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Pied Piper of stem cell research: A Californian with high
By Andrew Pollack The New York Times
Friday, February 25, 2005
IRVINE, California Hans Keirstead might be the Pied Piper of stem cells - and not just because he makes rats walk. He also helped lure Californians to the polls last autumn to approve spending $3 billion of the state's money on embryonic stem cell research over the next decade.
But critics worry that he may be leading their new field too far, too soon into uncharted territory.
Keirstead, an assistant professor at the University of California campus here, has been making paralyzed rats walk again, using a treatment based on human embryonic stem cells. Next year he and his corporate partner, Geron, plan to try treating people who have recent spinal cord injuries, in what would almost certainly be the first human trial of any therapy derived from such cells.
"You've got a patient community out there that is in desperate need," Keirstead said in an interview. "If the treatment is safe, let's get it out there and try it."
And to those who argue that it is too soon to test his technique on humans, he has an answer. "There will always be people who say slow down, slow down," he said. "I guarantee you none of them have relatives in wheelchairs."
With his gung-ho attitude, the good looks of a surfer and a compelling story to tell, Keirstead, 37, emerged as one of the leading scientific voices behind the movement that persuaded California voters last November to approve a measure to sidestep national funding restrictions on stem cell research. His supporters included people with spinal cord injuries, most notably Christopher Reeve, the wheelchair-bound actor who taped a campaign ad citing Keirstead's research just before he died in October.
But for all of Keirstead's fans and backers, a number of researchers in California and elsewhere say the scientific validity of his work has not been proved and the technique might not be ready for testing in people. A failure in the first high-profile human test could dash some of the hope spawned by the passage of the California ballot measure.
"A lot of things make rats better," said Jerry Silver, a neuroscientist at Case Western Reserve University, who argued that Keirstead should test his treatment in dogs or monkeys first. "You can't announce you are going into humans because you've gotten good results in rats."
The new California stem cell research board that was set up after passage of the ballot measure last autumn, Proposition 71, is still organizing itself and figuring out how to begin awarding public grants to scientists.
But Keirstead has been able to speed forward, fueled by the corporate money of Geron, a California biotechnology company that is eager to demonstrate to investors that practical use of stem cells is not a distant dream.
Because embryonic stem cells can form any other kind of cell in the body, scientists envision using them to replace cells and tissues that have been damaged by disease or injury.
The administration of George W. Bush has restricted government-funded research to certain colonies of stem cells, arguing that creating additional cells involves the destruction of human embryos. But proponents of the research say the early embryos have no feeling or consciousness and most of them used in research are left over from fertility clinics and are destined to be discarded anyway.
California's ballot measure was propelled by people with diseases and their families and backed by big contributions from some wealthy businessmen. Robert Klein, a real estate developer who has a son with diabetes, helped draft the ballot and put his money behind the vote effort. After its passage he was named chairman of the board that will oversee distribution of the $3 billion.
Klein said it was "extremely welcome" that embryonic stem cell therapy was moving toward clinical trials under Keirstead. But he said the public needed to know in advance that, as with many new therapies, the first trial is not expected to succeed. "It may take several years, or many years, to refine," he said.
Keirstead's work was a rallying point during the Proposition 71 campaign; he gave 14 speeches to various civic, political and business groups to whom he showed a video of his rat research. In it, an untreated rat struggled to pull itself along the ground using its forelimbs as its paralyzed hind legs, tail and belly scraped along the ground. A rat treated with Keirstead's cells was then shown moving its hind legs, though not perfectly, and keeping its tail in the air.
"Stem cells have already cured paralysis in animals," Reeve, the actor, said in the commercial he filmed, which was broadcast after his death. He urged voters to "stand up for those who can't."
But some spinal cord researchers criticized Keirstead for having shown his video for three years but not publishing his work with rats in a peer-reviewed journal that would allow experts to evaluate it fully.
Keirstead said that he was in the process of publishing his results but that he had wanted to do other tests first. He said that he expected to release further research results well before starting clinical trials next year but that showing the video before publication, even at the risk of annoying fellow scientists, was important to give patients hope.
"I've had people call me up and say, 'I'm about to commit suicide, do you have anything to stop me?"' he said. "People don't realize how close we are."
Indeed, during a two-hour interview in his cramped office here, his phone rang several times with calls from injured people, some volunteering to be guinea pigs in any study he conducts.
John McDonald, director of the international spinal cord injury and paralysis center at the Kennedy Krieger Institute in Baltimore, said that "to date, not enough has been shown" by Keirstead and Geron to allow drug regulators to authorize a clinical trial. Even so, he said Keirstead was being unfairly criticized.
"Scientists aren't too kind to other scientists' receiving too much attention," McDonald said. "I think that's what you're seeing."
For all their promise, stem cells could pose dangers if not carefully controlled. Scientists do not envision implanting raw stem cells into patients' bodies because the cells might turn into undesirable types of tissues. The idea, instead, is to turn embryonic stem cells into the desired type of cell, like heart cells or liver cells, in the laboratory and then transplant these more specialized cells.
But it remains unclear how much of a difference this will make to people with spinal cord injuries.
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