How to reboot the human body

Sitting in his sunlit office in downtown Toronto, renowned geneticist Andras Nagy clicks through a computer slide show. The images show various people: different ages, different shapes and sizes. “This person has diabetes,” he says, gazing at the screen. “She needs insulin producer cells in her body.” He clicks to the next slide. “This person has multiple sclerosis. He needs myelin,” which insulates the nerves. Another: “This person had a tumour on his spine, which was removed,” but the resulting spinal cord injury left the patient with a disability.

“This is where the field of stem cells is promising,” says Nagy, looking up from the screen. With an unlimited source of the missing cells, “we could cure the disease.” Today, as senior investigator at Mount Sinai Hospital’s Samuel Lunenfeld Research Institute, Nagy is one of a handful of superstar researchers working to finally bring stem cells out of the lab, and into the clinic. Every day, they’re using the building blocks of human life to do what was once thought impossible. But doing the impossible is not exactly new for Nagy.

Over a decade ago, Nagy succeeded in creating an entire mouse from stem cells, proving they can change into virtually any cell type in the body. “No mother, no father. Just the petri dish,” says Nagy. In 2005, he established Canada’s first stem cell lines from human embryos. Now they’re focusing on a new area of research—one that suggests it may be possible to “reboot” human cells, creating heart cells or neurons out of skin. “We’re moving faster than everyone thought possible,” says Michael Rudnicki, scientific director of Canada’s Stem Cell Network, which connects more than 80 leading experts across the country.

For the millions around the world suffering with chronic disease, they can’t move nearly fast enough.

For decades, scientists have known that, in their embryonic form, stem cells can morph into any cell type in the body. Last year, Kyoto University’s Shinya Yamanaka made a startling announcement: it also works the other way round. Working with human skin cells, Yamanaka found a way to push cells backwards, to an embryonic-like state. These induced pluripotent stem cells (IPS cells for short) offer a way to treat patients with their own body’s cells. “It enabled us to overcome the barrier of having relatively few embryonic stem cell lines,” says Gordon Keller, director of the McEwen Centre for Regenerative Medicine in Toronto. “Suddenly, we can make cells directly from the patient.”

Imagine treating a car accident victim for a broken back, and injecting her own cells into the spine to speed recovery. Or giving drugs to a stroke patient that harness his stem cells to stimulate repair. One day, “you will probably be able to buy a reprogramming kit from a company,” Keller suggests. It sounds too incredible to be true, and for now, it is.

For one thing, IPS cell therapy would be expensive and time consuming: turning an adult cell into a stem cell, then into a new cell type, currently takes about three to four months, Nagy says. When a car accident victim gets rushed into hospital, doctors don’t have that kind of time. And compared with embryonic stem cells, IPS cells are still not entirely understood. “The biggest challenge is differentiating stem cells into a stable, safe form,” says Janet Rossant, chief of research at Toronto’s Hospital for Sick Children (SickKids).

Above all, experts warn, tinkering with the human genome could be dangerous. To create an IPS cell, Yamanaka isolated four genes that are active in embryonic stem cells, but dormant in adult ones (humans have an estimated 30,000 genes). He then used a virus to push these four genes into the adult cell, forcing it to reboot. The risks involved are unclear. Virus insertion is totally random: it could ding up other genes along the way, creating rogue cells, mutation and even cancer. “The virus method is not safe,” Nagy says. “We have to find a way to reprogram without genetic change.”