The recent anthrax attacks have done more than frighten already anxious Americans. They have created confusion in the public health ranks over how to identify and treat people at risk. They have also triggered deep fears that we may run out of antibiotics just when we need them most. And with people in Canada and the U.S. recently pressuring their governments to override Bayer's patent on the antibiotic Cipro, the very stability of the drug patent system may be in question.
This reality highlights an imperative in medical research: More must be done to stimulate development of new antibiotics. Despite the bioterrorist threat and the ongoing battle being waged in the nation's hospitals against drug-resistant microbes, antibiotics remain a relatively low priority in many drug companies--mainly because they don't produce the lush profits that Big Pharma demands. "You have a huge science-based industry that is not aimed properly [at this problem]," says Martin Rosenberg, retired head of antibiotic discovery at GlaxoSmithKline PLC (GSK). "The government simply must put the right carrot in front of the companies."
Economics are at the heart of this problem. For one thing, these drugs are typically administered for just a few days. Compare that to lucrative blockbusters, such as cholesterol-lowering medicines, that are taken daily for years. In addition, compounds that are effective against drug-resistant bugs are often used sparingly. That's because widespread use of antibiotics accelerates the evolution of resistant strains. But while holding powerful antibiotics in reserve makes sense, those drugs are often less profitable. "Market forces aren't in the right direction for antibiotic development, relative to other classes of drugs," says Dr. David C. Hooper, chief of the infection control unit at Massachusetts General Hospital.
Despite those economic obstacles, new technologies gave antibiotic research a big boost in the 1990s. A number of drug companies stepped up their efforts, using gene-based techniques to identify critical proteins in bugs that could serve as new drug targets. But researchers express concern that some of that momentum may be waning. Dr. Gail H. Cassell, vice-president of infectious disease research at Eli Lilly & Co. (LLY), says developing safe, effective antibiotics against these new targets "is much more of a challenge than people appreciated." True, Lilly is expanding its efforts against infectious diseases in general, including antivirals and drugs aimed at blocking the disease-causing effects of bacteria. But the company has pared spending on new antibiotics that actually kill the bugs.
That's unfortunate, because the need for new antibiotics has never been greater. For one thing, bacteria evolve quickly, going through the equivalent of one human generation in as little as 30 minutes. And drug resistance genes are often swapped by different bugs. As a result, Staphylococcus aureus for example--a major source of hospital-acquired infections--has shown signs it may be developing resistance to the powerful drug vancomycin. And it would be relatively easy for someone with microbiology expertise to cultivate a Cipro-resistant strain of anthrax, contends Gigi Kwik, a fellow at the Center for Civilian Biodefense Studies. "To have a good defense against bioterrorism," says Lilly's Cassell, "you need a steady stream of [medical] innovations, particularly antibiotics."
CASH AS CARROT. The government has taken steps to make this happen. Agencies such as the National Institutes of Health and the Defense Advanced Research Projects Agency have provided some research funding to companies to attack diseases with limited market potential. More money should be funneled to such projects, encouraging pharmaceutical companies to develop broadly effective drugs that will work on such threats as plague or anthrax, as well as more common problems such as strep infections.
Economic incentives could also spur the big companies. One possibility is to offer an extended patent life for antibiotics that would be reserved for only the toughest infections. But any such patent expansion for these restricted compounds should include steps to close other legal loopholes that drug companies exploit. Specifically, drugmakers should not be allowed to delay generic competition for drugs on which they have had ample time to recoup their costs. And the Food & Drug Administration should look for ways to streamline the process for antibiotic drug approval. The agency should also study any new rules to make sure they don't unintentionally dampen antibiotic development.
All these steps, however, could be undermined if drug companies don't have confidence in the strength of their patents. Canada has reversed an earlier decision to override the Cipro patent, and Bayer has cut the price it will charge the U.S. government. In the future, any move to override patents should first be vetted by an independent body that can determine whether alternative treatments exist. The imputed shortages of Cipro didn't justify Canada's intervention, since other antibiotics are effective against anthrax.
If drugmakers believe their patents can be violated with little warning, that could be yet another strike against developing new antibiotics. And the public can ill afford that, considering how the stakes are rising in the war against microbes. By Amy Barrett
With John Carey in Washington