Secrets of the Human Body. Andrew Cohen

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СКАЧАТЬ 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 СКАЧАТЬ