Lyme Disease Vaccines: A Cautionary Tale 253 Disease Foundation, the Lyme Disease Association, and, more recently, the International Lyme and Associated Diseases Society. But the net- works of heterodox patients and their families and fellow-traveling physicians are close-knit, largely independent of organizations, held together by informal meetings and collaborations, and aided by the introduction of the Internet. (For an insightful overview of these indi- viduals and groups and the personal journey many LD patients follow, prompted by the limitations of existing knowledge and medical care, which lead them and their families to find other members—patients and doctors—of the heterodox community, see Weintraub 2009). Twenty years after LD made its appearance in the United States, con- troversy erupted over the efficacy and safety of the new LD vaccines. At first glance, these vaccines, like LD itself, might have followed an uncontroversial script. Two pharmaceutical companies, in concert with leading scientists and clinicians, developed similar vaccines based on a B. burgdorferi outer surface protein (OspA). Developing an effective vac- cine faced steep challenges. In general, we do not have effective vaccines for infectious diseases such as malaria, which do not reliably produce im- munity against subsequent disease. People can get LD multiple times. Ingeniously, the LD vaccines work by blocking the transmission of B. burgdorferi from the tick vector to the human host. Vaccine-induced OspA antibodies in the tick’s human blood meal neutralize B. burgdorferi within the tick itself before it is transmitted to humans. After animal and laboratory studies, two different vaccines based on the OspA antigen were tested in human populations and found to be effective and safe in premarketing clinical trials. Yet one of these vaccines was never submitted for FDA approval, and the other was withdrawn from the market by the manufacturer after only a few years of use. Why did these promising vaccines fail? What does their failure tell us about risk and efficacy in modern U.S. medicine and society? What Happened? In the 1990s, SmithKline Beecham (SKB) and Connaught Laborato- ries independently conducted extensive laboratory and animal studies of OspA vaccines and then launched highly publicized phase III clini- cal trials involving large numbers of volunteers and clinical sites (Sigal et al. 1998; Steere et al. 1998). The main difference between the two