Michael Samuel Neuberger. 2 November 1953—26 October 2013

Michael Neuberger was an outstanding molecular immunologist whose discoveries showed how antibody diversity arises, and he laid the basis for the current wide usage of antibodies as therapies for human diseases. After taking a first-class degree in biochemistry at Cambridge, he received his PhD from Imperial College London for work on bacterial evolution and selection of enzymes of increased or altered activity. His thesis earned him a research fellowship at Trinity College, Cambridge. On advice from Sydney Brenner, he joined César Milstein at the Laboratory of Molecular Biology. Milstein was interested in how the affinity of antibodies improved during immune responses. Semi-random genetic recombination of antibody gene segments was known to create diverse functional antibodies, but Neuberger showed how recombination also drove antibody expression, by bringing enhancer elements close to the start of transcription. This paved the way for the expression of recombinant antibodies in tissue culture, and enabled him to engineer ‘humanized’ therapeutic antibodies by grafting antigen-combining loops from mouse onto a human antibody, thus reducing rejection in patients. He pioneered the creation of transgenic mice with fully human antibody genes, the foundation of a multibillion-pound biotechnology industry. Neuberger’s work on the antibody diversity question uncovered that diversity is driven by deamination of cytosine bases into uracil in the DNA of antibody genes, a mechanism also involved in driving mutations in cancer cells and in viral restriction. The discovery of programmed DNA deamination was a major finding and, of all his results, was the one of which he was most proud.