Mind. Blown.

In one of the TWiV (This Week in Virology) podcasts, they briefly mentioned a book by Ed Yong, I Contain Multitudes. [I guess the publishers are not Bob Dylan fans] Several of the doctors said they thought it was great, or it was on their reading list, so I added it to mine.

Since I had a bunch of stuff to haul, I chose the audiobook version, and had it playing in my earbuds all day yesterday as I worked. There were times, however, that I just stopped and listened. There’s a lot of those sort of moments – not because it’s hard, but because it’s really interesting.

I’ve added it to my recommended reading list [stderr] in accordance with my policy on recommended reading [stderr]. I will note that the audiobook recording is merely OK; the narrator does a fine job, but some of the edits are obvious cuts and distracting if your brain is the kind that catches that sort of thing. The book has a subtle sort of wry humor, and the narrator’s reading does a good job of preserving the tone and keeping it light.

I have to say that some of the science sounded so far-out that I felt it was sketchy, except that Yong does a good job of explaining the experiments and results that led to the far-out conclusions. Generally, I don’t have trouble following science-for-the-layman books, and I didn’t have trouble with this one either – but a lot of what Yong discusses seemed like hardcore woo-woo to me. For what it’s worth, the doctors on TWiV only had good things to say about the book, and I’d expect that if it was woo-woo, they would have only mentioned it to dismiss it. I do plan to do some checking around to see if there are any errors of fact – although with something like this, there are many axes to grind so I’m not sure I’d trust the internet. Here’s a review on The Guardian, [guard] which I’d say is generally highly positive.

The topic is huge: how our lives interact with our micro-biomes; how we shape them and they shape us. Most of us know that (for example) we may each have our own species of eyebrow-mites, which engage in genocidal combat with the eyebrow-mites of everyone we come in close contact with – but that’s just the beginning of the story. [By the way, I have now figured out what Joe Biden is doing: he is being controlled from below by his eyebrow-mites, which have adopted a new strategy for getting their carrier to spread them within the human population. Selfish gene indeed!] As I just wrote that little aside, I realized that it’s not significantly more incredible than some of the other stuff that Yong writes about. The book is chuck full of accounts of how various creatures depend on bacteria to the point where it’s hard to say that specific highly-evolved bacteria are a separate form of life from them. The broader point is: we need to rethink the idea that we have a distinct “edge” to ourselves – we’re not just “us” we’re the cloud of things that go into and out of us, which build us and destroy us. This is a somewhat unsettling understanding; I had always realized that we’re in a wobbly balance between our body’s ability to repair itself and the bacteria around and inside us’ ability to eat us – who can do it faster? If we fall behind, it’s an infection. If we keep ahead of the game, it’s called “good health” for now.

If you enjoyed David Attenborough’s rapturous explanations of the life-cycle of some wasp or other, this is a book for you; it’s like Attenborough doing “The Inner Life Of Your Gut” (which I would totally love to watch!) and – like Attenborough – it flips past things that make you realize that there’s another entire book worth of material, there. Several times I caught myself saying, “wait, what?” and going back. For example: [from chapter titled “Body Builders”]

Why should animals rely on microbes to make these chemical signals? Thiess offers the same reason that Rawls, King and Hadfield did: “it’s inevitable.” Every surface is populated by microbes which release volatile chemicals. If those chemical cues reflect a trait that’s useful to know about – say: gender, strength, or fertility, the host animal might evolve scent organs to nourish and harbor those specific microbes. Eventually, the inadvertent cues turn into full-blown signals. So, by creating airborne messages, microbes can affect the behavior of animals far outside of their original hosts. And, if that’s the case, it shouldn’t be surprising to learn that they can affect animal behavior in more local ways.

In 2001, neuroscientist Paul Patterson injected pregnant mice with a substance that mimics a viral infection and triggers an immune response. The mice gave birth to healthy pups, but as the babies grew into adults, Patterson started noticing interesting quirks in their behavior. Mice are naturally reluctant to enter open spaces, but these mice were especially so. They were easily startled by loud noises. They would groom themselves over and over, or repeatedly try to bury a marble. They were less communicative than their peers and they shied away from social contact. Anxiety, repetitive movements, social problems: in his mice, Patterson saw reflections of two human conditions, autism and schizophrenia. Those similarities weren’t entirely unexpected. Patterson had read that pregnant women who incur serious infections like flu or measels, are more likely to have kids with autism and schizophrenia. He thought that a mother’s immune responses might somehow affect the development of her baby’s brain, he just didn’t know how.

The penny dropped several years later, when Patterson was having lunch with his friend Sarkis Mazmanian, who discovered the anti-inflammatory effects of gut bacterium B.Frag. Together, the scientists realized that they had been looking at two halves of a same problem. Mazmanian had shown that gut microbes affect the immune system and Patterson had found that the immune system affects the developing brain, and they realized that Patterson’s mice had gut problems in common with actual autistic children. Both were more likely to have diarrhea and other gastro-intestinal disorders, and both harbored unusual communities of gut microbes. Perhaps, the duo reasoned, those microbes were somehow affecting behavioral symptoms in both mice and kids. And, perhaps, they reasoned, fixing those gut problems might lead to changes in behavior. To test this idea, the duo fed B.Frag to Patterson’s mice: the results were remarkable. The rodents became keener to explore, harder to startle, less prone to repetitive movements, and more communicative. They were still reluctant to approach other mice, but in every other respect B.Frag had reversed the behaviors caused by their mother’s immune responses.

How? And why? Here’s the best guess: by mimicing a viral infection in the pregnant mothers, the team triggered that landed their offspring with an excessively permeable gut, and one with an unusual collection of microbes. Those microbes produced chemicals that enter the bloodstream and travel to the brain, where they triggered atypical behaviors.

Of course, as Yong points out, that’s hardly an explanation for autism in humans, but it shows an interesting path for further research. There have been plenty of researchers that have pursued the gut/mind communication connection, including Michael Gershon’s The Second Brain (1999) which I read when it came out. [nyt] Yong also touches (albeit briefly) on the apparent anti-anxiety effect of lactobaccilus (the little guys who make yoghurt) which appears to be the basis for probiotics, which I had dismissed as woo-woo. By the way, probiotics still seems a bit woo-woo, to me, since it appears to be a bit premature; messing with things we don’t understand, yet. If the premise is that bacteria affect your mood, the situation is clearly more complicated than we thought before, therefore commercializing human experiments may not be a great idea. One of the other points Yong makes is that the near eradication of H.Pylori (the bacteria that can cause stomach ulcers) has not moved the mortality needle in the human population – fewer stomach ulcers appear to cause more acid reflux and esophageal cancer may be replacing ulcers as a cause of death.

H. Pylori, Ia! Ia! Ftaghn!

There’s a lot of “we don’t know, yet!” in this book, which I consider a good sign. Given the complexity of the topic, namely that our interactions with micro-biomes are more complex than we understand – it would be unseemly to rush to some kind of recommendation. It’s more like a grand summary of the current state of play.

The book made my mind wander in all sorts of directions, searching for implications beyond the words. One thing I was thinking, as I listened, was that terraforming new planets, as the techno-optimists fantasize about, is almost certainly a non-starter. We’d take our personal biomes with us, but we might forget some critical bacterium that gets transmitted to a plant via a bug, and life-sustaining crops would fail. We seem to have the idea that we could judiciously re-construct a biome, when we’re not even savvy enough to deal with a novel virus. For every element of our micro-biome, Yong points out, there are balances that keep it from swinging to far in either direction; if we lose a regulator that keeps that balance in one direction, we might wind up with an infection, or a missing ability. Just for one example, Yong describes, in great detail, how certain squid adopt photophosphorescent bacteria – they are evolved to identify and contain them in their bodies, but they don’t produce them, themselves. If we didn’t understand that, we might think merely “squid are phosphorescent” and think it’s the squid that’s doing it (somehow) and only take the squid along to our new eden. Then, when we got there 5,000 years of travel later, the squid would not glow. More likely, of course, they’d be immediately infected by the existing micro-biome and obliterated. We might expect that, after millions of years and billions of deaths, transplanted life-forms might evolve to survive in a new biome, but that’s the problem with depending on evolution as an algorithm: it only works if you are willing to wait a long time and tolerate massive casualties. And, even then, it serves up something you don’t expect.

Serving up something you don’t expect is a central theme of this book, and it’s a wild ride. Highly recommended.


  1. Jazzlet says

    We can’t even reliably reproduce habitats on earth, it’s something that road developers are supposed to do in the UK, if their proposed road crosses some rare habitat they must provide somewhere locally for the same area of habitat to be built. It’s a lovely idea, but in practise it is impossible to do even when they bodily tranplant as large as possible chunks of the habitat. There are so many reasons for this, but messing up the microbiota is certainly one.

  2. cvoinescu says

    The permeable gut notion veers very close to some deep woo. I reserve extra scrutiny for any claim regarding autism. Particularly, autism and gastro-intestinal disorders in the same sentence put me on high woo alert. I also consider comparisons between mouse and human behavior to be highly suspect. This nevertheless sounds very interesting, but cum grano salis and caveat emptor and all that.

  3. says

    Particularly, autism and gastro-intestinal disorders in the same sentence put me on high woo alert.

    Me too. For one thing, he didn’t dwell on it (which is wise) and for another, he immediately pointed out that mouse behavior and human behavior are not matchable. It’s interesting, though, and I would not be shocked if scientists eventually figure out it’s some kind of environmental factor in development, that is exacerbated by the genome of the parents. The description in Yong naturally omits the heredity of autism, because I believe they are talking about mice that are basically clones.

    Anyhow, it’s a chunky book full of amazing nuggets of thoughty-stuff!

  4. xohjoh2n says

    If you’d not previously come across Ed Yong, then definitely no woo peddler. He became a well respected science writer with his (mainly bio) blog Not Exactly Rocket Science (first self-published, then to ScienceBlogs, then to Discover.) For a while now he’s been a staff writer at The Atlantic.

    https://notexactlyrocketscience.wordpress.com/ (archives)
    https://scienceblogs.com/notrocketscience (archives)
    (Discover-era posts basically unfindable.)

  5. xohjoh2n says


    I think you’re possibly reading the situation the wrong way round.

    Consensus reality is, I believe, that microbiome interactions appear to do some seriously crazy shit, just how crazy we’re only scratching the surface of. And we certainly know almost nothing about how. There are some exciting therapeutic possibilities there for sure, but we’re nowhere near the level of regular clinical use. Not even close.

    If a description of some of that area like particular actual instances of woo, it’s because of course the woo peddlers took that ball and ran and immediately turned this *highly* speculative and young area of science into “and we know for a *fact* that this particular change definitely causes all your problems, and of course we have this *very reasonably priced* cure for you to buy!”

  6. invivoMark says

    This is exactly the sort of stuff that got me interested in biology way back when I was an undergraduate trying to figure out my major.

    @cvoinescu #2:

    Autism has been known to correlate with certain gastrointestinal pathologies for a long time, I don’t think this is controversial. I think just about any serious mechanistic hypothesis about autism supported by science these days is going to involve that correlation. Some woo theories will, too, but that’s just a natural consequence of every naturopath and holistic practitioner in the world thinking they are an expert on autism.

    I remember following the autism-microbiota link around when Mazmanian’s lab published a paper in Cell in 2013. It’s a very reasonable hypothesis, and it seems to have only gained traction since its introduction. Recently, a group has been testing fecal transplants in treatment of children with combined GI issues and autism. Their results are fairly striking, showing improvement even two years after treatment, but they haven’t been able to do a controlled, blinded trial yet. Their most recent paper is here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456593/

  7. flexilis says

    Ed Yong is an educating and entertaining writer. When you consider that each of us has far more microbe cells than Homo sapiens cells (estimated from 3 to 10 times as many) you wonder if we are individual animals or walking ecosystems. Probably both. I first heard some of this in a book I read in high school, Life on Man by Theodore Rosebury. I remember freaking out about the eyebrow mites. Then there is the discussion of how a newborn acquires her intestinal flora that are essential for life. Fascinating stuff.

  8. invivoMark says

    I also want to point out that in addition to having these subtle, beneficial effects, microbes can also have deleterious effects that are equally subtle. A large range of viruses and bacteria can increase your risk of various types of cancer (some ~15% of cancers are caused by viruses). There are some lymphomas that are caused by something colonizing your body and stimulating your B cells into making too many antibodies (H. pylori can do this, for instance). Clearing the microbe can, in some cases, cure the cancer. And of course there’s all the weirdness that’s been attributed to Toxoplasma gondii.

    How subtle are these microbes? I spent years and earned a PhD trying to figure out how one of the herpesviruses affected a host cell’s behavior during latent infection, which is when it is known to cause cancer. The virus barely did anything to the host cell, and the host cell barely knew the virus was there. The host cell’s gene expression was damn near unaffected.

  9. cvoinescu says

    invivoMark @ #8:

    I don’t dispute that.

    It’s just that, as xohjoh2n points out, general gut health and particularly the microbiome are some of the most popular targets of general woo. Autism is too. Their intersection, even more so, and it’s further darkened by the shadow of Andrew Wakefield. So I’m a lot more cautious when reading non-peer-reviewed literature about these things, especially when they occur together.

  10. xohjoh2n says

    @11 I think we can trust that Ed Yong will have used peer-reviewed papers as a lot of his source material, as well as talking directly to the authors of said papers and other established scientists in the field.

    The book isn’t itself a peer-reviewed paper, it’s a popular science book. But I’d bet its foundations are solid.

  11. says

    The book isn’t itself a peer-reviewed paper, it’s a popular science book. But I’d bet its foundations are solid.

    I doubt the TWiV guys would have even mentioned the book, if it had been woo-ey. When a professor of virology says it’s good, I expect it is.

    Woo seems to take ideas from popular science and then extrapolate profitably from there. This book lacks the extrapolation.

  12. sonofrojblake says

    “we might forget some critical bacterium that gets transmitted to a plant via a bug, and life-sustaining crops would fail”

    Interesting example to choose. Larry niven used this as a critical plot point in his Known Space books decades ago. SPOILERS:
    Humans, it turns out, are the evolved remnants of breeder – stage Pak,seeded on earth. On the homeworld, breeders metamorphose into Protectors by eating Tree of Life root. The Protector who seeded earth didnt realise there was a symbiotic bacterium in the root, so the plant “failed” by being just sweet potato, and the breeders multiplied and got smart. Us. Made exactly your point, with almost exactly your example, in a novel in 1973. Coincidence?

  13. Rob Grigjanis says

    chigau @15: I love scifi. I can cope with dodgy stuff like FTL, wormholes, and even telepathy and time travel if it’s done well. But “Neutron Star” easily snapped my disbelief suspension cables. A technologically advanced, interstellar species (the Puppeteers) that doesn’t understand tidal forces because they don’t have a moon? Hilarious. All you need to understand tidal forces is Newton’s law of universal gravitation. And if you’re building space ships, you certainly know that.

  14. chigau (違う) says

    Rob Grigjanis #17
    yeah. so it goes.
    there was also that thing where Louis Wu was following his birthday backwards

  15. says

    Speaking of autism and woo, another thing that bothers me is that people who claim to have a cure for autism proclaim this to be a disease that needs to be treated and prevented. It’s a spectrum and there certainly are people with autism who actually have serious problems that worsen their life quality. If medicine could alleviate the suffering of these people, then that would be nice. But there are also the so called “high-functioning” people with autism who are perfectly happy with how their brain works and who don’t even want to be treated or made “normal.” There is no problem with these people and they don’t need to be treated, instead the problem is that we have a society that expects everybody to be neurotypical and abuses people who are on autism spectrum.

    It is actually the same problem as with trans people. Even if science could figure out the cause and ways how to prevent transsexualism or treat trans people’s minds, I’d hate it. At least personally I am perfectly happy with the atypical gender identity I have and I do not want to be cis. Well, I would have liked to be born with a male body, but I sure as hell wouldn’t want doctors to change anything about my brain and turn me into a cis woman.

    And while I haven’t sought a specialist who could diagnose me with anything, I am pretty certain that I am not exactly neurotypical. Again, I am happy with this and wouldn’t want to change it.

    As long as humans don’t know the cause or “treatment” for being non-neurotypical or trans, I am safe. There is no cure, thus nobody will try to cure me. If medicine actually discovered a cure for these conditions, then I would perceive this as a threat. Some supposedly well-meaning people would undoubtedly want to kill the person who I am and replace my brain with that of a neurotypical cis woman. In my opinion, my mind is who I am. Changing such core aspects of who I am would require killing the person I am and replacing me with a totally different person. And I am really glad that something like this cannot be done in real life and exists only in science fiction novels.

    Thus, on some level, I do not want medicine to discover what causes people to be non-neurotypical or trans. Simultaneously, I am also aware that some people on the autism spectrum actually have severe problems that negatively impact their life quality and that these people do wish there existed some cure.

    Assuming that humanity some day discovers the cause and treatment for autism, I hope that by then our social acceptance of neurodiversity and medical ethics will advance to the point that nobody will get subject to any treatment against their will.

  16. says

    Andreas Avester@#20:
    Speaking of autism and woo, another thing that bothers me is that people who claim to have a cure for autism proclaim this to be a disease that needs to be treated and prevented.

    That’s not an unreasonable fear. As we saw in China, the “one child” policy, coupled with gender selection, resulted in a big boom of male children (followed by a swing-back of suddenly more marketable female children) – people will not hesitate to select if they have a way of determining pretty much anything about a child in advance of its birth (and even then…)

    I suspect that medicine will eventually figure out what’s going on, in which case it will be a problem. Perhaps humans will figure out a theory of mind that is separated from the plumbing, but I doubt it, since the mind and the plumbing are inextricably entwined.

  17. says

    Beyond the microbiome, any understanding of biology includes the idea that a multicellular organism is basically a highly organised colony organism. The human brain has developed a sense of self that leads us to believe, incorrectly, that we are individuals, rather than vast masses of differentiated cell types cooperating for mutual benefit.

    The hard question: does your liver exist to keep you alive, or do you exist to keep your liver alive?

    The easiest example is mitochondria. Cell biology relies on the presence within every cell of arguably foreign lifeforms. Lifeforms with their own life cycle and their own DNA.

    We consider cancers to be pathological because they have stopped cooperating, but in the short term of a single cell generation it’s hard to argue that they’re not more successful than the non-cancerous cells around them. Malignancy and metastasis are measures of the individual success of cancerous cells. I feel a clumsy political metaphor coming on, so I’ll stop there.

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