Andrew David Hamilton Wyllie. 24 January 1944—26 May 2022

Abstract

Andrew Wyllie graduated from the University of Aberdeen, becoming an academic pathologist in Aberdeen, Edinburgh and Cambridge. He was the co-discoverer of apoptotic cell death, having observed single cells dying following carcinogen exposure. Together with Alastair Currie and John Kerr, he realized the profound importance of this novel mode of cell death that showed a distinctive series of morphological changes, which he first described as a new cell death process. Wyllie and Currie introduced the term ‘apoptosis’ for this cell death process in a seminal paper in 1972. Another landmark discovery was of chromatin fragmentation in apoptosis, due to activation of an endogenous endonuclease that caused internucleosomal DNA cleavage (‘chromatin laddering’), which was the first biochemical mechanism of apoptosis described. He further characterized chromatin fragmentation in the 1980s, followed by investigations of cell surface changes to produce ‘eat-me’ signals to trigger rapid phagocytosis of the apoptotic cells and bodies, intracellular calcium ion signalling, caspase activation and other mechanisms of apoptosis. His cancer research helped identify the location of APC and generated his demonstration that apoptosis was regulated by oncogenes MYC and RAS and by tumour suppressor genes, such as TP53 . He showed how apoptosis occurred in response to DNA damage and was a key process influencing both carcinogenesis and tumour growth. Andrew made a major scientific observation that changed the understanding of how cells die in health and disease, although it took time for the scientific establishment to understand its fundamental importance. Andrew Wyllie is widely known as the ‘Father of Apoptosis’.