The Shape Of Life

With the birth of molecular biology, genes came to define what it means to be alive. In 2000, President Bill Clinton announced that scientists had completed a rough draft of the human genome—the entire sequence of humans' DNA. He declared, "Today, we are learning the language in which God created life."

But on their own, genes are dead, their instructions meaningless. If you coax the chromosome out of E. coli, it cannot build proteins by itself. It will not feed. It will not reproduce. The fragile loop of DNA will simply fall apart. Understanding an organism's genes is only the first step in understanding what it means for the organism to be alive.

Many biologists have spent their careers understanding what it means for E. coli in particular to be alive. Rather than starting from scratch with another species, they have built on the work of earlier generations. Success has bred more success. In 1997, scientists published a map of E. coli's K-12's entire genome, including the location of 4,288 genes. The collective knowledge about E. coli makes it relatively simple for a scientist to create a mutant missing any one of those genes and then to learn from its behavior what that gene is for. Scientists now have a good idea of what all but about 600 genes in E. coli are for. From the hundreds of thousands of papers scientists have published on E. coli comes a portrait of a living thing governed by rules that often apply, in one form or another, to all life. When Jacques Monod boasted of E. coli and the elephant, he was speaking only of genes and proteins. But E. coli turns out to be far more complex—and far more like us—than Monod's generation of scientists realized.

The most obvious thing one notices about E. coli is that one can notice E. coli at all. It is not a hazy cloud of molecules. It is a densely stuffed package with an inside and an outside. Life's boundaries take many forms. Humans are wrapped in soft skin, crabs in a hard exoskeleton. Redwoods grow bark, squid a rubbery sheet. E. coli's boundary is just a few hundred atoms thick, but it is by no means simple. It is actually a series of layers within layers, each with its own subtle structure and complicated jobs to carry out.

E. coli's outermost layer is a capsule of sugar teased like threads of cotton candy. Scientists suspect it serves to frustrate viruses trying to latch on and perhaps to ward off attacks from our immune system. Below the sugar lies a pair of membranes, one nested in the other. The membranes block big molecules from entering E. coli and keep the microbe's molecules from getting out. E. coli depends on those molecules reacting with one another in a constant flurry. Keeping its 60 million molecules packed together lets those reactions take place quickly. Without a barrier, the molecules would wander away from one another, and E. coli would no longer exist.

At the same time, though, life needs a connection to the outside world. An organism must draw in new raw materials to grow, and it must flush out its poisonous waste. If it can't, it becomes a coffin. E. coli's solution is to build hundreds of thousands of pores, channels, and pumps on the outer membrane. Each opening has a shape that allows only certain molecules through. Some swing open for their particular molecule, as if by password.

Once a molecule makes its way through the outer membrane, it is only half done with its journey. Between the outer and inner membranes of E. coli is a thin cushion of fluid, called the periplasm. The periplasm is loaded with enzymes that can disable dangerous molecules before they are able to pass through the inner membrane. They can also break down valuable molecules so that they can fit in channels embedded in the inner membrane. Meanwhile, E. coli can truck its waste out through other channels. Matter flows in and out of E. coli, but rather than making a random, lethal surge, it flows in a selective stream.

E. coli has a clever solution to one of the universal problems of life. Yet solutions have a way of creating problems of their own. E. coli's barriers leave the microbe forever on the verge of exploding. Water molecules are small enough to slip in and out of its membranes. But there's not much room for water molecules inside E. coli, thanks to all the proteins and other big molecules. So at any moment more water molecules are trying to get into the microbe than are trying to get out. The force of this incoming water creates an enormous pressure inside E. coli, several times higher than the pressure of the atmosphere. Even a small hole is big enough to make E. coli explode. If you prick us, we bleed, but if you prick E. coli, it blasts.

One way E. coli defends against its self-imposed pressure is with a corset. It creates an interlocking set of molecules that form a mesh that floats between the inner and outer membranes. The corset (known as the peptidoglycan layer) has the strength to withstand the force of the incoming water. E. coli also dispatches a small army of enzymes to the membranes to repair any molecules damaged by acid, radiation, or other abuse. In order to grow, it must continually rebuild its membranes and peptidoglycan layer, carefully inserting new molecules without ever leaving a gap for even a moment.

E. coli's quandary is one we face as well. Our own cells carefully regulate the flow of matter through their walls. Our bodies use skin as a barrier, which must also be pierced with holes—for sweat glands, ear canals, and so on. Damaged old skin cells slough off as the underlying ones grow and divide. So do the cells of the lining of our digestive tract, which is essentially just an interior skin. This quick turnover allows our barriers to heal quickly and fend off infection. But it also creates its own danger. Each time a cell divides, it runs a small risk of mutating and turning cancerous. It's not surprising, then, that skin cancer and colon cancer are among the most common forms of the disease. Humans and E. coli alike must pay a price to avoid becoming a blur.

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