[4][5][6][7][8] Milstein shared the Nobel Prize in Physiology or Medicine in 1984 with Niels Kaj Jerne and Georges J. F. Köhler for developing the hybridoma technique for the production of monoclonal antibodies.

In 1958, funded by the British Council, he joined the Biochemistry Department at the University of Cambridge to work for a PhD under Malcolm Dixon on the mechanism of metal activation of the enzyme phosphoglucomutase.

It was as part of this quest that, in 1975, he worked with Georges Köhler (a postdoctoral fellow in his laboratory) to develop the hybridoma technique for the production of monoclonal antibodies—a discovery recognized by the award of the 1984 Nobel Prize for Physiology or Medicine.

In collaboration with Claudio Cuello, he helped lay the foundation for the use of monoclonal antibodies as probes for the investigation of the pathological pathways in neurological disorders as well as many other diseases.

The emphasis of his research then shifted towards the mRNA encoding antibodies, where he was able to provide the first evidence for the existence of a precursor for these secreted polypeptides that contained a signal sequence.

[23] The development of the hybridoma technology coupled to advances in nucleic acid sequencing allowed Milstein to chart the changes that occurred in antibodies following antigen encounter.

In this process, localized mutation of the immunoglobulin genes allows the production of improved antibodies, which make a major contribution to protective immunity and immunological memory.