The question of how, exactly, the immune system responds to various kinds of flu is already a hot topic. In 2007, researchers took a sample of the deadly 1918 virus and infected a group of monkeys in order to study their responses and ensuing (ugly) deaths. This work, which made even some scientists queasy, contributed to the theory that the 1918 flu caused an aberrant and unusually strong immune response—and that this was what killed a lot of people, especially healthy young ones. A similarly overwrought response, characterized by massive inflammation, seems to occur in cells infected with the avian flu H5N1, in contrast to less pathogenic strains. (H1N1 appears to have some similarities to the 1918 strain but is nowhere near as dangerous.) Other researchers are untangling why and how the immune system goes haywire in response to certain viruses, with the hope of finding treatments that might calm it down, says Ben Greenbaum of the Institute for Advanced Study in Princeton (who is also a good friend).
Other researchers are running with the signatures-of-response approach, too. When parents bring babies with fevers to the emergency room, for instance, doctors often don't have a fast, reliable way to tell which infections are bacterial as opposed to viral and which are truly serious. As a result, babies tend to be admitted to the hospital for two to three days of observation, says Octavio Ramilo, chief of infectious diseases at Nationwide Children's Hospital in Columbus, Ohio. His group is studying whether tests of molecular changes in the babies' blood might spare unnecessary hospitalizations—or allow for better, faster care of those who require antibiotics. Ramilo's team is also working on immune signatures of a condition called Kawasaki disease, which causes fevers and is sometimes confused with other kinds of infection. Again, the goal is to understand how, exactly, different diseases provoke the body and which patients are most likely to become very sick. Another aim is to develop portable technologies to give clinicians and patients fast access to this information.
Meanwhile, researchers are also homing in on signatures related to cancer, heart disease, and other complex conditions. Geoff Ginsburg and colleagues have shown that profiles of the gene expression from tumor tissues in blood may predict how well cancer patients respond to specific chemotherapeutic drugs. Similar methods can reveal the extent of coronary artery disease in patients undergoing an imaging procedure called angiography. Others have reported on potential applications related to aortic aneurisms, Type 2 diabetes and autoimmune diseases. By the looks of it, researchers are just starting their engines.
To be sure, none of this will replace traditional methods of hunting down pathogens directly, especially in the midst of new and weird outbreaks. Consider the success of pathogen-focused work in untangling West Nile virus and a hemorrhagic virus called LuJo, among others. But for some diseases, looking at molecular responses in infected people may prove easier and faster. It may also work better for screening, assessing how bad a sickness is, and figuring out the best response. This is the new game in town—and someday it might save us.