10% Human: How Your Body’s Microbes Hold the Key to Health and Happiness. Alanna Collen

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