Friday, 1 June 2018

Book Review: I Contain Multitudes by Ed Yong

5 stars: Fascinating, packed with information and evolutionary explanations, taking the microbiome on its own terms, and full of twists and turns. What I've been looking for from popular science.

This book is brilliant. It addresses the astonishing strategies and lifestyles found in the symbioses between animals (from corals to humans) and bacteria that make up the microbiome. He manages to avoid doing the obvious and boring thing with the topic, of focusing on diet, health and probiotics (which he says in the Acknowledgements that he specifically wanted to avoid), and instead studies the microbiome on its own terms, acknowledging that it’s interesting for itself, not just for what it means to humans.

It had an immense amount of information that was totally new to me even as a biology student who’s into evolution, and what I think I loved most was the very evolutionary perspective from which he approaches things; not just descriptions, but strategies used by organisms, ways they can help and betray each other, and how they all adapt and counteradapt in counterintuitive ways.

When it comes to health, he advocates looking at the immune system not as an army ready to kill pathogens, but as a park ranger tasked with maintaining the ecology of the microbiome, keeping numbers steady and kicking out any intruders that will upset the balance.

Another great thing is that he’s good at talking to scientists about their research and gets lots of interesting perspectives with loads of cool perspectives and contacts. I looked him up and noticed that he has a degree in Zoology and a Masters in biochemistry, so that could very well be why.

In any case, he’s a brilliant science journalist and this book was exactly what I’ve been looking for from the many pop sci books I’ve read over the last two years.


A Frog Pandemic

There’s a fungus called Batrachochytrium dendrobatis that’s wiping out amphibians everywhere. It kills frogs on six continents, everywhere they exist, by thickening their skin so that they can’t absorb sodium and potassium and have something like a heart attack. It can wipe out whole populations in weeks, and has sent many species extinct including the sharp-snouted day frog, the gastric brooding frog and the Costa Rican golden toad. It’s been called the worst infectious disease recorded among vertebrates, which is a hell of a title. There’s some hope: a bacterium that some amphibians carry makes them resistant to the fungus, and when transferred to frogs without the bacterium makes them resistant too; but this has only worked in specific types of frogs and otherwise has been a disappointment. I imagine it must have been terrifying trying to do experiments on extremely endangered frogs in order to save the species when it meant giving them the fungus (after giving them the hopefully-protective bacteria), especially in the cases where it didn’t work.

The Microbiome and Medicine

The microbiome affects the activity of drugs, even well-characterized small molecule ones. For example:
  • Sulfasalazine can be used to treat rheumatoid arthritis and IBD, but only after gut microbes convert it into its active form
  • Irinotecan can treat colon cancer but some bacteria convert it to a toxic form that gives serious side effects
  • Paracetemol’s effectiveness varies with the types of microbes you carry.

He tells the story of a clinical trial on treating recurrent C difficile infections with either the antibiotic vancomycin or with Fecal Microbiota Transplant, i.e. giving them the stool of someone with a healthy gut microbiota because an unhealthy gut microbiota can lead to C difficile infections. They planned to recruit 120 patients but only got to 42 because by that point vancomycin had cured only 27% of patients while FMT had cured 94%, so it was unethical to keep giving vancomycin and they just put everyone on the FMT arm.

Do probiotics work? According to a review by the Cochrane Collaboration, they can shorten bouts of infectious diarrhoea, reduce risk of getting diarrhoea after antibiotic treatment, and save lives from necrotizing enterocolitis. The jury’s still out on all their other promised benefits, including for allergies, eczema, obesity, diabetes and (ugh) autism (it’s not a disease dudes). And even for those that do help, it’s not clear that the effect comes from changes in the microbiome. Probiotics are usually classified as foods rather than medicines, so they’re free from heavy regulatory oversight but they’re not allowed say they have specific medical benefits.

There’s a tradeoff between how effective probiotics are in terms of how good they might be at sticking around in the gut, and how dangerous they might be if they do turn out to be pathogenic.

The book also talked about how the bacteria have needs to; for example, Oxalobacter is the name of a bacterium that loves eating oxalate, and it can be given to people to help with kidney stones (made of calcium oxalate). But sometimes when that doesn’t work it’s because people with kidney stones might go on a no-oxalate diet, so even if they ingest the bacterium it will starve.

New Approaches to Eradicating Dengue: Releasing Mosquitos into Neighbourhoods

There’s a really interesting project described being run by a group called Eliminate Dengue, which involves infecting mosquitos with Wolbachia bacteria. Wolbachia are carried by many mosquito species but not the Aedes mosquitos that transmit dengue, and when infected with them Aedes mosquitos become worse at transmitting the virus to humans. Wolbachia is harmless/doesn’t get transmitted to predatory spiders or fish that bit the mosquitos, and doesn’t get transmitted to humans who are bitten by the mosquitos. The idea was to infect a bunch of mosquitos with Wolbachia then release a bunch of those mosquitos outside to have sex with the other mosquitos and infect them too, decreasing all the mosquitos’ effectiveness at transmitting Dengue. It’s a super cool idea, but definitely a scary concept because they’re releasing these mosquitos outside. They had to do a bunch of releases so the researchers spent ages getting the local community on their side, doing focus groups, talks in pubs, running a drop-in explanation service, and knocking on lots of doors to ask if they could release these things on people’s property even though it hadn’t been done before and the residents might get bitten. The local volunteer group helped out with going door to door and eventually the project had the approval of eighty-seven percent of residents. 

That sounds like a brilliant example of science communication and getting the public involved, I love it. This could also work on Chikungunya and Zika viruses and on malaria, and it has evolutionary insight applied to it; while the mosquito or virus could mutate to resist the effect, the Wolbachia itself can counteradapt.

Wolbachia also has a thing against dudes; it kills males of some species (for example, causing female blue moon butterflies in Fiji and Samoa to outnumber males 100 to 1) and in others turns them into females.

Animal Symbioses with Bacteria

The case of the mealybug and its two major symbionts is really interesting. The mealybug is a sap-feeding insect and, like many other insects that feed on sap, relies on intracellular microbial symbionts for essential nutrients. It has a bacterium inside each of its cells, called Tremblaya, and Tremblaya has a smaller bacterium inside each of its cells (or bodies since y’know, unicellcular), called Moranella. These are incredibly integrated symbionts, and have lost many of the genes that an organism would normally need for survival because they share them. The example given in the book is of the biosynthetic pathway of phenylalanine; there are nine enzymes needed to make it, and none of the three organisms have all nine. Tremblaya can make 1, 2, 5, 6, 7 and 8; Moranella can make 3, 4 and 5; and the mealybug itself makes number 9. For metabolic purposes, they’re essentially one superorganism. Also, the mealybug’s genome has traces of three other bacteria that are no longer present so it can make bacterial genes – including peptidoglycan, which Moranella needs for its stability-giving cell wall, and which could then lead to it withholding that from Moranella in theory as a strategy. It’s absolutely fascinating from an evolutionary perspective, especially if you consider when its advantageous to cooperate and when it might not and then the whole mutualism/altruism aspect comes in and yeah basically evolution is awesome. There’s a super interesting article (by the author of the book) that gives more info on this here.

Aphids carry Hamiltonella defensa to protect them from wasps. The Hamiltonella bacteria have a phage inside them, and this is what protects the aphids from the wasps (aphids with Hamiltonella that don’t have phages aren’t protected). At high temperatures having the phages is too much of a disadvantage, and when the aphids are being farmed by ants they’re less likely to carry Hamiltonella because the ants are already protecting them from wasps. An aphid-bacteria-virus alliance.

Counterintuitive Cleanliness

Toilets that are scrubbed first get colonised by faecal bacteria from flushing. Those ones are then outcompeted by a wide range of skin bacteria, until the surfaces are scrubbed and the cycle repeats. So toilets that are scrubbed often actually have more faecal bacteria rather than skin bacteria.

Breastfeeding your Bacteria

Human mothers secrete 200 oligosaccharides in their breastmilk ... but babies can’t actually digest oligosaccharides. Why do they do that? Because an important probiotic bacterium called Bifidobacterium longum infantis can, and they want to feed that, so it will digest the oligosaccharides into short-chain fatty acids which the baby’s gut cells can digest. ‘Bif’ is also anti-inflammatory and (I think) good for gut integrity.

He also had some really interesting bits on corals and how they need a certain microbiome to avoid their ecosystem becoming algae-dominated. And just so much more besides honestly, the book is absolutely PACKED with fascinating information well-explained and thought out, from squids using Vibrio fischeri bacteria for their luminescence (which cancels out their shadow, hiding them from predators) to mucus in the gut having phages embedded in it that target bacteria and animals possibly customizing the mucus to attract certain phages to kill certain bacteria they don’t want.

Basically, it’s brilliant. Please read it.

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