Over the course of its 16-year existence, the California Institute for Regenerative Medicine in Oakland has helped transform its state into an innovation hub of stem cell science. But CIRM announced last year that its first $3 billion of funding has dried up, and now it’s up to voters to decide on November 3 whether to give the agency a second life. 

The Stem Cell Research Institute Bond Initiative, Proposition 14, would issue $5.5 billion in general obligation bonds for the agency to continue funding stem cell studies, training scientists, and building new research facilities, with the aim of developing and testing treatments for a range of diseases. 

The measure isn’t facing significant organized opposition, but it has drawn criticism from newspaper editorial boards and others for what they see as conflicts of interest between CIRM board members and institutions applying for funds. Critics...

“I have a company now that would not have existed if I didn’t have CIRM funding, and I may be able to treat people with Parkinson’s disease” in the future, says Jeanne Loring, a stem cell biologist and professor emeritus at Scripps Research who last year launched the biotech company Aspen Neuroscience, which is developing a stem cell–based neuron replacement therapy for Parkinson’s. But she says she has concerns about the proposition due to conflicts of interest on the board and other factors. 

CIRM was created in 2004 as an apparent rebuke to the federal restrictions on funding for human embryonic stem cell research implemented by then-President George W. Bush. At the time, the National Institutes of Health (NIH) was only allowed to fund research involving a limited number of pre-existing stem cell lines. California voters approved a ballot measure that year that established a state constitutional right to conduct stem cell research and authorized the sale of $3 billion worth of bonds to fund the agency. 

See “Stem Cell Funding Agency CIRM Is Nearly Out of Funds

The Bush-era restrictions were lifted during Barack Obama’s presidency, but CIRM has continued to fund stem cell science, including research involving both induced pluripotent stem (iPS) cells and embryo- and blood-derived stem cells. To Loring, who says she’s received nearly $30 million in CIRM grants over the years, the agency’s most important legacy is that it invested in physical infrastructure such as buildings and labs as well as training programs for early-career stem cell scientists. 

For instance, the agency ran an internship program for undergraduate and master’s students to spend a year in a mentor’s lab to learn the ropes of stem cell research, through which Loring says she’s trained some 30 students, making them more employable in a thriving stem cell research field in California and beyond. CIRM also offered pre-doctoral and postdoc training programs. “What worries me about the funding going forward is [potentially losing] the internship programs and the support for graduate students and postdocs. I think those were the diamonds in that whole program,” Loring says.

Larry Goldstein, a stem cell scientist at the University of California, San Diego, says the agency has filled a critical funding gap by supporting the progression of interesting scientific discoveries to late-stage clinical trials. Using CIRM funding—Goldstein has received some $21 million as a principal investigator, according to the agency’s website—he’s created an in vitro model of hereditary forms of Alzheimer’s disease using iPS cells and used it to identify drug candidates that target pathological processes in the disease. He says the project was “too risky” to attract NIH funding, but CIRM funded “most of the work, up to getting it to the point where we can get it into trials.” 

Loring reckons that most of CIRM-supported early research didn’t take off beyond the first stages of development. But according to a dataset available on the agency’s website, it has funded 66 ongoing, mostly early-stage clinical trials targeting a broad range of diseases, and has contributed to initial steps in the development of more than a dozen drugs. These include the recently Food and Drug Administration (FDA)-approved small molecule inhibitors fedratinib and glasdegib to treat the cancer subtypes myelofibrosis and acute myeloid leukemia, respectively. 

However, the editorial boards of the San Francisco Chronicle and the Los Angeles Times argue that CIRM-funded medical advancements have yet to live up to the rosy promises made to voters during the 2004 campaign to create the agency, which included curative treatments for a number of diseases. 

The [federal] funding is not at risk—there’s no unmet need here.

—Jeff Sheehy, CIRM board member

Critics also argue that CIRM no longer fills an unmet funding need. Jeff Sheehy, a longtime HIV/AIDS activist and the only CIRM board member to oppose the new proposition, points out that last year alone, the NIH put more than $2 billion toward stem cell research, including studies involving embryonic stem cells, dwarfing the $5.5 billion CIRM would spend over a number of years if the ballot measure passes. “The [federal] funding is not at risk—there’s no unmet need here,” Sheehy says. Goldstein, however, expresses concern that if reelected, President Donald Trump’s administration could enact new restrictions on stem cell research.  

Another reason why Sheehy opposes Proposition 14 is, he says, that its language doesn’t address mitigating conflicts of interest that could arise given that the majority of CIRM’s 29 board members are executives at institutions that are competing for grants—an issue noted in a 2013 Institute of Medicine report requested by CIRM. While board members cannot vote directly on grants requested by their own institutions, “it’s very hard for them not to try to exert some kind of influence. It’s just human nature,” says Loring, who in a recent blog post detailed a situation she says involved such influence.  

Sheehy and Loring both say that a smaller board would make it easier to manage conflicts of interest, as would diversifying its members so that institutions competing for grants are less strongly represented. The new proposition could worsen the situation by raising the number of board members to 35, Loring adds. Goldstein, however, says he thinks the board’s procedures, and the measure itself, manage the conflicts appropriately. “There are enough protections in the measure and in the practices that the board has developed.”  

Sheehy also voices concern about the potential economic impact of approving the measure, especially at a time when the state is facing a huge pandemic-driven budget deficit. Bonds are effectively loans that need to be paid back by taxpayers, with interest, over time. The nonpartisan federal Legislative Analyst’s Office (LAO) estimates it would cost the state a total of $7.8 billion to pay off the bonds, or around $260 million annually over 30 years, in addition to the $327 million annually in debt payments the state is still paying off from the 2004 proposition’s bonds.  

“I have huge issues with paying for this with debt to begin with because stem cell research could get in line with everyone else: healthcare, education, housing, wildfire fighting and mitigation,” not to mention managing the pandemic, Sheehy says. “Stem cell research should be judged in the context of all the other state needs.” 

Given that it would effectively be funded with debt, the measure should include wording that would allow the state to reap greater returns on its investment, Sheehy adds. Figures from the LAO suggest that CIRM-funded inventions have brought far less revenue to the state than voters were initially promised with the 2004 measure, he notes in a recent opinion article. Furthermore, the new proposition would require the state to put royalty revenues from CIRM-funded discoveries toward making stem cell therapies more affordable, in what Sheehy sees as a “giant subsidy for pharmaceutical and biotech companies.”

You’re putting money into the development of products and businesses that California will ultimately benefit from.

—Larry Goldstein, UC San Diego

Goldstein argues that the measure could stimulate the state’s economy and aid its recovery from the pandemic: “You’re putting money into the development of products and businesses that California will ultimately benefit from.” He adds that a large part of California’s healthcare bill is driven by chronic diseases such as Alzheimer’s disease, and that investing in developing treatments will pay off in the long term. “These are reasonable investments [and] this is good for the state.” 

There’s no organized opposition to Proposition 14, in part because public concerns around embryonic stem cell research have waned over the years, Loring says. According to California’s Secretary of State, the “No on Proposition 14” committee has raised only $250 so far, whereas the campaign in support of it has raised more than $16 million. Much of that comes from San Francisco real estate investor Robert N. Klein II, who spearheaded the measure, according to The New York Times

“I have mixed feelings” toward the measure, Loring says. If it’s approved, “I’ll be happy. If it doesn’t, I’ll be fine.” 

Clarification (October 24): This article has been edited to reflect the number of funded clinical trials listed on CIRM’s website, rather than the number given in the counter at the top of that webpage.

Interested in reading more?

a pipette dropping clear liquid into a well plate

The Scientist ARCHIVES

Become a Member of

Receive full access to more than 35 years of archives, as well as TS Digest, digital editions of The Scientist, feature stories, and much more!
Already a member?