Control and Prevention, the number of sepsis cases linked to microbial infections in hospital patients tripled from 1979 to 1992-partly because of the increased vulnerability of the patient population, which includes more older patients and more AIDS patients. Both groups have weakened immune systems that predispose them to sepsis. This burgeoning market could be a pot of gold for the 20 or so companies now developing pOSSible antisepsis drugs. But, as the experiences of Synergen, Centocor, and Xoma show, the route to this prize is neither straight nor easy." Even though sepsis is a relatively attractive target for a biotech company, it's also one that everyone has tripped over," says Richard Rose, vice president of drug development for Cytel Pharmaceuticals of San Diego, which currently doesn't have sepsis in its sights. Yet the prize is attractive enough that, no matter how many runners trip, others are there to vie for the inside track. Preying on the weak. Like a wolf stalking the sickly members of a herd of elk, sepsis finds its victims among the weak, w particularly among

~ patients in hospital>: 11<·.......-.:.. 0··. 15 mtenslve-care units~ who come down with~ infections. All told,~ about 95% of sepsis~ cases are caused by infections of some kind; most of the remaining 5% occur, for reasons that are poorly understood, in people with severe injuries but no signs of infection. Even among the cases caused by infection, there's plenty of variety. While most used to be caused by Escherichia coli and other gram-negative bacteria (so-called because they fail to absorb a particular stain), an increasing proportionnow 55% ofthe total-are triggered by grampositive bacteria and fungi." There's been a dramatic shift recently in the pathogens that cause sepsis," says sepsis researcher Roger Bone of the Medical College ofOhio in T0-ledo.

Despite the dizzying array of microbes that trigger sepsis, researchers in the past decade have learned enough about the molecular biology of the initiating pathogens as well as the immune cascade that causes sepsis to begin identifying targets for antisepsis drugs." The clinical research done so far has put us