Essays. FSF Columns

Penicillin makes bacteria lyse because of a chemical structure called "beta-lactam." Beta-lactam is a four-membered cyclic amide ring, a molecular ring which bears a fatal resemblance to the chemical mechanisms a bacterium uses to build its cell wall.

Bacterial cell walls are mostly made from peptidoglycan, a plastic- like molecule chained together to form a tough, resilient network. A bacterium is almost always growing, repairing damage, or reproducing, so there are almost always raw spots in its cell wall that require construction work.

It's a sophisticated process. First, fragments of not-yet-peptided glycan are assembled inside the cytoplasm. Then the glycan chunks are hauled out to the cell wall by a chemical scaffolding of lipid carrier molecules, and they are fitted in place. Lastly, the peptidoglycan is busily knitted together by catalyzing enzymes and set to cure.

But beta-lactam is a spa

Gram-negative bacteria, of the tank-car sort we have been describing, have a double cell wall, with an outer armor plus the i

Beta-lactam can not only mimic, subvert and destroy the assembly enzymes, but it can even eat away peptide-chain mortar already in place. And since mammalian cells never use any peptidoglycans, they are never ruptured by penicillin (although penicillin does sometimes provoke serious allergic reactions in certain susceptible patients).

Pharmaceutical chemists rejoiced at this world-transforming discovery, and they began busily tinkering with beta-lactam products, discovering or producing all kinds of patentable, marketable, beta-lactam variants. Today there are more than fifty different penicillins and seventy-five cephalosporins, all of which use beta-lactam rings in one form or another.

The enthusiastic search for new medical miracles turned up substances that attack bacteria through even more clever methods. Antibiotics were discovered that could break-up or jam-up a cell's protein synthesis; drugs such as tetracycline, streptomycin, gentamicin, and chloramphenicol. These drugs creep through the porins deep inside the cytoplasm and lock onto the various vulnerable sites in the RNA protein factories. This RNA sabotage brings the cell's basic metabolism to a seething halt, and the bacterium chokes and dies.

The final major method of antibiotic attack was an assault on bacterial DNA. These compounds, such as the sulphonamides, the quinolones, and the diaminopyrimidines, would gum up bacterial DNA itself, or break its strands, or destroy the template mechanism that reads from the DNA and helps to replicate it. Or, they could ruin the DNA's nucleotide raw materials before those nucleotides could be plugged into the genetic code. Attacking bacterial DNA itself was the most sophisticated attack yet on bacteria, but unfortunately these DNA attackers often tended to be toxic to mammalian cells as well. So they saw less use. Besides, they were expensive.

In the war between species, humanity had found a full and varied arsenal. Antibiotics could break open cell walls, choke off the life-giving flow of proteins, and even smash or poison bacterial DNA, the central command and control center. Victory was swift, its permanence seemed assured, and the command of human intellect over the realm of brainless germs was taken for granted. The world of bacteria had become a commercial empire for exploitation by the clever mammals.

Antibiotic production, marketing and consumption soared steadily. Nowadays, about a hundred thousand tons of antibiotics are manufactured globally every year. It's a five billion dollar market. Antibiotics are cheap, far cheaper than time-consuming, labor-intensive hygienic cleanliness. In many countries, these miracle drugs are routinely retailed in job-lots as over-the-counter megadosage nostrums.

Nor have humans been the only mammals to benefit. For decades, antibiotics have been routinely fed to American livestock. Antibiotics are routinely added to the chow in vast cattle feedlots, and antibiotics are fed to pigs, even chickens. This practice goes on because a meat animal on antibiotics will put on poundage faster, and stay healthier, and supply the market with cheaper meat. Repeated protests at this practice by American health authorities have been successfully evaded in courts and in Congress by drug manufacturers and agro-business interests.

The runoff of tainted feedlot manure, containing millions of pounds of diluted antibiotics, enters rivers and watersheds where the world's free bacteria dwell.

In cities, municipal sewage systems are giant petri-dishes of diluted antibiotics and human-dwelling bacteria.

Bacteria are restless. They will try again, every twenty minutes. And they never sleep.

Experts were aware in the 1940s and 1950s that bacteria could, and would, mutate in response to selection pressure, just like other organisms. And they knew that bacteria went through many generations very rapidly, and that bacteria were very fecund. But it seemed that any bacteria would be very lucky to mutate to successfully resist even one antibiotic. Compounding that luck by evolving to resist two antibiotics at once seemed well-nigh impossible. Bacteria were at our mercy. They didn't seem any more likely to resist penicillin and tetracycline than a rainforest can resist bulldozers and chainsaws.

However, thanks to convenience and the profit motive, once- miraculous antibiotics had become a daily commonplace. A general chemical haze of antibiotic pollution spread across the planet. Titanic numbers of bacteria, in all niches of bacterial life, were being given an enormous number of chances to survive antibiotics.

Worse yet, bacteriologists were simply wrong about the way that bacteria respond to a challenge.

Bacteria will try anything. Bacteria don't draw hard and fast intellectual distinctions between their own DNA, a partner's DNA, DNA from another species, virus DNA, plasmid DNA, and food.

This property of bacteria is very alien to the human experience. If your lungs were damaged from smoking, and you asked your dog for a spare lung, and your dog, in friendly fashion, coughed up a lung and gave it to you, that would be quite an unlikely event. It would be even more miraculous if you could swallow a dog's lung and then breathe with it just fine, while your dog calmly grew himself a new one. But in the world of bacteria this kind of miracle is a commonplace.

Bacteria share enormous amounts of DNA. They not only share DNA among members of their own species, through conjugation and transduction, but they will encode DNA in plasmids and transposons and packet-mail it to other species. They can even find loose DNA lying around from the burst bodies of other bacteria, and they can eat that DNA like food and then make it work like information. Pieces of stray DNA can be swept all willy-nilly into the molecular syringes of viruses, and injected randomly into other bacteria. This fetid orgy isn't what Gregor Mendel had in mind when he was discovering the roots of classical genetic inheritance in peas, but bacteria aren't peas, and don't work like peas, and never have. Bacteria do extremely strange and highly inventive things with DNA, and if we don't understand or sympathize, that's not their problem, it's ours.