MAGAZINE: FEATURE
Stem-Cell Gamble
After years of controversy, a therapy based on human embryonic stem cells is finally being tested in humans. The treatment holds out hope to paralyzed people, but at how great a risk?
JULY/AUGUST 2011BY ANTONIO REGALADO
technologyreview.com
Hans Keirstead wakes up every morning at his home near Los Angeles and checks CNN. He's looking for news about the first-ever human test of embryonic stem cells, launched in October by the biotechnology firm Geron. Mostly, he's looking for bad news. "If someone dies, or is in pain, then it's over," he says, pushing a hand through his tawny hair. Keirstead, dressed in a loose linen shirt and wearing a thumb ring, is a biologist at the University of California, Irvine, who has variously been called the "rock star," "miracle worker," and "Pied Piper" of stem-cell science. Today he has a corner office in a new $67 million research center paid for in part by California voters, whom he helped persuade to vote for a $3 billion stem-cell spending plan in 2004 with a video of partially paralyzed rats walking again after stem-cell transplants performed in his laboratory.
That same treatment is now being tested in human beings. No wonder Keirstead is anxious. Although he is not directly involved in the clinical trial, the discovery he patented, promoted to Californians, and later licensed to Geron has now become the leading test of whether embryonic stem cells will finally live up to their medical potential. "I'm dying to know if it works," he says.
As Technology Review went to press, Geron had so far treated two patients: a 21-year-old nursing-school student named T.?J. Atchison, who was paralyzed at the chest in a car crash last September, and a second person who has not been publicly identified. The hope is that cells injected into their spinal cords could help mend damaged nerves and restore at least a degree of mobility and sensation. Even if the treatment fails, many researchers believe the test is a critical step toward a time when bodies are healed and regenerated with living cells, not chemical drugs. "Cell therapy is now here to stay," says Wise Young, a professor at Rutgers University and an expert on spinal-cord injury. "I tell my students that this will be the future—that they will be the first generation of doctors to use cell therapy."
Thirteen years of public debate, scientific surprises, lawsuits, and presidential decrees have gone by since embryonic stem cells were first isolated, in 1998. Stem cells drawn from early-stage human embryos have the potential to develop into any type of cell in the body. In a lab dish, they can give rise to nerves, skin, even pulsating heart cells. And Geron, a 180-person biotech outfit in Palo Alto, has promised for a decade that treatments based on the cells could be just around the corner. The company says it spent $45 million on amassing the evidence needed to persuade the U.S. Food and Drug Administration to allow the first-of-a-kind human trial to proceed—an effort that included animal tests it calls exhaustive. "The agency told us our application was the largest they'd ever received," says Geron's interim CEO, David Greenwood, sweeping his hand over a double-length conference table that once creaked under the weight of all 22,500 pages.
Geron's success in getting the FDA to green-light the trial has already triggered a small explosion of other embryonic-stem-cell studies. Advanced Cell Technology, a smaller competitor in Marlborough, Massachusetts, has been cleared to begin two trials that will involve replacing cells in the eyes of people going blind from macular degeneration: lab workers will use stem cells to manufacture a type of retinal pigment cell that the disease kills off. Next in the pipeline is a startup company's effort to transplant lab-grown replacement nerves into infants with a fatal genetic disease called spinal muscular atrophy. That trial is planned by California Stem Cell, which has raised $10 million from wealthy donors and has signed up Keirstead as its chief scientific advisor. Keirstead, bounding through the still empty offices with a tape measure in hand, says he is considering leaving his lab to join the company full time. He thinks that with the Geron trial now under way, other human studies can advance much more quickly and cheaply.
But that depends on what happens in the Geron trial. And even some of stem cells' most ardent advocates worry that things may be moving too fast. Arthur Caplan, a bioethicist at the University of Pennsylvania and a defender of stem-cell research (see Q&A, September/October 2006), calls the Geron study poorly designed and says it should never have been allowed to proceed. "This is nuts and hugely risky," says Caplan. "The animal studies are not adequate to justify the trial." Those studies provide too little proof of safety, he contends, and Keirstead's original findings in rats offer thin evidence that people will be helped.
Looming large is the history of gene therapy, another advanced biomedical technology, which badly misfired when a young volunteer named Jesse Gelsinger died in a safety study in 1999. Caplan, who was close to those events, sees worrisome similarities (see "The Glimmering Promise of Gene Therapy," November/December 2006). "If they get an adverse event, there will be hell to pay," he says.
NO MIRACLE
Spinal-cord injuries cause paralysis by killing off nerves that transmit sensory impulses and leaving others stripped of their myelin sheath, the layer of fatty insulating material that helps nerve signals travel. Geron manufactures its treatment, known as GRNOPC1, by coaxing embryonic stem cells to form what are known as oligodendrocyte precursor cells. Those cells are bottled and frozen, and Geron scientists believe they may help restore some degree of sensation and limb movement to patients if transplanted soon after a spinal-cord injury. That is because oligodendrocyte cells produce myelin and may serve other purposes as well, such as encouraging new blood vessels to form. In Geron's initial human trial, designed to test the safety of the treatment, doctors plan to inject two million cells each into the spines of 10 people whose legs have been paralyzed in accidents.
Will the treatment be a cure? The odds are against it. In general, most new treatments, never mind highly experimental ones, bomb out early. What's more, GRNOPC1 faces an uphill fight against medical dogma, which says that it's impossible to reverse damage to either the brain or the human spinal cord. That means few experts expect a miracle from GRNOPC1. Richard Fessler, a surgeon at Northwestern Memorial Hospital in Chicago who is leading patient recruitment for the Geron trial at seven U.S. medical centers, calls the study a "rational" attempt to reverse spinal-cord damage. But he cautions against expecting too much. "We wouldn't be doing this if we didn't have hope, but I don't want to instill false hope," Fessler said in a news conference in May, after the second patient received the treatment. "I'm not going to go to one of these patients and say, 'We're going to give you a transplant and you're going to walk.'"
Still, some patients are clamoring to join the Geron study, even though only people with extremely recent injuries—the kind that lab research suggests might be helped—are allowed to participate. A Dutch man offered Geron $1 million to treat his son, and Keirstead says he received an even bigger offer from a paralyzed Texas millionaire. "He said he'd pay me whatever millions it takes to set up a clinic in Mexico, and another $2 million for me, just to treat him," he says. "It made me pause, but not for long."
Continues... |
