’s about vulnerability to exploitation. That is why this book is not an anatomy book: the secrets we’re interested in lie deeper. Your body is in the business of keeping secrets from everything that wants to exploit it: bacteria, viruses, fungi, parasites, larger predators and, crucially, other people. All these things are constantly probing our bodies, looking for weaknesses and opportunities. We survive by not giving anything away that we don’t absolutely have to. This book is about those secrets, how we keep them and the people who uncover them.

The scientists who study the human body are not stargazers or map-makers, charting the features and dimensions of some territory in ever greater detail. They have to have the mindset of detectives or spies or tabloid journalists: they are digging for things that are deliberately concealed, information of life and death importance to those who keep it and those who seek it. This is what makes the stories in this book so thrilling: they are about stuff we are not meant to know. The important scientific discoveries about our bodies have both the deliciousness of gossip about who slept with who, and the heft of state secrets about where the nuclear submarine fleet is stationed. Let me explain.

There are two things you have to understand if you want to expose a secret. First, that a secret is a thing that is known, but only to a few. Secrets are not simply mysterious things that we can’t explain; they aren’t just obscure facts, or stuff that’s too complicated to understand. They are hidden, deliberately, and they are ‘knowable’.

The second important thing to understand about a secret is that it is a hole in the truth. A missing piece of a jigsaw. We notice secrets in their absence: a non-explanation; a story that doesn’t make sense.

The last secret I was involved in keeping was pregnancy: my son was on the way. Like most people we kept it secret from just about everyone until the 12-week scan. But to keep this secret you can’t just not mention that you’re pregnant. You’ll need to conceal or explain changes in your habits. So if people are watching you closely and consider your age, relationship status, recent weight gain and refusal of blue cheese and booze at the company picnic, they won’t struggle to figure out the missing piece of the puzzle. To keep a secret you either have to lie or conceal a much wider array of facts. Whether you’re pregnant and trying to keep it to yourself, or you’re a government intelligence agency hiding their knowledge of the location of that fleet of nuclear submarines, the tactics must be the same: dissemble and confuse. And the tactics of anyone wanting to discover either secret take this into account: gather as many of the facts as possible until you can see the exact shape of the hole in the truth. Only the secret can fit in that hole. This is how much of biological science works. Using the facts you know to tell a story and then seeing if new facts are consistent with that story and revising it to make them fit.

The human body keeps secrets for the same reason that companies and states and you, as an individual, keep secrets: we live in an environment of relentless competition and exploitation. All of life is exploitation. In most cases this exploitation is about who eats who; occasionally about who eats what. This might sound dramatic if you live in the UK. We don’t seem to be in competition with much of what we eat or at much risk of getting eaten. But we all have an extensive set of defences to prevent us being eaten or exploited. Some of these things are complex behaviours, some of them work at a cellular level via antibodies and the killer cells of the immune system. But without all of them constantly functioning, we would be consumed within hours.

The relentlessness of the attacks on your body becomes clear when a person stops fighting them, even briefly. I used to work in the Bone Marrow Transplant Unit at King’s College Hospital. In order to give someone a new bone marrow (this might be done because they have a bone marrow cancer like leukaemia), you have to kill their original one with radiation and chemotherapy, and this completely wipes out most of their immune system: they lose their ability to make antibodies or white blood cells. Sustaining life without a functioning immune system can be done for a short period of time. Our patients lived in positive pressure rooms, with minimal human contact and sterilised food. Even so they were often overwhelmed by infections and needed almost constant antibiotics and antifungals. They were, for an inexperienced junior doctor, some of the most terrifying patients in the hospital because they had no defence mechanisms of their own. They had to rely entirely on their medical team to keep them well.

We can also see the speed of attack on the defenceless body when you die. You switch off your resistance to being eaten and within hours you start to rot as your cellular immune system packs up and the bacteria take hold. And since your behaviours that should keep you safe – moving out of danger, for instance – also stop working at the point of death, your cat may start to eat you before the bacteria get a chance. Either way, the organisms that consume you have finally been given the break they’ve been searching for your entire life.

Every breath you take is filled with viruses, fungi, bacteria and, in many places in the world, nematode eggs (gut worms and the like). Every surface you touch is coated with other organisms. Every drop of seawater contains over 50,000 viruses. Your body is in constant battle: you endure wave after wave of assault every second of the day. It is in this fight that secrets become a matter of life or death.

So the body is a machine that has evolved to resist enquiry; to be inscrutable and unpredictable to those that would seek to exploit it. Throughout our entire evolutionary history, humans have been bombarded with organisms that would like to know much more about us: the limits of our genes, how fast we can run, the state of our antibodies are all valuable bits of information. Potential mates also want to know how ill you are or how long you’ll live. If you know how far or how fast an organism can jump, or which molecules on your surface its immune system uses to recognise and destroy you, then defeating it becomes straightforward. Much of this information must be concealed for most of the time. This presents a challenge to anyone wanting to understand the human body, but it also presents an opportunity.

Many of our tools for probing the human body at the molecular and genetic level are stolen from other organisms that use them to probe us, or fight their own wars. Molecular biology laboratories might look like they are dominated by high-tech machines, row upon row of gleaming works of precise modern human engineering, but in fact the machines that sequence DNA or screen for cell surface markers or identify different biological molecules in different cells are entirely dependent on ancient biological materials: antibodies, enzymes and genetic fragments. The only way we are able to do genetic engineering is because bacteria and viruses have spent millions of years figuring out how to manipulate and exploit our cellular machinery to help them reproduce: they are the original genetic engineers. We could never design a DNA-polymerase enzyme – probably the most important single component of the genetic revolution – on our own. We have co-opted bacteria and viruses to be our double agents to make us stronger.

There are other barriers to discovering the secrets of the human body. If the route to uncovering a secret is through understanding what is known, and filling in the gaps, this is because the facts can be assembled into a coherent narrative. Those narratives are extremely hard to assemble in the case of humans because they played out in ancient history. We have genes that are millions of years old and our human bodies evolved under conditions that no longer exist for many of us. It would be a mystery why we have such an active anti-parasite system if we only considered life in contemporary Britain. But we evolved to co-exist with a vast parasitic burden: gut worms, liver flukes and malaria among many other invaders. An adaptation to resist a disease can only be understood if you know about the disease. Indeed, any aspect of the human body can only be understood in the context of the ecological niche we occupied millennia ago: our food supply, competitors, predators and environmental hazards. The world that we evolved in is largely gone and we face new threats now: old age, car crashes, high-calorie diets, sedentary lifestyles and others. Our bodies are designed to fight the previous battles in the same way that armies, their choices of camouflage, tactics and weaponry, frequently reflect the last war, not the coming one. Our genetic code contains millions of years of alteration through mutation and selection. Each alteration adds caveats and subclauses to our genetic code, like amendments to the body’s constitution: impossible to understand without an accurate knowledge of the circumstances in which these changes became desirable, much as it would be impossible to understand the laws of England without understanding the situations in which they were created. The right to move your sheep across Westminster Bridge, for instance, is unfathomable to the denizens of contemporary London. And yet the law still exists, a remnant of a previous time like some defunct part of our genetic code.

So if we want to understand the human body, we must understand it in the context of evolutionary history. This may seem straightforward: being able to outrun the sabre-tooth tiger (or at least run faster than the person next to you) will allow you to pass on your genes. Adaptations that allowed our ancestors to mate with more people and outcompete our human non-ancestors for food seem like valuable explanations for how we came to be the way we are. In fact the vast bulk of evolution is driven by a more universal phenomenon. The need to fight every organism in every square metre we occupy for what we call ecological capital (but can think of approximately as food and nutrients). Every place on earth only has a fixed amount of ecological capital. Some areas have more than others – the equatorial rainforests with their fertile soil and year-round sunshine have more than the Arctic or Antarctic – but for any given place it is fixed. This means that every kind of life from single-celled organisms to vertebrates is constantly evolving to try to get a little more. And so in order to survive we had to evolve, too. Not just to beat the human living next door, but just to keep pace with the other organisms. This is is the Red Queen Hypothesis. It forms the foundation of much of the work done in Professor Greg Towers’ Lab at UCL where Chris completed his PhD. It was first described by Leigh van Valen, a towering genius who had to count a hell of a lot of fossils to demonstrate he was right. The Red Queen refers to the scene in Through the Looking-Glass in which the chess board changes so rapidly that Alice must keep running just to stand still. It is an almost literal arms race: and no one ever really gets ahead (though quite a few species drop out and become extinct, while other species are created from the changes to take their place).

John Tenniel’s illustration of The Red Queen’s race in Lewis Carroll’s Through the Looking-Glass: ‘“A slow sort of country!” said the Queen. “Now, here, you see, it takes all the running you can do, to keep in the same place. If you want to get somewhere else, you must run at least twice as fast as that!”’ This quotation gave the title to Leigh Van Valen’s ‘Red Queen’ Hypothesis that describes the continuous competition between organisms, where no one species ever gets ahead despite ongoing evolution.

This vast accumulation of ‘improvements’ simply to keep up is not limited to our fight with other organisms. The extent of the complexity of the human body can be seen in a phenomenon described in a Nature paper in 2014 with the seductive title ‘An evolutionary arms race between KRAB zinc-finger genes ZNF91/93 and SVA/L1 retrotransposons’. What on earth does this mean? Well, we have mobile genes in our DNA called retrotransposons. They are old viruses that have inserted themselves into our DNA so effectively that we have inherited them for millions of years. Our bodies cannot be in the business of just replicating viral DNA for free. Otherwise we would become walking virus factories. That’s the trouble with viruses: you give them an inch and they take a mile: these bits of mobile DNA can ruin our useful DNA. So we have developed genes called zinc-finger genes that act to bind to the retrotransposon DNA and stop it replicating. So far, so good. But remember we’re in an arms race. They don’t quit! These retrotransposons are forever adapting and breaking free of the zinc fingers. Over many generations they find a way to start replicating again. And so our zinc fingers expand to suppress them again. Just the way that when the cheetahs get faster to catch the antelope the next generation of antelope get faster too. We are in an arms race inside our own bodies against parts of ourselves. The lovely part of this – which seems on the face of it to be extremely annoying, like a rumbling civil war or secession movement – is that the technologies we develop to suppress the retrotransposons turn out to be useful ways of regulating other parts of our genome. Much in the way that military technologies can often have beneficial civilian uses: advances in aviation and radar and so on. Our internal battles make us stronger.

‘WE ALL CARRY IN OUR BODIES REPTILIAN GENES AND FISH GENES. FOR MOST OF THE ENZYMES WE MAKE, WE HAVE THE SAME SET OF GENES AS FISH.’

SUSUMU OHNO

This is one of many examples of the vast complexity of our genome, which contains so much of our ancient past, and it creates a kind of fog of war. Complexity is an excellent way of keeping secrets.

There is a detailed explanation of DNA and the nature of our genome on pp. 130–3. But it is far from a simple blueprint. When it was decoded (one of the few vast public projects that arrived on time and under budget) it seemed we were on the brink of some new moment in science. We had finally been given the keys to the kingdom. But instead we were presented with further secrets.

The variation in genome sizes is bizarre: the lungfish, a particularly unglamorous and uncomplex vertebrate, has a genome 40 times larger than ours. It is reasonable to ask why ours is so small? (We don’t know.) But it is also reasonable to ask why it is so much bigger than it apparently needs to be? We have vast quantities of genetic material that doesn’t code for proteins. It doesn’t seem to do anything. It is reasonable to suggest that these sequences may have a function … but that it is a secret. But in 1972 it was written off as ‘junk DNA’ – a term coined by Susumu Ohno, one of twentieth-century America’s greatest scientists.

Susumu Ohno was a Japanese-American geneticist, and was said to have ‘thought at least half of the thoughts’ that form the basis of modern genetic research. He was showered with prizes and honorary degrees for his work on genetics and on his death in 2000 the Emperor of Japan sent his family condolences, a rare honour. His brilliance is not in question but he seemed to have an impish sense of humour. It may be that he used the term ‘junk DNA’ facetiously: he certainly seemed to believe that there were secrets locked up in our genes that might only be revealed in unusual ways.

In 1986 he gave an interview to the Chicago Tribune about his attempts to convert the human genetic code into musical form so that the vast repetitive sequences of code could be experienced in new ways. Whether or not this shed any truly useful light on the secrets of the genome, it does force you to encounter the rhythmic, repetitive nature of the code of life, and his arrangements have a surreal beauty that is hard to deny. In the same interview, he said the following: ‘It is surprising that our ancient genes are not expressed more often. I think it’s possible that babies sometimes are born with tails. But the surgeons just snip them off, and we never hear about them … we all carry in our bodies reptilian genes and fish genes. For most of the enzymes we make, we have the same set of genes as fish.’

There is no medical conspiracy to conceal the tails we are born with – or if there is, I’m out of the loop – but it’s a great line from a revered scientist and captures the bizarre accumulated nature of what is sometimes described as a conventional blueprint: the instructions to build a human. Our genome is more like the instructions to build a human, and also the instructions to build a ton of other ancient equipment and viruses, and also the instructions on how to prevent anyone using the wrong sets of instructions.

So it seems like it’s not junk – the bundles of DNA allowing for complex evolution keep the secrets of our past. Even once we have the entire code in a computer database, as we do now, we barely understand its functions. This is also why this book is not an anatomy book: you can have a lot of facts, in this case all the facts, and still they can conceal secrets.