CIRM Faces Its Future

The California Institute for Regenerative Medicine (CIRM) is running out of money. It is also running out of time to prove that California’s $6 billion dollar investment in the agency was worthwhile. (Half of that money was for interest.) Current estimates are that the last grants funded by 2004’s Proposition 71 will be made in 2019.

What next? CIRM won’t immediately fold in the fourth quarter of next year; the administrative budget will run through at least 2020. But unless another source of funds becomes available, all the staff will be doing is checking on ongoing projects and cleaning out the office.

However, after more than a decade of activity, a whole ecosystem has evolved that depends on CIRM — not just its employees, who are quite well paid, but its grantees, who are generally doing important work, in basic research and increasingly in clinical trials. That is where the money is going now. Naturally, there is pressure to keep the cash flowing.

At one time, CIRM had a deserved reputation for funding buildings, some of them at private universities, and was heavily criticized for that, but the $270 million “major facilities” budget approved in 2008 has all been spent. Some of the conflict of interest scandals are largely in the past, though ripples persist, and some of the institutional ones remain; several universities that receive large grants are still represented on the board. But there has been a new regime in place (“CIRM 2.0”) for several years.

Things have improved, though not enough. But how well has the agency done in terms of its stated goal of developing clinical applications, or (as the original promotional campaign put it) Cures for California?

CIRM has funded 49 clinical trials. That’s listed on the front page of the website. So is a link to “Patient Stories” featuring four “Stories of Hope” that were presented at the December 2016 Board meeting. So is a link to “Our Impact,” which includes some fluff, some financial discussion and a link to the 2016 Strategic Plan [large pdf], a glossy but informative 49-page brochure that details CIRM’s proposals for “the timeframe for which the Institute is certain to have funds available to make additional investments.”

There is nothing about FDA-approved therapies. There aren’t any.

Nevertheless, Robert Klein, the mastermind behind Proposition 71 and the first Chairman of the agency (he wrote the job description to be tailor-made for himself), has been advocating at least since 2014 for a $5 billion initiative to continue and expand the work of CIRM.

The agency itself is not allowed to campaign — it is a California government agency, even though it was set up to be resistant to government oversight. The Proposition that founded CIRM established a constitutional right to stem cell research and required 70% supermajorities in both Assembly and Senate, as well as the governor’s signature, to change it. (These are some of the reasons the Center for Genetics and Society actively opposed Prop 71.) But it certainly seems that CIRM is positioning itself for others to campaign on its behalf.

What other options are there, in practice? The Feds are not really a possibility; CIRM was set up as an alternative. Venture capitalists want to see a strong financial return, and politicians have to balance many competing interests. California has a budget surplus right now, but Governor Brown, approaching the end of his term, is warning of “darkness, uncertainty, decline and recession.”

CIRM is well aware of all this. Last December, it announced it was seeking $222 million in private funds. It has developed a program to develop “global industry partners,” touting the institute as “essentially a built-in concierge service for the stem cell space.” In April, 2018, it signed up the first two partners, but capital does not seem to be knocking down the doors; there have been no more announcements.

It has also tried some pure public-relations efforts, such as the cringe-worthy “My 2017 Stem Cell Resolution” contest. The winners were awarded T-shirts. (Distinguished stem-cell researcher and commentator Paul Knoepfler was awarded an Honorable Mention.)

Sacramento is beginning to take an interest. The Assembly Select Committee on Biotechnology is holding an “informational hearing” on August 15th, to bring legislators up to speed. The hearing, which will be live-streamed here, and later archived, will consist of:

• An Introduction from the Chair and Committee Members
• An Update from CIRM’s CEO Maria Millan and Chairman Jonathan Thomas
• A Patient Perspective from the parents of Ronav “Ronnie” Kashyap (see below)
• A Partner Perspective from Dr Jan Nolta of UC Davis
• An External Perspective from Dave Jensen of California Stem Cell Report

Jensen probably knows more about CIRM than anyone outside the organization and most of its employees, and is not shy about either criticizing or complimenting its actions. Otherwise, this is set up as a promotional vehicle. CIRM’s CEO has not testified since 2005, when Zach Hall introduced himself as Interim President. UC Davis is the fifth largest beneficiary of CIRM grants ($138 million), so obviously an interested — and worthy — partner. And the parents of a one-year-old who was cured in a clinical trial funded by CIRM provide exactly the image that CIRM wants.

Going forward, there are two separate questions to consider: Is continued state funding of stem cell research at a rate of roughly half a billion dollars a year the best use of state funds? If it is, should those funds be spent through CIRM as it is presently constituted?

The first question is debatable; the second deserves a flat “No.” There is something obviously wrong when an agency is funded by public money but never has to submit a budget to the legislature, and can even go 13 years without appearing before an oversight committee. Two major reports, in 2009 by the Little Hoover Commission and in 2012 by the then Institute of Medicine (now part of the National Academies of Sciences, Engineering, and Medicine), both concluded that the governance structure of CIRM is seriously flawed.

Nevertheless, can Klein and CIRM convince the public to pony up even more money than last time? It’s going to be a hard push. There will likely be “plenty of funding measures on the 2020 ballot, including a parks bond and money for open space and schools, not to mention repeal of the gas tax.” So, will voters prioritize, and if so, how?

But we should never underestimate Klein’s continuing activism and fundraising history; he is looking to raise $50 million for the campaign, about $15 million more than last time (which was then the most ever spent on a ballot measure campaign). Once again, there would be a flood of TV ads, doubtless featuring celebrities and scientists (almost) promising cures for deserving patients.

Hope rises eternally. Indeed, the San Francisco Chronicle is running a substantial series about stem-cell treatments under the title “The Miracle Cell.” Part One was headlined “In Search of a Miracle” and Part Two “Merchants of Hope.” The text makes it quite clear (without exactly saying so) that many customers of unlicensed stem cell clinics are fooling themselves, and that “none of the treatments the clinics offer have been shown to be safe or effective.”

But look again at the title of the series. Miracles sell.