CIRM: Is it really targeting cures or just boiling the ocean?

A multibillion-dollar matter was on the table when the 35-members of the governing board of the California stem cell agency huddled electronically to put together a strategy for the next five years.

“Real Life” popped up during last week’s meeting along with diversity, legacies, voters, ballot measures. transformative medicine and cures.

“Good medicine starts with strong science,” Maria T. Millan, CEO and president of the stem cell agency, told its directors.

Voters approved the creation of CIRM in 2004 because then-President George Bush had restricted funding of the controversial research.

The state stem cell program is formally known as the California Institute for Regenerative Medicine — CIRM. It is freshly funded with $5.5 billion and is embarking on a new stage in its life.

Its name and charter obviously includes much more than stem cells. It owes existence, however, to those tiny, human, building blocks, more specifically human embryonic stem cells.

Voters approved the creation of CIRM in 2004 because then-President George Bush had restricted funding of the controversial research that uses four- to five-day-old embryos left over from human, in vitro fertilization procedures. Opponents of the research equated it with the killing of unborn children.

Bush’s restrictions were much discussed during the ballot campaign, which also led voters to expect that miraculous cures were right around the corner — but only if California would leap in to fill the funding void left by Bush’s restrictions.

Last week — 16  years and 11 months following the creation of CIRM — its leaders were not talking about federal restrictions or unborn children. Nor were they talking directly about the fact that CIRM has not yet fulfilled the voters’ expectations that they would see widely available, miraculous cures.  Nor did the agency directors explicitly address such questions as “what is CIRM really?”

• Is it primarily a research organization — a sort of mini-National Institutes of Health, the vaunted, $42 billion, federal, scientific research effort?

• Is it an educational and training program that starts at the high school level?

• Is it a state-funded, industrial development program that provides major backing for industry?

• Or is CIRM principally a product development enterprise? What do its investors (Golden State taxpayers) expect to receive?

CIRM leaders did talk last week about the objectives of the agency, which is one way to back into those four areas. The answers are important because a product development enterprise, for example, may not want to spend $100 million on training and then subtract that amount from the all-important clinical trials, which are enormously expensive.  Helping to build manufacturing enterprises also may take a higher priority than basic research.

Only two members of the CIRM staff (then only 23 strong) who worked on the first plan are still at the agency.

All of which is significant when an organization’s funds are limited, and a real deadline exists for the organization to achieve its goals. Such a deadline exists for CIRM, courtesy of the measure that created it. CIRM will run out of funding in a decade or so, depending on its pace of spending. That’s “Real Life,” a phrase that was on all 26 pages of the presentation of the proposed strategic plan by CIRM CEO Millan.

Millan began with a recap of CIRM’s record over the last 16 years. She then turned to the new mission statement, provided a brief explanation and asked for comments from board members.

None of the 35 were on the board in 2006 when the first strategic plan was approved. Only two members of the CIRM staff (then only 23 strong) who worked on the first plan are still at the agency. That document mapped out five years of CIRM’s work and stretched out even to 10. It ran to 149 pages.

“We are in a race against disease,” declared Robert Klein, who was at the time the first chairman of the agency and often stressed the urgency of CIRM action.

Klein was the sponsor of both Proposition 71 of 2004 and Proposition 14 of 2020, which created and funded CIRM with money borrowed by the state (state bonds). He was also responsible for the financing mechanism that will cut off CIRM’s cash. (The interest on the state bonds will bring the cost of CIRM to an estimated $12 billion.)

Looking at the mission statement of 2006 and the proposed statement for 2020 provides some indication of the changes in the field and the perceptions of what CIRM should be doing. The 2006 statement said CIRM’s mission was:

“To support and advance stem cell research and regenerative medicine under the highest ethical and medical standards for the discovery and development of cures, therapies, diagnostics and research technologies to relieve human suffering from chronic disease and injury.”

Several members of the board said that they thought CIRM’s education and training programs would be CIRM’s most important legacy.

The draft 2020 statement said,

“Accelerating world-class science to deliver transformative regenerative medicine treatments to California and worldwide.”

Based on the board discussion last week, it seems virtually certain that three or four words will be added to the latest statement. They reflect a major effort by the board to beef up both the inclusion of underserved communities and diversity in research.  At the suggestion of CIRM board member Deborah Deas, dean of the UC Riverside School of Medicine, the final 2020 mission statement (expected in December) is likely to have “diverse and equitable manner” added to its wording.

That is in keeping with the stronger emphasis in the last two years by the board on diversity, equity and inclusion. It has moved to require that applications include a statement on how the application will support diversity, equity and inclusion. The statement is officially scored during the closed-door reviews of the award proposals. (See below for a sample.)

Several members of the board said that they thought CIRM’s education and training programs would be CIRM’s most important legacy. David Martin, a CIRM director and CEO of AvidBiotics of South San Francisco, said, “Education is obviously key….I firmly believe that the legacy is going to be the effect of our educational programs….”

Five billion dollars is a lot of money. However, when compared to the challenges and ambitions of the stem cell agency, the billions seem to shrivel.

Several board members raised questions about voter expectations. “I’m wondering what the voters charged us with,” said Fred Fisher, a CIRM director and president of the ALS Association Golden West Chapter. “I think we’d want to be careful that the mission…is completely in alignment with what the voters charged us to do with their money.”

It was an emphasis shared by Millan. “California citizens have supported us because we bet their belief that (our work) will impact their lives….It’s really important that we follow those signals,” she said.

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Five billion dollars is a lot of money. However, when compared to the challenges and ambitions of the stem cell agency, the billions seem to shrivel.

The agency is currently focusing heavily on clinical-stage research, which is expensive. Individual awards reach $20 million each and perhaps more going forward. CIRM currently is funding 76 clinical trials and other clinical work approaching $1 billion and is likely to be doing much more. Trials are the critical, last stage of research before a treatment can be certified for use by the general public.

At the same time, CIRM has already this year authorized $165 million for education and training. It is legally required to spend up to $82.5 million on new buildings and facilities, a stipulation of Proposition 14 of 2020. It is proposing to join in a yet-to-be-defined partnership with industry to “build a California manufacturing network that accelerates manufacturing development from early translation through to commercialization.” The cost is unknown but it will be large.

Earlier this year, CIRM convened a group of advisors to help with the strategic plan.  As the lengthy session progressed, several persons warned of attempting to “boil the ocean.” They included Linda Boxer, a CIRM board member and vice dean of the Stanford medical school, and Kristiina Vuori, also a CIRM board member and president of the Sanford Burnham Prebys Medical Discovery Institute.

It was a sentiment that Millan agreed with.  “I’d like to really…make sure that we don’t try to boil the ocean,” she told the board last winter.

CIRM’s strategic plan, at this point, does not link dollars to its goals. When that actually happens, perhaps in December, Californians will have a better idea of whether CIRM will actually be zeroing in on cures or boiling the ocean.
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Editor’s Note: David Jensen, a regular contributor to Capitol Weekly,  is the founder and editor of the The California Stem Cell Report,  which will carry more on CIRM’s strategic plan over the next week. How it spends its next $5 billion could affect your professional or personal life, along with half of the families in California, so says CIRM.