- Email: [email protected]
Anthony James Pawson
Obituary
Anthony James Pawson Molecular biologist whose work illuminated the mechanism of intracellular communication. Born in Maidstone, UK, on Oct 18, 1952, he died in Toronto, Canada, on Aug 7, 2013, aged 60 years. In a lecture delivered to mark his 2008 Kyoto Prize Professor Tony Pawson recalled how, as a biology student in the 1960s, he was gripped by the realisation that it was at last becoming possible to discover the scientific principles underlying the evolution and workings of all organisms, including ourselves. That revelation, he added, had gripped him ever since. “To my mind there can be no experience so thrilling as to uncover some unexpected, and previously undiscovered, aspect of living beings, and the universe that we inhabit.” While many scientists will share that sentiment, far fewer have been able to match Pawson’s own contribution to our grasp of these principles. His field of study was the mechanism by which chemical signals arriving at the cell’s surface are received and then transmitted to the target organelles within its interior. The key molecular players in this process are, of course, proteins. James Woodgett, Director of Research of the Lunenfeld-Tanenbaum Research Institute in Toronto and a long-time colleague, summarises Pawson’s achievement: “Before his insight we saw the interior of the cell as being just a mash-up of proteins doing all sorts of things. What he identified was a sort of a code. There were addresses on particular parts of proteins that helped them find where they should be in the cell. The code dictated what each protein bound to, and when.” Another colleague, Alan Bernstein, President of the Canadian Institute for Advanced Research, describes the work as central to much of biomedical research and medicine. “Tony appreciated early 1398
on that intracellular communication is essential not just to cancer, but to other diseases including diabetes and mental illness, and also to embryological development. And it also contributes to our understanding of evolution.” Pawson read biochemistry at Cambridge University, an experience he found disappointing until the third year when his lecturers included the Nobel Prize winning crystallographer Max Perutz. He also worked on a protein synthesis project with another future Nobellist, Tim Hunt. His consequent thirst for experimental science took him to London’s Imperial Cancer Research Fund as a PhD student. It was here he became fascinated by cell signalling; he began to wonder if this communication process goes awry in diseases such as cancer, and if understanding the process might lead to better anti-cancer drugs. In 1967 he made what was to be a one-way journey across the Atlantic. After time at the University of California, Berkeley and the University of British Columbia, he moved to Toronto to join what is now the Lunenfeld-Tanenbaum Research Institute, attached to the Mount Sinai Hospital, where his work was on proteins and cell signalling. The chains of aminoacids that make up proteins are arranged in domains, many of which are responsible for the protein’s particular function or interactions. Pawson identified one particular domain, found in more than 100 different proteins, which he called SH2. “What this domain does is bring other proteins together”, Woodgett explains. “It’s like a Lego brick that doesn’t do anything but act as a linker.” Or as Bernstein puts it, “You can think of it as a barcode that determines what other proteins that protein will interact with.” As Pawson realised, recombining domains in different arrangements creates proteins with different functions: a mechanism of molecular evolution. Malfunctions in certain domains can lead to uncontrolled growth. “A lot of the proteins found in cancer cells are these signalling proteins which are being produced all the time instead of being regulated”, explains Woodgett. “For example CML, chronic myelogenous leukaemia, is due to an activated form of a protein called BCR-ABL.” The search for an agent to block its production led to the discovery of imatinib, one of the first drugs to work exclusively against cancer cells. “As a colleague Tony was fantastic, full of ideas and a real catalyst of scientific collaboration”, says Woodgett. “He was always trying to promote interactions, collaborations between other colleagues.” Bernstein remembers Pawson’s talent for promoting such collaboration. “He was warmhearted and enthusiastic. He loved the camaraderie of science.” He also loved communicating his ideas, Woodgett adds. “Whenever he gave talks or lectures he suddenly became very animated. He was like a Jack-in-the-box, full of life with amazing enthusiasm. And very inspiring.” Pawson leaves a daughter and two sons.
Geoff Watts www.thelancet.com Vol 382 October 26, 2013
Anthony James Pawson Molecular biologist whose work illuminated the mechanism of intracellular communication. Born in Maidstone, UK, on Oct 18, 1952, he died in Toronto, Canada, on Aug 7, 2013, aged 60 years. In a lecture delivered to mark his 2008 Kyoto Prize Professor Tony Pawson recalled how, as a biology student in the 1960s, he was gripped by the realisation that it was at last becoming possible to discover the scientific principles underlying the evolution and workings of all organisms, including ourselves. That revelation, he added, had gripped him ever since. “To my mind there can be no experience so thrilling as to uncover some unexpected, and previously undiscovered, aspect of living beings, and the universe that we inhabit.” While many scientists will share that sentiment, far fewer have been able to match Pawson’s own contribution to our grasp of these principles. His field of study was the mechanism by which chemical signals arriving at the cell’s surface are received and then transmitted to the target organelles within its interior. The key molecular players in this process are, of course, proteins. James Woodgett, Director of Research of the Lunenfeld-Tanenbaum Research Institute in Toronto and a long-time colleague, summarises Pawson’s achievement: “Before his insight we saw the interior of the cell as being just a mash-up of proteins doing all sorts of things. What he identified was a sort of a code. There were addresses on particular parts of proteins that helped them find where they should be in the cell. The code dictated what each protein bound to, and when.” Another colleague, Alan Bernstein, President of the Canadian Institute for Advanced Research, describes the work as central to much of biomedical research and medicine. “Tony appreciated early 1398
on that intracellular communication is essential not just to cancer, but to other diseases including diabetes and mental illness, and also to embryological development. And it also contributes to our understanding of evolution.” Pawson read biochemistry at Cambridge University, an experience he found disappointing until the third year when his lecturers included the Nobel Prize winning crystallographer Max Perutz. He also worked on a protein synthesis project with another future Nobellist, Tim Hunt. His consequent thirst for experimental science took him to London’s Imperial Cancer Research Fund as a PhD student. It was here he became fascinated by cell signalling; he began to wonder if this communication process goes awry in diseases such as cancer, and if understanding the process might lead to better anti-cancer drugs. In 1967 he made what was to be a one-way journey across the Atlantic. After time at the University of California, Berkeley and the University of British Columbia, he moved to Toronto to join what is now the Lunenfeld-Tanenbaum Research Institute, attached to the Mount Sinai Hospital, where his work was on proteins and cell signalling. The chains of aminoacids that make up proteins are arranged in domains, many of which are responsible for the protein’s particular function or interactions. Pawson identified one particular domain, found in more than 100 different proteins, which he called SH2. “What this domain does is bring other proteins together”, Woodgett explains. “It’s like a Lego brick that doesn’t do anything but act as a linker.” Or as Bernstein puts it, “You can think of it as a barcode that determines what other proteins that protein will interact with.” As Pawson realised, recombining domains in different arrangements creates proteins with different functions: a mechanism of molecular evolution. Malfunctions in certain domains can lead to uncontrolled growth. “A lot of the proteins found in cancer cells are these signalling proteins which are being produced all the time instead of being regulated”, explains Woodgett. “For example CML, chronic myelogenous leukaemia, is due to an activated form of a protein called BCR-ABL.” The search for an agent to block its production led to the discovery of imatinib, one of the first drugs to work exclusively against cancer cells. “As a colleague Tony was fantastic, full of ideas and a real catalyst of scientific collaboration”, says Woodgett. “He was always trying to promote interactions, collaborations between other colleagues.” Bernstein remembers Pawson’s talent for promoting such collaboration. “He was warmhearted and enthusiastic. He loved the camaraderie of science.” He also loved communicating his ideas, Woodgett adds. “Whenever he gave talks or lectures he suddenly became very animated. He was like a Jack-in-the-box, full of life with amazing enthusiasm. And very inspiring.” Pawson leaves a daughter and two sons.
Geoff Watts www.thelancet.com Vol 382 October 26, 2013