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Stem-cell stalemate: The push for cures may produce only disappointment - or worse 

Wednesday, Apr 15 2009

The first few months of 2009 have been among the most auspicious for stem-cell research since the field's inception. In January, the Palo Alto–based biotech firm Geron Corporation announced it had received U.S. Food and Drug Administration approval to begin clinical trials of a stem-cell–based spinal cord therapy in humans. Just last month, President Barack Obama announced that he was reversing Bush administration restrictions on government funding for embryonic stem-cell research.

In light of such developments, you might expect that these would be exciting days for Arnold Kriegstein, who oversees the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UC San Francisco. Kriegstein's research facility is one of the biggest of its kind in the world. It is also the second-largest recipient of grants from the California Institute for Regenerative Medicine (CIRM), the state agency created to fund stem-cell research through Proposition 71, the 2004 state ballot initiative designed to sidestep Bush-era research restrictions.

But Kriegstein isn't rejoicing. Right now, he's worried.

On a recent afternoon, he sat in his 12th-floor corner office at UCSF's Parnassus campus. On his desk was a month-old Israeli study describing the story of a teenage boy who had traveled from Israel to Russia — a country known for its loose regulations on cell therapies — for an implant of neural stem cells to treat a rare degenerative disease. Four years after the procedure, according to the study, the therapy hadn't worked, and the transplanted stem cells had morphed into a brain tumor. As Kriegstein shuffled through his papers, looking for the report, he explained his fear that current efforts in California to create stem-cell–based cures, which he views as premature, could have similar results.

"The likelihood of something going wrong is pretty high," he said. "Something like tumors are probably going to happen. This is an area where the risks are great. The public has to be prepared."

Almost five years after Californians approved Prop. 71, the field of stem-cell research is at a turning point. Many scientists like Kriegstein say their understanding of stem cells has not advanced sufficiently to benefit the severe degenerative diseases for which the field once held such promise, or to administer safe tests of therapies for those ailments in humans. You wouldn't know it from listening to Obama or the promises of the Prop. 71 campaign, but human embryonic stem cells are, when not tightly controlled, a substance akin to poison. Their potential for developing into any tissue type is also a source of great danger. Implanted in mice, embryonic stem cells have been frequently observed to create teratomas, potentially cancerous tumors that can sprout hair and teeth as the cells mutate and multiply into the various organs they can create.

But with the clock ticking, CIRM — allowed a 10-year lifespan by California voters — is seeking to deliver on its campaign promises and push stem-cell science from the lab benches to patients' medicine cabinets. In its next round of grants, the agency plans to devote up to 10 times as much money to research projects that offer to produce cell-based medical therapies in the next several years as it will to basic scientific inquiries into how stem cells work. (The latter have so far consumed a majority of CIRM funds.)

The rub is that many of the stem-cell therapies ready for safe clinical applications — the ones medical researchers are more comfortable with — don't exactly live up to the public's expectations of what their tax dollars are funding. The success of the ballot initiative, a remarkable authorization of $3 billion in research money by 59 percent of the electorate in a state wracked by chronic budget deficits (with repayment of the bonds' interest, the total cost of the initiative is expected to reach $6 billion) was driven by the promise of cures and therapies that appeared, to the layperson, little short of miracles. Neural tissue derived from embryonic stem cells capable of becoming any part of the body — scientists call them pluripotent — would rebuild the spinal cords of paraplegics, allowing them to walk again. Lab-made pancreatic cells could regulate the blood sugar of diabetics, freeing them from daily injections of insulin.

By contrast, the conditions first in line for stem-cell therapies in 2009 seem pedestrian. Two diseases expected to see near-term trials of a cell therapy are arthritis and age-related macular degeneration (failing eyesight). The reason is that these conditions can be treated using adult stem cells, a safer and better-researched form of cells with a narrower range of possibilities than their embryonic precursors. Indeed, many in the medical community, while paying lip service to the optimism of 2004, acknowledge the very real possibility that people suffering from the incurable conditions typically associated with stem cells — not just Parkinson's or diabetes but Huntington's disease, multiple sclerosis, and HIV/AIDS, among others — will not see a therapy or cure from the state's $3 billion investment.

The J. David Gladstone Institutes — a triad of laboratories devoted to researching heart disease, brain disease, and AIDS — reside in a state-of-the-art research facility amid fenced dirt lots a few hundred yards from the Mission Bay canal. Bruce Conklin, a senior researcher in Gladstone's cardiovascular disease division, has been hard at work here with the help of CIRM grant money. His work offers evidence of where stem-cell research has gone since the fall of 2004: While Conklin is seeking to develop embryonic-stem-cell–derived therapies that could help those with heart disease, he is also still laboring to understand the cells' basic biological workings.

Conklin's lab is a long, open room with low ceilings. Informally divided by shelves and counters packed with cardboard boxes, bottles of solution, and lab-grade cleaning wipes, it resembles a Walgreens stockroom more than Hollywood images of austere research centers. "Molecular biology's a lot like cooking," the boyish-looking cardiologist says. At one end of the lab, a door opens into a small room dominated by glass-hooded SterilGARD III Advance machines, sterile workstations where stem cells can be developed and harvested. Chris Schlieve, a 24-year-old research associate wearing sterile green gloves and an eyebrow stud, sits at one such station. Working with a pipette, Schlieve teases at the edges of a culture of pluripotent stem cells, visible on his microscope's television-sized display as a grainy expanse resembling telescopic images of the Moon.

About The Author

Peter Jamison


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