California Institute for Regenerative Medicine: Fool Me Once…

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Way back in 2004, a plurality of California voters approved a multi-billion dollar bond issue to support embryonic stem cell research. Now the cupboards are bare and the reasons why CIRM didn’t work are emblematic of what’s wrong with letting bench scientists control regenerative medicine adoption. Let me explain.

The California Institute for Regenerative Medicine (CIRM)

The idea for CIRM began at a time during the Bush administration when evangelicals were in the political driver’s seat. Scientists had begun to understand that embryonic stem cells (ESCs) could repair tissue. However, many ESCs were sourced from aborted fetuses, which didn’t work for Bush, hence he put through a ban on federally funded embryonic stem cell research. What happened next shaped what we’re still dealing with in regenerative medicine almost two decades later.

Faced with literally being out of a job, ESC researchers organized. They formed the ISSCR or the International Society for Stem Cell Research in 2002. This helped with putting together California proposition 71 which also got support from many wealthy individuals and actors.

Frankly, looking back, this is where CIRM’s problems first began. In order to sell the idea of spending 3 billion dollars on research usually funded by the feds, ESC research was way oversold to the public. At some point, the then known scientific reality of ESCs became obvious science fiction. This messaging then got picked up by countless news organizations who then poured gasoline on the hype bonfire.

The bond issue was passed in 2004 by 59% of the voters and the CIRM was born. However, how the CIRM was sold, as a center for producing practical cures quickly, was not what was delivered. That stark disconnect was caused by inherent conflicts of interest in lettering bench scientists control medical breakthroughs.

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CIRM-A Great Idea with Conflicts of Interest Galore

At face value, the idea of a state sponsoring research that the federal government doesn’t have the stomach for is not a bad idea. However, things were set up badly from the beginning. The governing board of the organization (who had the final say on grants awarded) had scientists representing the same universities who were the recipients of the grants. That, of course, should never have happened. That’s a bit like the NIH awarding research grants among a closed cabal of professors, most of whom are from the universities getting the grants.

In addition, the scientists had zero skin in the game when it came to actually producing cures. Meaning, their grants were not tied to actual progress towards a commercial or real-world application of the technology. There were also perverse incentives. Meaning, the need for more bench research meant more grants, hence why would anyone complete the basic science research phase and move the technology into the clinic? This was truly the fox guarding the proverbial 3 billion dollar hen house.

There are several examples of how bad this all got. For example, CIRM has spent hundreds of millions of dollars erecting new buildings on university campuses. Why? These universities already had plenty of buildings in which to perform their research. How would new buildings ever get CIRM closer to a real cure?

In fact, in 2013 the Institute of Medicine put out a scathing report on the governance of CIRM. The group cited institutionalized conflicts of interest which raised questions about the “the integrity and independence of some of CIRM’s decisions.” That report was supposed to bring in reform. However, just three years later, the California Stem Cell Report wrote that the former president of CIRM received more than 400K in compensation for a board seat just seven days after leaving his post. The company who paid him had received tens of millions in CIRM funding while he was in charge.

Another example is really the simplest. Here we are 15 years later and not a single commercially viable product has gained FDA approval for the clinic based on California’s 3 billion dollar bet. In addition, CIRM has spent most of the money, so it’s no longer awarding grants. Finally, the uber-wealthy who could write a check know a bad investment when they see one, which is how they got wealthy, so they are not stepping up to write more checks. Hence, CIRM is broke.

Anybody Who Knew How the Basic Science Research Game Works Could Have Seen This Coming

On the one hand, basic science medical research has produced and will produce many earth-shattering and groundbreaking new medical therapies and cures. These new therapies can save lives. Hence, basic science medical research is a good thing.

Having said that, basic science medical research is a business industry with commercial interests. Meaning, this industry thrives when there are more research grant dollars and starves when those dollars dry up. Considering that universities take about 30-40% of these grant dollars off the top as a fee (called Facilities and Administrative (F&A)), it’s fair to say that CIRM was a huge income source for universities. Which public and private universities benefitted? See below for an infographic:

How do we know this really happened? Just look at the STAT expose on CIRM:

“The National Institutes of Health has supported three and a half times as many human trials of stem cell therapies, dollar for dollar, as the California agency…”

“CIRM has…given more than $300 million to 27 projects that include clinical trials — though much of that funding also supported preclinical work. Meanwhile, the agency has committed about $540 million to new labs and buildings.”

There’s also an interesting piece in the SF Chronicle on how CIRM never delivered on its promises. For example, Stanford spent only 12% of the 360 million it received on four early-stage clinical trials, while 88% was spent on basic science research and buildings! You see a trend here? Bench scientists in control of stem cell research grant money funnel the vast majority of that money not toward clinical trials which get to real cures, but towards more bench science.

What’s Next? Fool Me Once…

Well, now CIRM wants a do-over. They want 5.5 billion more (you know, with inflation and all, that’s really 3 billion in 2004 dollars)! Hmmm…

However, we could have a perfect round 2 storm coming our way. In a move that looks like déjà vu, the current administration just halted all federally funded fetal tissue research. This, of course, may now create another political polarization around science, which by itself could be enough to fool California voters into reauthorizing the CIRM.

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The CIRM Legacy is Alive and Well

While bench science talking heads go after stem cell clinics in news stories, the stem cell hype that fuels these clinics was begun by the CIRM! Ironic, isn’t it? The very scientists who are now against the clinical translation of stem cells are the same ones that lit the hype bonfire with prop 71. The same crew who have funneled billions of dollars into pet basic science projects while real clinical cures remained elusive.

Having said all of that, as you know from reading this blog, the prop 71 stem cell hype has been further morphed by many out of control clinicians. So I don’t often disagree with the university talking heads that patients are being misled and abused. However, it’s sure is fun to have been around all of this long enough to see the subtle ironies.


I love stem cell research and the more the merrier! However, let’s let NIH dole out those dollars. Why? They’re frankly better at it. But what about the current administration getting rid of fetal tissue coming from abortions? The science of the last two decades has taught us that ESC research was a boondoggle. If you want a stem cell with embryonic-like qualities, they can now be created through the reprogramming of adult cells. If you need stem cells derived from fetal tissue, you can get them from planned c-sections. So while this recent action will play well in politics, it doesn’t impact much of any real stem cell science at this point.

The upshot? This will be interesting to watch. As a physician-scientist, I’ve never been dialed into the CIRM gravy train. Hence, I really don’t have a dog in this upcoming fight. However, I do hope California voters look at all the facts here, as CIRM was a bait and switch if I ever saw one. In addition, I hope everyone takes notice that letting bench scientists with no skin in the game drive medical discoveries is a bad idea.

Chris Centeno, MD is a specialist in regenerative medicine and the new field of Interventional Orthopedics. Centeno pioneered orthopedic stem cell procedures in 2005 and is responsible for a large amount of the published research on stem cell use for orthopedic applications. View Profile

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