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California's stem cell program ponders a future of new challenges and old promises

Evangelina Padilla Vaccaro of Corona is the new face of stem cell science in California. Born with “bubble baby” disease that deprived her of a functioning immune system, she was cured with stem cell therapy developed in Donald Kohn’s lab at UCLA, which has received millions of dollars in grants from the California stem cell program.

Now she’s a vivacious 4-year-old, depicted astride a hobby horse and clad in a pink sweatshirt bearing a lightning bolt on the program’s 2016 annual report under the legend “CURED.” 

“Thank you all for the amazing work you do,” her father told the program board during its Dec. 13 meeting.

Evangelina represents the great potential of the $3-billion state program, formally known as the California Institute for Regenerative Medicine, or CIRM, but also its dilemma as it ponders its next chapter. Established in 2004 by a nearly 60-40 vote for Proposition 71, CIRM began issuing grants in 2006. Now, after 10 years, the program has committed $2.2 billion of its bond-funded war chest. It’s expecting to spend the rest by the end of 2020.

So it won’t be long before CIRM must confront the question of whether to fold up shop when its well runs dry, seek outside funding from foundations and industry, or appeal to voters for more public money. If it returns to the ballot, CIRM would have a chance to reconsider its administrative structure, the inflated expectations it gave voters in 2004, its embedded conflicts of interest and even whether it should be limited to funding research into stem cells. All these features of Proposition 71 have created complications during the program’s first decade.

Robert Klein II, the real estate investor who was the driving force behind Proposition 71 and chaired the institute for its first seven years, already has said that he intends to place a funding measure on the November 2018 ballot.

CIRM officials, wary of rules limiting how far public agencies can go in lobbying for ballot measures, aren’t yet taking an official stand on Klein’s effort. “We’re leaving it to Bob,” Chairman Jonathan Thomas says; he told the oversight board in December, “We keep him updated on CIRM’s progress so that his effort is fully informed.”

Thomas added, however, that he and other officers have started discussions with philanthropists and medical foundations that could be “potential sources of funds to keep CIRM going in the event Bob’s measure is not successful.” Klein didn’t respond to a request for comment.

The success of any ballot initiative will depend on two factors, says Henry T. Greely, director of the Center for Law and the Biosciences at Stanford University: “The two big variables are whether any of their clinical trials pay off, and what the Trump administration does.”

The public wants evidence that its heavy investment in CIRM has yielded cures for diabetes, Alzheimer’s, Parkinson’s, spinal cord injuries or other conditions that were touted as research targets by the Proposition 71 campaign. Evangelina’s improvement notwithstanding, no CIRM-funded research has yet reached the marketing stage, although CIRM officials say some initiatives are getting close. 

Greely’s allusion to White House policy harks back to the very genesis of the stem cell program, President George W. Bush’s 2001 ban on federal funding for research on stem cells derived from human embryos. The imposition of an essentially ideological test for scientific research was what spurred California voters to enact Proposition 71 as a constitutional amendment three years later. The measure endowed CIRM with $3 billion in bond revenue to fund California stem cell laboratories and attract world-class researchers.

The program certainly has helped turn California into a global center of stem cell research. “California is the place to be if you want to develop stem cell treatments,” says Jeanne Loring of Scripps Research Institute in La Jolla, a CIRM grantee who is researching possible treatments for Parkinson’s. “A lot of my colleagues in other states are envious.”

President Obama lifted the Bush ban in 2009, but by then CIRM’s role as a bulwark of California’s research infrastructure was secure. Whether Trump might reimpose the ban is unknown.

Trump himself hasn’t left a record of his views on embryonic stem cells, which typically are derived from unused embryos developed for in vitro fertilization and donated for research. But Vice President Mike Pence labeled such research “morally wrong” in the pages of Christianity Today.

A new ballot campaign would present an opportunity to fix some of the stem cell program’s flaws that were written into Proposition 71 and consequently embedded in the state Constitution.

The measure gave CIRM unique exemptions from most legislative oversight and state laws mandating public accountability and transparency. By dictating that seats on CIRM’s 29-member oversight board would be filled almost exclusively by representatives of grant-eligible institutions or patient advocacy groups, it institutionalized conflicts of interest and an atmosphere of cronyism.

The Institute of Medicine of the National Academy of Sciences found in a 2012 report that this setup bedeviled the program with persistent questions about “the integrity and independence of some of CIRM’s decisions.” Indeed, an analysis by David Jensen of the California Stem Cell Report found that about 90% of the $1.7 billion in CIRM grants by 2013 had gone to institutions with present or past representatives on the board.

Lasting damage to CIRM’s mission also may have been done by the tenor of the Proposition 71 campaign, which used such high-profile victims of neurological conditions as Michael J. Fox and Christopher Reeve to give voters the impression that money was the sole obstacle to miraculous stem cell cures, and that successful treatments would yield immense profits for the state. Neither claim was realistic, but they set benchmarks for success that CIRM has been unable to meet. 

A new funding campaign could give the program  a much-needed reboot. The ballot measure could restructure CIRM as an “ordinary agency of the state” subject to legislative oversight, open meetings laws and other good-government statutes, says Marcy Darnovsky, executive director of the Berkeley-based Center for Genetics and Society.

Especially in its early years during Klein’s chairmanship, the program guarded its independence from oversight truculently. Since then, Darnovsky says, it’s been more accommodating: “They’ve been much better than they have to be by the letter of the law,” she says approvingly. But she says the program has never resolved the conflicts of interest inherent in “who decides where the money goes and who gets it.”

A new campaign could instill more public realism about the potential of the research being funded. “If they ask for money, it would be really important that they level with the people of California and educate them about how science really works,” Darnovsky said.

CIRM’s leadership knows that the public’s inflated expectations threaten to obscure the program’s real accomplishments. With multiple clinical trials of CIRM-funded research underway, the first government approval of treatments is expected “in the not-too-distant future,” C. Randal Mills, the program’s president, said in an interview.

But he acknowledged that expectations “need to be tempered with humility at the enormity of the task before us. We don’t want to overpromise or overhype. CIRM is doing what it was set up to do, but it might be taking longer than people thought or hoped.” 

Still, the program’s future may depend more on politics than science. “If it looks like Washington is flipping off California, that could have political ramifications” at the ballot box, Greely says. Some researchers aren’t optimistic about the prospects for independent, federally funded science under the Trump administration.

“The only thing I can predict,” Loring says, “is that it will be neutral or negative. It won’t be positive.”

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