I Contain Multitudes Read online

  Critics say that the popularity of the microbiome is undeserved, and that the majority of studies in the field amount to little more than fancy stamp collecting. So what if we know which microbes live on a pangolin’s face, or in a person’s gut? That tells us what and where, but not why or how. Why do some microbes live on some animals but not others, or on a few individuals but not everyone, or on certain body parts but not all of them? Why do we see the patterns that we see? How did those patterns arise? How do microbes first find their way into their hosts? How do they seal their partnerships? How do microbes and hosts change each other, once together? How do they cope if their alliances break down?

  These are the deep questions that the field is trying to answer. In this book, I will show you how far we have come in addressing them, how much promise there lies in understanding and manipulating microbiomes, and how far we have to go to realise that promise. For now, let us note that these questions can be answered only by collecting small pieces of data, just as Darwin and Wallace did on their seminal voyages. The stamp collecting is important. “Even Darwin’s Journal was just a scientific travelogue, a pageant of colourful creatures and places, propounding no evolutionary theory,” wrote David Quammen.22 “The theory would come later.” Before that came a lot of hard graft. Classifying. Cataloguing. Collecting. “If new continents are unexplored, before you find out why things are where they are, you need to find out where they are,” says Rob Knight.

  It’s in the spirit of exploration that Rob Knight first approached San Diego Zoo. He wanted to swab the faces and skins of different mammals to characterise their microbiomes, as well as the chemicals – metabolites – that those microbes produce. These substances shape the environment in which the microbes live and evolve, and they also show what those microbes are doing, rather than just which ones are present. Surveying metabolites is like running an inventory of a city’s art, food, inventions, and exports, rather than just doing a census of its citizens. Knight recently tried surveying the metabolites of human faces, but found that beauty products, like sunscreens and face creams, drowned out the natural microbial metabolites.23 The solution: swab the faces of animals. After all, Baba the pangolin doesn’t moisturise. “We’re hoping to get oral samples too,” says Knight. “And maybe vaginal.” I raise an eyebrow. “The breeding programmes here for the cheetahs and pandas have freezers and freezers full of vaginal swabs,” he assures me.

  The zookeeper shows us a colony of naked mole rats skittering around a set of interconnected plastic tubes. They are distinctly unattractive animals, like wrinkled sausages with teeth. They are also incredibly weird: insensitive to pain, resistant to cancer, extremely long-lived, terrible at controlling their body temperature, and possessed of misshapen, incompetent sperm. They live in ant-like colonies with queens and workers. They also burrow, which makes them interesting to Knight. He has just secured a grant to study the microbiomes of animals that share specific traits or lifestyles: burrowing, flying, living in water, adaptations to hot and cold, and even intelligence. “It’s pretty speculative but the idea is that you might have microbial pre-adaptations to get the energy you need to do some of those more exotic things,” he says. Speculative, certainly, but not far-fetched. Microbes have opened many doors for animals, allowing them to take up all kinds of peculiar lifestyles that would normally be closed off to them. And when animals share habits, their microbiomes often converge. For example, Knight and his colleagues once showed that ant-eating mammals, including pangolins, armadillos, anteaters, aardvarks, and aardwolves (a type of hyena), all have similar gut microbes, even though they have been evolving independently for around 100 million years.24

  We walk past a gang of meerkats, some upright and alert, others playing together. The lone female – the group’s matriarch – is the only one Knight could potentially swab but she is old and has a heart condition. That’s not uncommon. Meerkats will sometimes attack each other’s pups or abandon their own, and when this happens, the zoo steps in to hand-raise the youngsters. They survive, but the keeper tells us that, for unknown reasons, they often develop heart problems when they get older. “That’s very interesting,” says Knight. “Do you know anything about meerkat milk?” He asks because mammalian milk contains special sugars that infants cannot digest, but that certain microbes can. When a human mother breastfeeds her child, she isn’t just feeding it; she is also feeding the child its first microbes, and ensuring that the right pioneers settle inside its gut. Knight wonders if the same applies to meerkats. Do the abandoned pups start their lives with the wrong microbes because they don’t get mother’s milk? Do those early changes affect their health in later life?

  Knight is already working on other projects to improve the health of the zoo’s animals. As we walk past a cage full of silvered langurs – beautiful, pewter-furred monkeys with electric facial fuzz – he tells me that he is trying to work out why some monkey species frequently suffer from inflammation of the colon (colitis) in captivity, while others do not. There’s good reason to think that their microbes are involved. In people, cases of inflammatory bowel disease are usually accompanied by an overabundance of bacteria that provoke the immune system and a lack of those that restrain it. Several other conditions show similar patterns, including obesity, diabetes, asthma, allergies, and colon cancer. These are health problems re-envisioned as ecological ones, where no single microbe is at fault, yet an entire community has shifted into an unhealthy state. They are cases of symbiosis gone wrong. And if these distorted microbiomes actually cause the various conditions, it should be possible to restore good health by manipulating the microbes. Even if the microbial communities are changing as a result of a disease, they could still be useful in diagnosing a condition before symptoms become apparent. That’s what Knight hopes to see in the monkeys; he is comparing animals with and without colitis, across different species, to see if there are signatures of disease that keepers could use to identify a symptomless animal at risk. Such studies might also help us to understand how the microbiome changes in people – or dogs – with inflammatory bowel disease.

  Finally, we walk into a back room where several animals are being temporarily housed out of the public eye. One of the cages houses a giant shadow: a three-foot-long, black-furred creature that has the shape of a weasel but the countenance of a bear. It’s a binturong: a large, shaggy civet which Gerald Durrell described as a “badly made hearthrug.” The keeper reckons that we could easily swab its face and feet, but the real action lies further down. Binturongs have scent glands on either side of their anus, which produce a smell that’s reminiscent of popcorn. Again, it seems likely that bacteria create the odours. Scientists have already characterised the microbial scents that drift from the scent glands of badgers, elephants, meerkats, and hyenas. The binturong awaits!

  “Could we swab the anus?” I ask.

  The keeper looks at the intimidating animal in the cage and then slowly back at us. He says, “I . . . don’t think so.”

  When we look at the animal kingdom through a microbial lens, even the most familiar parts of our lives take on a wondrous new air. When a hyena rubs its scent glands on a blade of grass, its microbes write its autobiography for other hyenas to read. When a meerkat mother breastfeeds its pups, it builds worlds within their guts. When an armadillo slurps down a mouthful of ants, it feeds a community of trillions that, in turn, provide it with energy. When a langur or human gets sick, its problems are akin to a lake that’s smothered by algae or a meadow that’s overrun with weeds – ecosystems gone awry. Our lives are heavily influenced by external forces that are actually inside us, by trillions of things that are separate from us and yet very much a part of us. Scent, health, digestion, development, and dozens of other traits that are supposedly the province of individuals are really the result of a complex negotiation between host and microbes.

  Knowing what we know, how would we even define an individual?25 If you define an individual anatomically, as the owner of a particu
lar body, then you must acknowledge that microbes share the same space. You could try for a developmental definition, in which an individual is everything that grows from a single fertilised egg. But that doesn’t work either because several animals, from squids to mice to zebrafish, build their bodies using instructions encoded by both their genes and their microbes. In a sterile bubble, they wouldn’t grow up normally. You could moot a physiological definition, in which the individual is composed of parts – tissues and organs – that cooperate for the good of the whole. Sure, but what about insects in which bacterial and host enzymes work together to manufacture essential nutrients? Those microbes are absolutely part of the whole, and an indispensable part at that. A genetic definition, in which an individual consists of cells that share the same genome, runs into the same problem.

  Any single animal contains its own genome, but also many microbial ones that influence its life and development. In some cases, microbial genes can permanently infiltrate the genomes of their hosts. Does it really make sense to view them as separate entities? With your options running out, you could pass the buck to the immune system, since it supposedly exists to distinguish our own cells from those of intruders, to tell self from non-self. That’s not quite true, either; as we will see, our resident microbes help to build our immune system, which in turn learns to tolerate them. No matter how we squint at the problem, it is clear that microbes subvert our notions of individuality. They shape it, too. Your genome is largely the same as mine, but our microbiomes can be very different (and our viromes even more so). Perhaps it is less that I contain multitudes and more that I am multitudes.

  These concepts can be deeply disconcerting. Independence, free will, and identity are central to our lives. Microbiome pioneer David Relman once noted that “loss of a sense of self-identity, delusions of self-identity and experiences of ‘alien control’” are all potential signs of mental illness.26 “Small wonder that recent studies of symbiosis have engendered substantial interest and attention,”. But he also added that “[Such studies] highlight the beauty in biology. We are social creatures and seek to understand our connections to other living entities. Symbioses are the ultimate examples of success through collaboration and the powerful benefits of intimate relationships.”

  I agree. Symbiosis hints at the threads that connect all life on Earth. Why can organisms as disparate as humans and bacteria live together and cooperate? Because we share a common ancestor. We store information in DNA using the same coding scheme. We use a molecule called ATP as a currency of energy. The same is true across all life. Picture a BLT sandwich: every component, from the lettuce and tomatoes to the pig that produced the bacon, to the yeast that baked the bread, to the microbes that surely sit on its surface, speaks the same molecular language. As Dutch biologist Albert Jan Kluyver once said, “From the elephant to the butyric acid bacterium – it is all the same!”

  Once we understand how similar we are, and how deeply the ties between animals and microbes extend, our view of the world will become immeasurably enriched. Mine certainly has. All my life, I have loved the natural world. My shelves are lined with wildlife documentaries and books bursting with meerkats, spiders, chameleons, jellyfish, and dinosaurs. But none of these talk about how microbes affect, enhance, and direct the lives of their hosts, and so they are incomplete – paintings without frames, cakes without icing, Lennon without McCartney. I now see how the lives of all these creatures depend upon unseen organisms that they live with but are unaware of, that contribute to and sometimes entirely account for their abilities, and that have existed on the planet for far longer than they have. It is a dizzying change in perspective, but a glorious one.

  I have been visiting zoos ever since I was too small to remember (or to know that you shouldn’t climb into the giant tortoise enclosure). But my visit to San Diego Zoo with Knight (and Baba) feels different. Although the place is a riot of colour and noise, I realise that most of the life here is invisible and inaudible. At the main entrance, vessels full of microbes part with money so that they can file through gates and see differently shaped microbial vessels that loiter in cages and enclosures. Trillions of microbes, hidden within feather-coated bodies, fly through aviaries. Other hordes swing through branches or scuttle through tunnels. One bacterial throng, nestled within the backside of a black hearthrug fills the air with the redolent twang of popcorn. This is the living world as it actually is, and although it is still invisible to my eyes, I can finally see it.

  2. THE PEOPLE WHO THOUGHT TO LOOK

  Bacteria are everywhere, but as far as our eyes are concerned, they might as well be nowhere. There are a few extraordinary exceptions: Epulopiscium fishelsoni, a bacterium that lives only in the guts of the brown surgeonfish, is about the size of this full stop. But the rest cannot be seen without help, which means that for the longest time they weren’t seen at all. In our imaginary calendar, which condenses Earth’s history into a year, bacteria first appeared in mid-March. For virtually their entire reign, nothing was consciously aware of their existence. Their anonymous streak broke just a few seconds before the very end of the year, when a curious Dutchman had the whimsical notion of examining a drop of water through handmade lenses of world-beating quality.

  In 1632, Antony van Leeuwenhoek was born in the city of Delft, a bustling hub of foreign trade permeated by canals, trees, and cobbled paths.1 By day, he worked as a city official and ran a small haberdashery business. By night, he made lenses. It was a good time and place to do so: the Dutch had recently invented both the compound microscope and the telescope. Through small circles of glass, scientists were peering at objects too far or too small to see with the naked eye. The British polymath Robert Hooke was one. He gazed at all manner of minute things: fleas, lice clinging to hairs, the points of needles, peacock feathers, poppy seeds. In 1665 he published his observations in a book called Micrographia, complete with gorgeous and extraordinarily detailed illustrations. It became an instant bestseller in Britain. Small things had hit the big time.

  Leeuwenhoek differed from Hooke in that he never went to university, was not a trained scientist, and spoke only Dutch rather than the more scholarly Latin. Even so, he taught himself to make lenses with a skill that no one else could match. The exact details of his technique are unknown but, broadly speaking, he would grind a bauble of glass into a smooth and perfectly symmetrical lens, less than two millimetres across. This he sandwiched between a pair of brass rectangles. He would then fix a specimen in front of the lens with a tiny pin, and adjust its position with a couple of screws. The resulting microscope looked like a glorified door hinge, and was little more than an adjustable magnifying glass. To use it, Leeuwenhoek had to hold it so that it was practically touching his face, while squinting through the tiny lens, preferably in bright sunlight. These single-lens models were much harder on the eye than the multi-lens compound microscopes that Hooke championed. But they produced clearer images at higher magnification. Hooke’s instruments magnified objects by 20 to 50 times; Leeuwehoek’s did so by up to 270 times. In their day they were easily the best microscopes on earth.

  But Leeuwenhoek was “more than a good microscope maker”, observes Alma Smith Payne in The Cleere Observer. “He was also an excellent microscopist – a user of microscopes.” He documented everything. He repeated observations. He conducted methodical experiments. Even though he was an amateur, the scientific method instinctively ran deep within him – as did a scientist’s untrammelled curiosity about the world. Through his lenses, he gazed at animal hairs, fly heads, wood, seeds, whale muscle, skin flakes, and ox eyes. He saw marvels, and he showed them to friends, family, and scholars in Delft.

  One such scholar, the physician Regnier de Graaf, was a member of the Royal Society, an esteemed and newly founded scientific guild based in London. He recommended Leeuwenhoek, whose microscopes “far surpass those which we have hitherto seen”, to his learned colleagues and implored them to make contact. Henry Oldenburg, the Society’s secretary
and the editor of its leading journal, did so, and eventually translated and published several of the outsider Leeuwenhoek’s disarmingly rambling, informal letters that described red blood cells, plant tissues, and louse guts with matchless detail and care.

  And then, Leeuwenhoek looked at some water – specifically, water of Berkelse Mere, a lake near Delft. Sucking some of the turbid liquid into a glass pipette and mounting it on his microscope, he saw that it was teeming with life: “little green clouds” of algae, along with thousands of tiny, dancing creatures.2 “The motion of most of these animalcules in the water was so swift, and so various upwards, downwards and round about that ’twas wonderful to see,” he wrote, “and I judged that some of these little creatures were above a thousand times smaller than the smallest ones I have ever yet seen upon the rind of cheese.”3 They were protozoa – the diverse group of organisms that includes amoebas and other single-celled eukaryotes. Leeuwenhoek had become the first person ever to see them.4

  In 1675, Leeuwenhoek used his lenses to look at rainwater, which had gathered in a blue pot outside his house. Again, a delightful menagerie appeared. He saw serpentine things that wound and unwound themselves, and ovals “furnished with diverse tiny feet” – more protozoa. He also saw examples of an even tinier class of creature, a thousand times smaller than a louse’s eye, which would “turn themselves about with that swiftness as we see a top turn round” – bacteria! He looked at more water, from his study, his roof, Delft’s canals, the nearby sea, and the well in his garden. The little ‘animalcules’ were everywhere. Life, it turned out, existed in untold numbers beyond the threshold of our perception, visible only to this one man and his superlative lenses. As historian Douglas Anderson later wrote, “Almost everything he saw, he was the first human ever to see.” And more to the point, why did he look at the water in the first place? What on earth possessed this man to scrutinise rain that had collected in a pot? A similar question could be asked of many people throughout the entire history of microbiome research: they were the ones who thought to look.