August 2010 - Stem Cell Rock Star - Orange Coast Magazine

 

Stem Cell Rock Star

UC Irvine’s Hans Keirstead is a charismatic, tradition-bending, action-figure of a researcher who not only wants to heal the sick, but change the way academic scientists do business.  Is the world  ready for him?

by Patrick J. Kiger / photograph by Joseph Escamilla

Sci-fi movies and TV sitcoms have conditioned us to envision a scary smart, paradigm-shifting, scientific genius as a pale, distracted-looking guy with taped-up glasses, who speaks in an incomprehensible technical argot and exudes a cracklingly tense, impatient ambience, like a human Tesla coil about to spark the gap. Meeting Hans Keirstead is a shock of a different sort.

The UC Irvine stem cell researcher who startled the world by enabling paralyzed rats to walk—and aims someday soon to do the same for humans—is in his second-floor office at the Gillespie Neuroscience Research Facility, where the afternoon sun streaming through the window accentuates his tanned, finely chiseled features and the highlights of his lush mane.

On his desk is a high-end MacBook running what appears to be a gigantic queue of iTunes downloads, and on the wall behind him hangs “The Jam,” an enormous poster of the history of rock music drawn by his brother, artist Michael Evans Keirstead. In the corner is Keirstead’s slightly battered Martin Backpacker guitar, damaged when Men’s Vogue borrowed it for his photo shoot. 

At 43, the Canadian-born Keirstead, who was lured to UC Irvine in 2000 from the University of British Columbia by the promise of funding for a world-class facility, looks less like a neurobiologist and one of the fastest-rising stars of the scientific world than he does a youthful clone of Eagles drummer Don Henley. You half-expect him to embark on a hockey-arena tour this fall. Instead, he’s working with Geron, a Northern California biotech company, to launch the first federally approved clinical trial of a stem cell treatment for humans with spinal cord injuries, called GRNOPC1, based on his discoveries at UC Irvine. And instead of a Grammy, the gleaming trophy sitting nonchalantly on the edge of his desk—between framed photos of Keirstead riding a motorcycle and posed alongside his personal helicopter—is a plaque he recently received from the National Institutes of Health in Bethesda, Md.

“I don’t mean to brag,” Keirstead says, with the sort of shaken-not-stirred serenity that makes you believe he really means it, “but I just got back from the NIH, where I received this. The reason I love it so much, and that I’m so honored, is that it’s an endorsement by the think-tank scientific institute in America. This is the NIH saying, ‘Hans, you’re on the right track.’ And I can’t tell you how appreciative I am of that. Because one does experience a lot of antagonism from people who don’t understand the corporate realm and the priorities. People think I’ve made millions from the Geron deal, but I didn’t take a cent. 

“I have made money from other ventures—making therapies and doing little spinoffs to try to increase my personal income … but people assume that’s my primary motivation—just to make money off [discoveries]. I’ve walked away from so much money, I can’t tell you.”

Indeed, he can’t tell you precisely how much money he has walked away from. But in Geron’s case, it might be an awful lot, because if the stem cell treatment for spinal injuries succeeds, it possibly could work for a much wider range of neurological diseases, including Alzheimer’s, multiple sclerosis, and stroke.

But Keirstead, who could become the 21st century’s Jonas Salk, has set out to do something far more ambitious at UC Irvine. He’s fashioned himself into a prototype for a revolutionary new breed of university researcher. Part academic and part entrepreneur, he runs his lab with the market-oriented methods and urgency of a for-profit business, and is adept at doing big-dollar deals with companies—that is, when he isn’t lining up investors to start one of his own.

His goal is to radically speed up the drawn-out, cumbersome, and dicey process of transforming discoveries into medical treatments that can improve, or save, lives. To accomplish this, he has been willing to leverage his good looks and charisma to become a celebrity scientist, a media-friendly spokesman for stem cell research who’s no less comfortable appearing on “60 Minutes” or in the pages of a men’s fashion magazine than he is in the Journal of Neurotrauma.

Keirstead makes the Most Interesting Man in the World from those Dos Equis commercials look like a couch potato. At the University of British Columbia, Keirstead played guitar in a pub band and earned his black belt in tae kwon do two days after successfully defending his Ph.D. dissertation on spinal cord regeneration. He skis, rides motorcycles, flies a helicopter, and reportedly has a great recipe for pork loin in wine reduction. He’s married to a tall, blond, surfing neuroscientist, Niki Keirstead, with whom he has a young son. (They have dressed him in a onesie emblazoned with: “I would have made a great batch of stem cells.”)

When he’s not trying to find a cure for paralysis or ALS, he helps his father, Ken, a retired pharmaceutical executive who grew up in a missionary family in Africa, improve health care there. Like the Dos Equis guy, who once had an awkward moment just to see how it felt, Keirstead once felt a little awkward when Men’s Vogue, which had requested some of his prized possessions for a photo, sent him back former Florida Gov. Jeb Bush’s stuff by mistake. He couldn’t resist trying on President George W. Bush’s handmade presidential cowboy boots, which Dubya apparently had given to his brother as a keepsake.

There was an overpowering irony to the mix-up. “This was while Bush was in office, you know, putting into effect his policy,” Keirstead says, referring to the 2001 presidential order to allow stem cell researchers to receive federal funding only if they restricted themselves to using a handful of existing stem cell lines, rather than new ones from unused embryos at fertility clinics. At the time, the ban, which was rescinded by President Obama, was seen by many as a potentially crippling blow to efforts to find an effective treatment for spinal cord injuries and neurological diseases.

For Keirstead, it was no biggie, just an annoyance. He called a former girlfriend from Cambridge, where he did his postdoctoral work in the late 1990s, who now worked for Geron,  the first company to obtain embryonic stem cells after they were isolated by researchers in 1998. “Can you get me in the door and get me some cells?” he recalls asking.

Of course, Keirstead needed more than personal contacts to persuade Geron management to grant him access to one of the precious existing lines of stem cells, but fortunately, his proposal to try restoring spinal cord function in paralyzed rats was even more compelling than his charm. Three weeks after President Bush complicated access to new stem cell lines, Geron and Keirstead struck a $272,300 deal in which Keirstead would become one of the first researchers in the nation to obtain human embryonic stem cells for experimentation.

What followed rocked the world.

The UC Irvine scientist figured out how to push stem cells to develop into a certain type of nerve cell—the sort that’s lost in spinal injuries—and created the first high-purity mixture of such a specialized cell. He then injected the cells into the spines of paralyzed rats. The new cells wrapped themselves around nerves, making connections and allowing signals to flow through the rats’ bodies. In six weeks, they could walk again.

The 2002 achievement turned Keirstead into neurobiology’s equivalent of The Beatles, who were idolized by fans to such an extreme that some actually brought sick children to their concerts, in the hope that the Fab Four could heal them. Paralysis and neurological disease patient groups saw him as the scientific savior who finally was going to do something about their suffering. It helped that Keirstead welcomed patients into his lab for tours, so he could show them what he was accomplishing. 

“I went back to the community and told them, ‘I think this is the guy we need to back,’ ” Christopher Chappell, a paralyzed activist and participant in the CareCure newsgroup on the Internet, told Wired magazine in 2005. “Because it’s rare we get a scientist who is willing to be aggressive and has the same urgency the community does. He is looked at as a maverick by scientists, but the injured look at him as a kind of hero because he’s willing to take a chance.”

Keirstead also got a call from Robert Klein, who was spearheading the effort to pass Proposition 71, a 2004 California initiative to provide state funding for stem cell research to circumvent the federal ban. Klein sent Keirstead on an evangelical road show to convert politicians and the public to the cause. Having such a visible example of stem cell therapy’s potential undoubtedly was a major factor in Proposition 71’s passage. “I was just a simple scientist, trying to get a treatment working,” Keirstead says. “But [the campaign] got me into some incredible circles.” 

Keirstead’s accomplishment, along with his good looks and infectious charm, made him a spokesman nonpareil. Since then, he has been to Capitol Hill many times to lobby for support for stem cell research.

 

As Keirstead’s media star-dom grew, so did outsized expectations. “Paralyzed Rats Walk; Humans Next?” Wired asked. Men’s Vogue boldly proclaimed that Keirstead “is fast approaching a cure for paralysis”—a cringe-worthy bit of hyperbole, considering that his treatment so far has been shown to work only with newly paralyzed rats, and still has to be tested in humans. Not that it makes any difference to those desperate for hope, even after Geron’s clinical trial of Keirstead’s discovery ran into regulatory snags in early 2009 that delayed it until this year. Miss Wheelchair California 2009, Alyson Roth, still wanted to have her picture taken with Keirstead in his UC Irvine lab. (Roth gushed about him on her blog: “What an amazing man who has a true heart and passion for getting things done and for improving the lives of so many people, one step at a time.”) Paralyzed motocross star Ricky James unabashedly tweeted: “yep, i still know the best scientist in the world. Dr. Hans Keirstead. mark my words, if anyone will fix spinal cord injury, it will be him.”

On several occasions, Keirstead found himself taking phone calls from despondent callers who needed to hear some good news to deter them from suicide. “I said to one guy, ‘Whoa! Give me 30 minutes so I can tell you about some things that are going on,’ ” says Keirstead. He says he talked the man—and, by his count, three others—out of ending it all. “I told him: ‘We got paralyzed rats to walk again, and we did it in a way that can be done in humans. We’re just doing the paperwork. But, my God, we’re already doing it in rats.’ ”

Eventually, Keirstead had to begin screening his calls. “I feel badly about this, but I would be on the phone six to eight hours a day, talking to people,” he says. He still sees the ones who come to the lab. “I like that. You can see the difference in someone when they realize that someone else is on their side, that they’re not alone and that, holy shit, this might actually work one day. It’s inspiring to me, and to them.”

 

That simple-but-persuasive argument—my God, we’re already doing it in rats—also gets at Keir-stead’s core motivation. He grew up in Canada, wanting to become a doctor, but realized in his first year of pre-med that “I didn’t want to see patients receiving treatments that were insufficient to have a substantial benefit.” That’s what drove him through the lean years as a grad student and postgrad at Cambridge. And it led him to bolt for UC Irvine in 2000 from his first reasonably well-paying position at the University of British Columbia’s Collaboration on Repair Discoveries, a top Canadian spinal research center, even though he’d been on the job for barely a year and had bought his first house in Vancouver. (“Another brilliant Canadian slips down the brain drain,” a headline in The Vancouver Province newspaper groused.) UC Irvine had eight times the research funding, a sparkling new state-of-the-art lab, and an association with the late Christopher Reeve to speed his progress.
“I want to fix spinal cords,” he explained to a reporter at the time. “And if I really want to fix spinal cords, I’m going south.”

Keirstead’s subsequent scientific and media stardom at UC Irvine turned him into an invaluable asset for the university. His presence undoubtedly made it a lot easier to raise the $80 million needed to build the Sue and Bill Gross Stem Cell Research Center, dedicated May 14. (In addition to $10 million from the Grosses, the university received $27.2 million in funding from the state’s California Institute for Regenerative Medicine, or CIRM, which might not have existed except for Keirstead’s political activism to help pass Proposition 71.)

At the same time, though, Keir-
stead’s meteoric rise, and his willingness to tout the game-changing potential of his stem cell work, have invited criticism. In 2007, the San Francisco Chronicle revealed CIRM reviewers’ less-than-flattering comments on his application for a $2.4 million grant for spinal cord research; among other things, they called his proposal “scientifically thin” and said he hadn’t presented enough preliminary data or backup plans, should his main approach fail. They gave him the money anyway, and Keirstead told the Chronicle he was unfazed by the slam.

He also hasn’t made many friends in academia with his nonchalant attitude toward publishing scientific articles, traditionally the merit badge of research achievement. (After Keirstead revealed his breakthrough with paralyzed rats, for example, fellow scientists had to wait three years to read his findings in a journal because Keirstead wanted his report to be “airtight.”) 

Keirstead also was criticized for  Geron’s upcoming clinical trial for the spinal cord treatment based on his work. In a January 2009 New York Times article, for example, a couple of eminent medical critics urged Geron to slow down, and warned that the treatment might not be safe. Steven Goldman, chairman of neurology at the University of Rochester and a member of the U.S. Food and Drug Administration committee that examined stem cell research, was particularly blunt, expressing concerns that raw stem cells injected into the body might cause tumors. “It’s not ready for prime time, at least not in my mind, until we can be assured that the transplanted stem cells have completely lost the capacity for tumorogenicity,” Goldman said. 

Keirstead, who framed the criticism and hung it on the wall of his lab, says it’s an example of the disconnect between the old-school research establishment and the new, fast-track method of developing treatments he has pioneered. “They’re saying, ‘Slow down. All these things need to be done,’ ” he says. “And in fact, we had done all those studies. … I don’t mean to be anti-academic, but in industry, you don’t publish. We did a tremendous amount of work showing, for instance, safety. But none of those [studies] was ever published. So I have been attacked by certain academics who say, ‘My God, how can you move forward?’” 

 

To Keirstead, the venerable way of doing medical research—relying strictly on government and nonprofit sources of funding, publishing numerous studies, designing basic studies to test an approach, and then laboriously redoing the work with the actual manufacturing-grade treatment to pass FDA approval—just isn’t fast enough. As much as he’s peeved by criticism from fellow scientists, he’s more pained by the knowledge that there may be patients in wheelchairs trying to decide whether to call him on the phone or reach for a lethal dose of sleeping pills.

From the start, he has sought backing from for-profit companies willing and able to spend the money needed to speed treatments to market. When he can’t find the right corporate partner, he starts one himself. His role model is his dad, who after leaving Big Pharma, founded a number of smaller, successful startups. 

To further streamline the development process, Keirstead says he designs his studies from the get-go to meet the eventual FDA requirements for a finished treatment. “If you do the early research with a research-grade preparation, then you’ve got to redo all of it when you progress to a clinical grade product that you could actually use in humans,” he says. “That’s a waste of time. What we do is talk to doctors and nurses and patients at the outset. What’s the volume that we can actually put in the spinal cord, for example? That’s the volume that we want to use in the research. We use clinical-grade preparations, which have been tested in safety studies.” That way, when the results come through, the new treatment is ready to be submitted for approval for human trials.

Such front-loading is risky and expensive, which is why Keirstead needs backers accustomed to playing for high stakes. “Geron spent
$45 million for the preclinical development work [for the spinal cord treatment],” he says. “I don’t have that kind of money. But I don’t need to, because they do. It’s wonderful to have a partner throwing such resources at a project.” He couldn’t do that if he had stayed inside the strictures of academia. On the other hand, Keirstead points out, private-sector investors aren’t exactly inclined to risk millions of dollars on any project that comes along; his proposals have to withstand due diligence that can be even more exacting. “They’re looking for a return on their investment,” he says. “So it’s a different kind of hard.

“I run my lab like a company. I have staffers who are like vice presidents, almost—somebody to run rats and mice preclinical efficacy stuff, somebody to run safety, somebody to run cell culture, someone to manage the lab. It just reflects my affinity for business.”

The private-sector approach already has worked for Keirstead. Early this decade, his first startup, a Canadian company called Ability Biomedical, developed MDX-1100, an antibody treatment for immune disorders such as ulcerative colitis and rheumatoid arthritis. The company was acquired in 2004 for $4.7 million by Medarex, which was bought by multinational drug maker Bristol-Myers Squibb. The drug has completed Phase II human trials, and Keirstead says that several hundred patients have been successfully treated with it. 

Given that rheumatoid arthritis is a multibillion-dollar drug market, there’s the prospect of someone—that is, besides Keirstead—making a ton of money off his work. He seems unconcerned about that. “The day that I learned that it had been used to treat a human subject, that was probably the best day of my professional career,” Keirstead says. “I’ll be lying on my deathbed someday smiling, thinking how wonderful that is. I don’t think you carry that kind of joy around with you from knowing you have $10 million.”

Keirstead says he has turned down numerous cushy corporate offers to stay at UC Irvine, where, according to a salary database published by The Orange County Register in 2008, his gross pay that year was just short of $140,000, far less than the 350 UC Irvine employees on the list who made more than $200,000. Keirstead politely declines to discuss the amount he has made from his for-profit ventures, but his personal $250,000 Robinson R-22 helicopter, his Harley, and a Ducati racing bike, suggest that he probably has done pretty well. All the same, he seems to believe that it helps scientists to have Adam Smith’s Invisible Hand on their shoulders, that doing good and doing well can occur simultaneously.

“I differ in my views with a lot of other academics,” he says. “I think that incentivizing with money is fantastic. It’s probably the most common way of getting things done in our society. … Capitalism works, because people are incentivized to set up Starbucks stores and proliferate them throughout the nation. That’s why I work with companies. I don’t have a primary motivation to make money in my life. I think that’ll all just come, and to some degree, it has.”

 

Mostly, though, Keirstead is simply jazzed by the idea of getting things done. Sure, he has a serene façade, an affect of his martial arts training, and the Zen-like mindfulness that comes from flying helicopters for fun. “When you get in a chopper, you’ve got to be thinking every second about staying alive,” he says. “There are about seven ways you can kill yourself in three seconds, so you can’t be thinking about something else. It’s like meditating.”

But underneath that, he admits to being the classic Type A, driven to get results. Keirstead once showed up at a hospital in impoverished Guinea and asked the staff doctors, “What do you need?” Vitamins to fight malnutrition, they told him. He persuaded Vita-Tech, a Tustin manufacturer, to donate 2,000 pounds of them, and then worked with grassroots activists in Guinea to set up a distribution network to ensure that the vitamins would actually get to the kids and sick people who needed them. 

He also has organized an Africa initiative at UC Irvine to send medical students there to help with the work. “My dad was just out here, and we met with [Chancellor Michael V. Drake] to talk about Africa. We’re planning a bigger meeting at UCI at the end of the year, to bring more of the community into it.” He pauses, clearly striving to be diplomatic. “UCI actually has a lot of strengths in Africa, but a lot of them are policy and analyzing, rather than actually making things. Not to denigrate that, but what we do is simply action-based.”

Keirstead himself would make a great action figure. For him, spinal cord injuries are just the start.  

“Remember, the way that the central nervous system degenerates is the same, regardless of the trigger, whether it’s a spinal cord injury or a disease. It sets off the same sequence of events. That means that if you develop a treatment for one condition and get the biology working for it, you can leverage that, and translate it into treating other diseases as well.”

And if that happens, the world is Hans Keirstead’s lab bench. “I want to be able to say I’ve done something,” he says. “I’m not satisfied to think about it. I think that anything that just goes on in your head is largely irrelevant for the real world. But there’s nothing better than vision realized.” 


This article originally appeared in the August 2010 issue.

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