How to reboot the human body

It is unusual, in the competitive arena of stem cells, for two facilities like the IPS Cell Facility and the McEwen Centre to collaborate. Yet it’s this kind of co-operation that helped make Toronto the birthplace of stem cell research: it was here that Ernest McCulloch and James Till discovered so-called “seed cells” over 40 years ago. “They trained a legion of students, who went on to train more,” says Rudnicki of the Stem Cell Network. Founded in 2001, it was the first network of its kind in the world.

Today, Toronto’s Discovery District—several city blocks encompassing the University of Toronto and its affiliated hospitals, Mount Sinai and SickKids—brings together thousands of researchers working in every imaginable discipline. It’s home to the MaRS Centre,
a science and business hub where lab technicians rub shoulders with patent lawyers, investors and biotech entrepreneurs. “Everything is a five-minute walk away,” says Nagy, who can point to some of his collaborators’ offices out his office window.

Ontario has been eager to support the stem cell industry, kicking in $1 million for the IPS Cell Facility (the SickKids Foundation also provided money), part of its $3-billion innovation agenda. “Our researchers are an essential precondition to prosperity in the 21st century,” says John Wilkinson, Ontario’s minister of research and innovation. All this has made Toronto a magnet for stem cell scientists from around the world, says Keller, a Saskatchewan native who left a job in New York to take the reins at the McEwen Centre (New York magazine called him a medical mind that the city couldn’t afford to lose). In 1988, Nagy left his home in Budapest to take a research job in Toronto. He’s been here ever since.

The spirit of collaboration has spread beyond provincial borders. Nagy and other University of Toronto scientists recently travelled to Japan to forge a research-sharing pact with Kyoto University’s team, including Shinya Yamanaka, who discovered IPS cells. U of T and SickKids have also partnered with California’s Gladstone Institute of Cardiovascular Disease, a stem cell centre where Yamanaka has another office. (Ontario and California account for 70 per cent of all North American stem cell research.)

But collaboration can only go so far. Driven by an aging population, regenerative medicine is set to become big business: it could be a $500-billion opportunity worldwide by 2010, notes a MaRS industry briefing. As of last year, over 500 companies were dipping their toes into cell therapy. In 2005, the Stem Cell Network and its academic partners created Aggregate Therapeutics Inc., a company aimed at getting Canadian stem cell technologies to market (it’s now managed by MaRS). “The commercialization of stem cell science is still in a very early stage,” says Ilse Treurnicht, CEO of the MaRS Discovery District. “This field is going to transform medicine over the next 50 years.”

With so many world-class minds working toward a common goal, science is moving at an incredible pace. “In the last two years, it seems anything’s possible,” says Benoit Bruneau, associate investigator at the Gladstone Institute in San Francisco. Before the discovery of IPS cells, the work that’s now under way was “sort of pie in the sky,” he says. “I honestly didn’t see any of this coming.”

If the idea that a skin cell can morph into a stem cell is a mind-bender, here’s another: adult cells aren’t just able to move backwards, it seems. They might be able to go sideways, too. In August, a team of Harvard biologists announced they’d successfully changed one type of adult cell directly into another, inside a living mouse—without turning it into an IPS cell first. They flipped three molecular switches to convert a pancreas cell into an insulin-producing one, the kind that diabetics need.

It’s a notion that intrigues Andras Nagy. When an adult cell is reprogrammed into an IPS cell, and begins to move into an embryonic-like state, Nagy hypothesizes it hits a “point of no return”—a grey zone where it’s not quite an IPS cell, and not quite an adult cell either. This he calls “Area 51.” Unlike an IPS cell (which can become virtually any cell type), what falls inside Area 51 might be a bit more specialized: “Maybe they can make only blood, or only muscle,” he says. Because they’re already on the path to becoming adult cells, they might be more efficient to work with than IPS cells—so, when that car accident victim is rushed to hospital, these Area 51 cells can be more quickly and easily changed into the cell type that’s needed to help her.

“Most likely what will happen is a cell bank will be created,” Nagy says. Unlike those stored at Ontario’s IPS bank, though, Nagy believes these cells will be maintained in that in-between zone, Area 51. “They will be properly typed for compatibility, like organ transplantation,” he explains. “They will be ready on the shelf. When a doctor needs it, they must simply look for a match.”

Leaving his office, Nagy walks into the lab and takes a petri dish from the refrigerator. He places it under the microscope. What it contains is beautiful: elongated shapes that look delicate as frost. They quiver with movement. Nagy’s lab created these skeletal muscle fibres directly from skin, through an alchemy they’re now working to understand.

In our bid to extend human life, one thing is clear: the meaning of “life” is perhaps much more complicated than we ever imagined. “When you see cells just sitting there, it’s hard to believe they’re alive,” Nagy says. “When you see them actually moving in the petri dish, it is evident.”