Jürg Tschopp (1951–2011)

Jürg Tschopp stood apart from most of his colleagues in immunology in that his discoveries in fundamental research brought striking and almost immediate benefits to patients suffering from painful, debilitating diseases. Of his numerous findings, one led to a treatment for the autoimmune disorder systemic lupus erythematosus, and another brought dramatic relief to patients with gout. Tschopp, who died on 22 March aged 59, trained as a biophysicist and obtained a PhD from the University of Basel in Switzerland in 1979. Yet it was immunological questions that captured his attention. He did postdoctoral work with molecular immunologist Hans Müller-Eberhard at the Scripps Clinic in La Jolla, California, before joining the Department of Biochemistry at the University of Lausanne in Switzerland in 1982. An early milestone in his career was the characterization of the final step in a signalling pathway called the complement cascade. This is a crucial component of the innate immune response, which protects animals from an infection through a generic mechanism, rather than on the basis of previous ‘remembered’ encounters with an infectious agent. In the early 1980s, immunologists knew that one protein involved in the complement cascade, C9, could kill bacteria, but how it worked was a mystery. Tschopp showed that C9 essentially drills holes in the cell wall of a bacterium by assembling into a pore within its cell membrane. Vital macromolecules leak out through the pore, and the bacterium quickly dies. Subsequently, Tschopp found that a class of white blood cells called T cells destroy tumour cells or those harbouring viruses using a similar mechanism. In this case, these T cells release perforin, a channel-forming protein that inserts itself into the membrane of the target cell, allowing an enzyme called granzyme to enter the cell and destroy it. Tschopp relished turning up clues in the detective stories unfolding in his laboratory. To his and everyone else’s surprise, T cells in mice lacking the gene encoding perforin could still destroy target cells. The back-up pathway turned out to involve a membrane protein called the Fas ligand. When this protein binds to its receptor protein Fas on target cells, a molecular cascade begins that activates a cell-destroying enzyme similar to granzyme. It was Tschopp’s later discoveries that had a direct impact on patients. Along with other groups, he identified BLyS as a ligand for a receptor that drives the proliferation of B cells — a type of white blood cell that produces antibodies. These antibodies are proteins that recognize and neutralize