Scientists were soon complaining that the Bush policy was unworkable. Many of the lines had chromosomal abnormalities or were contaminated with animal products, rendering them unsuitable for use in humans. Newer lines developed with private money could only be used in separate labs built without federal money.
Backers of the California Stem Cell Research and Cures Initiative, better known as Proposition 71, emphasized the potential for these flexible cells to reverse paralysis from spinal cord injuries and cure intractable diseases such as Parkinson's, diabetes and Alzheimer's. Scientists, not normally known for grandstanding, rallied voters across the state. Californians approved Proposition 71 in November 2004 with 59% of the vote.
The first grants went out in April 2006, after fighting off legal challenges. Hundreds of millions of additional dollars followed.
Money put to work
USC, for example, used a grant to build its Center for Regenerative Medicine and Stem Cell Research essentially from scratch.
The university hired Martin Pera, a colleague of Trounson's, to lead the effort. It was quite a coup: In Australia, Trounson and Pera's team was the first to show that human embryonic stem cells could grow into mature cells in laboratory dishes.
Within three months of his arrival, USC received a $600,000 grant to support graduate students and postdocs working on stem cell projects. The following year, the university racked up nearly $4 million in state funding for scientists to study basic properties of human embryonic stem cells.
An additional $2.2 million from the agency allowed USC to set up its Stem Cell Core Facility, where staffers can derive, grow and maintain stem cell lines for researchers. And $27 million more helped finance a new stem cell research building. By the time construction wraps up this summer, Pera said he hopes to recruit two additional research groups using more state grants.
It may seem extravagant, especially in light of California's broken budget. But Pera sees stem cell science as a sound long-term investment.
"This is going to be a key area of scientific research," he said. "What's wrong with making this state a national and worldwide leader in this technology?"
Until a few months ago, these types of grants were the institute's bread and butter. The agency has financed 29 new labs and more than 350 researchers at 51 California institutes, from UC San Diego to Humboldt State. Scientists funded by the California Institute for Regenerative Medicine have produced 412 publications describing heart muscle cells, liver cells, retinal cells and others grown from human embryonic stem cells, among other experiments.
But those academic achievements don't matter much to average taxpayers, Trounson said. People who voted for Proposition 71 "want to see some clinical treatments happen."
A better therapy?
Count Karen Aboody among the impatient masses.
Watching her sister-in-law struggle with breast cancer that spread to the brain, she saw up close how the side effects of treatment can be as devastating as cancer itself. Aboody is convinced that stem cells can provide more effective, less debilitating therapies.
It all hinges on her discovery that neural stem cells flock to a chemical that cells make when they need new blood vessels. Tumors, which need blood to grow, release that chemical in abundance. And so stem cells flock to tumors.
Now she is using her Proposition 71 money to engineer human neural stem cells that produce a key enzyme. The cells are injected into a patient's brain, and a drug called CPT-11 is administered. As the enzyme and drug interact, they produce a powerful chemotherapy agent that kills tumor cells as they divide but leaves surrounding tissues intact.
The team will spend the next few years honing the process while regulatory specialists compile toxicology data, details on the cell manufacturing process and other safety information that the FDA will need when it considers granting permission for a clinical trial in patients with recurring malignant brain tumors.
The institute grants also went to 13 other research teams that believe they are on the verge of bringing stem-cell-based therapies to patients.
Among them is a group from UCLA and Childrens Hospital Los Angeles that hopes to cure patients with sickle cell disease by genetically modifying their blood-forming stem cells so that they produce healthy red blood cells; and researchers at Cedars-Sinai Medical Center who want to inject heart-attack patients with concentrated amounts of their own cardiac stem cells, which naturally repair heart tissue.
Some scientists who study basic stem cell biology say the new emphasis on clinical trials is premature. They say many fundamental questions about stem cells still need to be answered, and diverting money from basic science means that revolutionary therapies -- still many years away -- will take even longer to materialize.
Trounson acknowledged that the shift has elicited "a bit of a reaction from scientists" despite the institute's commitment to continue steering millions of dollars to basic biology. But, he said, the investments will have to produce actual therapies "if we're going to be relevant to the community."
Even under the best of circumstances, Aboody's brain tumor therapy wouldn't win FDA approval for general use for at least a decade, she said.
But, she added, the Proposition 71 money will shave at least four years off the process.
"We can cure mice forever in our labs," she said, "but moving this from the lab to the patient is the ultimate goal."