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The Little Things That Rule the World

Talking to science writer Ed Yong about his gutsy new book

It all started, perhaps, with the mouse gut. Science journalist Ed Yong’s fascination with the microbiome—the microorganisms living inside of us—began when he encountered a study about transferring microbes from the stomachs of obese and skinny humans into the guts of baby lab mice. In 2013, a team of biologists at Washington University in St. Louis published their findings: After several weeks of eating standard mouse chow, the mice given obese humans’ microbes put on weight, while those given skinny humans’ samples remained skinny. But if the different mice shared a cage, the microbes from the skinny mice seemed to influence the fat mice, and they slimmed down. Microbes weren’t necessarily the secret to staying slim, but they certainly seemed to be influencing the mice in unexpected ways. And not just mice—as Yong’s reporting would show him—but humans and every other living creature, more or less.

Aphids, for example, transfer microbes that help them gain immunity to parasitic wasps via sex. (“A beneficial STD,” Yong says, “was too good not to write about.”) In another recent study, a strain of bacterium reduced symptoms of depression in people with irritable bowel syndrome. Then there’s fecal transplants — literally taking poop from a healthy person’s stool sample and reseeding the bacteria into a less healthy person’s gut via colonoscopy. One clinical trial showed that fecal transplants cured 94 percent of patients suffering persistent, severe diarrhea, while the standard treatment, antibiotics, only worked for 27 percent of patients. But fecal transplants, no matter how miraculous they may seem, are still poop, which means they can spread potentially harmful bacteria along with the desired ones.

Yong’s new book, I Contain Multitudes, is a deep dive into the universes of microbes, both inside and all around us. As Yong tells it, these “secret lords of life on earth” are living organisms in ridiculously complicated environments. Releasing several billion of them into one part of our body (like the gut, for example, or a patch of skin) is akin to releasing an animal into the wilderness: Maybe it will benefit the ecosystem, maybe it won’t, maybe it will die long before we have a chance to find out. There’s a lot we don’t know about microbes, but what we do know, as laid out in Yong’s book, is endlessly intriguing.

A lot of smart people view bacteria we encounter either as something to attack and repel or to cultivate and invite into our bodies. But something your book does very well is counter the notion that there are good microbes and bad microbes.

Right, because it’s a little bit narcissistic to do so, right? We’re thinking entirely from our own point of view. We humans like our clean buckets, we like putting things into neat categories, but the world of the microbiome is very resistant to that because it’s so messy and so contextual, it’s so dependent on circumstance. And from a microbe’s point of view, you’re right: We are just another habitat, just another world for them to colonize and live in. And sure, we have evolved these incredibly intimate partnerships that often work to the mutual interests and betterment of both parties, but we should never forget that they’re not our friends.

These partnerships can break if our immune system gets compromised, if the microbes get in the wrong place. There’s always that tension because we’re talking about separate entities which each have their own evolutionary interests. So the question then becomes not, how can we get the good bacteria? It’s more about, how can we control the ecosystems inside us, to improve the odds that our relationship with them will be a beneficial one?

I love your description of the immune system as acting more like park rangers, trying to keep these ecosystems inside us in check. It’s not simply going to war with invaders. Oftentimes the invader is in our body already; it’s just that one microorganism population suddenly tips the scales.

That was one of the things that most blew my mind: that we’ve long thought of the immune system through militaristic metaphors, as this defense force that recognizes self from non-self, domestic from foreign, then annihilates the latter. But obviously we have so much non-self in the body: We have all these microbes that are living with us all the time, and the immune system isn’t going berserk all the time. It’s sort of controlling which species are present, where they get to live, the make-up of these communities. And the bacteria themselves are also influencing the development of the organism. So the animals in the park are hiring the rangers in the first place.

Something you mentioned at the beginning of that answer, about how much “non-self” we have in us — this book kind of quietly but persistently demolishes the notion of self in this really wonderful way.

I think the majority of the book is devoted to showing how all these things that we think of as the province of individuals — digestion, development, health, the brain, our thoughts and behavior — all of these things have some kind of microbial component or influence. And then I wanted to end the book with this chapter showing that that influence extends into the world around us. So we are constantly extending our microbiome beyond the boundaries of our own bodies…. Not only do microbes influence our lives, but they also connect us to the world. I think there’s something kind of magical and a little bit moving about that.

Well, there’s also magic in how microbes influence our behavior, and how that might be harnessed medically to treat depression, or addiction, or a number of other persistent diseases.

There’s so much potential there. Firstly, because microbes are so influential in our lives. We see that they have a say in many aspects of our health and our existence and also that, theoretically, they’re very mutable — they’re flexible. You know, if you discover, like, a gene that increases your risk of a disease, it’s going to be really hard to rewrite or edit that. But if you find an aspect of the microbiome that is increasing your risk of disease, then theoretically it should be easier to fix that.

I think we should note, too, that it’s kind of astonishing that we’re even thinking about doing this at all. We are the first organisms in the 4.5 billion year history of the planet that can see microbes, that know that they exist at all, and that are now thinking about manipulating and shaping them. So I think that’s kind of extraordinary.

Right. But humans don’t have the best track record for manipulating and shaping our environments…

Yeah, right [laughs]. That’s the thing, right? I think the views of the scientists I’ve talked to vary greatly depending on their background, right?

I think clinicians and people who specialize in infectious disease are more used to this idea that if you see a problem you can sort of fix it — you can add or subtract something to improve health. But I think the ecologists I speak to are maybe a little bit more cautious and reserved about our chances, and what it will take to be successful at this.

We do have a pretty miserable track record of trying to fix large scale ecosystems. We’ve introduced species that have gone on to do terrible things; we’ve removed species that have had disastrous effects. So I think we need to learn from those large-scale lessons, and I think we can only do that if we truly understand that. What we’re talking about is ecosystem engineering: We’re shaping very, very vast worlds, even if those worlds are microscopic and contained within us.

Say we do begin to figure out how to meaningfully manipulate and engineer these ecosystems — do you worry that once this research and knowledge gets outside of the lab and into marketing and health culture, then it potentially becomes a problem, because there are so many subtleties?

Yeah, absolutely. And I think how you regulate the space is a very interesting issue because I think a lot of the possible solutions — whether it would be a sort of cocktail of beneficial microbes you swallow or something like that— these will probably need to be pretty personalized. They will need to be tweaked according to an individual’s disease or perhaps their own native microbiome. But then you’re talking about, how do you go about regulating and getting approval for a mixture of living organisms that needs to be made bespoke each time?

That seems… pretty hard.

On the other hand, a lot of these solutions, like fecal transplants, are so easy to do on your own that there’s this thriving DIY community. And I think we have to recognize that that’s been very, very helpful for people who’ve had intractable problems and have been ignored by their doctors and felt that they were running out of options. But it’s also being used for conditions where there’s just no evidence of efficiency or safety, and that’s more worrying.

People love a quick fix. It reminds me of the over-prescription of antibiotics. Now that we know what the end game of that is turning out to be — antibiotic-resistant bacteria — it might be worth waiting.

Right, absolutely. And I think you’ve hit the nail on the head… The thing to focus on is about judicious use. It’s about avoiding over-use.

If you’ve got a kid who’s really ill and antibiotics can help them, I think you’d be hard-pressed to decide not to give that to them on the grounds that maybe, based on science that’s still emerging, that there might be negative consequences in their microbiome. We also know that microbiomes are very resilient; they can bounce back from injuries and I think it’s when you get multiple pressures acting upon them over long periods of time that you get problems. But we still don’t know a lot of the details. What exactly does it take to perturb a microbiome and to keep it perturbed in the long-term? So those, I think, are the big questions now.

I live by this health-food market, and because it’s the market closest to me I end up there all the time. They have an entire aisle of probiotics and people hang out at the juice bar and talk about their gut bacteria situations and what pills and supplements they are going to take. I wonder what you make of this movement. Because, it really does seem like we’re at the beginning of our understanding.

We can still barely identify all the species that live in the microbiome—in us—and we can’t really explain why mine is different to yours. So the idea that we could be very precisely manipulating the microbiome by adding certain bugs or removing others or feeding them in whatever way is, I think, very premature.

There’s reasonable evidence that probiotics are pretty good for some kinds of infectious diarrhea, but not a huge amount else. And we know that when you take them you’re adding a very small concentration of often proprietary, heavily industrialized strains of microbes that aren’t massively well-suited for life in the gut anyway. So they sort of enter, they maybe do a few things, some of which might be beneficial, and then they leave again.

I was fascinated by this notion of endangered microbes and even more so by, I guess you’d call them “ancient man microbes” or microbes that appear in the guts of hunter-gatherer societies still. Paleo-microbes, I suppose. Can you see a future in this kind of boutique bacteria?

[Laughs] I mean, I’m sure that will happen. Whether it’s a good idea or not.

What I want to know, Ed, is if you want to start a paleo gut bacteria business with me. I’m ready. I know a market that would be very, very into it.

You know, there have been stories of people doing their own DIY transplants using hunter-gatherer poop. So this is already happening. Though I would highly advise against it because these procedures are not without risks, right? We know that when they’re done in hospitals they’re done under very strict screening conditions, so you can make sure that the donors have no pathogens or parasites. And even so, there are still long-term risks that haven’t been quantified, and I think that sort of casts a pall on the field and makes a lot of people who work on the microbiome a little bit worried that this is sort of the direction that people are heading in. It’s not the comic book thing where if I suddenly take all your microbes I gain all your powers and abilities, right? It just doesn’t work that way.

Yeah. And ancient man—well, he had a lot of problems too.

That’s right, exactly. I think it’s very, very clear from a lot of the studies now that people in urban environments have a much lower diversity of microbes in their gut than people from rural and hunter gatherer populations. And I think the thing we still don’t know, and needs to be tested before we assume that it’s true, is whether that lack of diversity is a bad thing. Has our health genuinely suffered because of that? Because as I’ve said, the microbiome is very flexible, it’s very dynamic. It responds to lots of things in the environment. Does it just reflect the fact that our diets have changed or is it the cause of health problems? And it’s very easy to assume that these losses are problematic because I think we have this sort of natural tendency to assume that the past was a nicer, rosier place where we were sort of living in harmony with the world around us and our modern lives have just screwed everything up. But I don’t think this is science.

You know, a good analogy might be shortsightedness. The population of the world is becoming more and more shortsighted over time. But then again, we also have glasses and contact lenses so it’s not actually that bad when you look at it deeply. Only on the surface it looks bad. And I think the same could be asked of the microbiome. What’s driving these changes? And are these changes really a bad thing? And then we can think about what we should do about it.

I Contain Multitudes will be released by Ecco on August 9.