Anthony James Pawson (1952-2013) Biochemist Whose Vision of Cell Signalling Transformed Cancer Research

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COMMENT OBITUARY Anthony James Pawson (1952-2013) Biochemist whose vision of cell signalling transformed cancer research.

ony Pawson’s research on protein from a descriptive to a mechanistic interactions transformed the science, and cancer research was accel thinking about how cells comm erating with the discovery of oncogenes,

Tunicate, how proteins evolve and tumour-suppressor genes and related TORONTO UNIV. how cellular messaging goes awry in signalling pathways. The two fields cancer. A creative experimenter, his were about to converge with the discov synthesis of diverse observations in ery that the normal equivalents of viral areas from biochemistry to mouse oncogenes have crucial roles in embryo genetics and developmental biology development. led to a coherent picture of how cellular Within a few years, the division grew processes work. from having just a handful of students In the 1980s, early in his career, and postdocs to having more than 100 Pawson and his team discovered the members. Pawson was at the centre, Src homology region 2 (SH2). A sub partly because cell signalling was core unit, or domain, of many proteins, to all our science, but largely because he SH2 directs how proteins interact and loved to collaborate. To him, collabo governs how cells respond to external ration was as much about camaraderie cues. This finding set a path for all his and friendship as it was about getting future work. a piece of science done. Working with Pawson went on to show that combi Tony was fun, and although he was nations of a small number of domains invited to give ten times the number could produce an enormous range of talks as everybody else, he would of cellular responses. This ‘modular’ always give credit to his collaborators. vision reshaped scientists’ under Pawson’s seminars were virtuoso standing of cellular regulation and performances, and they were eagerly paved the way for the development of attended. His talks and more than drug classes that interfere with these 450 published papers were not just protein interactions. assemblages of data, but elegantly But recognition did not come immedi where Tony began postdoctoral work on the presented expositions of how cells and ately for Pawson. The existence of modular protein products of avian retroviruses. organisms evolve, develop and function. At binding domains, now standard textbook In 1981, the couple moved to Vancouver, the time of his death, he was one of the most fare, was initially received with scepticism Canada, where Pawson was assistant profes highly cited biomedical researchers. by biochemists, and with benign neglect by sor in the department of microbiology at the When Pawson received the Heineken molecular biologists. But as the evidence, University of British Columbia. Pawson’s lab Prize for biochemistry and biophysics in largely from Pawson’s lab, grew more comp became immediately productive, publishing 1998, he spoke at the ceremony in Amster elling, it could no longer be ignored. important papers on oncoproteins — proteins dam about the joy of discovery, the privilege Pawson, who died suddenly at home on coded by genes that have the potential to of working with talented young people, the 7 August aged 60, was born in Maidstone, cause cancer. There, Pawson struck up collab potential for advances to lead to new treat UK, to an eminent British family. His father, oration with Mike Smith, a Nobel-prizewin ments for disease, and about the impor to some the more famous Tony Pawson, ning chemist who invented the technique of tance of family in a scientist’s life. One was a champion sportsman and a house site-specific mutagenesis that Pawson used in could have heard a pin drop. hold name in Britain. A fly fisher, crick his SH2 discovery. Our strongest memories of Tony are in eter, footballer and, later, sports writer, In 1985, when a research institute was those early years at the Lunenfeld, sharing his multivalent skills loomed large for the launched at the Mount Sinai Hospital in our latest results, writing grants, exchang younger Pawson, who was often mistaken Toronto (now the Lunenfeld–Tanenbaum ing gossip and sharing family joys and for his father. It was his mother, Hilarie, Research Institute), Pawson joined us as one sorrows — and watching Tony gesticulating a biology teacher, who stimulated his of the first appointments in its molecular wildly with his arms when he got excited. interest in science. and developmental biology division. With His enthusiasm was infectious. He will be Pawson read biochemistry at the Uni the addition of developmental biologist greatly missed. ■ versity of Cambridge, UK, and obtained his Alexandra Joyner and the late molecular PhD in 1976, working with Alan Smith at the biologist Martin Breitman, the five of us Alan Bernstein is president and chief Imperial Cancer Research Fund (now Can — young, ambitious and with a pioneering executive officer of the Canadian Institute cer Research UK) on proteins encoded by the spirit — knew that we were building some for Advanced Research in Toronto. Rous sarcoma retrovirus. While visiting a thing important. Janet Rossant is chief of research at the friend in Cambridge, Tony met his American The division was created at a propitious Hospital for Sick Children in Toronto. wife-to-be, Maggie. They married in 1975, time: developmental biology was about to be e-mails: [email protected]; and in 1976 moved to Berkeley, California, transformed by the latest genetic technologies [email protected]