I, Superorganism

Learning to love your inner ecosystem

Jon Turney

• Publisher: Icon Books
• Year: 2015
• Print ISBN: 9781848318229
• eBook ISBN: 9781848318236
• Topic: Biological Sciences
• Subtopic: Microbiology
• Index: Biological Sciences

Every human body carries a secret cargo: a huge population of microorganisms living in the mouth, on the skin, in the gut. They help digest our food. They make essential vitamins. They break down toxins and metabolise drugs. They exert an invisible influence on our hormones, our immune systems, perhaps even our brains.This is the human microbiome – a living, shifting system of previously unimagined importance and complexity.In this first book-length account of this new realm of human biology, award-winning science writer Jon Turney explores the microbiome in detail, charting its birth and development, investigating how it works, and assessing its many implications for our health, including its potential to shed new light on conditions such as bowel diseases, cancer, allergies and asthma. He considers the potential impacts of our modern disinfectant and antibiotic obsessions, and ponders a future of designer microbiomes and mood-altering probiotics. This book will make you think again about your relationship with your body, your habits – even your sense of who and what you are – as it reveals what it means to be a 21st century superorganism.

1 Strange new world

In 1676 Antonie van Leeuwenhoek, a prosperous Dutch draper, was ten years into one of the most breathtaking observational binges in the history of science. A decade earlier, he pored over the images in Robert Hooke’s celebrated Micrographia (1665), marvelling at its mind-expanding drawings of things never seen before – the multifaceted eye of a fly, the barbs on a bee sting, a louse clasping a human hair.

Inspired, Leeuwenhoek perfected a way of making simple handheld microscopes with minute spherical lenses. He soon saw what Hooke saw, but his superior instruments allowed him to go further. Yes, large organisms had extraordinarily intricate small parts. But there was more going on beneath the level of normal human vision. In a drop of pond water he reported seeing minute single-celled creatures, ‘animalcules’, as he called them. He also saw even smaller creatures, the first of them in water in which he had ground up pepper in an effort to investigate its spicy taste. His claims, included in a 1676 letter to the Royal Society in London – then the best way of informing others of new scientific findings – seemed bizarre, but Hooke returned to his microscopes and confirmed it was true. When the Dutchman’s findings were published in the Society’s Proceedings, Leeuwenhoek’s animalcules were a sensation – the first entrancing glimpse of microbiology.^a

Seven years on, and one of his now regular letters to the Royal Society described what he saw when he scraped some of the white matter from between his teeth, ‘as thick as wetted flour’, mixed it with rainwater or spittle, and examined it at high magnification. ‘To my great surprise … the aforesaid matter contained very many small living animals, which moved themselves very extravagantly’.

Motion was, for Leeuwenhoek, the sign of life. He assumed that the many small bodies he saw that did not seem to move were dead matter. Now we know they are just less mobile microbes. But his description of his miniature zoo was still a revelation. There were new kinds of life, invisible and unimagined in all earlier human history. And they were not just out there in the world but living on us.

The insatiably curious Dutchman was full of wonder at the life he had excavated from his own mouth. He described with delight the animalcules’ ‘pleasing motions’, the ways they moved, their variety of shapes, their sheer profusion. The smallest kind had motions that reminded him of ‘a swarm of flies or gnats flying and turning among one another in a small space’. They were so numerous that, he wrote, ‘I believe there might be many thousands in a quantity of water no bigger than a [grain of] sand’.

He found the same inhabitants in the mouths of two ladies – probably his wife and daughter – who, like Leeuwenhoek, cleaned their teeth regularly. Elsewhere he told how when he scraped the teeth of ‘an old gentleman, who was very careless about keeping them clean’, he found, ‘an incredible number of living animalcules, swimming about more rapidly than any I before had seen, and in such numbers, that the water which contained them (though but a small portion of the matter taken from the teeth was mixed in it) seemed to be alive.’ Urging his main conclusion on the Royal Society, he reached again for the right comparison. ‘The number of animals in the scurf of a man’s teeth are so many that I believe they exceed the number of men in a kingdom’.

The revelation that we teem with other life was a sensational exhibit in a catalogue of wonders that the microscope made visible. Along with the telescopic discoveries of Galileo, natural philosophers’ new access to the micro-world was the first thing to establish that science could only gain by using new instruments to go beyond the unaided human senses. At first, not everyone could accept that phenomena hidden from normal vision were real in the same way as those that pass the simpler naked-eye test of ‘seeing is believing’. But the majority believed that science was gaining unprecedented new access to important knowledge about things in the world. In this way, our own microbes had a starring role in the genesis of a recognisably modern way of doing science. That makes it more surprising, somehow, that so much about them remained unknown until so recently.

A molecular menagerie

A little over 300 years after Leeuwenhoek, another curious human scraped his own teeth in search of wildlife. To be accurate, David Relman got his dentist to do it. Instead of discarding the gunk from Relman’s gum crevices when he cleaned his teeth, the dentist put it in sterile collection tubes that the Stanford University researcher had taken with him to the surgery.

Relman had been getting to know new DNA-based techniques to pin down pathogenic bacteria that resisted identification because they refused to grow in culture in the lab. He got to wondering if many species were going overlooked in the complex population mixtures of our normal microbiota for the same reason. Back in the lab he followed normal microbiological routine and set up cultures from the samples. But the key results came from an addition to the routine.¹ He used some of the sample for the latest DNA analysis, seeking small pieces of gene sequence characteristic of bacteria and comparing them with known sequences in scientific databanks.

It would have been easy to assume there was nothing much more to find in the pockets between teeth and gums, the subgingival crevices. Over the years, careful bacterial cultivators had logged almost 500 different species of bacteria recovered from this well-populated region of the mouth.

However, working over this one-shot sample from two teeth in one mouth, Relman’s team found 31 new strains of bacteria, identified by their DNA sequences. Another six turned up on the culture plates for a final tally of 37 new kinds – out of 77 in total. Probing bacterial DNA uncovered a whole new dimension of life on us.

In the sober language of the Proceedings of the National Academy of Sciences in 1999, Relman and his colleagues reckoned that ‘Our data suggest that a significant proportion of the resident human bacterial flora remain poorly characterized, even within this well studied and familiar microbial environment’. Or, as he later told the San Francisco Chronicle, ‘We found much, much more with the molecular methods than we found with cultivation. That meant we’d been missing this huge fraction of the microbial world for more than 100 years. That’s a humbling thing. We were playing with half a deck.’

That realisation fuelled a big effort to apply the new technologies of DNA sequencing to microbial samples from as many human body sites as people could poke, scrape, rinse or mop up. Since the millennium, the results of this effort have transformed our picture of the human microbiome, and of how we and a myriad of other species coexist.

But before we look any more closely at the results of these deeper probes into the unseen world, and the questions of meaning with which scientists are now grappling, let us go back. Because in the three centuries between these two enterprising observers of teeth, we learnt a few other things about microbes.

Good guys, bad guys

Leeuwenhoek’s animalcules were fascinating to enlightened society, but seemed mainly a harmless novelty. Some simple experimentation showed that the newly fashionable 17th-century beverage coffee, or a little vinegar, destroyed the life in his field of view. Besides, the idea that creatures so small could have any important effects on their hosts seemed fanciful.

Now we know better. The most significant changes in knowledge came in the 19th century. The germ theory of disease emerged from a combination of a closer investigation of infection with a newly systematised science of microbiology. Contagion, or close contact, had long been associated with the spread of some diseases – but contagion with what? Now it became clear that the crucial contact was with microbes, and it was thus convincing to claim that microscopic life had momentous effects on much larger organisms, with microbes as the main actors in a compelling new explanation of some deadly illnesses.

That also had a big effect on how people thought about microorganisms – two kinds of effects, in fact: scientific and cultural. Both are still very much with us.

Scientifically, part of the legacy of germ theory is a template for how to reason one’s way through causes and effects in the moist, mixed-up world of biology – a template for microbial logic, if you like. It still conditions a lot of our thinking about links between the human microbiome and disease, although, as we will see, it is much harder to apply to the kind of results modern research delivers.

Back in the 19th century, the mysterious organisms that showed up under the microscope were mostly recovered from outside us. Finding them inside mainly happened when people investigated disease. But were the minute creatures recovered from patients or sick animals (and perhaps kept alive as cultures in the lab) causing the symptoms? It is hard to recover this mindset now, but there were reasons to doubt it, and plenty of sceptics. Persuading them that the theory was sound demanded a mass of evidence, and then some clear rules of inference. Then you could build a watertight case.

The germ theory codified those rules. At its simplest, the theory assumed the form of the ‘OGOD’ hypothesis – One Germ, One Disease (this later spawned a close relative, One Gene, One Disease, but that’s another story).²

If OGOD is true, and there are lots of germs about, how can you tell you have found the guilty organism? The rules derive from a general approach to scientific experiments that we now take for granted. It was first described formally in the 19th century by the philosopher John Stuart Mill, who called it the method of agreement and difference. It is the recipe for the perfect experiment that we learn in school. Define all the conditions in some controlled set-up. Vary them one at a time, and see what happens. If variable X causes a change in result Y, then the two are linked in some way. The easy example is working out what caused some of the party to get food poisoning after dining out, by detailing who did, and who did not, eat various things.

For germs, the details came from the German bacteriologist Robert Koch (1843–1910). In the early 1880s, he and his great rival Louis Pasteur had established connections between a few diseases, mostly in animals, and specific infectious agents. Koch wanted to generalise, and to quiet doubters.³ Along with ferociously energetic lab work, and advances in method (he pioneered both the use of microbiological plates instead of flasks of broth for growing colonies, and staining bacteria with dye to aid microscopic identification), he formulated the rules known as Koch’s postulates. There were just four. They translated easily into instructions for demonstrating that a germ really caused a disease. Do these four things and you could be sure you had the answer, and convince everyone else:

1. Find the microorganism in all the subjects (animals or people) who have the disease, but not in healthy specimens.
2. Isolate the microbe from a diseased organism and grow it in the lab, in culture.
3. Dose a healthy host from the culture, and give it the same disease.
4. Isolate the microbe again from the newly diseased host, and show that it is the same as the one you started with.

None of this was exactly easy, even in experimental animals, let alone human patients (step 2 was especially frustrating). But as methods improved, the four postulates proved their worth, advanced science and earned the gratitude of millions. The great scourge tuberculosis was the test case for these rules. Cholera, typhus, tetanus and plague followed and were all correctly identified as infectious diseases in the next dozen years.

The logic remains sound, provided it is the bug, and only the bug, that is involved in the disease. Many later cases – and quite a few of the classic ones, like tuberculosis – are a good deal more complicated than that. But it remains the often-cited gold standard for working out the links in chains of cause and effect that lead from other organisms to effects on people. Is it helpful in unravelling cause and effect in the complex ecologies of our microbiome? We will have to come back to that question later.

The power of Koch’s logic, though, reinforced the cultural impact of the germ theory. Along with spectacular medical successes, the newly white-coated microbiologists of the 19th century were also illuminating the beneficial roles of microbes. Pasteur, in particular, was interested in fermentation as well as infection. But the fanfare that accompanied demonstrations that microbes could cause disease tended to drown out the news about the good guys that were making cheese or wine. The idea took hold that germs, with a few honourable exceptions, were evil.

Don’t touch – dirty!

Here’s how to open a can of peaches. Remove the label, then scrub the can to remove all traces. Open the lid, and pour the peaches into a bowl. Do NOT let the can touch the bowl.

So staff were instructed in the kitchen of Howard Hughes, pioneering 1930s aviator, film-maker, billionaire recluse and long-time sufferer of obsessive-compulsive disorder.⁴ The same staff had to wash their hands until they were sore, and wrap them in paper towels when they served Hughes’ meals. There were detailed instructions on how to open the packaging for the towels.

Hughes’ deteriorating mental condition made him an extreme case of a common dread. He was fabulously wealthy, but had brain injuries from several air crashes and had contracted syphilis as a young man. Before any of these things happened he also acquired a lasting fear of germs. His later sad fixation on their dangers is emblematic of a culture preoccupied with an insidious microbial threat to health.

It is easy to see why. The germ theory of disease came when city dwellers were suffering from infections that spread through populations crowded together in unsanitary dwellings. The theory was a colossal success. It won over scientists when Koch, Pasteur and others showed that much-feared illnesses really were caused by tiny organisms. It won over the public by being easy to understand, and because – via vaccination and building proper sewers – it paved the way for their prevention and treatment. Some feared diseases were even eradicated. It remains a cornerstone of the new discipline of public health.

It was, in short, a scientific and medical triumph and the scientists who established it were heroes. Paul De Kruif’s classic The Microbe Hunters, a 1920s popular book by a writer who spent time at the Rockefeller Institute for Medical Research in New York, depicts a series of bacteriological pioneers in that light. It caught the tone of innumerable newspaper profiles and a clutch of later biopics.

They were heroes because they waged war against disease, and triumphed. And germs were the enemy. The celebration of science cemented a powerful association between germs, d...

Table of contents

• Copyright Page
• Contents
• Introduction: Organism, meet superorganism
• Chapter 1: Strange new world
• Chapter 2: Microbes aren’t us – or are they?
• Chapter 3: Invisible lives
• Chapter 4: Microbes, microbes, everywhere
• Chapter 5: The big one
• Chapter 6: A microbiome is born
• Chapter 7: Working together
• Chapter 8: There goes the neighbourhood
• Chapter 9: Gut feelings
• Chapter 10: Viruses are us, too
• Chapter 11: Civilising the microbiome
• Chapter 12: I, superorganism?
• Acknowledgements
• Notes
• Bibliography
• Further reading
• Index