Although scientists are supposed to be subjective, they are, of course, influenced by their social and political environment. The studies of Louis Pasteur and Robert Koch were intimately linked, but they lived and worked in feuding nations, France and Germany, respectively. It seems that fervent patriotism might have been a driving force behind Pasteur's remarkable advances in microbiology. On page 229, Alan Baxter discusses the role played by Pasteur's desire to develop the perfect beer for France in the emergence of the first vaccines.
The pioneering approaches of Koch and Pasteur have stood the test of time; successful vaccines today are still based on preparations of attenuated or killed microbes. But many important chronic infections — particularly those that do not naturally elicit protective immunity (for example, HIV) — have evaded vaccine developers. New understanding of immune regulation at the molecular level is facilitating the design of recombinant vaccines that induce more effective immune responses against both infection and cancer. On page 209, Jay Berzofsky and colleagues discuss these new approaches and their applications.
Other articles in this issue describe some of the basic research that has made these advances in immunotherapy possible. Maria-Luisa Alegre and co-workers, on page 220, detail our current understanding of how the co-stimulatory molecules CD28 and CTLA-4 regulate T-cell activation and tolerance, work that has depended on knock-out and transgenic mouse models. By contrast, Warren Leonard on page 200, describes how naturally occurring mutations that cause profound immunodeficiency in humans have increased our understanding of cytokine signalling pathways and their roles in the development and function of the immune system.