Canadian Researcher Hopes to Reverse Paralysis
Hans Keirstead is learning to surf. It's harder than it looks, he says. Maybe it was inevitable, living as he does in Irvine, Calif., a freeway exit or two from Orange County's finest beaches. At 39, he still looks the part of a southern California surfer, or so he's been told often enough. He's got a kind of dishevelled grace about him, and a fluid athleticism which, in fact, owes more to a black belt in tae kwon do than to wave riding. His new wife, Niki Keirstead, raised in San Diego, is the real surfer in the family. She's also a neuroscientist, as is her husband: Hans S. Keirstead, Ph.D., associate professor, Reeve-Irvine Research Center, University of California at Irvine, dude.
Surfing is just another challenge for Keirstead, like writing rock songs, or mastering a new recipe for pork tenderloin in wine reduction (delicious!). Or playing a lead role in successfully convincing California taxpayers to invest US$3 billion in human embryonic stem cell research - even though the religious right in general, and President George W. Bush in particular, consider it a mortal sin. Or (how's this for a goal?) his all-consuming belief that someday - maybe someday soon - his work will restore mobility for those who are paralyzed with spinal injuries or stricken with multiple sclerosis. He has already made partially paralyzed rats walk again, using derivatives of human embryonic stem cells. The next stop - as early as next spring - is trying the same therapy in human trials.
Challenge - exploring the mystery and wonder of the central nervous system - is what got him into neurobiology. The first time we talked, back in January 2000, after a winter afternoon he'd spent operating on rats in a battered old laboratory at the University of British Columbia, he told me that the beauty of the brain is this: "I know I'll have a full lifetime of unanswered questions."
That afternoon was one of Keirstead's last at UBC. He'd answered one nagging question. After long weeks of doubt he was leaving B.C. for California. At the time, much of his research at UBC was made possible by Rick HANSEN, the wheelchair athlete whose foundation has raised more than $178 million for spinal cord research. Then, in a manner of speaking, Superman came calling. Keirstead was invited to join the new Reeve-Irvine Research Center. The center is named for its founders: Christopher Reeve - the late actor who famously played Superman, and who became a champion of spinal cord research after being paralyzed in a riding accident - and philanthropist Joan Irvine Smith, of Irvine's founding family. The dilemma over whether to leave caught Keirstead between two wounded heroes: Hansen and Reeve. But back in those brain-drain days, UBC couldn't match the huge increase in start-up research funds that Keirstead was offered. "I wanna fix spinal cords," he said then. "If I really want to fix spinal cords, I'm going south. And that's it."
Fast forward to this perfect spring morning at the University of California campus at Irvine. The desk in Keirstead's cramped office is heaped with grant applications, the mother's milk of research. A mountain bike leans against a wall dominated by a brilliant 2.5-m-long portrait of the greats of rock 'n' roll, rendered in pen and ink by his artist brother, Michael. The past six-plus years have been an epic ride, with no end in sight. No one is walking away from their wheelchairs yet, but even Keirstead at his most optimistic couldn't have predicted all that's come to pass. He's gained fame, fortune and notoriety, far beyond the usual lot of an academic researcher. Most of all, he's riding a wave of "some cool, cool science," as he and the rest of the biomedical world struggle to keep ahead of the thunderous potential of human embryonic stem cell research, and the legal and ethical issues churned up by their use. "Stem cells," he says, "have brought me into a political and ethical world I never thought I'd belong to."
They've made him a symbol, especially in California, of hope, and occasionally of hate. Nowhere has the debate over stem cell research raged more passionately than here. In 2001, Bush stopped all federal funds to create new stem cell lines or to support research. California, with a rich and vibrant BIOTECH industry, moved to circumvent the ban with various private and state-funded initiatives. Don Reed of Fremont, Calif., the father of a son paralyzed in a college football game, inspired a state law that has raised millions for spinal cord research, with some of the money going to Keirstead's work at Reeve-Irvine. Keirstead, this uppity Canadian import, testified at state Senate hearings on the issue in 2002. Then, in 2004, he waded into the bruising public debate over state Proposition 71, an initiative to invest $3 billion to fund stem cell research through a new California Institute for Regenerative Medicine.
Christopher Reeve, shortly before he died, videotaped a heartfelt appeal in support of the initiative. Keirstead and many others spoke out at public forums. He repeatedly showed a powerful video of his paralyzed rats regaining their mobility. Even some fellow scientists condemned him for that because the experiment itself had yet to be published in a peer-reviewed journal. That has since happened, in the leading Journal of Neuroscience. And, as important in Keirstead's view, three other labs, one of them in Canada, have independently confirmed his work using different cell sources. In essence it shows that cells engineered to produce myelin, a fatty insulating sheath, will migrate to and re-insulate damaged, shorted-out sections of spinal cord. Restoring myelin is a process akin to taping up a frayed extension cord, restoring the electrical signals from brain to body. Researchers see potential for other stem cell derivatives, perhaps producing insulin for diabetics or regrowing damaged heart muscle. Keirstead has no regrets about using the video in the debate. "People needed to see the potential of the cells," he says. "I had one, not the only one, but one very good example. So, I decided to get on the stage. Many, many stages."
Proposition 71 passed with 59 per cent of the vote. It remains tied up in court appeals financed by the religious right. And Keirstead remains a target. "Ethics interrupted" screamed a headline over a passionate attack on Keirstead published in Christianity Today. A condemnation of the "wicked" lies of Keirstead and others ran in LifeNews.com, a pro-life website, under the heading: "Embryonic stem cell research scientists exploit paralysis for false hopes."
Don Reed, with his son Roman, first met Keirstead at the Reeve-Irvine Center in 2002. Reed held in his hands a squirming, and formerly paralyzed, rat, while his son looked on in wonder. "Hans knelt down beside us, and said, 'This would not have happened without you,' " Reed says, the memory still fresh. "That was a beautiful, beautiful moment." Reed is under no illusions this will help his son. Keirstead made clear the therapy doesn't work on old injuries such as Roman's - though he is now researching chronic injury treatment. Still, in Reed's view, stem cells offer a new era of hope. "To me, it's like the Wizard of Oz, where it changes from black and white to colour," Reed says. "There's that one section where [Dorothy] opens the door into a new world. That's right where I feel we are. It's magic."
The object of all this attention grows in petri dishes and flasks in a tiny, locked cell-culture room in Keirstead's laboratory. The stem cells are derived from frozen fertilized embryos that otherwise would have been discarded from fertility clinics. They're not much to look at: little white blobs representing colonies by the millions, feeding on specially concocted liquid "growth factors" that resemble garishly coloured sports drinks. Unlike stem cells harvested from adults, a palatable alternative to critics, these multiply quickly, and with great purity, and they are far more versatile, capable of morphing into any kind of body cell, says Keirstead.
The stem cells' therapeutic potential rests in that malleability. They are nothing and they are everything. In those first few days after fertilization, they're all-purpose instruments, awaiting instructions to become one of the 200 or so specialized cells that grow toenails, livers, hearts and the other component parts of the human body. "If you wish to say that is more than a biological, a scientific wonder, if you wish to say that is divine, then go for it," says Keirstead. "I think that you wouldn't be far off the mark and you might even be right. But doesn't that just say we shouldn't be wasting them and throwing them away?"
Still, they're also the earliest stage of life, though they lack form or nerves or human qualities, and are incapable of creating a baby unless implanted in a woman's womb. Harvesting their potential requires breaking open small balls of about 150 cells known as blastocysts, and for some it is flat out wrong to tamper with any embryo. "Like a snowflake," President Bush has said, upping the moral ante, "each of these embryos is unique, with the unique genetic potential of an individual human being."
Standing in the cell room, Keirstead offers a different take on this moral equivalence of life argument. If there was a fire in here, and a lab technician was unconscious on the floor from smoke inhalation, what is the priority? Do you first rescue the man, or the flask of stem cells, he asks. "No compassionate human on this earth would value more a three-day-old round ball of 150 cells that would fit in the eyeball of Lincoln on the dime," he says, answering his own question. "You don't value that as much as a grown adult who has culture and heart and history and love."
Critics have accused Keirstead of rushing ahead too fast, and of cozying up to biotech companies, but Keirstead is unapologetically entrepreneurial. If the purpose of the exercise is fixing spines, that means getting research out of the lab and into the market. With the cost of many human clinical trials for new therapies running about $500 million, that's not for the faint of heart. "Sorry if this sounds egotistical," he says, "but most scientists aren't as business savvy as I am."
Within a year of arriving here, he'd partnered with Tom Lane, a UCI colleague and immunologist studying multiple sclerosis, a disease that also results in insulating myelin being stripped away from the central nervous system. They created an antibody that, in animals, stops the extensive inflammation and secondary damage caused after a new spinal injury. It also halts, with a simple injection, the continued attack of MS in animals and appears to have potential to treat Crohn's disease and ulcerative colitis. They formed a private company, Ability Biomedical, to raise funds to move development along. Two years ago, they sold the rights to the therapy to biopharmaceutical giant Medarex for more than US$8 million. The drug is now in human trials, thanks to Medarex's deep pockets and expertise - a development that so excited Keirstead, he couldn't sleep for days.
He was also moving on other fronts. He signed a deal in 2001 with Geron Corp., a California-based biotech firm and stem cell pioneer. In essence, he traded his future intellectual property rights for millions in research funding and access to stem cells. His lab - with its 22 employees and "totally spaceship" array of equipment and facilities - was the first in North America to use stem cells for spinal cord research. Within a year, he'd developed a way to grow them into high-purity populations of human adult oligodendrocytes, the myelin makers of the central nervous system. It is these that restored movement to acutely injured rats and convinced Geron to move the therapy to human trials next spring.
Couldn't have happened - at least not this quickly - without crawling into bed with industry, he says. Couldn't have happened in Canada, either, he says, where the tone of the debate is lower, but the money is scarce, and funding approvals grind slowly through an oversight committee of the federal Canadian Institutes of Health Research. "I miss Canada. I love Canada. I go back to Canada all the time," he says. "But I could never run a laboratory where I support 22 people. I could never have the equipment I have. I could never have the industry relations I have."
Speed is a relative thing. Among those stoking Keirstead's impatience is an artist named Suzanne Short, 44, who lives just down the coast at Laguna Beach. Today, in her studio with its magnificent view of the Pacific, she's painting a giant blue eye. She uses pens and brushes held in her mouth, after the use of her hands, arms and legs was stolen from her 24 years ago by a drunk driver. She's been watching the slow state of spinal cord research for more than half her life.
She first met Keirstead five years ago. She likes how he's taken the potential of stem cell therapy and run with it. "I think it's great that Hans isn't doing research for the sake of research," she says. "He starts something and he wants to get it out there and into clinical trials to be used in humans." She especially likes that he's researching chronic injuries. Maybe it's too much to hope she'll walk again. But imagine what it would be like to awake in the morning and, without assistance, have the mobility to get into her wheelchair. "Hans," she says, "has got to get busy."
He smiles when told this a day later over lunch. He's attempting a couple of approaches, one trying to dissolve the old scars surrounding chronic injuries, the other to build a new connection that circumvents the scars altogether. "With both of those approaches, I'm having what I would call early shows of success," he says. "So, I'm trying. Cross your fingers."
That's the thing with stem cells. There's so much potential, he's pushing the research boundaries on many fronts, he concedes. A seasoned professor here - a surfer - told him, "Hans, you're moving further and further to the front of the wave." Not a good place to be, he advised. Hang back and let some hotshot just ahead show you how the wave is breaking so you can ride it better. Keirstead laughs. "I should listen to that advice," he says. Then he shrugs, not at all convinced.
See also NEUROSCIENCE.
Maclean's July 1, 2006