Monday, December 03, 2007

Microbes to the rescue

kw: book reviews, nonfiction, bacteria, public health, history

Decades ago, what was known about bacteria was mostly summed up in a picture like this one. A=a few kinds of bacilli, or rod-shaped bacteria; B,C,D=various clusterings of cocci, or spherical bacteria; E=a spirillum or two; and F=comma-shaped Cholera bacteria.

Living forms seen in an optical microscope are rather uninformative: cocci and rods look like the dot-dash diagrams of morse code; spirilli look like jittery bacilli at first, because they spin on their axis so fast, unless you add a touch of iodine to slow them down and see the helical shape; and I haven't seen live Vibrio (the Cholera bug)...fortunately!

The images I saw in 1950s and -60s articles in Scientific American, using electron microscopes, suddenly opened up a bewildering micro-world, but I was soon more enamored of plant cells—I could watch chloroplast streaming for hours—and didn't pay much attention to prokaryotes after about 1962.

I read Paul de Kruif's Microbe Hunters, already thirty years old in 1956, with great fascination, and wholly bought into the "all bugs are bad bugs" attitude of the time. I disdained the old proverb, "A healthy kid's gotta eat a peck of dirt". Yet I remember every sunbeam coming in through a window cast a dusty yellow streak as it crossed the room. My mother had to dust all the time. 1950s houses weren't tight, and if we didn't eat our quota of dirt, we surely breathed plenty of it. And we were quite healthy. When I see sunshine through a window these days, I can almost count the visible dust motes, there are so few.
A more modern illustration of bacteria morphology such as this one from Wikipedia shows a few more types, but only hints at the million-fold increase in knowledge we've gained in fifty years or so. However, most of that knowledge is aimed at understanding bacterial diseases and finding new ways to stop them, as once-conquered microbes evolve ever-stronger defenses against our antibiotics and biocides.

Fortunately, a little of the new knowledge is devoted to microbial ecology and understanding the many species that inhabit our bodies, inside and out, that are actually not just beneficial to us but necessary to our well-being.
This critter, a species of bifinobacteria, inhabits the milk ducts of all healthy women's nipples, and is one of the first microbes to colonize a newborn. It is a good bug, a very good bug. Just how good is detailed in an early chapter in Good Germs, Bad Germs: Health and Survival in a bacterial World by Jessica Snyder Sachs. Without these little forked germs to help a baby jump-start its immune system, and to muscle aside latecomers, millions of infants would die of later, less beneficial invaders. And they are just one helpful species.

It appears that a healthy mouth is a well-populated mouth. Of 500 or so bacteria now known to inhabit human mouths, at least 200 are present in any one person, except the very ill, who actually may be dying of monoculture! These many kinds of critters don't just tumble over one another. Many, probably most, form stable aggregates that help protect us from invaders.
If you leave them alone, bacteria form multi-species aggregations dwelling in a mucinous slime, a biofilm. This image, found at, shows a single-species biofilm in its early stages of formation, 3d imaged using a confocal microscope.

We are all quite familiar with one sort of biofilm: dental tartar, the whitish scum that forms on our teeth, the target of flossing and of the dental assistant's uncomfortable probing every year or half year.

Biofilms coat the insides of the pipes in our homes. Don't be dismayed; without them, the pipes would rust through in short order! The critters that form them are typically innocuous, and may actually absorb and degrade some pollutants found in the water...they are living on something, after all.
This image, though, is much more typical of a beneficial biofilm. If you look carefully, you'll see nine or ten species of bacteria. This image from Wichita State University shows villi in the small intestine with part of the biofilm stripped away to show the resident bacteria, all of which are supposed to be there. The largest are cigar-shaped bacilli with stringy flagella enwrapping them, and cocci of similar size. The smaller rods may be E. Coli but are more likely to be a species of Corynebacteria. There are lots of smaller forms.

This community of resident microbes digests part of our food and passes on much of the nutrition to us, produces some of the vitamins we need, and protects our gut from bacteria we ingest all the time with our food, that may be either unhelpful or pathological.

In Good Germs, Bad Germs the author outlines the history of public health, and the good news-bad news story of antibiotics, the "cleanliness is next to godliness" attitude we've had since about 1900AD, and the increasing cost of our attempt to eliminate infectious disease.

Folks, it is going to cost a lot more to develop a more time-stable (but never permanent) solution. Bacteria can out-evolve anything we do that kills them indiscrimately, such as using a broad-spectrum antibiotic. Though antibiotics save lives, they also train germs to resist their effects.

Consider for a moment, the difference in evolutionary effiency between us. There are six billion humans, with about half this number on the Asian/Indian supercontinent. A generation is about 20-25 years, or perhaps as little as 15-18 years among the poorly-educated multitudes we call the Third World. At the rate of population growth seen in most of Asia—2.5% yearly—population doubles in less than thirty years.

There are a few billion bacteria on your tongue. Depending on species, a generation is between 20 minutes and an hour or so. On average, bacterial population will double twice per hour. That is, one human generation is equal to half a million bacterial generations.

Suppose you were to dump a few trillion gallons of chlorine bleach upon Asia; enough of it, one might think, to poison all three billion residents. Of course, not all will die. Some will be lucky, some will be able to swim to safety without total lung collapse, and some will just be stronger and outlast the flood. Of one thing you can be sure: whoever is left will likely have children that are genetically better at living through another flood of bleach. However, it will take a few centuries to rebuild the population.

This happens every time you use mouthwash. The lucky survivors may be little different than those that died, but the ones who survived by being a little stronger will have some offspring that are stronger yet, and the next morning—40 or 50 bacterial generations, equivalent to 1,400 human years—you can repeat the exercise with a nearly identically-sized "continent" of oral critters. Yet each morning, a larger number will survive.

The trouble is, researchers are finding that most of the germs we kill with mouthwash, antibiotics, antibacterial hand soap, and other measures driven by modern paranoia, are good germs. A human body is not a single organism. Your skin is colonized with 10- to 100-billion "good germs" of a few hundred species. They keep you from getting funguses, for example. Your insides host between 10 and 100 trillion bacterial cells, of hundreds of known species, and perhaps thousands nobody has yet discovered.

Experiments with various animals have shown that totally germ-free mammals are very hard to keep alive. Those few "bubble babies" that need to live in total quarantine are equally hard to keep alive. For one thing, they need to eat 30% more to get the calories they need that aren't being supplied by a healthy internal biosphere, and they need vitamin supplements you and I seldom hear about. For another, any stray germ that does get into their isolation chamber is likely to grow almost without opposition and destroy them.

A human body is a colony, and many of the residents are actually part of our immune system. Some provide early warning of bad germs arriving; some keep them from gaining an attachment or entry point; some engage in "war games" with our immune cells to keep them in top shape; and some, constantly present and in constant chemical communication among themselves and with our immune system, help modulate our immune responses so we don't destroy ourselves buy using a cannon when a popgun will suffice.

Lewis Thomas may have been the first, in Lives of a Cell, to say that we are a minefield, and one side effect of public health efforts has been that we've lost track of where the mines are, and lost the stewards who keep them in proper order, so that small disturbances can results in an eruption that kills us, needlessly.

It turns out that septic shock, both acute and systemic, are immune-system meltdowns, and the toxins that kill us are our bodies' overreactions to germs that ought to be dealt with by a more "sniper-like" response. Many times, doctors can't even detect the organism that is setting off the reaction. Were the body more properly tuned, perhaps only a few hundred bacterial cells need to be hunted down and sliced up. Instead, a massive response intended to kill trillions of invaders, and damn the cost, takes off and can't be stopped.

Finally, our allergies are mostly inappropriate responses to signals the body ought to greet with a "Ho hum, another pollen season." The author shows how we've detuned our immune system so that it is like a horde of bored warriors who need little prompting to go on a spree.

So, the research needed just to find out how all the modulations work is going to be costly. That needed to rebuild what we've lost will cost even more. Since you can't patent a germ, there is little incentive for drug companies to research probiotics treatments, even though they will often be found to be the right way to go.

If you want to see a vision of how it might be, read the first chapter of Tomorrow Now by Bruce Sterling. He makes the statement, "Nothing will rot without your permission." This includes our bodies. An appropriate alliance with our little friends could make that so.

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