This is the next book in the Caltech book club. I, admittedly, skipped over the biological sciences when I was at Caltech, and that skipping is one of my regrets about my time at Caltech: I came in with these just plain wrong notions about science. Those ideas adversely affected my education, but, fortunately, not my love for science in all its (correctly science) forms.
I read this book, finishing before the first week's discussion, mostly because I keep checking these books out from the library, with due dates much sooner than the slower 1-2 chapters a week pace the book club has. Which is fine, I read the book club books quickly. That I subsequently don't participate in the book club discussions is less fine, I guess.
This book was a meandering survey of various studies, current research, and microbe history. I saw meadering because the book lacked a compelling narrative arc. I was expecting maybe a history arc, or a current research arc, or even the author's journey arc. Instead, the end of each chapter lead into the beginning of the next chapter, with each chapter a swirl of interesting information and sometimes a self-contained narrative. Mostly though, each chapter was a fascinating, meandering discussion of a new topic about microbes.
And by fascinating, I mean fascinating. My incoming supposition was, given how much influence chemicals have over our mental state and body composition, the idea that microbes could and do produce chemicals to induce a state in their host doesn't seem so farfetched. After reading the book, learning about how much we know about microbes, and seeing how much we don't know about microbes, my supposition is more like a fixed assumption in my world. One of those "but, of course" obvious things only after the fact.
I enjoyed reading the book. This book is very much worth reading.
Now we’ve seen that they can sway the brain too – the organ that, more than any other, makes us who we are. It is a disquieting thought. We put such a premium on our free will that the prospect of losing independence to unseen forces informs many of our deepest societal fears.
Wolbachia can only pass to the next generation of hosts in eggs; sperm are too small to contain it. Females are its ticket to the future; males are an evolutionary dead end. So it has evolved many ways of screwing over male hosts to expand its pool of female ones. It kills them, as in Hurst’s butterflies. It feminises them, as in Rigaud’s woodlice. It eliminates the need for them entirely by allowing females to reproduce asexually, as in Stouthamer’s wasps. None of these manipulations is unique to Wolbachia, but it is the only bacterium to use them all.
Huh. So, gay woodlice.
Here is a strange but critical sentiment to introduce in a book about the benefits of living with microbes: there is no such thing as a “good microbe” or a “bad microbe”. These terms belong in children’s stories. They are ill- suited for describing the messy, fractious, contextual relationships of the natural world.
A cut or a bruise can split some of your cells apart and spill fragments of mitochondria into your blood – fragments that still keep some of their ancient bacterial character. When your immune system spots them, it mistakenly assumes that an infection is under way and mounts a strong defence. If the injury is severe, and enough mitochondria are released, the resulting body-wide inflammation can build into a lethal condition called systemic inflammatory response syndrome (SIRS). SIRS can be worse than the original injury.
Some of these molecules get saddled with negative names, like “virulence factors”, because they were first discovered in the context of disease, but they are inherently neutral. They are just tools, like computers, pens, and knives: they can be used to do wonderful things and terrible things.
Couples might work well together, but if one partner can get the same benefits without spending as much energy or effort, it will do so unless punished or policed.
Well, this one hit home pretty hard.
These principles are easy to forget. We like our black-and-white narratives, with clear heroes and villains.
We do. Some of us more than others.
A well-functioning partnership could easily be seen as a case of reciprocal exploitation. “Both partners may benefit but there’s this inherent tension. Symbiosis is conflict – conflict that can never be totally resolved.”
To allow our first microbes to colonise our newborn bodies, a special class of immune cells suppresses the rest of the body’s defensive ensemble, which is why babies are vulnerable to infections for their first six months of life. It’s not because their immune system is immature, as is commonly believed: it’s because it is deliberately stifled to give microbes a free-for-all window during which they can establish themselves. But without the immune system’s full selective powers, how can a mammalian baby ensure that it gets the right communities?
I find this fascinating.
As humans make our presence felt, we disturb the ancient relationships between corals and their microbes, converting the vivid splendour of fish-filled reefs into bleak algal barrens submerged in a pathogenic soup.
And I find this depressing.
... a Grand Unified Theory of Coral Death. It shows how the largest sharks are connected to the smallest viruses.
The most obvious difference lay in the ratio of the two major groups of gut bacteria: obese people had more Firmicutes and fewer Bacteroidetes than their leaner counterparts.
An important lesson emerged: microbes matter but so do we, their hosts. Our guts, like all ecosystems, aren’t defined just by the species within them but also by the nutrients that flow through them.
Herbert “Skip” Virgin published a case study that beautifully supports this idea. He worked with mice that had a genetic mutation common in people with Crohn’s disease. Those rodents developed inflamed guts, but only if they were infected by a virus that knocked out part of their immune system, and were exposed to an inflammatory toxin, and had a normal set of gut bacteria. If any of these triggers was missing, the mice stayed healthy.
Dogs carry microbes from the outdoors to the indoors, offering us a bigger library of species with which to populate our developing microbiomes. When Lynch fed these dog-associated dust microbes to mice, she found that the rodents became less sensitive to various allergens.
Nonetheless, Burkitt was on the right track. “America is a constipated nation,” he said, indelicately. “If you pass small stools, you have big hospitals.”
Scientists will talk about Occam’s razor – the principle that favours simple, elegant explanations over convoluted ones. I think the truth is that scientists, like everyone else, find simple explanations psychologically soothing.
Still, they provide more questions than answers. Did the microbes set symptoms in motion or just make a bad situation worse? Was one species responsible, or a group of them? Is it the presence of certain microbes that matters, or the absence of others, or both?
But if you looked at these communities in isolation you might conclude that their owners were on the verge of chronic disease, when they were merely on the verge of motherhood.
Ecosystems are complex, varied, ever-changing and context-dependent – qualities that are the enemies of easy categorisation.
Hello, systems thinking!
So, mammalian success was founded on vegetarianism, and that vegetarianism was founded on microbes. Time and again, different groups of mammals swallowed plant-breaking microbes from their environments, and used their enzymes to mount assaults on leaves, shoots, stems, and twigs.
The macrotermites there build enormous mounds. Some can tower for up to 9 metres, scraping the skies with Gothic ensembles of spires and buttresses. The oldest one on record – now abandoned – is 2,200 years old.
I want to see one of these mounds now.
Bacteria offer an alternative. They are masters of biochemistry, and can degrade everything from heavy metals to crude oil.
Beetle outbreaks come and go but the current one, fuelled by a warming climate, is ten times bigger than any other. Since 1999, the beetles and their attendant fungi have killed more than half the mature pines in British Columbia and affect 3.8 million acres in the United States. They have even hopped over the cold Canadian Rockies, which long fenced them into the west coast, and are now spreading east. A continuous belt of lush vulnerable forests lies in front of them.
You can see this on any drive in any West Coast state.
Hornets, hawks, and humans might gradually accumulate beneficial mutations, but that individual hornet, or this specific hawk, or those particular humans can’t pick up beneficial genes for themselves. Except sometimes, they can. They could swap their symbionts, instantly acquiring a new package of microbial genes. They can bring new bacteria into contact with those in their bodies, so that foreign genes migrate into their microbiome, imbuing their native microbes with new abilities.
The genes they left behind, these ghosts of symbionts past, aren’t sitting idly among the mealybug’s DNA. Some make amino acids.
Whatever the case, it is clear that an insect, a bacterium, and a virus have formed an evolutionary alliance against a parasitic wasp that threatens them all.
Which is really, really cool.
This point is worth repeating: taking any fast or instant evolutionary shifts as a refutation of the slow, gradual changes we associate with Darwin’s vision is a fatal mistake because these quick shifts are still powered by gradualism.
That is the power of symbiosis: it allows gradual mutations in microbes to produce instant mutations in hosts. We can let bacteria do the slow work for us, and then quickly change ourselves by associating with them. And if these alliances are beneficial enough, they can spread with blinding speed.
When the parasite arrived, it spread like wildfire, riding through the forests in the bodies of its sterilised hosts. The flies needed a countermeasure and Spiroplasma rose to the occasion. It restored its hosts’ ability to reproduce, and allowed them to outcompete their sterile peers. Since the flies could pass these little saviours to their offspring, the proportion of infected insects grew with each generation. And Jaenike had caught this spread at exactly the right moment. “It made me doubt my sanity,” he says. “What are the chances?”
Say goodbye to dated and dangerous war metaphors, in which we are soldiers hell-bent on eradicating germs at whatever cost. Say hello to a gentler and more nuanced gardening metaphor. Yes, we still have to pull out the weeds, but we also seed and feed the species that bind the soil, freshen the air, and please the eye. This concept can be hard to grasp, and not just because the idea of beneficial microbes is new to many.
To control a microbiome is to sculpt an entire world – which is as hard as it sounds. Remember that communities have a natural resilience: if you hit them, they bounce back. They are also unpredictable; if you tweak them, the consequences ripple outwards in capricious ways. Add a supposedly beneficial microbe, and it might displace competitors that we also rely on. Lose a supposedly harmful microbe, and an even worse opportunist might rise to take its place.
These emerging infectious diseases of wildlife are emerging ever more quickly, and humans are at least partly to blame. On planes, boats, and boots, we carry pathogens around the world with unprecedented speed, overwhelming new hosts before they can acclimatise and adapt.
Yet despite the excessive hype, the concept behind probiotics is still sound. Given all the important roles that bacteria play in our bodies, it should be possible to improve our health by swallowing or applying the right microbes. It’s just that the strains in current use may not be the right ones. They make up just a tiny fraction of the microbes that live with us, and their abilities represent a thin slice of what the microbiome is fully capable of. We met more suitable microbes in earlier chapters. There’s the mucus-loving bacterium, Akkermansia muciniphila, whose presence correlates with a lower risk of obesity and malnutrition. There’s Bacteroides fragilis, which stokes the anti-inflammatory side of the immune system. There’s Faecalibacterium prausnitzii, another anti-inflammatory bug, which is conspicuously rare in the guts of people with IBD, and whose arrival can reverse the symptoms of that disease in mice.
We have already seen that what we eat can substantially change the microbes in our gut, and prebiotics like inulin are in plentiful supply in onions, garlic, artichokes, chicory, bananas and other foods.
Jim Collins is more circumspect. Given how much we still don’t understand about the microbiome, he is unsettled by the prospect of engineering microbes that can permanently establish themselves in our bodies. That’s why he is also focusing on building kill-switches that will force the microbes to self-destruct if something goes wrong, or if they leave their hosts.
Or that so many scientists would study it that they would organise a bi-annual, Wolbachia-devoted conference to share their results?
Of course they would! Humans love their communities, we are social creatures.
I contain multitudes, yes, but only some of them; the rest, I extend into the world like a living aura.
We all have our cloud of microbes! I love this!
Within 24 hours of moving into a new place we overwrite it with our own microbes, turning it into a reflection of ourselves.
We also change the microbes of our housemates. Gilbert’s team found that room-mates share more microbes than people who live apart, and couples are even more microbially similar.
In both settings, sterility is a curse not a goal, and a diverse ecosystem is better than an impoverished one.
In the developing world, around 5 to 10 per cent of people who check into hospitals and other healthcare institutions pick up some kind of infection during their stay, falling ill in the very places that are meant to make them healthier. In the United States alone, this means around 1.7 million infections and 90,000 deaths a year.
By removing harmless bacteria that would otherwise impede the growth of pathogens, perhaps we have inadvertently constructed a more dangerous ecosystem.
Gibbons showed this by studying public toilets. He found that thoroughly scrubbed toilets are first colonised by faecal microbes, which are launched into the air by roiling, flushed water. Those species are eventually outcompeted by a diverse range of skin microbes, but once the toilet gets scrubbed again, the communities go back to square one. So, here’s the irony: toilets that are cleaned too often are more likely to be covered in faecal bacteria.
Jessica Green, an Oregon-based engineer-turned-ecologist, found a similar pattern among the microbes that float inside air-conditioned hospital rooms.7 “I assumed that the microbial community of the indoor air would be a subset of that of outdoor air,” she says. “It really surprised me that we saw little to no overlap between the two.” Outdoors, the air was full of harmless microbes from plants and soils. Indoors, it contained a disproportionate number of potential pathogens, which are normally rare or absent in the outside world, but had been launched from the mouths and skins of hospital residents. The patients were effectively stewing in their own microbial juices. And the best way of fixing that was remarkably simple: open a window.
And I see, in the driver’s seat, a guy who notices those rivers of microscopic life and is enthralled rather than repelled by them. He knows that microbes are mostly not to be feared or destroyed, but to be cherished, admired, and studied.
We see how ubiquitous and vital microbes are. We see how they sculpt our organs, protect us from poisons and disease, break down our food, uphold our health, calibrate our immune system, guide our behaviour, and bombard our genomes with their genes.
A bacterium in your gut might be able to transfer its genes into one of your intestinal cells, but once that cell dies, the bacterial DNA goes with it. The gene might become part of a human genome, but never the human genome.
In 2013, Dunning-Hotopp showed that these short-lived unions are surprisingly common (Riley et al., 2013). She analysed hundreds of human genomes that had been sequenced from body cells – the ones from kidneys or skin or livers, none of which get passed on to offspring. She found traces of bacterial DNA in around a third of them. They were especially common in cancer cells; an intriguing result with unclear implications. It might be that tumours are especially prone to genetic intrusions, or that bacterial genes help to transform healthy cells into cancerous ones.