The Invisible Kingdom

Unfortunately for me, I don't know much about baseball, so I don't have a clear idea of what's going on. How do you scratch runs? Does it require special equipment? What's a squeeze bunt? Who's squeezing whose bunt? Is it considered a naughty thing to do? What are twins doing in a bullpen? How many bulls, if any, are in there with them?

It's no use. If I want to appreciate baseball, I have to sit down with someone who'll explain what's going on, first. It's the same with just about anything from hot rods to quantum mechanics: If you really want to get it, you need to speak a bit of the language and understand a few of the rules; otherwise, it just seems like a whole lot of running around.¹

Understanding jargon isn't a mark of intelligence or ability; it's just a matter of becoming familiar with the subject. Case in point: My favorite pastime in a supermarket line is to try to figure out what the tabloid headlines mean, without peeking inside.² Not Nobel Prize-winning stuff, you'd think, but it can be quite a puzzle if I haven't been keeping track of current events in the celebrity sector.

The jargon barrier is a simple-enough principle, but we tend to forget it. Professionals of every kind use special terminology that sounds very impressive to the outsider, but is usually nothing more than shorthand for something that could be understood by anyone, given a little time and a dictionary.

I want to tell you a few stories about microbes, but I have a problem: If I go into detailed and rigorous explanations of biological terms and ideas, it would take a lot of time and paper, this book would become a textbook, and I'd lose you. On the other hand, if I just start yapping on about sigma factors and siRNA, you might decide to tell me to get lost.

I don't want to turn you into a microbiologist; being a microbiologist is what microbiologists were put on this Earth for. So I've opted for the middle path: a quick run-through of some of the basics, names, and principles of biology. If you want to know more, have a look at the Further Reading section at the back of the book and, if you get lost along the way, be sure to refer to the glossary.

But what exactly is a microbe? A microbe is a general name for any creature that is, individually, too small to be seen with the unaided eye. This definition is very old and very loose, so it embraces a lot of different sorts of creatures: bacteria (the group we commonly think of when we say "germ"), archaea (superficially resembling bacteria but recently found to be quite different in many respects), fungi (from yeast to mushrooms), and protists (this group includes primitive algae, amoebas, slime molds, and protozoa). Viruses are microbes, too, but we'll save for later the juicy question of whether they're truly alive or not.

These groups are as different from one another as we are from them—usually even more. From a microbe's point of view, you are virtually identical to, say, a flea because you and the flea share many processes and structures that the microbe doesn't. This is why an antibiotic can kill bacteria, but not people (or fleas): It jams a process that is unique to bacteria. This is also why antibiotics don't work on viruses, which aren't remotely like bacteria (which means that taking penicillin for your flu is useless); nor do they work on fungi, which have their own distinctive way of doing things, and which we need to develop special antifungal drugs to deal with.

A microbe is a single-celled creature. You and the flea are composed of many different types of cells that hold themselves together and depend on each other for survival: Your brain cells are useless without your liver, muscle, and heart cells, for example. A single microbial cell, however, is an independent creature that can survive and reproduce without help from other cells.³

Microbes are also rather teensy. Your average Escherichia coli (E. coli) cell is about two micrometers long, which means that it would take about 50,000 cells back to back (and a lot of convincing) to circle your little finger.⁴ A typical virus is ten to a thousand times smaller than that, which means, proportionally, if a virus were the size of a tennis ball, you'd be big enough to lie down with your feet in San Diego and your head crushing the Golden Gate Bridge.

There's much yet to learn about microbes, including how prevalent they are, how intimately we are involved with them, and how much we rely on them for sustaining life on Earth.

I'll try not to hammer on too much about how grateful we should be to microbes for our continued survival. (Well, why should we? It's not as if they're doing it out of the goodness of their hearts, which they haven't got.) To be evenhanded, I'll also try to minimize any unnecessary preoccupation with disease and death. While I won't hesitate to delve into gruesome tales (some of which you'll dearly wish were fiction), it seems to me that the numerous harmful interactions between microbes and humans have received enough attention as it is; nonetheless, if you particularly relish matters of doom and gloom, refer to the Further Reading section for a few excellent books on that sort of thing.

Are you still lying there between San Diego and San Francisco? Come on, get up. We've got work to do. We need to take a bit of a hop backwards to look at the basic makeup of all living things, microbes included.

We don't know what the original copiers looked like, but it seems like a safe bet that they were similar to a type of molecule we call RNA (ribonucleic acid). This molecule, together with a very similar type of molecule called DNA (deoxyribonucleic acid), is responsible for very nearly all the things we refer to as living.⁷

DNA, DNA . . . we hear about it so often: Its famed double-helix structure has become a familiar design motif, and its name is now tossed around in everyday conversation. So why all the fuss?

Simply, it's because DNA is the cornerstone for every living thing: All organisms are made up of either one or many cells, and each cell contains DNA molecules, which comprise the cell's repository of information. If you're wondering, pure DNA looks and feels like cloudy white snot. You'd think this wondrous material should be some sort of golden, shimmering filament, but nature doesn't give a hoot about our aesthetic sensibilities.

When we refer to DNA, we usually talk about its sequence. Just as low-level computer code is made up of a string of ones and zeros, a DNA molecule encodes information using a genetic code that is made up of a string of four alternative bases: A, T, G, and C (adenine, thymine, guanine, and cytosine). A DNA sequence looks something like this, when written down on paper: . . . ATTTGCAGTT-TACCCGTG . . . To us, this is as meaningless as binary code, 000101010000100, but the cell's mechanisms know how to read it.

The total genetic information encoded in these sequences is called the genome. It's important to understand that there are a lot of different kinds of information in a genome. There are bits that tell other bits how and when to work, bits that point to other bits, and bits whose function, if there is one, we don't know yet. The most straightforward bits, however, are called genes.

Gene: another popular word that's bandied about all over the place. Mercifully, we encounter far fewer misleading ideas about genes in the media nowadays (for example, the notion that you can have "a gene for" complex traits like aggressiveness, depression, or fashion sense), but there's still a lot of creative misunderstanding of the concept. Part of the problem is that even biologists have differing definitions of the term. The most popular include "a hereditary unit," which is useful for theoretical evolutionary studies, and the more hands-on explanation, which lab people favor: "a DNA sequence responsible for making a functional product." No definition is the correct one, because people who didn't know, and couldn't possibly have known, what DNA was (or how it worked) coined the term way back in the nineteenth century. Sixty years later, the theoretical concept suddenly became a physical reality—something you could actually see and touch (if you enjoy handling snot, of course).

So a microbe is a single cell, a cell contains a genome, and genomes are made up of genes (and some other stuff). Now for the part you've all been waiting for: reproduction.

DNA is packed as two complementary strands in a cell. This enables the cell to create two copies of its genome when it divides, so that each new copy of the cell (the "daughter cell") gets a complete copy of the information it needs to function.

In a bacterial or archaeal cell, the bulk of the DNA is contained in one circular molecule called a chromosome. In fungi, protists, and most multicellular organisms, we find more than one chromosome. A human cell contains twenty-three different kinds of chromosomes with two copies of each kind, because humans reproduce sexually, and sexual reproduction is all about the offspring receiving one copy of each chromosome from each parent. Microbes, on the other hand, reproduce asexually: The microbial cell makes a copy of its genome, divides itself in two (so that each half receives one whole copy), and both halves start growing again. Cycle completed. No arguing about which parent the kid looks like, or whose nose she got.

An intricate apparatus called a ribosome then uses the RNA transcript to create a protein molecule.⁸ Which protein molecule? It depends on the gene that's being read.

Proteins are a very large category of molecule. There are countless types of proteins, and they do an astounding variety of things. If a cell were a house needing to be built, proteins would be the tools, the craftsmen, and the building materials.

The "building materials" are called structural proteins (good examples of these are the actin and tubulin fibers that prevent our cells from collapsing into themselves, and keratin, which makes up our hair and nails), and the "craftsmen and tools" are called enzymes. Every type of enzyme is able to do one specific thing: They attach themselves to a specific target molecule, or substrate, and then act on it in some way, either by cutting it, joining it, or modifying it.⁹ Digest food? Enzymes. Move a muscle? Enzymes. Think? Enzymes.

Another category of protein moves stuff around. They latch on to a target molecule and then either move the molecule from place to place (transport proteins), or just signal to the cell that they have caught and identified a particular molecule (receptors).

Proteins can also act as the signals themselves—hormones (for example, insulin) are a well-known class of these signal proteins.¹⁰

It's very important at this point to emphasize that a cell doesn't just read its entire genome from start to finish and churn out all the proteins that the genes encode. Nearly every cell in your body has a complete set of genes, but they don't use them all. Your skin cells don't produce liver enzymes, and your liver cells don't try to become muscles. There are very elegant regulatory mechanisms in place to make sure that each cell expresses only those proteins (and only the correct amounts of each protein) that it should. If all proteins were expressed at once, it would be a chaotic jumble—like the meaningless din that you create (rather than music) when you hit all the keys on a piano at the same time.

Remember the oft-quoted scientific fact that says that humans share 98 percent of their genes with chimpanzees? Although it seems to suggest how alike the two species are, that's not quite the case. True, we share a lot of genetic information with our chimpy cousins, but it's read and used in very different ways (the growth of body hair springs to mind). As usual, it's not what you have that really matters: It's what you do with it.

The microbial cell works much the same way. Because it's single-celled and does everything by itself, it does use its genome quite comprehensively—but not all at once. It can sense its surroundings and react to them, produce enzymes that break down a particular nutrient when that nutrient is around, and switch to different enzymes if there's another, better nutrient to be used. If it's hot, it manufactures proteins that help cope with heat (disappointingly, they don't look like tiny electric fans), and it disassembles and recycles these when it cools down again.

If we combine all this together, we can visualize what a living cell looks like: There is a genome (a very long DNA molecule), which is being manipulated by regulatory proteins and RNA polymerase in order to churn out shortish RNA sequences. These sequences go out to the ribosomes, which then make all sorts of new proteins. Around the genome, thousands of processes are going on—enzymes are working on substrates, proteins are moving material from place to place, and things are constantly being built up, broken down, replaced, and modified. If you picture a factory reduced by a scale of about 100 million, sped up ten-thousandfold, duplicating itself occasionally, you'll get the general idea.

All this activity is contained within a cellular membrane, which separates "inside" from "outside."¹¹ On (and in) the membrane are receptor and transport proteins, which are the cell's link to the outside environment: They sense it, react to it, and bring things in and out of it.

In humans, this environment is mainly composed of neighboring cells: As I mentioned before, a human cell is a machine inside a machine—it can only survive and function as a component of a much larger structure.

A microbe's environment, on the other hand, may contain its siblings (read: competitors), members of other microbial species (read: competitors), and things that eat microbes (read: bad news). Important physical conditions—temperature, salinity, energy sources, the chemical composition of its surroundings—also affect the microbe, every second of its life. A microbe attempting to set up house inside a human lung, for example, has to deal with our immune system trying to get rid of it, while a microbe in a muddy puddle, or up a tree, has a very different set of problems.

Mostly, it multiplies. A microbial cell is an object primarily concerned with getting enough energy and materials to repeatedly duplicate itself. This is not because it wants to (microbes don't have brains to want things with), but because that's the basic principle of evolution—if something tends to reproduce effectively, it will spread. If it doesn't, its numbers will dwindle away into nonexistence so that, eventually, we just don't see microbes that aren't that good at multiplying around anymore.

Therefore, microbes that have randomly developed something to help them survive and multiply in their environment will (nonran domly) outbreed the others. That is the classical theory, at least; but, later on, I'll introduce you to some microbes that also develop tricks and shortcuts to speed up and optimize their evolution.

On the flip side of the race, some microbes actually lose something to gain an advantage, rather than developing something. As professionals in any field of racing will tell you, stripping the machine down is absolutely crucial for gaining a competitive edge because—and this is a principle that is as important in biology as it is everywhere—everything has its price. If a microbe has lost an unnecessary system, it no longer needs to allocate time, material, and energy towards keeping that system functioning, and it can put more resources into reproduction. That microbe is one step ahead in the perpetual race. Sometimes, a particular system or quality isn't necessary for a microbe's survival; for instance, the ability to survive intense heat is useless in a cool environment, so after some time, most microbes in a cool environment would be the offspring of the first individual microbe to have lost that ability.

Of course, not all environments are the same. After the first cells came into being, the natural optimization process meant that if you saw the same type of microbe in two different environments, over time, each would develop in radically different ways.¹² Microbes living in warm places, for instance, became better and better at dealing with high temperatures, and could venture out further into hotter places. Why would they adapt like that? Because of the reward: A microbe that could move out into new territory would have the place to itself. We're not just talking about physical territory here: If a microbe evolves so that it is able to use something in its present environment in a beneficial way (say, a food resource), it will suddenly be much better off, and will be able to reproduce the hell out of everyone else.

And reproduce they do: Given good conditions, an E. coli cell can become two cells within twenty minutes. Multiply this process by a lot, give it a few billion years to run, and you get what we see today: Microbes of all sorts, everywhere, swimming in every droplet of water, and hanging on to every surface.

The name of a microbe usually marks where that particular species was first found. The dreaded Ebola virus, for example, was named after the river valley near where the first outbreak of the disease occurred. Geographical location, however, is hardly the most engaging thing about the places in which microbes find themselves. Microbes excel at surviving in unusual, even extreme, environments that are usually much too rough for other types of life.

Finding some of these microbes involves journeying to the ends of the Earth; but, before we do that, let's first stop at a slightly less captivating location to meet a microbe that's being grown by the billions—and find out why.

There is, of course, no such thing as a typical microbe, just as there's no such thing as a typical human being; but E. coli will do to begin with, and it will give us something against which to compare some of the more extreme examples of microbehood.

E. coli belongs to the Enterobacteriaceae