Saturday, May 06, 2017

Not a book for the squeamish

kw: book reviews, nonfiction, science, biology, microbiology, microbiome, microbes

Anyone who pays attention to at least a little news of science should know by now that 9/10 of the cells in our bodies are bacterial cells, primarily in the gut (intestines plus stomach). The human colon in particular is packed with them. They are tiny, but 80-100 trillion bacterial cells take up a volume of about one pint, or ½L, and weigh a pound or so (half a kilo). They comprise a significant percentage of our feces. They multiply rapidly enough that their numbers don't diminish.

But there are numerous bacteria on our skins also, in the millions. As Ed Yong writes near the end of I Contain Multitudes: The Microbes Within Us and a Grander View of Life, shaking someone's hand is to exchange microbes with them. Certain germophobes who know this will not shake hands. One man I know keeps a bottle of Purell in his pocket and uses it frequently. But maybe the situation is not quite so dire as folks like him think it is.

Numerous experiments that produced germ-free mice, rats, and other animals have shown that the animals cannot develop normally, and have shorter lives, compared to their "dirtier" species-mates. Bacteria and viruses were around for something like two billion years before larger organisms arose, starting with protozoans ("protists" to most systematic biologists now). Symbiosis between critters of a whole range of sizes has been the rule for the ensuing 1.5-2 billion years.

When a human child is born "naturally", that is, through the vagina, it picks up a cocktail of symbiotic bacteria—hundreds to thousands of species—that immediately begin to cover the infant's skin and fill its innards. And this is good! The mother's milk contains hundreds of special compounds that the infant itself cannot digest, but that feed the bacteria within, ensuring that the baby's development will be normal and its immune system will operate properly. As long as the mother is not desperately infected during delivery, the "Mom germs" are good germs, and the immune system takes them for "our guys". Babies delivered by C-section and/or fed only "formula" (germ-free cocktails that rather badly imitate the nutritional composition of human milk) are not going to develop as they would have, nor have as robust an immune system.

This is ubiquitous throughout the animal kingdom. The "body" of any animal, from a nematode 1mm long to an elephant or whale, is covered and filled with enormous numbers of microbes, and most of those are at worst neutral, and usually beneficial. There are foods animals (us included) cannot digest without them. There are amino acids a vegetarian cannot get in sufficient abundance from food, but effective amounts are supplied by internal microbes. Microbes ensure the survival of pandas, which would otherwise starve on a bamboo-only diet.

There are five kinds of microbes:

  1. The smallest are viruses, and are typically a few tens to a few hundreds of nanometers in size. Most viruses in our environment, and in us, prey on bacteria, or form symbioses with them so they can be properly symbiotic with us. Such "bacteriophages" are probably mis-named. "Bacteriophage" means "bacteria eater", and while many of them do invade bacteria and destroy them, others live with the bacteria, within them, and cause them to produce biomolecules that are useful to the bacteria or to their animal hosts.
  2. Bacteria are the next largest, from half a micron to several microns in size. Now that genetic tools can be used to take a proper census, it is found that there are hundreds to thousands more species of bacteria than we ever thought, when we were confined to knowledge of those that could be cultured in the lab and peered at with microscopes. But the concept of "species" is a little slippery with bacteria. They have a "sideways sex" operation called conjugation, by which even rather widely unrelated kinds can exchange genetic material. This is how antibiotic resistance can spread not just through a population of, for example, Salmonella, but through the whole microbiome of which they are a part. Bacteria are also called "prokaryotes", meaning their genetic material is not found in a nucleus, but is spread throughout the cell.
  3. Archaea are similar in size range to bacteria but are a different kingdom, very different. Many of them are extremophiles, living best at temperatures near or even above the boiling point of water, or in very salty water. Their relationships and history with animals is very poorly known. These are also prokaryotes.
  4. Fungi range from the very tiny, slightly larger than bacteria, to enormous. The ones of interest in the context of this book are primarily single-celled for most of their life cycle, but they have a nucleated cell, and are thus called "eukaryotes". Nearly all life big enough to see without a microscope is composed of eukaryotic cells.
  5. Protists, or protozoa, are eukaryotes that used to be considered either one-celled plants if they had chlorophyll, or one-celled animals if they didn't. All can move about, so they seem to be on the boundary between plant and animal kingdoms, and are now considered a kingdom of their own. The critters that help both cattle and termites digest cellulose are protists. They could not live without them.

The book discusses numerous research programs aimed at finding out just how widespread these mutualisms are. Mutualism is often a better word then symbiosis, because the latter implies a more positive, almost meaningfully positive, relationship. A deeper look shows that animal bodies all have systems for keeping their "inner critters" where they will do good, and keeping them out of the circulatory system or the bodies of cells, where they are more likely to do harm. Indeed, septicemia is a serious failure of such systems, in which bacteria are allowed into tissues or blood, and can quickly lead to death. When we do die, whatever our cause of death, it results in these systems collapsing, and our bodies are invaded and devoured by our inner symbionts, unless we are soon embalmed.

As a result of much recent research, it is becoming apparent that pathological behavior is comparatively rare, and is usually short-lived (ending in either death or cure), while mutualistic relationships are life-long, numerous, and range from innocuous to very beneficial for us.

Some bacteria have become very general in application, across entire phyla. The best example is Wolbachia, which can strongly influence the reproductive behavior of insects. It also tailors their internal microbiome, allowing some microbes and disallowing others. It is found in specimens of more than half the species of insect in which it has been sought. It has the potential to be a great friend to us: research going on as we speak is aimed at using a strain of Wolbachia as a symbiont in Aedes mosquitos, making it impossible for them to harbor the dengue virus, while also giving Wolbachia-carrying female mosquitoes a reproductive edge. This incredibly painful disease infects millions annually. What a blessing if dengue could be wiped out! Early tests show that this might come to pass in as little as a decade or two. Research is also going on to work a similar miracle with mosquitoes that carry malaria.

Mr. Yong strove in his writing to avoid sounding like a pro-germ cheerleader. Our understanding is growing rapidly, and must remain balanced. We have for a century or so treated all bacteria as evil denizens to be extinguished at every opportunity. We need a more nuanced response. Widespread use of antibiotics can make the microbiome in many of us quite dysfunctional, leading to further problems, that we try to cure with more medicines. A fecal microbe transplant (FMT) might have done the job right the first time. So far, the only condition that FMT is known to usually cure is infection with Clostridium difficile (C-diff). And why does someone get C-diff to start with? Aggressive treatment with antibiotic, which cleans out the gut, allowing the C-diff bacteria a fertile field to colonize. As FMT and other probiotic methods become better understood, it may be that we will one day cure many of our ills by taking a microbe-laden pill that is designed to scoot through our stomach and release its payload in the intestine, where it might re-formulate the mix of critters in there to drive out the problem microbes and strengthen the immune system, all at once.

I have touched on just a tiny few of the matters raised in the book. It is well worth the read. Unless, of course, you are such a germophobe that the very idea gives you the willies! Then, maybe it would be best to make the book a gift for your physician, with strict instructions not to tell you what goes into your treatment in the future.

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