Nobel buzz surrounds Toronto scientists
October 3, 2009
Megan Ogilvie
Joseph Hall
The hope – and signs – are there.
This may well be the year of the Nobel for two Toronto scientists, whose work began on a Sunday afternoon in 1960 when Ernest McCulloch peered down in surprise at a newly dissected mouse.
There were lumps on its spleen, clumps of cells that had formed in the 10 days since the mouse had been injected with blood-forming bone marrow. McCulloch – and his partner James Till – saw promise in these strange nodules embedded in the slick, tiny organ.
And so the pair embarked on a set of remarkable and rigorous experiments that proved the existence of stem cells – a feat that now, almost half a century later, may finally garner them the coveted Nobel Prize in Medicine on Monday.
No one outside the Nobel committee knows who will get the early morning phone call from Sweden. But there's a buzz in the medical community that Till and McCulloch will be the first Canadians to win the Nobel for medicine since Frederick Banting and J.R.R. Macleod. They took home the prize in 1923 for their discovery of insulin.
Top scientists have lobbied on their behalf. The prize can't be awarded posthumously, and for the pair – McCulloch is 83 and Till is 78 – time is running out. They have taken home every other major medical prize, including the 2005 Lasker Award, which is said to predict who will capture a Nobel.
And there is the almost universal agreement that Till and McCulloch, known as the fathers of stem cell science, are long overdue to win the world's top scientific prize.
"Without question, they are very deserving of a Nobel Prize," says Alan Bernstein, an internationally renowned scientist who heads the Global HIV Vaccine Initiative in New York.
"What's unequivocal is that it was Till and McCulloch who discovered stem cells."
The impact of Till and McCulloch's groundbreaking discovery continues to permeate the field. Scientists around the world still use the terminology and principles they defined while toiling in their labs at the old Ontario Cancer Institute (now the research arm of Princess Margaret Hospital).
"They laid out the path for stem cell research for the next 50 years," says Michael Rudnicki, scientific director of the Stem Cell Network. "There is no question, to use an old cliché, that we stand on the heads and shoulders of those who went before us. And all of what we do today in stem cell research can be traced back to these two scientists."
Ironically, says Robert Phillips, deputy director of the Ontario Institute for Cancer Research, the pair's long wait for Nobel recognition is likely due to the fact their work was so far ahead of the field.
Until the technological advances of the 1980s illuminated the critical importance of stem cells, there was no yardstick by which to judge Till and McCulloch's seminal research, he says.
And yet, he adds, the pair had laid down, right from the beginning, the properties that stem cells must possess. Stem cells have the potential to develop into all cell types, including skin cells, heart cells and blood cells, and are capable of renewing themselves. With their regenerative capabilities, they offer new ways to treat diseases, from diabetes to heart disease.
Till and McCulloch's work in the 1960s also laid the foundation for bone marrow transplantation for cancer patients.
The pair provided a stem cell mechanism for the success of marrow transplants in replenishing the blood. They also devised precise measurement and quantification criteria for the entire research area.
"Without their work, we would never have had bone marrow transplants," says Rudnicki. "We might have muddled our way through it... but their work provided the theoretical underpinnings for bone marrow transplant as a therapy, which has been in the clinic now for 40 years and has saved countless lives."
Born on a prairie farm in Saskatchewan and trained as a biophysicist at Yale, Till was recruited to the Ontario Cancer Institute (OCI) when it launched in 1957.
McCulloch, whom friends still refer to by his childhood nickname of `Bun,' received his medical degree from the University of Toronto. He, too, joined OCI in 1957, and set out to find the function of bone marrow.
At the time, the marriage of biology and physics seemed a strange mix. But under the inspired leadership of physicist Harold Johns and biologist Arthur Ham, the cross-pollination of the two disciplines became the signature research strategy of the newly formed OCI. Bernstein, who trained as a post-doctoral fellow under Till, and who knows McCulloch well, says the two are considered a scientific odd couple.
"As a student watching this, it was fascinating because you couldn't imagine two human beings who were so different as Jim and Bun," says Bernstein.
Till, he says, projected his prairie outlook on life – that you work hard and don't try to grab attention. McCulloch, who grew up in a sophisticated, intellectual environment, was a clinician at heart who wanted to cure disease, and was unafraid of bold claims.
"The two of them were very different in personality and background, and I think that was a perfect marriage," Bernstein says. "They had huge admiration for each other's strengths."
"I think Jim and Bun knew, from the beginning, that the other guy was absolutely key to what the other was doing," he says.
"It was a mutually respectful relationship. It was a model for us students to watch."
Till and McCulloch left a living legacy in the students they mentored and in the scientists they recruited to the city.
Dr. Gordon Keller, head of Toronto's McEwen Centre for Regenerative Medicine, says Till and McCulloch quickly became ruling planets in the rapidly expanding universe of stem cell research, drawing a constellation of young and talented researchers into their orbit and this city.
"When you have such influential and powerful science going on in a centre it typically draws in some of the best trainees," says Keller. Even today, almost 50 years since their partnership, most of the city's top stem cell scientists can trace their academic lineages directly back to Till and McCulloch, he says.
Indeed, Keller's post-doctoral studies at the University of Toronto were conducted under Phillips, who came from the U.S. to train under Till.
Like Bernstein, Rudnicki says Till and McCulloch are undoubtedly deserving of a Nobel Prize.
"Because of them, today, stem cell research is an area of true strategic strength in Canada, as measured by many metrics, including publications and patents," he says.
"This is an area where Canada has a deep and broad strength. We're among the best in the world in this area – if not the best. Without question."
Toronto Star