He survived a terrifying accident. Now this U of T biologist wants to give our cells an upgrade.

One morning in July 2006, Michael Garton was making a solo ascent up Norway’s notorious Troll Wall. At 3,300 feet, it’s the tallest vertical rock face in Europe. The U.K.-born Garton, then 24 years old, had scaled many of the continent’s major peaks and was ready for a bigger challenge. He calculated a week of 18-hour days would be enough to get him to the top. This would be the climb of his life.

On the second day came catastrophe. A rockslide ripped out most of his climbing equipment and Garton, his neck broken, fell nearly 120 feet before his final anchor held. He woke up an hour later, dangling upside down hundreds of feet off the ground, paralyzed. “I couldn’t move. All I could do was hang there and contemplate the end,” he says. “There didn’t seem to be any chance of surviving.”

Garton didn’t know that another climber he had met on the ground a few days earlier was following his ascent through a telescope. Noticing that something had gone terribly wrong, that climber summoned help. Nine hours after the fall, Garton was rescued by a Norwegian air force helicopter.

“Having experienced that proximity to death helps remind me to focus on what matters,” he says. “All the stuff we obsess about every day — what other people think of you, or what you think they expect from you — none of that is important.”

Garton spent a year in hospital, not only learning how to adapt to life with limited mobility, but also deciding what to do with that life. “I had wanted to be a professional climber,” he says. “But after being the recipient of care 24/7, my perspective changed. I wanted to do something to help others.” Today, rather than push his own boundaries, Garton pushes scientific ones.

After completing a PhD in computational biology at the University of Nottingham, Garton moved to Canada, earning his own lab at the University of Toronto’s Institute of Biomedical Engineering in 2018. Garton works in the emerging field of synthetic biology, which involves designing and engineering biological components to give them new abilities — essentially creating super cells. His lab has recently been working on viral vectors, capsule-like structures that protect gene therapies on their way into cells where they’re needed. Usually, these vectors are inert forms of viruses, but Garton’s team has shown that artificial intelligence can design bespoke versions that could be tailored to maximize their effectiveness.

Taking a breath … or not

His team is also exploring more elaborate ideas. Since 2021, with support from University of Toronto’s Medicine by Design program, which receives funding from the Canada First Research Excellence Fund, the Garton lab has been looking at how to design cells that can survive for long periods without oxygen.

“Humans need 21 per cent oxygen in the air to survive, but other animals have an amazing tolerance for low-oxygen environments,” Garton says. He points to Cuvier’s beaked whale, which holds the world record for the longest-ever dive and can survive more than 3.5 hours on a single breath. “Whales can make these deep dives for hours. That ability doesn’t come from an anatomical advantage — their lungs are actually smaller than ours in terms of body mass. It’s a molecular adaptation.”

Other animals, such as the Tibetan antelope and the naked mole rat, have similar capabilities. Because the genomes of those animals have been completely mapped, Garton and his team can take genes they think are responsible for low-oxygen tolerance, synthesize that DNA and then combine it with human tissue, testing it at lower and lower levels of oxygen.

They are hoping to solve one of the problems that has plagued attempts to grow new heart tissues from stem cells. About 95 per cent of these tissues die from lack of oxygen when they’re implanted, because it takes about a week for new blood vessels to form. “We’re giving the cells batteries so they can run by themselves until they get hooked up to the grid,” says Garton.

In the future, the approach might form the basis of a gene therapy for people at high risk of stroke and heart attack, enabling their brain and heart tissue to survive longer without oxygen.

Catching some rays

Another project is even further out. NASA has identified the deadly gamma rays in space — which shred human DNA — as one of the key challenges for future missions to Mars. It’s difficult and expensive to equip a spaceship with radiation shielding, so Garton’s team is trying a different approach. “I thought, rather than try to block rays, just accept them as a factor.”

Humans are exposed to low levels of radiation every day — uranium in the soil, radon in various building materials, even radium in our blood and bones — and our cells work to repair any damage this might cause. “We already have that capability,” says Garton. “Now, what we want to do is find a way to juice it up.”

Again, the lab looked to the animal world for possible solutions. What they found was the tardigrade, a 0.04-mm-long aquatic animal that can tolerate all manner of extreme conditions, including boiling water, subzero temperatures and being shot out of a gun at 3,000 kilometres an hour. It can also survive space travel.

When exposed to high doses of radiation, the tardigrade expels 95 per cent of the water in its body, reducing metabolic activity to almost nil. In this desiccated state, its cells build a protein called Dsup (short for “damage suppressor”), which binds to DNA and is theorized to shield the tardigrade from further harm. No other animal can create Dsup, so Garton’s team has been searching for ways to program human cells to mimic this capability. Early results with an irradiator have shown 20 per cent reduction in DNA damage. They are planning more advanced tests with the NASA-funded Space Radiation Laboratory at the Brookhaven National Lab in Long Island, N.Y.

There could be applications for this research closer to home, protecting people whose jobs expose them to radiation. But this work also speaks to a broader story about who we are as a species, where we came from and where we’re going.

Space is an extreme example of an environment that’s beyond the design specs of the human body. But even on the ground, we’re moving out of our evolutionary comfort zone. For instance, many of the most groundbreaking ideas in medicine — like growing replacement organs to replace failing ones — could require us to do some molecular tinkering to persuade our bodies to accept them. “The world we now live in is going to require synthetic biology and our own design, in order to allow us to take those next steps,” says Garton.
“It’s definitely a different type of exploration than climbing,” says Garton. “But probably even more exciting.”

 
Photography: Colin Sneyd