I Contain Multitudes: The Microbes Within Us and a Grander View of Life

by Ed Yong

But his most distinctive features, by far, are his scales. His head, body, limbs and tail are covered in them – pale orange, overlapping plates that create an extremely tough defensive coat. They are made of the same material as your nails – keratin. Indeed, they look and feel a lot like fingernails, albeit large, varnished, and badly chewed ones.

The vast majority of them are bacteria, but there are also other tiny organisms including fungi (such as yeasts) and archaea, a mysterious group that we will meet again later. There are viruses too, in unfathomable numbers – a virome that infects all the other microbes and occasionally the host’s cells. We can’t see any of these minuscule specks.

When Orson Welles said ‘We’re born alone, we live alone, we die alone’, he was mistaken. Even when we are alone, we are never alone. We exist in symbiosis – a wonderful term that refers to different organisms living together. Some animals are colonised by microbes while they are still unfertilised eggs; others pick up their first partners at the moment of birth. We then proceed through our lives in their presence. When we eat, so do they. When we travel, they come along. When we die, they consume us. Every one of us is a zoo in our own right – a colony enclosed within a single body. A multi-species collective. An entire world.

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All of the concepts that ecologists use to describe the continental-scale ecosystems that we see through satellites also apply to ecosystems in our bodies that we peer at with microscopes. We can talk about the diversity of microbial species. We can draw food webs, where different organisms eat and feed each other. We can single out keystone microbes that exert a disproportionate influence on their environment – the equivalents of sea otters or wolves. We can treat disease-causing microbes – pathogens – as invasive creatures, like cane toads or fire ants. We can compare the gut of a person with inflammatory bowel disease to a dying coral reef or a fallow field: a battered ecosystem where the balance of organisms has gone awry.

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Microbes move between animals, too, and between our bodies and the soils, water, air, buildings, and other environments around us. They connect us to each other, and to the world.

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All zoology is really ecology. We cannot fully understand the lives of animals without understanding our microbes and our symbioses with them. And we cannot fully appreciate our own microbiome without appreciating how those of our fellow species enrich and influence their lives.

Animals belong to a group of organisms called eukaryotes, which also includes every plant, fungus and alga.

All eukaryotes share these traits because we all evolved from a single ancestor, around two billion years ago. Before that point, life on Earth could be divided into two camps or domains: the bacteria, which we already know about, and the archaea, which are less familiar and have a fondness for colonising inhospitable and extreme environments.

For roughly the first 2.5 billion years of life on Earth, bacteria and archaea charted largely separate evolutionary courses. Then, on one fateful occasion, a bacterium somehow merged with an archaeon, losing its free-living existence and becoming entrapped forever within its new host. That is how many scientists believe eukaryotes came to be. It’s our creation story: two great domains of life merging to create a third, in the greatest symbiosis of all time.

The archaeon provided the chassis of the eukaryotic cell while the bacterium eventually transformed into the mitochondria.

It’s why our genomes contain many genes that still have an archaeal character and others that more resemble those of bacteria. It’s also why all of us contain mitochondria in our cells. These domesticated bacteria changed everything. By providing an extra source of energy, they allowed eukaryotic cells to get bigger, to accumulate more genes, and to become more complex.

Wow

There’s a huge void between the simpler cells of bacteria and archaea and the more complex ones of eukaryotes, and life has managed to cross that void exactly once in four billion years.

By forging a union, those two microbes defied the odds and enabled the existence of all plants, animals, and anything visible to the naked eye – or anything with eyes, for that matter. They’re the reason I exist to write this book and you exist to read it. In our imaginary calendar, their merger happened some time in the middle of July. This book is about what happened afterwards.

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After eukaryotic cells evolved, some of them started cooperating and clustering together, giving rise to multicellular creatures, like animals and plants. For the first time, living things became big – so big that they could host huge communities of bacteria and other microbes in their bodies.

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Yersinia pestis, another bacterium, is similarly invisible to us, but the plague epidemics that it causes are all too obvious. These disease-causing microbes – pathogens – have traumatised humans throughout history, and have left a lingering cultural scar. Most of us still see microbes as germs: unwanted bringers of pestilence that we must avoid at all costs.

They help to digest our food, releasing otherwise inaccessible nutrients. They produce vitamins and minerals that are missing from our diet. They break down toxins and hazardous chemicals. They protect us from disease by crowding out more dangerous microbes or killing them directly with antimicrobial chemicals. They produce substances that affect the way we smell. They are such an inevitable presence that we have outsourced surprising aspects of our lives to them. They guide the construction of our bodies, releasing molecules and signals that steer the growth of our organs. They educate our immune system, teaching it to tell friend from foe. They affect the development of the nervous system, and perhaps even influence our behaviour. They contribute to our lives in profound and wide-ranging ways; no corner of our biology is untouched. If we ignore them, we are looking at our lives through a keyhole.

Functions

Wallace’s observations and specimens led him towards the defining insight of biology: that species change. ‘Every species has come into existence coincident both in space and time with a pre-existing closely allied species,’ he wrote, repeatedly and sometimes in italics.

Darwin, Wallace and their peers were particularly fascinated by islands, and for good reason. Islands are where you go if you want to find life at its most outlandish, gaudy, and superlative. Their isolation, restricted boundaries, and constrained size allow evolution to go to town. The patterns of biology resolve into sharper focus more readily than they would do on the extensive, contiguous mainland.

Island

When microbiologists first started cataloguing the human microbiome in its entirety they hoped to discover a ‘core’ microbiome: a group of species that everyone shares. It’s now debatable if that core exists.18 Some species are common, but none is everywhere. If there is a core, it exists at the level of functions, not organisms.

"core" microbiome

There are certain jobs, like digesting a certain nutrient or carrying out a specific metabolic trick, that are always filled by some microbe – just not always the same one. You see the same trend on a bigger scale. In New Zealand, kiwis root through leaf litter in search of worms, doing what a badger might do in England. Tigers and clouded leopards stalk the forests of Sumatra but in cat-free Madagascar that same niche is filled by a giant killer mongoose called the fossa; meanwhile, in Komodo, a huge lizard claims the top predator role. Different islands, different species, same jobs. The islands in question could be huge land masses, or individual people.

The variations that exist between body parts dwarf those that exist between people. Put simply, the bacteria on your forearm are more similar to those on my forearm than to those in your mouth.

The exact pattern of succession will vary between different animals, because we turn out to be picky hosts. We are not just colonised by whatever microbes happen to land on us. We also have ways of selecting their microbial partners.

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.

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.

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.

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.

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.

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.

inflammation - overabundance of bacteria that provoke the immune system and a lack of that restrain it

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.

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...

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 ma...

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.

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.

In one letter, he complained that students were more interested in money or reputation than in ‘discovering things hidden from our sight’. ‘Not one man in a thousand is capable of such study, because it needs much time, and spending much money,’ he lamented. ‘And over and above all, most men are not curious to know: nay, some even make no bones about saying: What does it matter whether we know this or not?’

Things started changing in the mid-nineteenth century, thanks to a cocky, confrontational French chemist named Louis Pasteur.8 In short succession, he demonstrated that bacteria could sour liquor and putrefy flesh. And if they were responsible for both fermentation and decay, Pasteur contended, they might also cause disease. This ‘germ theory’ had been championed by Plenciz and others, but was still controversial.

Meanwhile, in Germany, physician Robert Koch was working on an epidemic of anthrax that was sweeping local farm animals. Other scientists had seen a bacterium, Bacillus anthracis, in the victims’ tissues. In 1876, Koch injected this microbe into a mouse – which died. He recovered it from the dead rodent and injected it into another one – which also died. Doggedly he repeated this grim process for over 20 generations and the same thing happened every time. Koch had unequivocally shown that the bacterium caused anthrax.

anthrax

Inspired by Pasteur, British surgeon Joseph Lister started using antiseptic techniques in his practice, forcing his staff to chemically sterilise their hands, instruments, and operating theatres and sparing countless patients from raging infections. Others searched for ways of blocking bacteria in the name of curing disease, improving sanitation, and preserving food. Bacteriology became an applied science, which studied microbes in order to repel or destroy them.

This type of partnership gained a new term – symbiosis, from the Greek for ‘together’ and ‘living’.13 The word itself was a neutral one, implying any form of coexistence. If one partner benefited at the expense of the other, it was a parasite (or a pathogen if it caused disease). If it benefited without affecting its host, it was a commensal. If it benefited its host, it was a mutualist.

Once described as a ‘hysterical character out of one of Dostoevsky’s novels’,20 he was a study in self-contradiction: a profound pessimist who tried to kill himself at least twice, yet wrote a book called The Prolongation of Life: Optimistic Studies. And in that book, published in 1908, he projected his contradictions onto the world of microbes. On the one hand, Metchnikoff said that intestinal bacteria produce toxins that cause illness, senility, and ageing and were ‘the principal cause of the short duration of human life’. On the other, he also believed that some microbes could prolong life.

In this, he was inspired by Bulgarian peasants, who regularly drank soured milk and lived well past the age of 100. The two traits were connected, said Metchnikoff. The fermenting milk contained bacteria, including one that he called the Bulgarian bacillus. These made lactic acid, which killed the harmful life-shortening microbes in the peasants’ intestines.

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Theodor Rosebury, an oral microbiologist, started doing that for the human microbiota in 1928. For more than thirty years, he collected every bit of research he could find, and in 1962 he wove those flimsy gossamer strands into a single sturdy tapestry: a groundbreaking tome called Microorganisms Indigenous to Man

He described the common bacteria in every body part in considerable detail. He wrote about how these microbes colonise babies after birth. He suggested that they might produce vitamins and antibiotics, and prevent infections caused by pathogens. He said that the microbiome reverts to normal after bouts of antibiotics, but might be altered more permanently through chronic use. And he was right about most of it.

So it was that Relman, starting a grand tradition of microbiologists sequencing their own microbiomes, asked his dentist to scrape some plaque from the crevices of his gums and dunk it in a sterile collection tube. He took the gunk back to his lab, and decoded its DNA. It could have led to nothing. The mouth was arguably the most well-studied microbial habitat in the human body. Leeuwenhoek had looked at it. Rosebury had examined it. Microbiologists had cultured nearly 500 strains of bacteria from its various niches. If any body part was immune to new discoveries, it would be the mouth.

Jeff Gordon, a pioneer we will meet in a later chapter, showed that our microbes control the storage of fat and the creation of new blood vessels, and that obese individuals have different gut microbes to lean ones.

The museum opened in September 2014, after twelve years of development and cost 10 million euros. It is fitting that such a place should open in the Netherlands.

the squid and other animals tell us that development is more than this. It progresses using instructions in an animal’s genes, but also in the genes of its microbes. It is the result of an ongoing negotiation – a conversation between several species, only one of which is doing the actual developing. It is the unfolding of an entire ecosystem.

Interesting

‘The germ-free animal is, by and large, a miserable creature, seeming at nearly every point to require an artificial substitute for the germs he lacks,’ wrote Theodor Rosebury.