How Long Will the California Institute for Regenerative Medicine Survive?

CIRM, as the California stem cell agency is always called, is almost 20 years old, and seems to be in serious trouble. The state-funded agency, created by a $3 billion ballot proposition in 2004 and renewed for over $5 billion more in 2020, was set up to promote stem cell research (“and cures”), but results so far have been disappointing. Maria Millan, an 11-year veteran of CIRM who was President and CEO for six years, resigned unexpectedly last November (exactly why remains a mystery) and has not yet been replaced. The annual meeting of the agency’s Citizens Financial Accountability Oversight Committee on May 29 was not accessible to the public, an apparent violation of the state open meetings law. David Jensen, whose Substack, The California Stem Cell Report, is the only regular, reliable, outside source for news about CIRM, reported on both of these events. Asked for further comment on the current outlook for the agency, Jensen responded by email:

CIRM is at a watershed moment in its nearly 20-year history. It is looking for a new president and may have one at the end of this month, who may be its last. It is engaged in a momentous review of its priorities for spending its remaining billions, including the first-ever examination of its scientific portfolio, a project that has been off-limits to such third-party evaluators as the National Academy of Medicine. The review, scheduled to be completed by late September, could generate a stronger drive to bring the promised stem cell and gene therapies to the general public.  

However, it has yet to come to grips with whether it should live or die — the question of its sustainability. CIRM’s billions are finite, courtesy of the same initiative that created it in 2004. The agency can’t wait around until the last minute to seek refinancing either through another ballot initiative, which is problematic, or by seeking state legislative support, also problematic. Both endeavors involve political complexities along with tactics and timing, including just when another initiative might be mounted and the task of building support among lawmakers, the current governor and the next governor. …

A little historical background is needed here. Twenty years ago, George W. Bush was US President, the Raelian cult had recently claimed to have created a cloned baby they called Eve (they had not), human reproductive cloning was being actively promoted by some scientists and others, and research on stem cells derived from surplus IVF embryos and from cloned human embryos was extremely controversial. While most liberals and progressives were enthusiastic about embryonic stem cell (ESC) research, others were wary – about reproductive cloning, about the prospect that massive numbers of women’s eggs would be needed for embryo cloning research, and about the over-the-top hyperbole that surrounded ESCs. Anti-abortion right-to-lifers opposed any scientific use of ESCs, although the embryo from which stem cells are extracted is not a fetus, has no recognizable human features or form, and is not implanted and growing in a woman’s uterus. Acknowledging that position, Bush vetoed federal funding but stopped short of banning research, a contradiction with which he was comfortable.  

The scientific consensus was that ESCs might be both scientifically interesting and medically valuable. Some optimistic researchers touted them as holding “great promise for understanding and curing diabetes, Parkinson’s disease, spinal cord injury, and other debilitating conditions.” Stem cells derived from cloned human embryos were particularly enticing to some enthusiasts. In 2004, Korean scientist Hwang Woo-suk claimed to have created the first cloned human embryonic stem cells, a breakthrough that stoked cloning and stem-cell fever and led to talk of a Nobel Prize. (Hwang had faked it, but that was not revealed until late 2005.) 

Also in 2004, a California coalition led by Robert Klein, a wealthy developer, raised the money to place on the state ballot Proposition 71, the Stem Cell Research and Cures Initiative. (Note what we might politely call the overly hopeful emphasis on “cures.”) The specific goal of the initiative was to establish what became CIRM. Prop 71 would grant $3 billion of dedicated public money to stem cell research, filling the gap created by federal restrictions. The opposition, which included the Center for Genetics and Society and other good government and pro-choice organizations, was enormously outspent (about $25 million to $400,000), and Prop 71 passed 59%–41%. 

Legal and logistical challenges – and the arrogance of some CIRM leadership, who wanted the state’s money but didn’t want to comply with state regulations like open meeting laws –  complicated the agency’s early years. CGS issued a critical assessment of CIRM’s first year (pdf), with an overall grade of C–. Two external reviews, by the state’s Little Hoover Commission and the Institute of Medicine (now the National Academy of Medicine), echoed much of the CGS analysis and proposed reforms to CIRM’s structure that in the end made little difference.

Over the next 15 or so years, the California Institute for Regenerative Medicine funded infrastructure — new buildings for stem cell research, mostly on the public and private collage campuses — and a gradually expanding list of clinical trials, all documented on the CIRM website. By 2020 the money had essentially run out and a coalition similar to the one that had sponsored the 2004 ballot measure spearheaded Proposition 14 to keep funding CIRM, this time with a further $5.5 billion. The opposition was outspent by an even larger proportion (literally thousands to one) and the Proposition passed, but only by 51%–49%.

Today, stem cell treatments are still controversial, and still not widely used in conventional medicine. Yet hundreds of dubious stem cell clinics in the US alone peddle unregulated, unproven, and sometimes harmful therapies for a wide range of conditions. Fortunately, a few widely respected stem cell researchers have taken it on themselves to track the shady claims and offer accurate advice. Meanwhile, CIRM seems to have shifted its focus from stem cells to gene therapy.

CIRM is a government agency and not a money-making concern: The theory was that the public would benefit in the long run from the development of cures. The “Delivering on our Mission” webpage (dated 2022) lists clinics, projects, laboratories, and clinical trials that have been funded by CIRM. On first glance, it may look impressive, with over a thousand patients enrolled in CIRM-funded clinical trials. But it shows a depressingly small number of effective treatments or cures. CIRM’s greatest accomplishment, of which it can justifiably be proud, is the success of a therapy that has cured more than 40 children born with Severe Combined Immunodeficiency (SCID). Unfortunately, that is the only cure so far developed, and the first attempt to market it was abandoned for financial reasons. It is not currently available outside of a clinical trial funded by CIRM, although a UCLA team is working to develop it and make it available more widely.

Obviously, CIRM is not going to close its doors any time soon. And perhaps the organization can “reboot” as suggested last month in the San Francisco Business Times. Jensen again:

… It is not clear exactly when CIRM's funds will run out. CIRM has not explored that subject in any depth publicly. But the best chance for winning the support of voters for more billions is likely November 2028. Waiting another four years would put the agency on the brink of financial extinction, if not past it. 

Why 2028? That is because the larger voter turnout during presidential elections increases the chances of approval of large bond measures such as those used to support CIRM. 

Most startups fail. Has CIRM? Not necessarily. The large public investment has generated a great deal of scientific activity, including infrastructure that will be useful for years. Is it time to wrap up this experiment in public funding? Not immediately, certainly, since there are over 100 CIRM-funded clinical trials under way. Some of them may pay off. Should CIRM declare victory and retire gracefully?