Kitabı oku: «10% Human: How Your Body’s Microbes Hold the Key to Health and Happiness»

CONTENTS

Cover

Title Page

Copyright

Dedication

Epigraph

Prologue: Being Cured

Introduction: The Other 90%

1. Twenty-First-Century Sickness

2. All Diseases Begin in the Gut

3. Mind Control

4. The Selfish Microbe

5. Germ Warfare

6. You Are What They Eat

7. From the Very First Breath

8. Microbial Restoration

Coda: Twenty-First-Century Health

Epilogue: 100% Human

Picture Section

References

List of Illustrations

Index

Acknowledgements

About the Publisher

PROLOGUE
Being Cured

As I walked back through the forest that night in the summer of 2005, with twenty bats in cotton bags hanging around my neck and all manner of insect life dashing for the light of my head torch, I realised my ankles were itching. I had my repellent-soaked trousers tucked into my leech socks, with another pair underneath for good measure. The humidity and drenching sweat, the muddy trails, my fear of tigers, and the mosquitoes were enough to contend with as I made my rounds, collecting bats out of traps in the darkness of the rainforest. But something had got through the barrier of fabric and chemicals protecting my skin. Something itchy.

At twenty-two, I spent what turned out to be a life-changing three months living in the heart of Krau Wildlife Reserve in peninsular Malaysia. During my biology degree, I had become fascinated by bats, and when the opportunity came up to work as a field assistant to a British bat scientist, I signed up immediately. Encounters with leaf monkeys, gibbons and an extraordinary diversity of bats made the challenges of sleeping in a hammock and washing in a river popu-lated by monitor lizards seem worthwhile. But, as I was to discover, the trials of life in a tropical forest can live on far beyond the experience itself.

Back at base camp, in a clearing next to the river, I peeled back the layers to reveal the source of my discomfort: not leeches, but ticks. Perhaps fifty or so, some embedded in my skin, others crawling up my legs. I brushed the loose ones off, and turned back to the bats, measuring and recording scientific data about them as quickly as I could. Later, with the bats released, and the forest pitch-black and buzzing with cicadas, I zipped myself into my cocoon-like hammock, and, with a pair of tweezers, under the light of my head torch, I removed every last tick.

A few months later, at home in London, the tropical infection introduced to me by the ticks took hold. My body seized up and my toe bone swelled. Weird symptoms came and went, as did various blood tests and hospital specialists. My life would be put on hold for weeks or months at a time as bouts of pain, fatigue and confusion gripped me without warning, then released me again as if nothing had happened. By the time I was diagnosed many years later, the infection was entrenched, and I was given a course of antibiotics long and intense enough to cure a herd of cattle. At last, I was going to be myself again.

But, unexpectedly, the story did not end there. I was cured, but not just of the tick-borne infection. Instead, it seemed I had been cured as if I were a piece of meat. The antibiotics had worked their magic, but I began to suffer new symptoms, as varied as before. My skin was raw, my digestive system was choosy, and I was prone to picking up every infection going. I had a suspicion that the antibiotics I had taken had not only eradicated the bacteria that plagued me, but also those that belonged in me. I felt like I had become inhospitable to microbes, and I learnt just how much I needed the 100 trillion friendly little creatures who had, until recently, called my body their home.

You are just 10 per cent human.

For every one of the cells that make up the vessel that you call your body, there are nine impostor cells hitching a ride. You are not just flesh and blood, muscle and bone, brain and skin, but also bacteria and fungi. You are more ‘them’ than you are ‘you’. Your gut alone hosts 100 trillion of them, like a coral reef growing on the rugged seabed that is your intestine. Around 4,000 different species carve out their own little niches, nestled among folds that give your 1.5-metres-long colon the surface area of a double bed. Over your lifetime, you will play host to bugs the equivalent weight of five African elephants. Your skin is crawling with them. There are more on your fingertip than there are people in Britain.

Disgusting, isn’t it? We are surely too sophisticated, too hygienic, too evolved to be colonised in this way. Shouldn’t we have shunned microbes, like we did fur and tails, when we left the forests? Doesn’t modern medicine have the tools to help us evict them so that we can live cleaner, more healthy, independent lives? Since the body’s microbial habitat was first discovered we have tolerated it, as it seemed to do us no harm. But unlike the coral reefs, or the rainforests, we have not thought to protect it, let alone to cherish it.

As an evolutionary biologist, I am trained to look for the advantage, the meaning, in the anatomy and behaviour of an organism. Usually, characteristics and interactions that are truly detrimental are either fought against, or lost in evolutionary time. That set me thinking: our 100 trillion microbes could not call us home if they brought nothing to the party. Our immune systems fight off germs and cure us of infections, so why would they tolerate being invaded in this way? Having subjected my own invaders, both good and bad, to months of chemical warfare, I wanted to know more about the collateral damage I had caused.

As it turned out, I was asking this question at exactly the right time. After decades of slow-paced scientific attempts at learning more about the body’s microbes by culturing them on Petri dishes, technology had finally caught up with our curiosity. Most of the microbes living inside us die when they are exposed to oxygen, because they are adapted to an oxygen-free existence deep in our guts. Growing them outside the body is difficult, and experimenting with them is even harder.

But, in the wake of the seminal Human Genome Project, in which every human gene was decoded, scientists are now capable of sequencing massive quantities of DNA extremely quickly and cheaply. Even our dead microbes, expelled from the body in the stool, could now be identified because their DNA remained intact. We had thought our microbes didn’t matter, but science is beginning to reveal a different story. A story in which our lives are intertwined with those of our hitchhikers, where our microbes run our bodies, and becoming a healthy human is impossible without them.

My own health troubles were the tip of the iceberg. I learnt of the emerging scientific evidence that disruptions to the body’s microbes were behind gastrointestinal disorders, allergies, autoimmune diseases, and even obesity. And it wasn’t just physical health that could be affected, but mental health as well, from anxiety and depression to obsessive–compulsive disorder (OCD) and autism. Many of the illnesses we accept as part of life were not, it seemed, down to flaws in our genes, or our bodies letting us down, but were instead newly emerging conditions brought on by our failure to cherish the long-held extension to our own human cells: our microbes.

Through my research, I hoped not only to discover what damage the antibiotics I had taken had done to my microbial colony, but how it had made me unwell, and what I could do to restore the balance of microbes I had harboured before the night of the tick bites, eight years earlier. To learn more, I signed up to take the ultimate step in self-discovery: DNA sequencing. But rather than sequence my own genes, I would have the genes of my personal colony of microbes – my microbiome – sequenced. By knowing which species and strains of bacteria I contained, I would have a starting point for self-improvement. Using the latest understanding of what should be living in me, I might be able to judge just how much damage I had done, and attempt to make amends. I used a citizen-science programme, the American Gut Project, based at the laboratory of Professor Rob Knight at the University of Colorado, Boulder. Available to anyone around the world for a donation, the AGP sequences samples of microbes from the human body to learn more about the species we harbour and their impact on our health. By sending a stool sample containing the microbes from my own gut, I received a snapshot of the ecosystem that called my body home.

After years of antibiotics, I was relieved to find I had any bacteria living in me at all. It was pleasing to see that the groups I harboured were at least broadly similar to those in other American Gut Project participants, and not the microbial equivalent of mutant creatures eking out a living on a toxic wasteland. But, perhaps predictably, the diversity of my bacteria seemed to have taken a beating. At the highest level of the taxonomic hierarchy, the diversity was relatively low, looking a bit bipartisan compared with the guts of other people. Over 97 per cent of my bacteria belonged to the two major bacterial groups, compared with around 90 per cent making up these two groups in the average participant. Perhaps the antibiotics I had taken had killed off some of the less abundant species, leaving me with only the hardy survivors. I was intrigued to know whether this loss might be related to any of my more recent health troubles.

But, just as comparing a tropical rainforest and an oak woodland by looking at the proportion of trees to shrubs, or birds to mammals, reveals little about how both ecosystems function, comparing my bacteria at such a broad scale may not tell me all that much about the health of my inner community. At the other end of the taxonomic hierarchy were the genera and species that I contained. What could the identities of the bacteria that had either clung on throughout my treatment, or returned since it ended, reveal about my current state of health? Or perhaps more pertinently, what did the absence of species that might have fallen victim to the chemical warfare I had unleashed on them, mean for me now?

As I embarked on learning more about us – myself and my microbes – I resolved to put what I learnt into practice. I wanted to get back on their good side, and I knew I needed to make changes to my life to restore a colony that would work in harmony with my human cells. If my most recent symptoms were stemming from the collateral damage I had inadvertently inflicted upon my microbiota, perhaps I could reverse it and rid myself of the allergies, the skin problems and the near-constant infections? My concern wasn’t just for myself, but for the children I hoped to have in the coming years. As I would pass on not only my genes, but also my microbes, I wanted to be sure I had something worth giving.

I resolved to put my microbes first, altering my diet to better suit their needs. I planned to have a second sample sequenced after my lifestyle changes had had a chance to take effect, in the hope that my efforts might be evident from the change in the diversity and balance of the species I play host to. Most of all, I hoped that my investment in them would pay dividends, by unlocking the door to better health and happiness.

INTRODUCTION
The Other 90%

In May 2000, just weeks before the announcement of the first draft of the human genome, a notebook began circulating among the scientists sitting at the bar in Cold Spring Harbor Laboratory in New York State. Excitement was building about the next phase of the Human Genome Project, in which the DNA sequence would be split into its functional parts – genes. The notebook contained a sweepstake: the guesses of the best-informed group of people on the planet concerning one intriguing question: How many genes does it take to build a human?

Senior research scientist Lee Rowen, who was leading a group working on decoding chromosomes 14 and 15, sipped her beer as she pondered the question. Genes make proteins, the building blocks of life, and the sheer complexity of humans made it seem probable that the number would be high. Higher than the mouse, surely, which was known to have 23,000 genes. Probably also higher than the wheat plant, with 26,000 genes. And, no doubt, far higher than ‘The Worm’, a favourite laboratory species of developmental biologists, with its 20,500 genes.

Despite guesses averaging over 55,000 genes, and topping 150,000, Rowen’s understanding of the field meant she was inclined to go low. She placed a bet of 41,440 that year, and followed it up a year later with a second bet of just 25,947 genes. In 2003, with the true gene number only just emerging from the nearly finished sequence, Rowen was awarded the prize. Her entry was the lowest of all 165 bets, and the latest gene count had just dropped even lower than any scientist had ever predicted.

With just shy of 21,000 genes, the human genome is hardly bigger than that of The Worm (C. elegans). It is half the size of the rice plant, and even the humble water flea outstrips it, with 31,000 genes. None of these species can talk, create, or think intelligent thoughts. You might think, as the scientists entering the Genesweep pool did, that humans would have a great many more genes than grasses and worms and fleas. After all, genes make proteins, and proteins make bodies. Surely a body as complex and sophisticated as a human’s would need more proteins, and therefore more genes, than a worm’s?

But these 21,000 genes are not the only genes that run your body. We do not live alone. Each of us is a superorganism; a collective of species, living side-by-side and cooperatively running the body that sustains us all. Our own cells, though far larger in volume and weight, are outnumbered ten to one by the cells of the microbes that live in and on us. These 100 trillion microbes – known as the microbiota – are mostly bacteria: microscopic beings made of just a single cell each. Alongside the bacteria are other microbes – viruses, fungi and archaea. Viruses are so small and simple that they challenge our ideas of what even constitutes ‘life’. They depend entirely on the cells of other creatures to replicate themselves. The fungi that live on us are often yeasts; more complex than bacteria, but still small, single-celled organisms. The archaea are a group that appear to be similar to bacteria, but they are as different evolutionarily as bacteria are from plants or animals. Together, the microbes living on the human body contain 4.4 million genes – this is the microbiome: the collective genomes of the microbiota. These genes collaborate in running our bodies alongside our 21,000 human genes. By that count, you are just half a per cent human.

A simplified tree of life, showing the three domains and four kingdoms of Domain Eukarya.

We now know that the human genome generates its complexity not only in the number of genes it contains, but also through the many combinations of proteins these genes are able to make. We, and other animals, are able to extract more functions from our genomes than they appear to encode at first glance. But the genes of our microbes add even more complexity to the mix, providing services to the human body that are more quickly evolved and more easily provided by these simple organisms.

Until recently, studying these microbes relied on being able to culture them on Petri dishes filled with broths of blood, bone marrow, or sugars, suspended in jelly. It’s a difficult task: most of the species living in the human gut die on exposure to oxygen – they simply haven’t evolved to tolerate it. What’s more, growing microbes on these plates means guessing what nutrients, temperature and gases they might need to survive, and failing to figure this out means failing to learn more about a species. Culturing microbes is the equivalent of checking who’s turned up for class by running down a register – if you don’t call someone’s name, you won’t know if they are there. Today’s technology – the DNA sequencing made so fast and cheap by the efforts of those working on the Human Genome Project – is more like requesting ID at the door; even those that you weren’t expecting can be accounted for.

As the Human Genome Project came to a close, expectations were high. It was seen as the key to our humanity, God’s greatest work, and a sacred library holding the secrets of disease. When the first draft was completed in June 2000, under budget at $2.7 billion and several years early, the US President, Bill Clinton, declared:

Today, we are learning the language in which God created life. We are gaining ever more awe for the complexity, the beauty, the wonder of God’s most divine and sacred gift. With this profound new knowledge, humankind is on the verge of gaining immense new power to heal. Genome science will have a real impact on all our lives – and even more, on the lives of our children. It will revolutionise the diagnosis, prevention and treatment of most, if not all, human diseases.

But in the years that followed, science journalists the world over began expressing their disappointment in the contribution that knowledge of our complete DNA sequence had made to medicine. Although decoding our own instruction book is an irrefutable achievement that has made a difference to treatments for several important illnesses, it has not revealed as much as we expected about the causes of many common diseases. Searching for genetic differences in common to people with a particular disease did not throw up straightforward links for as many conditions as had been expected. Often, conditions were weakly linked to tens or hundreds of gene variants, but rarely was it the case that possessing a given gene variant would lead directly to a given disease.

What we failed to appreciate at the turn of the century was that those 21,000 genes of ours are not the full story. The DNA-sequencing technology invented during the Human Genome Project enabled another major genome-sequencing programme, but one that received far less media attention: the Human Microbiome Project. Rather than looking at the genome of our own species, the HMP was set up to use the genomes of the microbes that live on the human body – the microbiome – to identify which species are present.

No longer would a reliance on Petri dishes and an over-abundance of oxygen hold back research into our cohabiters. With a budget of $170 million and a five-year programme of DNA sequencing, the HMP was to read thousands of times as much DNA as the HGP, from microbes living in eighteen different habitats on the human body. It was to be a far more comprehensive survey of the genes that make a person, both human and microbial. At the conclusion of the Human Microbiome Project’s first phase of research in 2012, not one world leader made a triumphant statement, and only a handful of newspapers featured the story. But the HMP would go on to reveal more about what it means to be human today than our own genome ever has.

Since life began, species have exploited one another, and microbes have proved themselves to be particularly efficient at making a living in the oddest of places. At their microscopic size, the body of another organism, particularly a macro-scale backboned creature like a human, represents not just a single niche, but an entire world of habitats, ecosystems and opportunities. As variable and dynamic as our spinning planet, the human body has a chemical climate that waxes and wanes with hormonal tides, and complex landscapes that shift with advancing age. For microbes, this is Eden.

We have been co-evolving side-by-side with microbes since long before we were humans. Before our ancestors were mammals even. Each animal body, from the tiniest fruit fly to the largest whale, is yet another world for microbes. Despite the negative billing many of them get as disease-causing germs, playing host to a population of these miniature life-forms can be extremely rewarding.

The Hawaiian bobtail squid – as big-eyed and colourful as any Pixar character – has diminished a major threat to its life by inviting just one species of bioluminescent bacterium to live in a special cavity in its underbelly. Here, in this light organ, the bacteria, known as Aliivibrio fischeri, convert food into light, so that viewed from below, the squid glows. This obscures its silhouette against the moonlit ocean surface, camouflaging it from predators approaching from beneath. The squid owes this protection to its bacterial inhabitants, and they owe the squid for their home.

While housing a microbial light source might seem a particularly inventive way to increase one’s life chances, squid are far from the only animal species who owe their lives to their body’s microbes. Strategies for living are many and varied, and cooperation with microbes has been a driving force of the evolutionary game since living beings with more than one cell first evolved, 1.2 billion years ago.

The more cells an organism is made of, the more microbes can live on it. Indeed, large animals such as cattle are well known for their bacterial hospitality. Cows eat grass, yet using their own genes they can extract very little nutrition from this fibrous diet. They would need specialist proteins, called enzymes, that can break down the tough molecules making the cell walls of the grass. Evolving the genes that make these enzymes could take millennia, as it relies on random mutations in the DNA code that can only happen with each passing generation of cows.

A quicker way to acquire the ability to get at the nutrients locked away in grass is to outsource the task to the specialists: microbes. The four chambers of the cow’s stomach house populations of plant-fibre-busting microbes numbering in their trillions, and the cud – a ball of solid plant fibre – travels back and forth between the mechanical grinding of the cow’s mouth and chemical breakdown by the enzymes produced by microbes living in the gut. Acquiring the genes to do this is quick and easy for microbes, as their generation times, and therefore opportunities for mutations and evolution, are often less than a day.

If bobtail squid and cows can both benefit from teaming up with microbes, is it possible that we humans do as well? We may not eat grass and have a four-chambered stomach, but we do have our own specialisations. Our stomachs are small and simple, there just to mix the food up, throw in some enzymes for digestion, and add a bit of acid to kill unwelcome bugs. But travel on, through the small intestine, where food is broken down by yet more enzymes and absorbed into the blood through the carpet of finger-like projections that give it the surface area of a tennis court, and you reach a cul-de-sac, more of a tennis ball than a tennis court, that marks the beginning of the large intestine. This pouch-like patch, at the lower right corner of your torso, is called the caecum, and it is the heart of the human body’s microbial community.

Dangling from the caecum is an organ that has a reputation for being there simply to cause pain and infection: the appendix. Its full title – the vermiform appendix – refers to its worm-like appearance, but it could equally be compared to a maggot or a snake. Appendices vary in length from a diminutive 2 cm to a distinctly stringy 25 cm, and, rarely, a person may even have two of them, or not one at all. If popular opinion is to be believed, we would be better off without one at all, since for over one hundred years they have been said to have no function whatsoever. In fact, the man who finally put the anatomy of animals into an elegant evolutionary framework is apparently responsible for this persistent myth. Charles Darwin, in The Descent of Man, a follow-up to On the Origin of Species, included the appendix in a discussion of ‘rudimentary’ organs. Having compared it with the larger appendices of many other animals, Darwin felt that the appendix was a vestige, steadily withering away as humans changed their diets.

With little to indicate otherwise, the vestigial status of the appendix was barely questioned for the next 100 years, and the perception of its uselessness is only enhanced by its tendency to cause a nuisance. So pointless has the medical establishment assumed it to be, that by the 1950s, removing it became one of the most common surgical procedures carried out in the developed world. An appendectomy was even often tacked on as a bonus during other abdominal surgery. At one point, a man stood a one in eight chance of having his appendix removed during his lifetime, and for a woman, the odds were one in four. About 5–10 per cent of people get appendicitis at some stage in their life, usually in the decades before they have children. Untreated, nearly half of these people would die.

This presents a conundrum. If appendicitis were a naturally occurring disease, frequently causing death at a young age, the appendix would be quickly eliminated by natural selection. Those with appendices large enough to become infected would die, most often before reproducing, and would therefore fail to pass on their appendix-forming genes. Over time, fewer and fewer people would have an appendix, and eventually it would be lost. Natural selection would have preferred those without one.

Darwin’s assumption that it was a relic of our pasts might have carried some weight, were it not for the often fatal consequences of possessing one. There are two explanations, therefore, for the persistence of the appendix, and they are not mutually exclusive. The first is that appendicitis is a modern phenomenon, brought on by some environmental change. Thus, even a pointless organ could have persisted in the past simply by keeping out of trouble. The other is that the appendix, far from being a malign vestige of our evolutionary past, actually has health benefits that outweigh its dark side, making its presence worthwhile despite the risk of appendicitis. That is, natural selection prefers those of us who possess one. The question is, why?

The answer lies in its contents. The appendix, which averages about 8 cm in length and a centimetre across, forms a tube, protected from the flow of mostly digested food passing its entrance. But rather than being a withered strand of flesh, it is packed full of specialised immune cells and molecules. They are not inert, but rather an integral part of the immune system, protecting, cultivating and communicating with a collective of microbes. Inside, these microbes form a ‘biofilm’ – a layer of individuals that support one another and exclude bacteria that might cause harm. The appendix, far from being functionless, appears to be a safe-house that the human body has provided for its microbial inhabitants.

Like a nest egg stashed away for a rainy day, this microbial stockpile comes in handy at times of strife. After an episode of food poisoning or a gastrointestinal infection, the gut can be repopulated with its normal inhabitants, which have been lurking in the appendix. It might seem like an excessive bodily insurance policy, but it is only in recent decades that gut infections such as dysentery, cholera and giardiasis have been all but eliminated in the Western world. Public sanitation measures, including sewerage systems and water-treatment plants, have prevented such illnesses in developed countries, but globally, one in five of all childhood deaths are still caused by infectious diarrhoea. For those who do not succumb, possession of an appendix likely hastens their recovery. It is only in a context of relatively good health that we have come to believe that the appendix has no function. Indeed, the negative consequences of undergoing an appendectomy have been masked by the modern, sanitised lifestyle.