Organism, meet superorganism

WHO AM I? THE MIRROR REMINDS ME. HERE I STAND, UNCLOTHED (don’t worry, I’ll look so you don’t have to). I see a pale, upright biped. White, middle aged, male. Tall for a human, with a slight tendency to stoop. I’ve had a medically charmed life so far, as baby-boomers in the West may enjoy. Not too many signs of wear and tear yet. If I recall the image in the glass from 30 years ago, say, the current version of me has a thickening waist – and, I notice, toenails – and thinning hair. Otherwise I seem to look much the same.

That continuity, this body, is part of my sense of self. A human body, pretty large by the standards of Earth creatures, is a marker of individuality. I do not mean that in any philosophical sense – I am an autonomous human subject and this is my body. Or perhaps I do. I do not mean it, anyway, in any sense of the individual ‘me’ as unique.

But I do feel, for what it’s worth, that the infinitesimally tiny fraction of the universe’s matter and energy that is me can be separated out. The portion of biomass that I haul around – or that hauls me around – has the usual apertures and orifices where stuff goes in or comes out. If I want to stay alive, that has to happen with some regularity. But it looks to me as if this body has a pretty clear boundary. It seems clearly distinct from the rest of the world. I do experience conscious connections with other people, mainly because I have language. Today I am connected to thousands more, through our technologies. But the ‘I’ that is connected is also embodied. I am a biological entity; a human animal; an organism.

I have always felt that this organismic me, now one of 7 billion or so of the type, is a vessel built for a solo voyage. Artists and poets share that intuition. As Orson Welles said, we are born alone, we live alone, we die alone. He went on to say that love and friendship can still make life worthwhile – which is true. But the premise, it turns out, is entirely wrong. Science, quietly at first but with increasing insistence over the last decade or so, begs to differ. You, like me, are an individual human. But we’ve all got company. Lots of company.

Look again

Ever looked inside your mouth – not with a mirror, but a microscope? Chances are you did this at school. If you don’t remember, here’s what you do. Gently scrape the inside of your cheek. Use a clean cotton swab if you have one, the flat end of a toothpick or even the end of your fingernail if you don’t. Dab the goo on a microscope slide, add a drop of methylene blue dye, top with a cover slip, slide onto the microscope stand and ... focus. Even at low power, say ten times magnification, you’ll now see some cells. They are flat – and not just because they are squashed on the slide. Flat is normal for cells of this type, from the tissue known as squamous epithelium. You can see the nucleus, which looks after the hereditary instructions (the dye stains the DNA, among other things), separate from the rest, the cytoplasm.

A single cell at this magnification doesn’t look that impressive. But every one is a reminder of an astonishing fact. Each of us is a vast, highly organised coalition of many such cells, tiny morsels of a much bigger organism, which can usually grow and divide in their own right. Far beneath the everyday scale of an upright mammal are the elementary particles of life. Growing and dividing from a single cell, a newly fertilised egg, they eventually number in the trillions, and play their part in maintaining the highly organised assembly that is me, or you.

But there’s more. Up the magnification, and there will be small blue-dyed dots under and around the large, blobbier-looking epithelial cells. They are bacteria. They will be there even if you used the clean swab rather than your finger. Your mouth – cheeks, tongue, teeth, gums and all – is full of them. It is warm and moist in there, and you keep adding nutrients, on their way to the stomach. What’s not to like? You would find them, too, on every other surface of your body, including the internal ones like the intestine.

Until very recently, few gave much thought to the bacteria and other microbes to whom we give house room. But they have been there all through our evolution. Bacteria got here first. They are woven into our lives more closely than we ever imagined until recently. They congregate in complex, shifting communities that are shaped by, and help shape, the lives of our other cells. They carry out a surprisingly large portion of our digestion. They make essential vitamins and other molecules. They break down toxins and metabolise drugs. They exert an invisible influence on our hormones, our immune systems and perhaps even our brains. And they crowd out other, potentially harmful organisms by filling the niches that they would occupy if they could. We would miss our many, many microbes badly if they were not there.

Scientists call the whole ensemble of microbes that make their living as fellow travellers with some larger organism the microbiota, or more often these days the microbiome. My microbiome is as alive as I am. It develops, responds, adapts as life goes on, just as my own body cells do. So does yours. What that means for how our lives play out, and how we should think of the enlarged cellular community that constitutes a person, is just beginning to become clear – with the aid of techniques more powerful than any microscope.

Show us your DNA

We have been looking at microscopic organisms for 300 years or so. But very recently we started looking at them in a new way. The first human genome — the complete set of genes in each of a person’s body cells — was completely sequenced a bit over a decade ago. That achievement paved the way for routine, large-scale sequencing. There is still lots to work out about our genes and how they operate, but what we do certainly know is how to sequence large amounts of DNA. That has given us an amazing new window on to the microbial world.

Biologists used to work on microbes — mainly bacteria and viruses — one at a time. Most of what we know about DNA and how genes work comes from studies that began in bacteria, especially one that became a laboratory workhorse: E. coli. ‘What’s true for E. coli is true for an elephant’ was a tongue-in- cheek slogan heard among the pioneers of molecular genetics in the 1960s, in recognition of how much they had invested in one small organism.

That research in turn was founded on good microbiological practice first laid down in the 19th century. Generations of 20th-century molecular geneticists worked with colonies of bacteria grown up from a single cell in a shallow dish layered with nutrient jelly. That is not how microbial life is lived outside the lab, and it works only for a minority of types of microbe. Bacteria, like us, normally live in a world that everywhere teems with other life. We knew that, in theory. But the new-style DNA analysis has been revelatory, especially in showing how varied and complex microbial life is.

Nowadays it does not matter if you have a pure sample of anything. Just take whatever mixed-up matter you can lay hands on, extract the genetic material and work on all of it at once. This is the new science of ‘metagenomics’. It begins with taking a bunch of stuff that may contain living cells, or maybe viruses, cutting up all the DNA, and sequencing it. Seawater, soil, and shit are good things to sample. What usually comes out of this rough-and-ready analysis is a huge higgledy-piggledy list of genes. Then the researchers try to figure out what they all are, and where they come from.

This genetic window offers a startling new view of the complement of cells, human and microbial, that make up the person I see in the mirror. It is a quintessentially modern view. The kilo or so of bacteria in my colon, for example, are a considerable cell mass. They are also a great store of information.

How big a store? The answer comes as a jolt if you think that the self you can inspect in the mirror is you. Most of your genes do not really belong to you at all.

The Human Genome Project focused attention on our own chromosomes, the carefully packaged lengths of double- stranded DNA that reside in the nucleus of each human cell and help to define our individuality. They turned out to have 24,000 genes altogether. That was a lot fewer than the figure of 100,000 or so that was regularly quoted before we looked properly. Still, it appears to be enough to support a complex organism with trillions of cells divided into around 200 different cell types.

The way our microbes organise their genes is quite different from the one-size-fits-all approach that the cells in a large, multicellular creature adopt. First, the number of microbial cells is higher. Counting is hard, and calls for adding up population estimates for guts, mouths, noses and vaginas as well as sampling skin. Published figures for the number of bacterial cells we carry range from 30 to 400 trillion. If the total population of cells in a person decided what happened in our life by majority vote, the bacteria would probably win.

But that is only half the story. How many microbial genes are there? Again it is hard to be precise. These microbial cells do not share a genome, and there are many different species involved. But the DNA tells us that the total number of genes in one typical human microbiome is around 2 million. That is a hundred times as many as we maintain in our own cells. Moreover, as you move through a human population the number of our genes stays the same. Every human microbiome is different, though, so the number of microbial species, and genes, keeps going up as more samples are analysed. The number of genes that have ever been registered in any human micro- biome is now five times higher than in any single individual’s complete microbial complement. Let me spell that out again. Human cells have 24,000 genes. All the microbes that live on and in human beings incorporate 10 million of them.

Genes allow organisms to do things, and this is an enormously rich genetic resource. We are just beginning to find out what it can do for us. We already know that our personal load of bacteria help digest our food, process drugs, and activate our immune systems. They are involved in a raft of diseases, especially those affecting the bowel. Indirectly, they may affect whether we get fat, develop cancer, or even suffer high blood pressure, heart disease or strokes. They seem to affect asthma. And there are hints that the precise make-up of the bacterial population in our guts can even affect brain development and behaviour.

This is just the start, though. Many of the microbial genes already found are of unknown function. We are still finding new species, new genes and new interactions. As well as bacteria in the microbiome, there are single-celled organisms of other kinds. There are numerous fungi that find humans congenial hosts. And there is a largely uncatalogued array of viruses, which add more depth to the genetic reservoir. We are covered in life, awash with it, saturated with it, in such variety that it is hard to take in.

As well as an impressive genetic resource, we are also find- ing that our microbiome is the wellspring of a vast, largely unmapped reservoir of human diversity. The range of species and strains of bacteria can differ wildly in different people. Even close relatives or those who live together maintain some microbial differences. And we all have different microbial populations in different parts of the body, from the armpits to the anus. They change over time, as we eat different foods, grow older, move from place to place, swab, scrub, or disinfect ourselves, or swallow antibiotics. For once, science really has revealed a new world. This one is in inner space. It is part of us.

What about me?

Sometimes science advances because of some radical conceptual breakthrough, from a Newton or an Einstein. More often, it moves ahead more slowly, as small observations alter the picture we are building of reality bit by bit. What is happening now is different again. It is one those times when a sudden leap in observational power transforms the view – and itself leads to a kind of scientific revolution.

That is exciting, fascinating, and, as the news filters through to the rest of us, a bit puzzling. I want to know what the emerging picture of the microbiome means for me. It seems amazing, when science recovers signals from the origins of the universe or probes the ultimate constituents of matter, that the profusion of life we carry, and have always carried, has largely eluded us for so long – hidden in plain sight, almost. If science is one of the ways in which we can know ourselves more completely, we have taken a long while to get round to this part of ourselves.

I am usually wary of stories about what this or that scientific revolution means for us. What do the latest findings in cosmology, particle physics or earth science mean for humanity – or even (and I am never sure what to make of this phrase) ‘what it means to be human’? But the revolution in understand- ing the human microbiome is actually about us, and about me. It seems fair to ask what it all means, if not for what it means to be human then certainly for what it is like to be alive in the world

There is no single answer. Exploring this world is changing our view of many parts of our lives. The flow of new scientific publications about our innumerable microscopic companions is a steady stream now growing towards a flood. More and more labs are joining in the work of finding out who’s there and what they are up to. At the moment, following microbiome research is not so much like keeping moving goalposts in view as tracking a rocket accelerating off the launch pad.

All this new research will change the way we tackle lots of problems, especially medical problems. It will change how we think of ourselves. We are still upright primates, who share a common ancestor with chimps and have chattered our way to a new kind of culture, technology and civilisation we are proud to call human. But now we look a little different. We have, some suggest, a whole new organ to look after – a microbiome. Alternatively, we are walking, talking bioreactors, wearing thousands of other species, and incubating thousands more in our guts. Then again, the whole assembly can be described as an ecosystem, or really a collection of ecosystems, all busily oper- ating at the cellular level. But there is yet another description on offer, which may best sum up what it is to have such a huge collection of microbial fellow travellers. It is a description that recognises that many of them are useful, if not essential. They are not commensals, as biologists refer to cohabiting organisms that simply do no harm (it means ‘sharing a table’ in Latin); they are full, mutually supporting partners, each relying on the other for mutual support. That kind of sharing has another name: symbiosis. Microbiome studies tell us that we have more symbionts than we ever dreamed. And the whole ensemble they compose, along with us, is a superorganism.

In this book, I review as much of the latest research as I can squeeze in. Then I come back to this big question: what does it mean to be a superorganism? I cannot offer one big answer to that, so I give you lots of small ones. There is some advice, drawn from research, on how to look after your microbiome. I look at where the research is likely to go next, with some as yet unanswered questions and predictions for how answers might be teased out. And finally I go back to the mirror, to contemplate my new, composite self.

Whichever way we look at it, our bodily life is intimately involved with myriad other small lives. Reading genomes has already revealed a new dimension of our connection with the rest of life, in the genes we share with every other organism. Getting to know our own microbes shows yet another. Will we end up valuing them more, even admiring them? In a world of antibiotics, antisepsis, disinfection, and pasteurisation, will we try to look after them better? Or can a superorganism look after itself?

(more? go here —