The 1984 Nobel Prize in Physiology or Medicine celebrated the important contribution of theory and practice in shaping our understanding of the body’s immune system. The hypotheses formulated by Nils Jerne presented a clearer image of the way in which a diverse range of antibodies can be engaged to fight an invader. Georges Köhler and César Milstein constructed perpetual antibody-production lines that have become an essential laboratory tool for researchers worldwide.

Jerne’s first major theory, published in 1955, refuted the general opinion that the immune system custom designs new antibodies when it encounters unfamiliar molecules, or antigens, on an intruder. The body has already created its full repertoire of antibodies, proposed Jerne, and it selects the correct one for the task – a hypothesis later refined by MacFarlane Burnet, which stated that each individual white blood cell produces only one specific antibody. Jerne’s network theory in 1975 described how the immune response is exquisitely controlled, and was built on his premise that antibodies can themselves act as antigens. With the various sets of antibodies stimulating or suppressing the production of each other, he visualized the immune system as a self-regulating network that can switch itself on and off in response to a foreign invasion.

Köhler and Milstein were independently trying to test theories about antibody production in the laboratory, and to do so they both sought ways of creating long-living cell lines that could generate large amounts of a particular antibody. Milstein had developed cancerous forms of antibody-producing cells that grew and multiplied forever, but which churned out antibodies of unknown specificity; while Köhler had tweaked normal antibody-producing cells to produce specific antibodies, but they survived for a few days only in culture. Combining forces, the neat trick they came up with was to fuse a normal antibody-producing cell with a tumour cell, forming a hybrid that was both immortal and could create a specific antibody. Köhler and Milstein’s technique for creating any single predetermined type of so-called monoclonal antibody on demand has led to many medicine and biomedical applications, from creating more reliable probes for blood and tissue typing tests, to designing completely new therapeutic strategies for diseases such as cancer.