Safe havens

 作者:庞蜥     |      日期:2019-03-08 07:01:01
By Charles Seife DOCTORS are watching helplessly as HIV, tuberculosis and many other deadly infections grow resistant to drugs. Now two mathematicians believe they have pinned down the conditions that allow viruses and bacteria to mutate into these resistant strains. For a pathogen to develop resistance to a drug, the drug must tread a very fine line. It must be effective enough to kill much of the normal strain, giving drug-resistant mutants an evolutionary advantage. But it must not be so effective that it completely stops the normal strain reproducing and mutating. “It seems like the window of opportunity is incredibly narrow,” says Thomas Kepler, a biomathematician at North Carolina State University at Raleigh. This made Kepler wonder why drug resistance is so common, with some bugs developing resistance to several drugs. He and Alan Perelson have developed a mathematical model that mimics the way viruses and other pathogens reproduce in the body (Proceedings of the National Academy of Sciences, vol 95, p 11 514). By plugging various numbers into the model, the researchers showed that if a patient takes medicine regularly and the drug penetrates the body evenly, resistance is unlikely to develop. But if there are “sanctuaries” in the body where the drug does not penetrate well, the pathogen can reproduce in safety. When resistant mutants enter the bloodstream they reproduce better than non-resistant varieties. Kepler says this may explain how HIV, for instance, has developed resistance to several antiviral drugs. “There must be places where the drug is not penetrating completely,” he says. He suggests that drug designers should focus on trying to solve this problem. “The arguments make a lot of sense,” says Jon Condra, a virologist with Merck Pharmaceuticals in West Point, Pennsylvania. “I don’t really think that they have told us anything we didn’t know intuitively,