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Last Updated

29 Jun 2003

Source: Wall Street Journal, April 25, 2002.

Losing the Race With Bugs: Bacteria Beats New Drugs


Cheetahs eat gazelles. The fastest cheetahs catch more gazelles and breed more; and over generations, cheetahs get faster. But gazelles evolve, too. Faster gazelles live longer and breed more; over generations, they get faster, too.

The same evolutionary dynamics apply to humans and bacteria. We develop antibiotics that kill bacteria. They evolve resistance. We develop better drugs. They evolve resistance to the new drugs.

Cheetahs and gazelles evolve at the same pace. From about 1945 to the early 1980s, humans developed new drugs faster than bacteria evolved. But bacteria now are changing faster than our drugs.

The bugs are winning the race. The more antibiotics we use, the quicker they evolve resistant strains.

A common bacterium called pneumococcus, which causes ear and sinus infections as well as more serious illness, first showed resistance to penicillin in the 1960s. Into the early 1990s, only 5% of cases were resistant, according to the Centers for Disease Control and Prevention. By the end of the 1990s, penicillin couldn't touch nearly 40% of cases in some parts of the U.S.

Tuberculosis will kill more this year than last because a drug-resistant strain has evolved. "Strains of five bacterial species capable of causing life-threatening illnesses already evade every antibiotic in the clinician's armamentarium," says Stuart Levy, a Tufts University microbiologist.

The science is clear. The medical establishment is alarmed. The bioterrorism threat intensifies concern. The issue is: what to do?

Think of antibiotic effectiveness as a natural resource, like fish, that we're depleting rapidly, suggests economist Ramanan Laxminarayan of Resources for the Future, a think tank in Washington, D.C. "Everyone harvests this resource, caring only about himself and ignoring the potential harm to others," he says.

Each commercial fisherman profits by catching more fish, no matter how depleted the ocean stocks. Each parent will press a pediatrician for a drug if there's any chance it will cure a child. Yet if every parent and pediatrician does the same, they will speed the evolution of drug-resistant microbes. And what drug company will enlist its marketers to prod doctors to prescribe its antibiotics less?

Until now, the main remedy has been preaching, the equivalent of pleas to commuters to carpool. Government, doctors' groups and insurers are trying to persuade patients and doctors to avoid antibiotics where they won't work, in treating viral infections, for instance.

In northern California, Kaiser Permanente, the big HMO, has reduced antibiotic use by 30% during the past two years by showing doctors how their prescription patterns differ from peers and using posters to educate patients. The CDC, among other things, offers doctors "viral prescription pads" with treatment tips so patients whose ailments can't be helped by antibiotics don't go away empty-handed. It sees signs that this public-relations campaign is succeeding.

Such education is essential, but it won't suffice. So in quiet conversations, scientists and economists are beginning to think about stronger medicine.

One option is discouraging unnecessary drug use by charging consumers more for the most-overused antibiotics or for newer, heavily promoted drugs that ought to be held in reserve. Increasing drug prices -- even if only for people whose insurance policies cover most of the cost -- sounds jarring. But Mr. Laxminarayan draws the parallel to the campaign against smoking, which, he notes, "was accomplished through both cigarette-tax increases and information campaigns" after public pressure overwhelmed opposition from smokers and tobacco companies.

This approach assumes that resistance is simply caused by overuse. It isn't. Higher prices or an antibiotic tax won't solve the problem of incomplete treatment -- not finishing a prescribed dose or, in poor places, not having enough medicine to kill bacteria -- which also gives the bugs an edge.

The bugs also get an edge when doctors all tend to use the same drugs. Despite the famously decentralized U.S. health-care system, the five most commonly used antibiotics account for 80% of all antibiotic prescriptions.

To save money, insurers, hospitals and HMOs often limit the menu of drugs available, reasonably seeking to use the most cost-effective medicine. But using different drugs for the same ailment in different people or at different times, much as farmers rotate crops, may be prudent. This requires more coordination than is possible in the decentralized U.S. system, although some hospitals, prodded by the CDC, are moving in this direction.

Another solution would be to pull ahead of the microbes. A new pneumococcus vaccine will help. But we also need new potent families of antibiotics. We haven't found one in decades, and big pharmaceuticals firms are devoting R&D money to more-lucrative drugs that treat chronic conditions such as cancer or impotence.

So there is talk, and not just from drug companies, of new ways to stimulate research into new antibiotics. One possibility is tinkering with patent rules to make them broader, both to lure research money and to give drug companies more incentive to market drugs with an eye to the evolutionary dangers.

Devising the right remedies and selling them won't be easy. It never is when near-term interests, whether those of patients or of drug companies, diverge from the long-term interests of humankind.