Anthony Pawson, one of the world's top cell biologists and a pre-eminent cancer researcher, left behind two very different grieving families when he died suddenly in Toronto last Wednesday at the age of 60.
He was a devoted father to three grown children, a loving partner to Barb Bennett and a proud grandpa to seven-month-old Millicent.
His second family was at the Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital in Toronto, where he was instrumental in decoding signal transduction, a fundamental process in biology. He was one of the founding scientists of the institute in 1985 and ran the eponymous Pawson Lab there until his death.
Dr. Pawson cared deeply for his co-workers and the students he mentored, and inspired others with his enthusiasm for research, daughter Catherine Pawson said.
"From when I was a little kid, he would at least once or twice a year have his entire lab over to the house for a potluck dinner," she said. "I remember listening to them talk about science and talk about my dad, and how much they loved what they were doing and how much they loved him."
The excitement she soaked up while sitting at that table, all ears, really was contagious: She followed in her father's footsteps and became a cell biologist and postdoctoral researcher.
Dr. Pawson spoke at length about his own life in his commemorative lecture for the 2008 Kyoto Prize, known as "Japan's Nobel," which was later published as part of a book. (He was nominated at least eight times for a Nobel Prize, but that honour always eluded him.)
At the Kyoto lecture, he said: "The process of scientific discovery is rather like exploring for new continents in the age of sailing ships – there are long periods at sea, with not much happening."
"It is that moment of first seeing the land in the distance, of first realizing that one has a thread of evidence for a new way of looking at the world, that provides the most excitement."
Dr. Pawson had that exhilarating moment early in his career, when he was studying a family of proteins called tyrosine kinases in the late 1980s. They were known to be involved in cancer, but how that worked was almost entirely a mystery.
He discovered that part of a particular tyrosine kinase didn't seem to be performing any of its known functions. Instead, it regulated the actions of other proteins, like a kind of molecular traffic cop. When this protein piece, called a domain, was activated, it set off a chain of reactions – a signal – that changed the cell's behaviour.
When the domain didn't work properly because the proteins involved were scrambled in some way, such as from a mutation in DNA, the cell might grow and divide in an uncontrolled manner, causing cancer.
In the wake of the breakthrough, Dr. Pawson and others learned that this same general type of protein interaction happens in scores of cell types all across the living world, meaning that changes in their various signalling functions, both within and between cells, could be implicated in a whole gamut of diseases, from colon cancer to immune disorders to Alzheimer's.
"In hindsight it seems so obvious. At the time it was completely novel," said Jim Woodgett, who took over for Dr. Pawson as director of the institute in 2005. Dr. Pawson had a knack for making connections that were counterintuitive and the guts to take risks, Dr. Woodgett added. "His intelligence was off the charts."
Dr. Pawson named the protein part the Src homology 2 domain, or SH2 domain.
"Had I known how important it was to be, I would have tried to think of a more memorable name," he said in his Kyoto lecture.
Dr. Pawson was born on Oct. 18, 1952, in Maidstone, England, the eldest of three children in an upper-class family. He attended the prestigious Winchester College for boys, and later Clare College at Cambridge University, where he graduated with a BA in biochemistry. He earned his PhD in molecular biology from King's College at London University in 1976, and was a postdoctoral research fellow at the University of California at Berkeley in the late 1970s before moving to Canada in 1981 to become an assistant professor in the department of microbiology at the University of British Columbia.
He met Margaret (Maggie) Luman, an American living in Britain with her family, probably while visiting a school friend at Cambridge, Catherine Pawson said. They married in London in 1975, Maggie in a long, earth-toned shirt dress with a flower pattern in quintessential 1970s style, he rail-thin and with a mop of long hair, sporting a tri-colour tie.
Dr. Pawson's mother, Hilarie, was a botanist and taught high-school biology.
"I absorbed my interest in the natural world from her. She was the real academic in the family," Dr. Pawson said in Kyoto.
His father – the famous Tony Pawson, whom Brits often asked if Dr. Pawson was related to – was a champion fly fisher, footballer and cricketer who competed at the 1952 Olympics and later became a well-known sports writer.
"Tony came from a successful and eminent British family," said John Scott, a cell biologist at the University of Washington and one of Dr. Pawson's closest friends and collaborators. "There was an expectation of success, and what came along with that was an ability to interact with people. He always put people at ease, he was very polite, and he had that charismatic quality that makes people feel very special."
Dr. Pawson would gesticulate wildly and practically dance across the stage when explaining a concept as a professor of molecular genetics at the University of Toronto. The combination of his revolutionary ideas and ebullient personality would have an audience glued to their seats even if they didn't know what he was talking about, Dr. Woodgett said.
People who knew him agree that he deeply valued and desired recognition from scientific peers. In addition to the Kyoto Prize, he was appointed by the Queen to the Order of the Companions of Honour and received the Wolf Prize in Medicine, among dozens of others.
But he never did get science's top trophy, although Lou Siminovitch, the founding director of the institute, nominated him no fewer than eight times.
"His dream was the Nobel, and I thought he had a very good crack at it," Dr. Siminovitch said. "In the area he was in, there were too many people who were at the level or near the level that Tony was."
Dr. Pawson's singular focus on basic science – figuring out the fundamentals of how the world works, whether there is an obvious application or not – was sometimes at odds with trends in the scientific community, especially in the way funding is awarded.
He was more than happy that others found important applications for his work, his daughter said. In fact, Gleevec, a targeted cancer drug that was hailed as a "revolutionary new pill" by Time magazine in 2001, was developed as a direct result of Dr. Pawson's insights.
Dr. Pawson's vacant office tells the story of someone who left the field in his academic prime. On a large whiteboard is an elaborate diagram of a signalling pathway, with shapes and arrows representing proteins and interactions in the dizzyingly complex system of machinery within human cells. Underneath, scrawled in blue marker, are notes on half a dozen studies he was working on.
He was sought after all over the world as a speaker and as a collaborator in part because he was generous in giving credit to others, said former institute director Dr. Alan Bernstein. He published almost 450 papers and books, the most recent appearing in the journal Nature Immunology on Aug. 4.
Dr. Pawson's research family was always shifting, as people moved on to new opportunities and students came up through the ranks. But his own family changed drastically in 2011, when his wife died from lung cancer at age 63 after a loving marriage that lasted 36 years.
Catherine Pawson said her most treasured memories of her father are the long hikes they used to take together. She and her two brothers, Nick and Jeremy, each had their special activity they loved to do with him, and he would never miss a school play or a soccer game, she said.
"For someone who had such a high profile and such a successful career, he was always my dad first," Catherine Pawson said.