The Rise and Fall of the Lyme Disease Vaccines: A Cautionary Tale for Risk Interventions in American Medicine and Public Health

In George Bernard Shaw's play the philanderer (1893), Dr. Paramour reads with dismay a report in the British Medical Journal that proves that the disease bearing his name is nonexistent. His patient with the hitherto-real Paramour's disease, sitting nearby, feels liberated and is annoyed by Paramour's despondency. Shaw's caricature of late nineteenth-century medical pretensions elicited laughs when I saw the play in 1982, but I wonder if it would today, when patients often cling more tightly to controversial medical diagnoses than to their doctors. One such prominent contemporary controversy is over the diagnosis and treatment of Lyme disease (LD). In many ways, LD is an unlikely battleground. It is an old-fashioned “new” disease. In the late 1970s and early 1980s, entomologists and clinical researchers rapidly identified the tick vector and causative bacteria, the spirochete Borrelia burgdorferi (named after its discoverer, Willy Burgdorfer). Diagnostic tests were developed, and antibiotics were believed to be effective. These rapid developments might have led to a reassuring narrative about scientific ingenuity and medical efficacy. But events turned out differently. Nearly every aspect of the diagnosis, treatment, and prevention of LD has been fiercely contested. What is Lyme disease? Who gets to decide? The major issue since LD was named and “discovered” has been the legitimacy and reality of chronic Lyme disease (Aronowitz 1991). For many people in the LD lay advocacy community, LD is protean in its manifestations, often misdiagnosed and underdiagnosed and capable of causing months and years of debilitating pain, fatigue, and anguish. From this heterodox perspective, which has become a formidable opposition to LD orthodoxy, the chronic form of Lyme disease requires long-term, often repeated, courses of antibiotics. In contrast, the orthodox position held by most scientific experts is that LD is typically a straightforward acute infectious disease, readily diagnosed on the basis of rash and other clinical findings, with a supporting role played by laboratory tests, and treated by short courses of oral antibiotics. Late symptoms and syndromes can occur (rarely), but there is no need for a repeated course of intravenous antibiotics. Stricker, Lautin, and Burrascano called the controversies over the definition, diagnostic criteria, and treatment of LD the Lyme wars and noted that “suffering patients seek out ‘Lyme-literate’ providers because the ‘academic’ researchers have failed them” (2005, 5). The stakes in these controversies are high. The question of whether a protean condition called chronic Lyme disease with many different subjective and objective manifestations exists and should be treated with one or more courses of intravenous antibiotics remains the central issue. In a prominent consensus statement endorsed by the Infectious Disease Society of America (IDSA) in 2006, orthodox physicians stated that the evidence supported only three, narrowly defined, late manifestations of LD (Lyme arthritis, late neurological LD, and a rare skin condition called acrodermatitis chronica atrophicans), each characterized by objective diagnostic criteria in addition to subjective complaints and for which there were only limited indications for a single course of intravenous antibiotics (Wormser et al. 2006). Not only was this interpretation of the evidence contested by the heterodox community, but the IDSA was subsequently subjected to antitrust action by the Connecticut attorney general (for a discussion of what appears to be at stake in these long-lasting controversies, see Aronowitz 1991). The heterodox position on Lyme disease could be said to have started with its first patient, Polly Murray, who believed that investigators and doctors, with whom she collaborated and whom she respected, were “playing down the severity of the illness” (Murray 1996, 121), as well as focusing too narrowly on arthritis and other objective complaints. Local support groups were started in the 1980s to provide patient and physician education, practical support for patients, and fund-raising (Murray was involved in each of these activities), often in tandem with the Arthritis Foundation, but were shortly superseded by national and local groups that positioned themselves in opposition to the leading Lyme disease physicians and scientists and their view of the disease. The most prominent among these opposition groups are the Lyme Disease Foundation, the Lyme Disease Association, and, more recently, the International Lyme and Associated Diseases Society. But the networks 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 individuals 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, controversy 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 vaccine faced steep challenges. In general, we do not have effective vaccines for infectious diseases such as malaria, which do not reliably produce immunity 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?