The River That Runs Uphill

Barriers and genes are essential to life, but life cannot survive with barriers and genes alone. Put DNA in a membrane, and you create nothing more than a dead bubble. Life also needs a way to draw in molecules and energy, to transform them into more of itself. It needs a metabolism.

Metabolisms are made up of hundreds of chemical reactions. Each reaction may be relatively simple: an enzyme may do nothing more than pull a hydrogen atom off a molecule, for instance. But that molecule is then ready to be grabbed by another enzyme that will rework it in another way, and so on through a chain of reactions that can become hideously intricate —merging with other chains, branching in two, or looping back in a circle. The first species whose metabolism scientists mapped in fine detail was E. coli.

It took them the better part of the twentieth century. To uncover its pathways, they manipulated it in many ways, such as feeding it radioactive food so that they could trace atoms as E. coli passed them from molecule to molecule. It was slow, tough, unglamorous work. After James Watson and Francis Crick discovered the structure of DNA, their photograph appeared in Life magazine: two scientists flanking a tall, bare sculpture. There was no picture of the scientists who collectively mapped E. coli's metabolism. It would have been a bad photograph anyway: hundreds of people packed around a diagram crisscrossed with so many arrows that it looked vaguely like a cat's hairball. But for those who know how to read that diagram, E. coli's metabolism has a hidden elegance.

The chemical reactions that make up E. coli's metabolism don't happen spontaneously, just as an egg does not boil itself. It takes energy to join atoms together, as well as to break them apart. E. coli gets its energy in two ways. One is by turning its membranes into a battery. The other is by capturing the energy in its food.

Among the channels that decorate E. coli's membranes are pumps that hurl positively charged protons out of the microbe. E. coli gives itself a negative charge in the process, attracting positively charged atoms that happen to be in its neighborhood. It draws some of them into special channels that can capture energy from their movement, like an electric version of a waterwheel. E. coli stores that energy in the atomic bonds of a molecule called adenosine triphosphate, or ATP.

ATP molecules float through E. coli like portable energy packs. When E. coli's enzymes need extra energy to drive a reaction, they grab ATP and draw out the energy stored in the bonds between its atoms. E. coli uses the energy it gets from its membrane battery to get more energy from its food. With the help of ATP, its enzymes can break down sugar, cutting its bonds and storing the energy in still more ATP. It does not unleash all the energy in a sugar molecule at once. If it did, most of that energy would be lost in heat. Rather than burning up a bonfire of sugar, E. coli makes surgical nicks, step by step, in order to release manageable bursts of energy.

E. coli uses some of this energy to build new molecules. Along with the sugar it breaks down, it also needs a few minerals. But it has to work hard to get even the trace amounts it requires. E. coli needs iron to live, for example, but iron is exquisitely scarce. In a living host most iron is tucked away inside cells. What little there is outside the cells is usually bound up in other molecules, which will not surrender it easily. E. coli has to fight for iron by building iron-stealing molecules, called siderophores, and pumping them out into its surroundings. As the siderophores drift along, they sometimes bump into iron-bearing molecules. When they do, they pry away the iron atom and then slide back into E. coli. Once inside, the siderophores unfold to release their treasure.

While iron is essential to E. coli, it's also a poison. Once inside the microbe, a free iron atom can seize oxygen atoms from water molecules, turning them into hydrogen peroxide, which in turn will attack E. coli's DNA. E. coli defends itself with proteins that scoop up iron as soon as it arrives and store it away in deep pockets. A single one of these proteins can safely hold 5,000 iron atoms, which it carefully dispenses, one atom at a time, as the microbe needs them.

Iron is not the only danger E. coli's metabolism poses to itself. Even the proteins it builds can become poisonous. Acid, radiation, and other sorts of damage can deform proteins, causing them to stop working as they should. The mangled proteins wreak havoc, jamming the smooth assembly line of chemistry E. coli depends on for survival. They can even attack other proteins. E. coli protects itself from itself by building a team of assassins—proteins whose sole function is to destroy old proteins. Once an old protein has been minced into amino acids, it becomes a supply of raw ingredients for new proteins. Life and death, food and poison—all teeter together on a delicate fulcrum inside E. coli.

As E. coli juggles iron, captures energy, and transforms sugar into complex molecules, it seems to defy the universe. There's a powerful drive throughout the universe, known as entropy, that pushes order toward disorder. Elegant snowflakes melt into drops of water. Teacups shatter. E. coli seems to push against the universe, assembling atoms into intricate proteins and genes and preserving that orderliness from one generation to the next. It's like a river that flows uphill.

E. coli is not really so defiant. It is not sealed off from the rest of the universe. It does indeed reduce its own entropy, but only by consuming energy it gets from outside. And while E. coli increases its own internal order, it adds to the entropy of the universe with its heat and waste. On balance, E. coli actually increases entropy, but it manages to bob on the rising tide.

E. coli's metabolism is something of a microcosm of life as a whole. Most living things ultimately get their energy from the sun. Plants and photosynthetic microbes capture light and use its energy to grow. Other species eat the photosynthesizers, and still other species eat them in turn. E. coli sits relatively high up in this food web, feeding on the sugars made by mammals and birds. It gets eaten in turn, its molecules transformed into predatory bacteria or viruses, which get eaten as well. This flow of energy gives rise to forests and other ecosystems, all of which unload their entropy on the rest of the universe. Sunlight strikes the planet, heat rises from it, and a planet full of life—an E. coli for the Earth—sustains itself on the flow.

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