Tinkering with Evolution
Not so long ago, it looked as if medical research had pretty much whipped diseases caused by bacteria. The scourges of the past--bacterial pneumonia, tuberculosis, the various and often lethal illnesses generated by the streptococcus and staphylococcus families--seemed to be licked for good. Just as DDT wiped out noxious insects, so antibiotics promised to do away with deadly microscopic bugs. Thanks to the wonders of modern chemistry, research could move on to the more challenging realm of diseases caused by viruses or mysterious molecular malfunctions, such as those leading to cancer and various hereditary problems.
It's turning out that the DDT analogy is uncomfortably exact. At first, that powerful insecticide seemed to do the job perfectly. Then horrifying side effects turned up, leading to the near-extinction of numerous species of birds. Finally, the sprays were no longer effective. They had simply promoted development of insects resistant to DDT.
In essence, DDT let us watch evolution in action. We introduced an environmental toxin, and flies died by the millions. But the ones with a genetic defense against the toxin survived. Free of competition from their undefended kin, these resistant flies bred millions of offspring.
Through the widespread use of antibiotics--not just to cure disease, but to prevent it in both humans and the organisms we eat--we've forced evolution in bacteria as well. And bacteria have more tricks than insects do for developing resistance.
Consider: people harbor an array of harmless (in fact, some quite useful) bacteria all the time. The best known is Escherichia coli, a mild-mannered bug found in everyone's intestines. If a person takes an antibiotic to cure a bacterial disease, the antibiotic is likely to make resident E. coli sick--that is, they'll be under pressure from a substance toxic to bacteria. The ones that survive and multiply are the E. coli resistant to that particular antibiotic, and perhaps to other chemically similar substances.
Compared to insects, bacteria are positively leaky with their genetic material. A fly can't pick up heritable factors for DTT resistance by rubbing shoulders with a resistant mosquito, but a dysentery-causing Shigella bacterium can pick up resistance to ampicillin by hobnobbing with resistant E. coli.
It's enough to give researchers nightmares. So far, the struggle has been one of escalation--developing new and stronger chemical weapons to overcome mechanisms of resistance. That's been only partially successful. Sometimes biology outpaces chemistry: Jim Henson, the much-loved Muppeteer, died this spring from a bacterial infection caused by an organism apparently identical to the one responsible for scarlet fever--a once dangerous disease that had apparently disappeared for the past 30 years.
At best, escalation offers only temporary victory, until the bacteria develop resistance to the new chemical weapons. According to Science magazine, at least one scientist is taking an entirely new tack. Stanley Falkow of Stanford University thinks the whole use of antibiotics is a technique at the end of its tether. Eventually, he believes, people must learn to work with evolutionary processes rather than trying to buck them.
The crucial point is that disease is not in a microbe's best interest. If bacteria crank out toxins that make their host sick, the host system will crank out defenses to kill the bacteria or will add alien chemicals to wipe them out. Worse from the bacterial viewpoint is that even a full victory wins nothing: a dead host supports no germs.
Unfortunately, it's not useful to lecture bacteria about their counterproductive behavior. But it is conceivable that truly new methods could nudge them toward a biological nonagression pact. Falkow believes that the most effective treatment for bacterial infection would permit the bacteria to persist while forcing them to dismantle the portion of their genetic code that directs manufacture of the toxins distressing their host.
No one thinks that will be easy. Ironically, some support for the concept is coming from scientists working on controlling mosquito-borne diseases. They're tinkering with the genetic makeup of mosquitoes so that the insects can no longer transmit malaria, yellow fever, encephalitis--all the sicknesses that buzzing hordes have visited on humankind. That work is going well at the laboratory level, at least, though here too it will be many years before engineered insects offer large-scale disease control.
Thus it seems that on two fronts, the path to health in the future may come via genetic maps. Meanwhile, in self-defense, we can only keep clean--and keep swatting.
