I think the casual reader might be surprised to discover that the military made significant contributions to over half of the vaccines developed in the twentieth century.Just as military interest in weapons manufacturing, information systems, and machine control inspired innovation, so too has military interest in the problems of disease control. Fighting disease has always been equally, if not more important for the military than fighting the enemy. Prior to World War II, soldiers died more often of disease than battle injuries. War magnifies the spread and severity of disease by causing large-scale social dislocations and by consolidating large populations of physically stressed individuals. Preventive measures are preferable to therapeutic measures for operational reasons because they reduce sick days.Not only did military scientists develop a set of skills that were particularly well-suited for vaccine development, they had a number of built in advantages: excellent record keeping, a relatively homogenous demographic, and an international network of labs that brought them into close proximity with the populations directly affected by the disease under study. These circumstances facilitated efforts to identify new diseases and to evaluate new vaccine candidates.The Walter Reed Army Institute for Research (WRAIR) became a center of excellence for infectious disease research and vaccine development during the Cold War and instilled an entire generation of vaccine scientists with a unique set of interdisciplinary research skills. WRAIR alumni filled top positions in academia, industry, and government and they often worked together to facilitate the development of many mid-century vaccines.By the end of the cold war, funding for vaccine research began to shift from WRAIR to the National Institutes of Health (NIH). While the NIH excels at early stage discovery, it is not as well suited to the highly collaborative development work required to generate viable vaccine candidates for industry. The NIH began to produce a new generation of scientists with highly specialized skills and impressive publication records, but these scientists were less well adapted to the translational challenges of vaccine development.As we try to keep pace with the growing number of pathogenic threats to health and security, it is important to recognize that the most dangerous threats will be unforeseen and unannounced (such as SARS in 2003). With the exception of smallpox and anthrax vaccines, which can be used for post exposure prophylaxis, it makes more sense to invest in new tools and methods that will allow us to catch up to new threats, even if we can’t predict them. Large vaccine stockpiles are expensive and hubristic.Biodefense programs should emphasize research tools and technologies that will shorten development times and/or introduce flexibility into the medical countermeasure (MCM) development process. Flu manufacturers already develop vaccines for new strains on a six-month timeline every year. These response times were possible even before developers began to exploit currently available technologies (i.e., reverse genetics and cell culture techniques), much less invest in new ones.Critical areas for future investment include rapid detection and diagnostics to speed identification of novel pathogens and diseases, better disease models and biomarkers, rapid expression systems for injectable proteins, DNA vaccine scaffolds, and adjuvants to induce immunity more quickly and/or to improve the immunogenicity of DNA vaccines. Thermostable formulations, and “no needle” delivery systems will also facilitate efforts to distribute and administer MCMs in an emergency.Moving forward, we will also have to find ways to reintroduce integrated research practices. Rather than attempting wholesale reform the vaccine development process today, an emergency MCM program offers an opportunity to incubate new integrated approaches.This is easier said than done because we need to create a financial and organizational vehicle that can sustain a long-term investment in building a system to streamline everything that needs to happen from the moment we detect a new pathogen from the moment we administer a new medical countermeasure for that pathogen.It is increasingly possible to support integrated R&D through a growing array of public private product development partnerships (PDPs). For example, Aeras, a PDP for Tuberculosis vaccine development, incorporates many integrated research practices.This PDP uses top down direction to distill and apply relevant research findings from a wide array of sources and traveling development and clinical teams facilitate the type of on-site cross-disciplinary collaboration that enables tacit information transfer. Aeras also maintains many of their own labs and manufacturing facilities, which (unlike virtual models that outsource these functions) builds communities of researchers that can retain an institutional memory of lessons learned.Shifting the strategic focus of biodefense programs and re-introducing integrated research practices will address problems that have beset vaccine developers for the past several decades and restore our capacity to respond to a rapidly evolving array of threats to global health and security.