A health care trade association estimates that 52 million consumers use a product containing acetaminophen every week in the U.S. The drug is safe and effective when used as directed, but there is something surprising about it: no one is certain how acetaminophen works to relieve pain and fever. There are at least two theories about the mechanism of the drug, which was first synthesized in the late 1800s. “So it’s probably an indirect effect on prostaglandins,” Dudley says. “There could be no big incentive to figure out how it works,” Straiker says.