Drosophila determine the fly's body plan. Under his influence, Crick also became interested in morphogenetic gradients and how they may help specify biological patterns. Immunology César Milstein had over many years been working on antibody variation. He was joined in this by Georges Köhler and, together, they discovered how to produce monoclonal antibodies. For this they shared the Nobel Prize for Physiology or Medicine in 1984. This area was extended by Greg Winter who pioneered antibody engineering using phage display to make novel human antibodies and antibody fragments, for which he shared the Nobel Prize in Chemistry in 2018. Both monoclonal antibodies and their fragments are now of major medical importance. Michael Neuberger discovered the mechanism by which antibody diversification occurs by Activation-induced (cytidine) deaminase. This fundamental discovery is the keystone to understanding the molecular mechanism by which organisms can produce a diverse repertoire of antibodies to recognise new pathogens. This is of wider importance in understanding the role of directed mutagenesis and DNA repair in physiology. Finally, the molecular mechanisms elucidated by Neuberger may be of great importance in understanding the mutational pattern of kataegis in breast cancer. Sadly, Michael Neuberger died from myeloma - the irony of which was not lost on him. Cell biology The emphasis on classical molecular biology shifted towards cell biology and development, so that the Molecular Genetics division was renamed Cell Biology. Mark Bretscher discovered the topological way proteins are arranged in the human erythrocyte membrane and its phospholipid asymmetry. Richard Henderson and Nigel Unwin developed electron crystallography to determine the structure of two-dimensional arrays, applying this to the bacterial purple protein, bacteriorhodopsin. Barbara Pearse discovered the major components of clathrin-coated vesicles, structures formed during endocytosis, and a low resolution structure of the cage-like lattice around them was determined. How proteins become localised to different parts of the cell — such as to the endoplasmic reticulum, Golgi apparatus or the plasma membrane — and the role of this in cell polarity, have been elucidated by Bretscher, Hugh Pelham and Sean Munro. The spindle pole bodies — the large structures in yeast cells which act as the foci to which chromosomes are moved during mitosis — have been purified and a low resolution structure of them deduced by John Kilmartin. A continuing interest has been the structure of chromosomes. This was initiated by a visitor, Roger Kornberg, who discovered the first level of condensation