Secrets of the Human Body

Secrets of the Human Body Andrew Cohen Xand van Tulleken Chris van Tulleken 206 bones. One heart. Two eyes. Ten fingers. You may think we know what makes up a human. But it turns out our bodies are full of surprises.What makes tears of joy different from tears of sadness?Why is a gut feeling so much smarter than you think?And why is 90% of you not even human?You may think you know the human body – heart, lungs, brain and bones – but it’s time to think again. Your body is full of extraordinary mysteries that science is only just beginning to understand. This book, which accompanies a major new BBC TV programme, turns your knowledge of the human body on its head. Leading us through all of these revelations are stories of everyday miracles – the human stories that bind every one of us together through the universal stages of life. From the most extreme environments on Earth, to the most extreme events, we reveal the extraordinary abilities every human shares.Combining cutting-edge science with cutting-edge technology, we see the human body like never before. Featuring pioneering specialist photography, a new generation of digital effects will allow us to catch a tantalising glimpse beneath our skin, leading you to discover the secrets that make every ordinary human body … extraordinary. COPYRIGHT (#u3f9220c5-8be7-54af-b6f1-a8d42e9a2529) William Collins An imprint of HarperCollinsPublishers 1 London Bridge Street London SE1 9GF WilliamCollinsBooks.com (http://WilliamCollinsBooks.com) This eBook first published in Great Britain by William Collins in 2017, 2018 Text © Andrew Cohen, Chris van Tulleken and Xand van Tulleken 2017 By arrangement with the BBC. The BBC logo is a trademark of the British Broadcasting Corporation and is used under licence. BBC logo © BBC 1996 The authors assert their moral right to be identified as the authors of this work. Cover photograph © Sciepro/Science Photo Library All rights reserved under International and Pan-American Copyright Conventions. By payment of the required fees, you have been granted the non-exclusive, non-transferable right to access and read the text of this e-book on-screen. No part of this text may be reproduced, transmitted, down-loaded, decompiled, reverse engineered, or stored in or introduced into any information storage and retrieval system, in any form or by any means, whether electronic or mechanical, now known or hereinafter invented, without the express written permission of HarperCollins. Source ISBN: 9780008256562 Ebook Edition © May 2018 ISBN: 9780008256555 Version: 2018-05-02 Praise for Chris and Xand van Tulleken: ‘The van Tullekens are the pin-up doctors at the forefront of HIV research, medicine in war zones and the Ebola epidemic. They’re so warm and likeable that they’ve made roughly 20 TV shows between them in the past ten years. Proving that smart is indeed the new sexy, both van Tullekens are highly qualified doctors researching and treating infectious diseases, while their shows tend to involve hair-raising, death-defying or body-hacking challenges – all carried off with inexhaustible good humour in the name of science. Indeed, their bucket list is as short as Chris’ stubble: to date they’ve trekked to the North Pole, shoved spikes through their tongues and even won a BAFTA.’ Evening Standard To Kit and Anthony. For both the nature and the nurture. To Dinah. For the chromosomes and the hard yards you’ve put in with me and with Lyra. To Lyra and Julian – From your Dads and your Uncle Dads. Xand and Chris van Tulleken For my Mum and Dad, Barbara and the very much missed Geof Cohen. I couldn’t have asked for more loving parents to help me grow, learn and survive. Andrew Cohen CONTENTS COVER (#ue4cc4b15-41e8-51ab-bc92-c132076d7ebf) TITLE PAGE (#u937df199-83cd-58fd-8ae8-cd2cf065de90) COPYRIGHT PRAISE (#u67f978c7-1acc-5617-a0da-0b19b55a97f9) DEDICATION (#ud5c360f8-1786-5dca-810c-9debdac97823) INTRODUCTION: SECRETS GROW LEARN SURVIVE FUTURE PICTURE SECTION INDEX ACKNOWLEDGEMENTS ABOUT THE AUTHOR ABOUT THE PUBLISHER INTRODUCTION: SECRETS (#u3f9220c5-8be7-54af-b6f1-a8d42e9a2529) 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. This book is arranged around three themes: learning, survival and growth. There is a chapter devoted to each. Every aspect of the human body is shaped by the need to achieve these things. Human bodies, like all organisms, have one central job: to ensure the survival of their genes. Learning, growth and survival are all vital to achieve this goal. Counterintuitively, these three tasks may be even more important than reproduction. Reproduction is a useful but not essential task for gene survival: you don’t need to reproduce to ensure your genes survive. It helps because it puts more copies of them out there but if you look after your relatives, who share your genes, and help them survive and reproduce you are still giving your genes an advantage over your non-relatives. If you have an identical twin then your sibling will share all your genes, and their children will be – according to any genetic test – your children (my son Julian calls Chris ‘Uncle Dad’ and occasionally just ‘Dad’). But you can’t be any use to your family members unless you have managed to grow, learn and survive. These, the secrets of the human body, are the secret ways in which we all achieve these things in spite of the thousands of things that try to stop us every second of every day. Growth, learning and survival are interconnected: they are each part of a complex network of processes and forces that make us who we are. And they cannot happen independently. As we learn, our bodies grow and our survival is predicated on our ability to learn from threats and to learn how best to exploit our ecological niche. Learning is not simply the acquisition of facts and memories. The ‘Learn’ chapter is about the incorporation – the literal embodiment – of the physical and social world into ourselves. Ulysses, in Tennyson’s poem, reflects on his life and his worn-out body and his future: I am a part of all that I have met; Yet all experience is an arch wherethrough Gleams that untravelled world whose margin fades Forever and forever when I move. There is an ambiguity here: our bodies imprint themselves everywhere we go and our lives are incorporated into us. We shape the world as it literally shapes us. Our brains lay down our experiences not through some ineffable neural magic but with visible layers of fatty myelin – white matter – coating our nerves. In the ‘Learn’ chapter we will see how scientists are now able to watch our memories – or the proteins that write them in our brains – travel the length of neurons to be stored for retrieval. And we will see how we can track the timing and locations of our short- and long-term memories: the different processes by which we transiently remember a name at a party and store the feeling of our first day at school for the rest of our lives. We will meet unique people, each of them a Ulysses of their own world, exploring and pushing the boundaries of human experience: Danny MacAskill, the uniquely skilled cyclist; Deb Roy, the scientist with (surely) the largest home video collection in the world; Akash Vukoti, the youngest ever participant in the US spelling bee championships with a vocabulary that would shame most adults; Henry Molaison, the man who lost the ability to make new memories. These people in these stories will show us how our brains and therefore our selves are shaped by what we learn. Ulysses describes experience as an arch, a robust yet delicate structure built of the world through which we travel. Our bodies are literally built of our experiences. They learn and adapt to the untravelled world that faces all of us: our bones are shaped by the forces we experience: in the ‘Learn’ chapter we will meet astronauts and tennis players who are broken down and rebuilt by microgravity or the repeated impact of ball and racket and we see how the world writes itself upon us. Like Ulysses we never stop moving or changing: our bodies are designed to learn from experience and adapt to threats we can have no knowledge of until we meet them. Our ability to learn is what allows us to move into the untravelled future: I may never ‘drink delight of battle with my peers, far on the ringing plains of windy Troy’, but we are all constantly learning to overcome the particular challenges life throws at us. And don’t worry, you can teach an old dog new tricks: we will see Chris valiantly attempting to prove this as he goes up against an 8-year-old in a juggling competition. Parts of growth are about learning: we grow stronger, or we grow tougher in certain ways as we learn from the environment. But the growth chapter centres around the most striking aspect of growth: a typical human will increase its size by over 20 times from birth to adulthood and this vast increase must occur without interrupting learning or jeopardising survival. Growth is extraordinarily energy expensive and most of this energy in the early and most rapid phases of growth comes entirely from breast milk. Breast milk is the only stuff on the planet that has evolved specifically to feed humans, it has determined our ability to grow through our entire evolutionary history and yet we have only just managed to understand the role of its main ingredient. We will meet one of the tallest families in the world and through them examine what drives us upwards, what advantages and disadvantages it might confer, and see the extraordinary mechanics of growth, the architectural equivalent of building a miniature building and then expanding every part of it over the course of 20 years while constantly improving its function. This remarkable growth occurs in two spurts during childhood and adolescence, and we will see how the demands of growth must be balanced with the immediate demands of learning and survival. But even once we have reached adult size we do not stop growing. We will meet Lew Hollander who, at 87 years old, is still competing in Iron Man triathlons and making demands on his body that require new growth. We will see how he forces us to consider the role of wear and tear in stimulating growth and the way in which the body never stops growing. The fact that we never stop growing – that our cells have the ability to divide trillions of times – provides an enticing opportunity: the possibility of human growth without a complete human body. We will meet Professor Harald Ott who is growing human hearts in his laboratory. If he succeeds it will be an almost unprecedented milestone in the history of medicine, and we will see how much his work relies on one of the most important but uncelebrated parts of the body: the extracellular matrix. This is a lattice of proteins and sugars that tells dividing cells where to sit and what to do. It binds us together so that we are not simply slime. We will see how the architecture of the heart allows it to pump blood so efficiently and unfailingly as it grows and also see how the forces that the heart itself generates are essential in its growth and function. Learning and growth are fundamental to our survival and to the survival of our genes, allowing us to repair damage, reduce threats and learn from previous encounters to interact with our environment in a more sophisticated way, and the ‘Survival’ chapter presents the challenges of doing this. Why must we learn and why must we grow? Because we are so delicate. Because we are unable to withstand even the smallest changes to our internal environment. But we need to have innate mechanisms to protect us from the vast variability in the world because there is so little margin for error and we need ways of incorporating this variability into our behaviour and reactions to threats. We begin the chapter with Chris witnessing the moment of conception in a Harley Street IVF clinic. The miracle of this moment is almost overshadowed by the miracle of human homeostasis: our ability to keep our internal environment constant in almost every way. That cell will not change temperature, pressure, acidity, oxygen concentration or anything else until its owner dies. And at least one of its owner’s cells will endure in that same environment indefinitely as long as they have a direct line of descendants. Of course scientists are rarely happy to simply agree that the internal environment of the human body is pretty consistent. They want to see just what it is possible to endure in the way of external changes. And so Chris and I went to Professor Mike Tipton’s extreme physiology lab in Southampton, where we were taken on a journey from the high Arctic to the desert to see just how much temperature variation our bodies could handle. It is easy to imagine as a modern human that we live our lives in rational ways, our decisions based on education and experience. We have brains developed to cope with very different times, and parts of our brains are very old indeed. We will see how the more recently evolved parts of our brain govern the older, more instinctive, parts of our brain. We live in a delicate balance with emotions like fear and disgust that serve to protect us but simultaneously can potentially disable us. Disgust is particularly complicated. It is our least-considered emotion, but most of the time our disgust sensors are turned up full volume. Just occasionally we have to turn them off entirely, to reproduce or eat. Chris and I encounter the most disgusting meal we have ever eaten and realise that food and sex are linked in ways you might never imagine (… and might prefer to continue not imagining for the sake of both your love life and your dinner table). We tour through fear: experiments we are no longer allowed to do show how our bodies fine-tune our sense of what to be afraid of. And we learn about the one thing we are all born frightened of and what happens if you completely lack the capacity for fear. This book isn’t just a catalogue of the intriguing or miraculous. We want to show you the secrets to the way that the human body is interrogated, the way in which it gives up information agonisingly slowly and reluctantly. Much of writing this book, and making the accompanying television programme, felt like bring-your-child-to-work-day. Chris and I got to be naive and to ask simple questions of amazing people. Questions like ‘why does it do that?’ and ‘why is it made that way?’ are the sorts of thing children ask but when you pose them to the world’s best scientists you get extraordinary answers. We were able to arrange absurd scenarios like having the most disgusting dinner party with a scientist we had only just met and persuaded colleagues to torture us to make a point about homeostasis. We got to watch a baby get made. Why isn’t this just a textbook? Because this mad cascade of events and facts needs meaning. We wanted to give you a way of thinking about yourself, and to let you in on some of the secrets that your body has been keeping from you. ONE (#u3f9220c5-8be7-54af-b6f1-a8d42e9a2529) GROW (#u3f9220c5-8be7-54af-b6f1-a8d42e9a2529) BABY TO BABY-MAKER The simple process of growing is an extraordinary thing. During a lifetime our growth rate is truly staggering: from starting out as a single fertilised egg at the moment of conception, we multiply into a mass of trillions of cells made up of over 200 different cell types organised into around 80 organs (the exact number depends on how you define an organ … not as straightforward as you might think!), and that’s before we are even born. At birth the average human weighs about 3.5 kg and is approximately half a metre in length from head to heel. On our journey from baby to adult we then go through an amazing transformation: we quadruple in height. We add, on average, 70–80 kg to our body weight, although far more than this is increasingly common. At our fastest rate of growth we can elongate by up to 1.5 cm in a single day. It’s a process that we hardly notice but exploring how, why and when we grow reveals an extraordinary secret inside our bodies, which ultimately leads to a transformation that every one of us goes through. In this chapter we will explore the latest understanding of that process of growth and the magic ingredient that fuels it through the beginning of our lives. We will uncover the mystery of human childhood, a childhood longer than any other creature on earth, and explore the mysterious moment that triggers the body of a child to suddenly transform itself into an adult. We will also discover that growing doesn’t just end at adulthood, because throughout our lives our bodies are endlessly replenishing and regenerating, and even in old age, in some ways, we still continue to grow. We are now using this knowledge at the very cutting edge of medical science to redefine our perception of human growth by learning how to replicate it, control it and ultimately build new human organs and tissues grown entirely in the laboratory. I was born at 13.45 on 18 August 1978 with Chris taking an extra seven minutes to emerge into the welcoming arms of a midwife at the Queen Charlotte Hospital in London. At birth I weighed in at 6 lb 12 oz (3.06 kg) with Chris a slightly chubbier 6 lb 14 oz (3.12 kg). Thirty-nine years later and the vital statistics have not played out in my favour. Chris is not only an entire half an inch taller than me at 6 ft 1 in (185 cm), but he is also from the last available records approximately 5 kg lighter than me as well. Small differences to you perhaps but when you’re an identical twin it’s these differences that really matter! But the changes in our height and weight are just two of the miraculous transformations that we have gone through over the last 39 years. Each one of us sees our body transform throughout our childhood and beyond under the influence of a multitude of different factors, a complex web of genes and environment that combine together to turn a baby into a baby-maker. As we’ll see in the ‘Learn’ chapter, the transformation of our brains from newborn to highly skilled adult is a miraculous journey of its own, but our bodies undergo an equally extraordinary transformation. The size, shape, strength, appearance and function of our bodies are completely altered through those first 18 or so years of our lives. It’s such a gradual process that until we compare young and old photographs we often miss just how comprehensive and extreme a physical change this is. To put the extraordinary nature of this process into a slightly different context, just imagine attempting to build a machine that has such an inherent ability for self-transformation in both its structure and function, adapting constantly to the demands made on it. In engineering terms it would be a plane strengthened by turbulence, a car that got faster the more you drove it and used less fuel per mile, a computer that got quicker and more accurate with age. On top of that these machines would be able to fuel and reproduce themselves. As we will see in this chapter, attempts at bioengineering reveal just how superb and precise a designer nature is compared to even our most impressive innovations. For most animals on the planet the journey to maturity is a quick and efficient process. Many mammals, including dogs and cats, reach adulthood within six months of birth, blue whales (the largest animals on the planet) are able to reproduce as quickly as five years after birth and our nearest cousin the chimpanzee completes its journey to maturation years ahead of us, being fully grown, sexually mature and reproducing on average by the age of 13. It seems an elongated childhood is a uniquely human process. No other animal on the planet takes longer to reach maturity and no other animal goes through such a convoluted stop–start process of growth and development than a human child. In many parts of the developed world the average age of a first-time mother is well into her thirties. Many of the reasons behind this elongated adolescence are of course cultural, heavily influenced by the way we structure our societies and the growing balances between the lives of men and women. But underneath the social influences there is an intriguing biological story with mysteries that we are still trying to understand. Why, for instance, do we have two discrete growth spurts, one just after birth and one on average more than 10 years later, just before puberty? What is the reason for this elongated lull in our growth? And what triggers the sudden onset of puberty? All of these are questions that until very recently we have struggled to answer, but in the last few years many of the secrets of the journey from baby to reproduction are beginning to be revealed. SELF-REPLICATING MACHINES A quick interesting side note while we are talking about this is that the concept of self-replicating machines has a long history in both fact and fiction with perhaps the most famous being devised by the Hungarian mathematician, scientist and general genius John von Neumann. Von Neumann machines that could explore and colonise whole galaxies have been the subject of much conjecture for decades and the fact we have never found one has been used by some as evidence that advanced civilisations are absent from this and perhaps every other nearby galaxy. MIRACLE MILK There is only one substance on earth that is specifically produced as a nourishing food: milk. A few fruits have evolved to be palatable, persuading animals to eat them and distribute seeds in faeces, but these are just sweet-treats. And yes, we can extract nutrition from animal flesh and a handful of plants and fungi, but our relationship with these foodstuffs is more complex, more competitive. They didn’t evolve specifically to be food. Milk, and only milk, did. Breast milk is what makes mammals, mammals. There are other characteristics that most mammals share but the platypus, and a few of its Australasian friends, mess things up, with their egg-laying and lack of placentas. But even the platypus makes milk. Milk is extraordinary stuff. It is, most obviously, a complete source of nutrition. It contains fat, protein, carbohydrate, water, vitamins, minerals, amino acids and fatty acids, all in an available form, tailored perfectly to each stage of development. You can build a human child for several years entirely on breast milk. But it’s not just food. It also contains an immune system in the form of antibodies, and a cocktail of hormones and other factors that regulate and stimulate infant development. And far from being a single substance, it is constantly changing, as the child grows, between left and right breast and throughout the day. Even within a single feed the milk shows complex fluctuations in what it contains in terms of lipids, carbohydrates and total calories. Milk composition. Note how much more protein there is in cow’s milk and how much less HMO mass. Breast milk is made when a set of genes are turned on in the cells of the mother’s breast during pregnancy. These genes encode proteins, including the enzymes that turn the mother’s body into the end product. The genes for milk production have been selected by evolution over around 150–200 million years since the first shrew-like creatures gave their young primitive breast milk from barely modified sweat glands. Yes, for all its erotic and maternal associations, the breast is a modified sweat gland. It’s impossible to know what that first milk, produced somewhere around the late Jurassic era, would have consisted of, but considering that modern shrews can barely get enough calories to sustain themselves for more than a few hours, that early milk may have been more about the transfer of antibodies, to fight infection, than calories. THE COST OF A PINT OF MILK For Bruce German, a chemist at the University of California, Davis, milk was the obvious starting point to understand nutrition. Nutritional science made a few huge leaps early in the twentieth century, before stalling around the 1970s. It had been established that to stay alive, we need three macronutrients (carbohydrate, protein and fat) and all but invisible amounts of a few vitamins, minerals, amino acids and essential fatty acids. Biochemists figured out the chemical reactions that are required to turn what we put into our mouths into flesh and energy. They discovered the enzymes that enable these reactions to happen. They described how the molecular constituents of our cells are recycled and replaced in response to the world around us. But the ideal human diet continues to elude detailed description. There are some broad brushstrokes that we’re confident about: eat lots of plants. Meat seems to be OK in small amounts. Fish is good. Refined sugar may be bad. But dig a little deeper and confusion reigns: saturated fats were bad, then good, then bad. Oily fish, vitamin supplements, low-carb vs. high-carb? These questions still generate inconsistent answers. A MOTHER WILL, ON AVERAGE, MAKE ABOUT 750 ML (ALMOST A PINT AND A HALF!) OF BREAST MILK PER DAY FOR THE FIRST FIVE MONTHS AFTER BIRTH. ‘Milk offered the opportunity to take an evolutionary perspective. What food should we eat?’ says Bruce. It’s worth saying that there is a lot of bad science based on an evolutionary perspective. It usually involves scientists discovering something about the way people behave towards their mates, friends or enemies and then inferring causality from hypothesised ancestral sabre-tooth tiger encounters. This is often not very useful because we don’t understand much about how we used to interact with sabre-tooth tigers (probably very little). Bruce German and his team at UC Davis do not involve sabre-tooth tigers in their evolutionary perspective. They study the genes, enzymes and constituents of milk. Not all genes in the human body are treated equally by evolution. There are many ancient genes that remain stable, barely changing over long periods of evolutionary time. But the genes involved in breast milk production have been under intense evolutionary scrutiny since it first evolved. Because while milk is great for the offspring, it’s pretty bad for the mother. This is because it is massively expensive for her to produce. And this was the reasoning that the team at UC Davis started with: human breast milk has evolved to be perfect nutrition for a human infant but it needs to be extremely efficient because it is so costly for the mother. How costly? A mother will, on average, make about 750 ml (almost a pint and a half!) of breast milk per day for the first five months after birth. This will gradually increase with demand to almost a litre a day if exclusive breast feeding continues, assuming the mother is herself well-nourished and hydrated. As drinks go it is rich in energy containing around 65 calories per 100 ml. Unsurprisingly this is about the same as whole milk from a cow. By comparison a sugary cola drink will have about 40 calories per 100 ml. The cost to the mother is immense. She will produce milk by breaking down her own body. Even if milk was made 100 per cent efficiently, it would still be a huge number of calories stripped from the mother, but to calculate the true cost you have to first work out the efficiency of milk production. And it’s not a trivial calculation. Experiments have been done all around the world using isotope labelled water, special metabolic chambers and biochemical calculations about milk composition. Estimates vary, but 1 calorie of milk takes about 1.2 calories of energy from the mother. All this adds up such that, on average, exclusively breast feeding a 6-month-old child will demand a large burger’s worth of energy from the mother each day. And I mean a proper 650-calorie burger. So that’s with bacon. And cheese. For the vast bulk of mammalian evolution, obtaining this amount of energy came at a huge cost. It costs the mother her own body, but there is also the evolutionary cost of the risks required to obtain nutrients. Foraging isn’t just exhausting, it increases the risks of being eaten (but probably not by sabre-tooth tigers). All this told Bruce and his collaborators two things about breast milk. Firstly, since you can grow a healthy human for many years exclusively on breast milk, it will have everything that a baby needs. Secondly, there is not likely to be anything in it that the baby doesn’t need. From the moment the earliest mammals started producing milk, any mothers that wasted energy on putting unnecessary stuff into it would have quickly been plucked out of the gene pool. The solid components of milk that cost the mother most of the calories by order of amount are 1) fat; 2) sugar; 3) complex chains of sugar molecules called Human Milk Oligosaccharides or HMOs; and 4) protein. Each of these must be of absolutely vital importance to the infant. But here’s the bizarre thing. The third largest solid component of milk, those Human Milk Oligosaccharides, are totally indigestible by a human infant. More than bizarre, it seems absurd. In the words of Bruce German, ‘the mother is expending tremendous amounts of energy to produce these varied and complex molecules and yet they have no apparent nutritional value’. Human Milk Oligosaccharides are chains of sugar molecules. To put that in context it may be useful to understand a little about different sugar molecules. Monosaccharides are single molecules, usually rings of carbon with a few hydrogen and oxygen atoms added on. Glucose is a familiar example. As a single molecule, it can be absorbed into cells and used for making energy without any breaking down in the gut. Disaccharides are made of two molecules. The white refined sugar in your kitchen is a disaccharide called sucrose, made of a glucose molecule joined to a fructose molecule. The chemical bond that joins the two molecules needs to be broken down by enzymes in your gut before you can use the individual sugar molecules for generating energy. Polysaccharides are long chains of 200–2,000 sugar molecules. They’re often indigestible, like cellulose. Oligosaccharides sit in the middle. The ones in breast milk are branched chains of between 3 and 22 sugar molecules with unhelpful names like di-sialyl-lacto-N-tetraose and lacto-N-fucopentaose V. There are around 200 unique and different types of oligosaccharide in human breast milk, each with different sugar molecules joined together in different chains. Crucially these all need different enzymes to digest them. And humans have none of them. We know that because, in the words of Bruce, if you feed a modern American child human breast milk, ‘the HMOs come out the other end’. So why is there the same amount of these totally indigestible oligosaccharides as there is protein in human milk? To feed bacteria. In fact, to feed a single bacteria: Bifidobacterium infantis. BUG FOOD The idea that the HMOs might be present to feed bacteria rather than humans is an old one. Over a century ago paediatricians, microbiologists and chemists were already trying to understand the health benefits and constituents of breast milk. In the last part of the nineteenth century in Europe and America one in three children died before the age of 5, but it was clear that the chances of survival were higher for breast-fed infants. By 1900 Austrian doctors and scientists had detected differences in the bacteria found in the faeces of breast-fed compared with bottle-fed infants, a remarkable achievement considering the technology of the time. As early as 1888 sugars other than lactose were identified as being in milk, and by 1926 it was reported that there were factors in human milk to promote the growth of a genus of bacteria called Bifidobacterium, but the extraordinary details of the relationship between human mothers and these bacteria took almost another century to determine and required huge advances in genetics and microbiology. THE HUMAN MICROBIOTA Estimates for the total number of bacterial cells found in association with the human body have varied between 10 and 1.5 bacteria for each and every human cell. The total number of bacterial genes associated with the human microbiota could exceed the total number of human genes by a factor of 80 to 1. Conservative estimates suggest that an average 70 kg human being is composed of about 30 trillion human cells … and 40 trillion bacterial cells. The human body provides a rich and varied environment for bacteria with different parts of the body hosting very different communities. In the right location the bacteria perform useful functions, but the concept of ‘good and bad bacteria’ is simplistic. The crucial thing is to have the right bacteria in the right place. Mouth bacteria on a heart valve are bad. Gut bacteria in the urinary tract are bad. There are a wide range of Bifidobacteria species but they all have a bifurcating shape under a microscope. Aside from that, distinguishing them all is not easy. Starting with the hypothesis that Human Milk Oligosaccharides would nourish them, Bruce German, together with David Mills, a microbiologist, started testing different bacteria, including multiple Bifidobacteria species, to see if they could be cultured in the laboratory using Human Milk Oligosaccharides as their only source of food. Surprisingly initial tests showed very unenthusiastic growth by any of the species tested. They seemed to lack the enzymes necessary to digest the wide variety of sugars in breast milk. But then the team tested B. infantis, a bacteria first isolated from the stool of a breast-fed infant, and it flourished. If digesting HMOs required a single enzyme, then this ability could be put down to coincidence. Perhaps B. infantis had evolved to digest similar molecules in other environments. But digesting HMOs requires a vast toolkit of genes. B. infantis, and only B. infantis, has them all. An analysis of the genome of the bacteria revealed over 700 unique genes compared to other Bifidobacteria. These include genes for grabbing the HMOs and taking them inside the cell, as well as a series of enzymes able to break down the full range of linkages between the sugar molecules. They are the only bacteria able to completely break down HMOs and there can be no doubt that they have evolved to do this. More importantly the evidence from other species shows a process of co-evolution. As the bacteria evolved to digest milk so the milk evolved to feed them. In the case of humans, the reason why we produce such a complex range of HMOs must be to specifically advantage B. infantis over other bacteria. So what do we get from the deal? Why do we want a single bug flourishing in our infant gut? The primary reason is probably competition. Human infants are born with a gut that is ostensibly sterile and provides an amazing opportunity for bacteria. It is warm, wet and full of a steady supply of nutrition from food and milk. It is also relatively unprotected by the naive infant immune system. From the moment the mother’s waters break, the baby starts swallowing a range of bacteria. The vagina is full of a carefully controlled mix of bacteria. And what strikes anyone watching a normal vaginal delivery is that the baby is born, face down, into a pile of faeces. It was my job as a medical student to hold a little gauze over the stool, protecting the child and to some extent the dignity of the mother (today, with our advancing knowledge of the microbiome, I wonder if it would have been better not to). Part of the role of breast milk then is to encourage the growth of ‘good’ bugs. This is the most obvious way in which B. infantis protects us: by binding to the cells lining the baby’s large intestine, preventing other, more harmful bacteria doing so. And crucially it seems to bind more strongly when grown on breast milk. It’s not just a matter of outcompeting the pathogens – B. infantis may keep them at bay with secretions. When grown on HMOs it produces short chain fatty acids (SCFAs). These are molecules that have become famous from their beneficial effects shown in adults eating a high-fibre diet, but they seem to be equally important in children. Some of them may directly kill harmful bacteria. Bruce describes this in terms of the concept of a ‘shelf stable baby’; preserved from the inside by the secretions of the friendly bacteria. Other SCFAs like acetate may feed the developing infant brain. This role in brain development may in part explain the huge complexity of the HMO in human milk compared even to our closest chimpanzee cousins. AT THE END OF MY CONVERSATION WITH MARK I ASKED IF HE HIMSELF HAD BEEN BREASTFED. ‘NO,’ HE REPLIED. ‘PERHAPS IF I HAD BEEN BREASTFED I’D HAVE BEEN A SURGEON.’ There is a catalogue of other benefits, too. It’s been shown to be anti-inflammatory, specifically in infant gut tissue when compared to adults. Understanding of the development of the infant immune system is still in its early stages, but Bruce thinks that the specific culturing of B. infantis, and the relative lack of diversity in the infant gut, may be crucial to the development of a mature immune system. In fact he is evangelical about this. He believes that the current epidemic of asthma, allergy and atopic disease in the US may be largely due to the loss of B. infantis from infant guts. B. infantis also seems to reduce intestinal permeability, tightening up the joins between cells. Leaking infant guts may cause sickness directly but also affect the long-term development of the immune system. Evidence for this comes from an extraordinary study in Bangladesh. The dominant species in the stools of the infants in the study was B. infantis and they were 96 per cent breast-fed. The more B. infantis in the stool, the more weight gain and the better the responses to oral polio, tuberculosis and tetanus vaccines. And there are the extraordinary little considerations that B. infantis makes in order to be a good houseguest. Other similar species of bacteria are not directly harmful but they do digest human mucus. When they do this they accidentally produce sugars that are useable by dangerous bacteria. By contrast B. infantis leaves the complex sugars in human mucus intact, starving the pathogens. Just as the early efforts to understand the link between breast feeding and infant health required collaborations between chemists, physicians and microbiologists to make remarkable progress, Bruce German has forged a multidisciplinary team at UC Davis. While Bruce was starting to dissect the chemistry of milk in the lab, neonatologist Mark Underwood, at the UC Davis children’s hospital, was treating and studying children born long before 37 weeks’ gestation. Over 10 per cent of children are born prematurely in the United States and they face a few singular challenges. Inadequate lung development is the most immediate problem, but in the weeks spent in intensive care after birth a devastating condition called necrotising enterocolitis, or NEC, claims many infant lives. In NEC the tissue of the gut becomes inflamed and dies, allowing the contents of the gut to leak into the abdomen, causing massive infection. It affects approaching 10 per cent of infants who are born weighing less than 1,500 g and half of those affected will die. In the decades he has spent caring for premature babies, the death rates from NEC have not changed significantly, but some clues that B. infantis may help to reduce this death rate are starting to emerge. Breast milk improves outcomes in NEC and additionally, a lack of Bifidobacteria seems to increase risk. Neonatal intensive care is a dangerous place to be. Paradoxically this may be because it is too clean, or perhaps clean in the wrong way. Antibiotics and continuous cleaning keep Bifidobacteria at bay, but disease-causing organisms flourish in even the most fastidiously clean units. A trial is just starting at UC Davis but the evidence from other studies shows that administering B. infantis as a probiotic (a dietary supplement containing live bacteria that promotes health benefits) together with human breast milk serving as a prebiotic (a dietary supplement to stimulate the growth or activity of commensal microbes), may help to further reduce the incidence of NEC. Bruce is enthusiastic about the use of probiotics even in term infants and suggested that I give my own child some B. infantis prebiotic. I asked why simply breast feeding wouldn’t be enough. ‘Because B. infantis is extinct in much of the developed world. It’s not a bacteria which acquires resistance easily and particularly in the USA the use of formula milk for multiple generations has simply starved it out of existence.’ Bruce has the infectious enthusiasm required for truly visionary science but I wondered if I was being seduced by his ideas too easily. The genetic case was certainly persuasive that B. infantis had co-evolved with breast milk to be the main colonist of the infant gut. Why else would it have the entire genetic toolkit to use molecules found only in human breast milk, molecules which humans were totally unable to digest? But I wanted a clinical perspective so I asked Mark Underwood for his view. Mark is no less visionary than Bruce but he has the sort of quiet, clinical caution that comes from being a doctor in a speciality where a lot of child patients die. He was no less enthusiastic than Bruce. He believes the evidence stacks up from all sides and he is about to start a trial of giving B. infantis as a probiotic in the neonatal ICU. From the second week of life, I have been giving Lyra once-daily B. infantis supplements sent by Bruce. At the end of my conversation with Mark I asked if he himself had been breast-fed. ‘No,’ he replied. ‘Perhaps if I had been breast-fed I’d have been a surgeon.’ He was being ironic: surgeons may think of themselves as being at the top of the tree, but physicians like to joke amongst themselves that surgeons are mere technicians. But his answer contained an interesting truth. He was a healthy, successful person. It is true that the mother–infant pair are what Bruce calls a ‘powerful Darwinian engine’ driving extraordinary evolutionary change. Together they have co-opted another species as the world’s most effective nanny, supporting brain development and the development of the immune system, as well as fighting pathogens. And loss of B. infantis from our ecosystem may well explain the rise in allergic and atopic disease. But contained in Mark’s answer is the idea that, despite multiple generations of formula-feeding and antibiotics rendering this seemingly vital bacteria functionally extinct, it’s possible to become a healthy professor without it. People continue to live longer and longer. The human body has extraordinary resilience and redundancy; regaining B. infantis in our infant guts may well have wide-ranging benefits, but it is testament to our adaptability that we can survive without it. GROWING UP, UP, UP … When it comes to growing up, the van Kleef-Bolton family from London are world-class. At 6 ft 5 in (195 cm) and 7 ft (213 cm) respectively, Keisha and Wilco are the tallest couple in Great Britain and have only just been knocked off the global top spot, outranked by the lofty Chinese couple Sun Ming, 7 ft 8 in (233 cm), and Xu Yan, 6 ft 1 in (185 cm), in 2016. While Keisha and Wilco are outliers at the far end of the distribution of human height, collectively as a species we have all gone through an incredible growth spurt in the last 150 years or so. Since the middle of the nineteenth century records show that the average height in industrialised countries has increased by about 10 cm. That’s a serious increase in such a short space of time, and as far as we know it is unprecedented. In fact the study of early human skeletons strongly suggests that human height stayed pretty much the same from the Stone Age until the mid-part of the nineteenth century. So what happened around the 1820s? Well, all of the available evidence suggests that this swift increase in height was not driven by any rapid-fire evolutionary selective pressures. The time frame is far too short for evolution by natural selection to play out and there is no reason to think that height has been under particular selective pressure in the last 100 years or so. The environmental influences, on the other hand, seem to track very tightly with the increase in height. We know that if a child is malnourished or suffering from disease at particularly critical moments in childhood, they will never reach their full potential adult height. But since boys stop growing around their late teens and girls in their mid-teens, proper nutrition before puberty is essential to fulfil genetic potential for height. Protein, calcium, vitamins D and A all have an effect on height, and deficiency in all of these nutrients in the early nineteenth century was commonplace. But starting around the mid-1800s the punishing lives of populations through the early years of the industrial revolution began to give way to more widespread benefits, including better sanitation, clean running water and improved nutrition. Slowly this allowed the populations of countries like the UK to start fulfilling the genetic potential of human height. The truth is (as many parents instinctively know) that eating up your greens and drinking your milk really will make you grow up strong and tall. EAT YOUR GREENS PROTEINS During childhood the most important food that influences your final height is protein. Meat, fish, eggs, nuts, legumes and dairy products are all good sources of protein (which is why it is a considerable nutritional challenge to bring children up on a vegan diet). Other minerals, in particular calcium, and vitamins A and D also have a direct influence on height. For this reason malnutrition during the key stages of childhood can have a direct and significant effect on growth. This means good nutrition is particularly important before and around the growth spurts of puberty. For girls this begins around 10 years old and continues until their mid-teens when maximum height is reached. For boys it’s later, with maximum height not being reached until the late teens. The most startling journey from low to high across this time has been made by the Dutch. For the data shows that the average nineteenth-century Dutchman waslooking up enviously at almost all of their European neighbours, but then a dramatic climb fuelled by increased living standards has taken them slowly but surely to the top of the global height charts. Although not without a few blips – both World Wars triggered a reversal in the upward trend in many countries as the availability of resources tightened dramatically. In recent years widespread increase in height has slowed down, stopped or even reversed. This is the case in the United States, where a lack of free health care, and a diet high in calories but low in nutrients, may be the major contributing factors. It is likely that the Dutch are approaching the maximum height their genes will allow. Supplementation with extra vitamins, calcium and protein beyond the recommended daily amounts will not increase gains (and in fact there are large studies showing that excess vitamin supplementation shortens life). BOY HEIGHT PREDICTOR (Father’s Height [cm] + Mother’s Height [cm] + 13 cm) / 2 GIRL HEIGHT PREDICTOR (Father’s Height [cm] + Mother’s Height [cm] ? 13 cm) / 2 But tall people aren’t just tall because they have eaten better as children. Human height is determined by both genetics and environment. Your genes are a hand of cards you are dealt. Your environment is the way you play them. It’s a case of nature via nurture. The major environmental influence on height is nutrition, affected by both diet and disease. Around 80 per cent of the variation in height between people is determined by their genes, and around 20 per cent can be attributed to the environment, although these numbers vary with different populations around the world. You can work out how much of your height has actually been influenced by your parents demanding you clear your plate, and how much was set in stone from the moment of conception. The average height of a man in the UK is around 5 ft 9 in (175 cm). Take me for example. I’m 6 ft 1 in (185 cm) so I’m 10 cm taller than the average. Eight of those 10 cm are determined by my genes (my dad is a 6 ft 4 in [200 cm] Dutchman) and 2 cm by my diet (my mother is, in the words of P. G. Wodehouse, ‘God’s gift to the gastric juices’). I tower over Xand by a full centimetre simply because I listened to mum a bit more. You don’t need to be a population scientist to see that tall parents beget tall children by passing on genes for tallness. In the case of Keisha and Wilco van Kleef-Bolton, this certainly seems to be playing out predictably. They are the proud parents of five children, Lucas, the oldest at 11, is already 5 ft 4 in (c. 163 cm) and towering over his classmates; Eva, 8, is the average height of an 11-year-old; and 4-year-old Jonah is standing shoulder-to-shoulder with boys twice his age. While it’s still a little too soon to judge the newest arrivals to the family, early indications point them to the skies as well: Ezra, the tallest of the 1-year-old twins, is in the 91st percentile, and Gabriel is not far behind. Map showing variation in average adult male height in various nations across the world. But we don’t really need to wait to see roughly how tall any of their children will be. Since the 1970s we’ve been using a rough and ready formula to predict the eventual height of offspring with nothing more than just the parents’ measurements. By simply adding the height of two parents together, adding 13 cm to the sum of the two numbers for boys and subtracting 13 cm for girls and then dividing the result by two (see here), you end up with a pretty good estimation for the height of the children. So in the case of the van Kleef-Boltons, the boys would be expected to be 210.5 cm, and the girls 195.5 cm. This is not, of course, a precise calculation, but its rough reliability does indicate that height is a trait that is significantly inherited. That doesn’t mean there is a single gene for height; very few traits have a direct one-to-one relationship. Instead your height, like many other characteristics, is controlled by a multitude of genes interacting with a multitude of environmental factors. Average female growth chart from birth to 20 years old: showing from the 3rd to the 97th percentiles. We now know that in the case of height your genes are about 80 per cent of the story in determining how tall you and your children will be. The reason we know this with such accuracy is because there have been a wide variety of studies that have explored the heritability of human height using a long-established method of teasing out the influence of nature vs. nurture. The principle of these studies is simple. Take a group of identical or monozygotic twins, to use the technical term, like Xand and myself, twins who have developed from a single fertilised egg and so share 100 per cent of the same genes. You then compare a trait such as height difference between each of the identical twins in the group with a group of dizygotic twins, or non-identical twins (or even just siblings) who all share only about 50 per cent of their genes. It is assumed that identical and non-identical twins grow up in equally similar or different environments, so this method of comparing groups of identical and non-identical twins enables you relatively easily to quantify the heritability of a trait. So, for example, in the case of a height study, if it shows that the identical twins are considerably closer in height than the non-identical twins then this strongly indicates that genes play an important role. The actual analysis that can be applied to a study like this, both statistically and genetically, is far reaching and complex but the principle remains the same – the greater the similarity between identical twins compared to non-identical twins, the greater the heritability of the trait. One of the most recent of these large studies conducted by Peter Visscher of the Queensland Institute of Medical Research in Australia looked at 3,375 pairs of Australian twins and siblings and found that the heritability of height is around 80 per cent. Other studies have come up with similar findings, including one that looked at 8,798 pairs of Finnish twins, in which the heritability was found to be 78 per cent for men and 75 per cent for women. Interestingly, similar studies in Asia and Africa have found the per cent heritability to be around 65 per cent or lower, because these regions tend to have populations that are less mobile and so more ethnically and genetically defined compared to the greater genetic homogeneity we see in the west. Regardless of the height you reach as an adult, the journey to get there is not steady, and only now are we beginning to truly understand the extraordinary process behind this rapid growth, a process that is dependent on an intricate interplay between your genes, brain, a cascade of chemicals and every bone in your body. GROWING PAINS In the first six months of your life, you grew more than at any other time since. It’s a growth spurt unlike anything else our bodies experience, with most of us growing a massive 30 cm in that first year. As a new parent this is particularly evident. It seems some days as if my daughter is growing in front of me. If we continued to grow at this rate, we would be 10 feet (~3 m) tall by the time we were 10 years old, but by the end of that first year that frenzied growth rate has slowed down and will continue at a far more subtle speed until the madness begins again at puberty. The secrets behind the process of growth reveal how the body works as an integrated system, not just separate organs and limbs functioning in isolation. Starting at the business end of the process, the bones that really define your growth are the long bones of your body, in particular the femurs in your thighs, the fibulas and tibias in your lower legs, and the humerus, ulna and radius in your arms. These are the site of the major longitudinal growth during that first year of development. These bones don’t just uniformly increase in size as they lengthen; the growth is focused around a particular part of the bone called the metaphysis found at the end of each long bone. If you looked at an X-ray of the metaphysis region of the fibula and tibia of a 10-year-old, you might conclude that the child has a broken leg. But what you are actually seeing in the ‘fracture’ across the bone is the location of growth, a line that is called the epiphyseal plate or growth plate. This is a soft disc made of hyaline cartilage (the same cartilage that you can feel in your nose) and it’s here that cells called chondrocytes divide throughout the first 15 or so years of life and the rate of division increases furiously during a growth spurt. As the chondrocytes divide they secrete cartilage, a protein matrix that forms the template for bone, and the continuous division pushes the older cells towards the shaft. These gradually die and become ‘mineralised’. The chondrocytes die, and cells called osteoblasts move in and secrete bone tissue into the cartilage. It’s this process that results in the elongation of the bone – this is how we grow. The long bones of the human skeleton. It’s only once you reach adulthood that the activity in this area stops due to a process of programmed cell death (oddly controlled by oestrogen, the female hormone, in both boys and girls) and the growth plate closes and stops growing. The old growth plate becomes visible on X-rays as an epiphyseal line, a faint scar notched into your bones that you will carry for the rest of your life. At this point, bones can no longer elongate, growing any taller is now impossible. BRAIN–BODY INTERFACE The full story of your miraculously extending bones starts far away from your skeleton. Nestled deep inside the centre of your brain, just behind your eyes, is a structure no bigger than the size of an almond, called the hypothalamus. It is from here that growth is controlled. Your brain facilitates your conscious desires by sending signals to your muscles. This is your ‘somatic’ nervous system, the one that allows you to consciously move about, to speak, to look at things. But, in parallel, you have another subconscious, or autonomic, nervous system governed largely by the hypothalamus. It integrates more data than it’s possible to calculate, from all your sense organs, your memory and experience, your cerebral cortex and amygdala, and it uses this data to control functions of your body that you likely take for granted. Digestion, heart rate, sweating, the size of your pupils and also growing. The hypothalamus is the link between the brain and the body. Part of this regulation is control of the body’s hormones or endocrine system. The hypothalamus secretes hormones itself which include vasopressin (which controls thirst and water reabsorption by the kidneys) and oxytocin (the ‘love’ hormone, which has a range of effects including stimulation of milk secretion and uterine contractions). But most of your endocrine or hormone system is located around your body in specialist endocrine organs, like your thyroid, gonads or adrenal glands. The hypothalamus controls these organs remotely through a cascade of hormone signals sent first to the pituitary. The pituitary gland is around the size of a pea and dangles beneath the hypothalamus from the underside of your brain, on a stalk. It sits behind and between your eyes resting in a little bowl of bone in the base of your skull called the sella turcica or Turkish seat. Via this tiny organ your hypothalamus controls your reproduction, sex drive, lactation, metabolism and of course your growth. It’s not a simple process. The hypothalamus secretes the unimaginatively named growth hormone releasing hormone (GHRH) or growth hormone release inhibiting hormone (GHRIH). These in turn signal to the pituitary to release or stop releasing growth hormone. Growth hormone then directly acts on the cells of your body, instructing them to divide, and it stimulates the liver to produce insulin-like growth factor 1 (IGF-1) which also makes you grow. It takes the brakes off cell division and causes the growth of almost every cell in the body. Levels of IGF-1 and growth hormone can be affected by a huge range of processes which feed into the hypothalamus: insulin levels, disease, protein intake, stress, genes, physical fitness and sex hormones. We see this kind of signalling cascade with almost all biological processes, whether it’s the immune signalling pathways inside cells that Chris studied in his PhD, or the whole body cascades of chemical signals from organ to organ. They allow for delicate control of biological processes at multiple levels, with each organ feeding back information to regulate the process. They are also remnants of our evolutionary past. As organisms became more complex, it was easier for evolution to add another layer of control than to redesign from scratch. As we’ve seen in other chapters, we still have ancient systems in our modern bodies but with extra lines of code to allow for more regulation. We all produce growth hormone (and thus IGF-1), every day throughout our lives. In adulthood the average healthy individual produces about 400 micrograms a day (a scarcely visible amount), and it plays a crucial role in the maintenance and renewal of our bodies as well as controlling a host of other bodily functions. In children and teenagers, the levels of growth hormone are much higher, reaching 700 micrograms a day in the midst of our most rapid periods of growth, and it’s these levels that drive the process in the growth plates of young bones. In this way, through the cascade of hormones from the brain, which travel through the blood vessels of your body to command the cells in the growth plates of your long bones to divide and push those bones a little longer, millimetre by millimetre, you grow. As is often the case in medicine, we have understood how body systems function in healthy people by studying those for whom these systems have gone wrong. Dwarfism occurs when IGF-1 is not produced or when the receptors on the cells’ surfaces that should detect it are absent or defective. Conversely, tumours of the pituitary may secrete excess growth hormone, and if this happens in childhood prior to fusion of the epiphyseal plates, then gigantism results. Although these tumours are extremely rare in childhood, they have produced two extremely well-known actors, including Richard Kiel (the infamous ‘Jaws’ villain from two James Bond movies) and Andre the Giant, a wrestler and actor from The Princess Bride. As well as being giants over 7 ft (213 cm) tall, both of these stars exhibited the other effects of excess growth hormone secretion, a condition called acromegaly. If growth hormone secretion occurs after the long bones have fused, then you can’t grow any taller, but bones and other tissues continue to grow. The brow ridge and jaw thicken, the tongue and hands become vast and thick, and the voice deepens. In athletes using growth hormone as an illegal performance-enhancing drug, jaw changes often necessitate orthodontic braces to realign teeth – a subtle tell-tale sign for doping. It’s a beautiful, complex cascade that we have been able to understand in greater and greater detail through the revolution in molecular biology and genetics over the last 50 years, but one particularly strange thing about our growth through childhood and adolescence has remained a mystery. Unlike any another primate, we have a very odd pattern of growth through to adulthood. As we’ve already seen in this chapter, the first six months of life witness the most rapid period of growth, but then this slows dramatically through the next 10 years – a time we humans call childhood. Unlike any of our nearest relatives, including chimpanzees and bonobos, we grow at a fraction of the maximal rate through this period. It’s as if the race to adulthood is on hold, until suddenly we burst into activity again around the age of 10 as we experience the growth spurt of puberty. The mystery is why. Why do we all follow this oddly stunted pattern of growth? In the last few years an intriguing hypothesis has emerged to explain the biological oddity we call childhood. GOOD THINGS COME TO THOSE WHO GROW In June 1765 Daines Barrington, the British lawyer, naturalist and distinguished fellow of the Royal Society, made his way the one mile from his home in King’s Bench Walk in the heart of legal London, to a rather less respectable address on the east side of Soho. The reason for his journey into this more unsavoury area of London was to visit the temporary occupants of 21 Frith Street – an Austrian man named Leopold and his two children 14-year-old Nanneri and 8-year-old Wolfgang. Under his arm Barrington carried a clutch of documents and papers, but most importantly a newly composed music manuscript written in a ‘challenging, contemporary Italian style’. The purpose of bringing the manuscript was to place it in front of the young boy Wolfgang so that Barrington could check for himself whether the rumours that had spread across London regarding this boy’s precocious musical talent were really true. The boy was, of course, Wolfgang Amadeus Mozart and Barrington’s test would be an easy trial for him to pass. Just by sight, the young Mozart played the piece effortlessly and perfectly, at the very first time of trying. ‘The score was no sooner put upon his desk than he began to play the symphony in a most masterly manner, as well as in the time and style which corresponded with the intention of the composer,’ he wrote. Barrington went on to further test the abilities of the 8-year-old boy, challenging him to improvise a song of ‘love and a song of rage’. Writing in a now famous letter to the Philosophical Transactions of the Royal Society some years later, Barrington described how Mozart’s astonishing readiness, did not arise merely from great practice; he had a thorough knowledge of the fundamental principles of composition … and his transitions from one key to another were excessively natural and judicious. ‘EVEN TODAY, AFTER A CENTURY OR SO OF SCIENTIFIC STUDY OF CHILD DEVELOPMENT, PRECOCIOUS TALENT REMAINS A MYSTERY. WE ARE STILL AS CURIOUS ABOUT TALENT NOW AS PEOPLE WERE IN THE EIGHTEENTH CENTURY.’ PROFESSOR UTA FRITH Barrington’s visit, tests and subsequent publication of his observations are widely regarded as one of the first examples of Behavioural Science. As Professor Uta Frith, a current FRS and one of Britain’s most distinguished cognitive scientists, wrote some 250 years later, ‘Naturally, the methods of observation he used are rather crude to our modern eyes, but, the crucial point is that he gives concrete examples of behaviour and not just opinions.’ It did not just take Barrington to prove that Mozart was undoubtedly a child genius. The historical records are full of details of his precocious talent, from his first compositions as a 4-year-old, to his first symphony, composed during that extended stay in London. This was a childhood that was truly full of extraordinary achievement, a unique talent that was maturing before the eyes and ears of the world. As Frith went on to conclude, ‘Even today, after a century or so of scientific study of child development, precocious talent remains a mystery. We are still as curious about talent now as people were in the eighteenth century.’ Achievement and emerging talent however, is not something that is in short supply with children of 4, 5, or 6 years of age. This is the moment that many of us sit our children down at the piano for the first time, sign them up for the local football team or send them off to ballet class as well as seeing them grasp the fundamentals of reading, writing and arithmetic skills that they will carry throughout their lives. Subconsciously or not, we are aware that this is a precious time, a moment when children are more than just sponges; they are receptive to developing new skills and abilities with an ease that will not be repeated at any other time in their lives. The foundation of all of this new-found knowledge, skill and ability is of course the brain, and intriguingly we now think the brain power that goes into all of this intensive learning is intricately linked to that mysterious and odd pattern of growth we were puzzling on earlier in the chapter. On a daily basis your brain demands a huge amount of the energy your body uses. Weighing around 1.4 kg, just 2 per cent of our total body weight, the average adult human brain consumes 20 per cent of our body’s energy expenditure (to be precise that is 20 per cent of the resting metabolic rate [RMR]). To put this massive power demand into some context, if your body needs 1,400 calories just to sit on the couch all day doing sod all (that’s what the RMR is), then your brain will be consuming 280 of those calories just to keep things ticking over, like deciding which channel to watch, or when to eat dinner. Put another way, it takes one Mars bar plus an extra bite for your brain to exist. No other organ in the body is so hungry for energy, but what is interesting is that the energy demands of the brain are far from constant throughout your life. Конец ознакомительного фрагмента. Текст предоставлен ООО «ЛитРес». Прочитайте эту книгу целиком, купив полную легальную версию (https://www.litres.ru/andrew-cohen/secrets-of-the-human-body/?lfrom=688855901) на ЛитРес. Безопасно оплатить книгу можно банковской картой Visa, MasterCard, Maestro, со счета мобильного телефона, с платежного терминала, в салоне МТС или Связной, через PayPal, WebMoney, Яндекс.Деньги, QIWI Кошелек, бонусными картами или другим удобным Вам способом.