CIRM's Scientific Advisors Laud California Stem Cell Agency

BURLINGAME, Ca. -- Although the California stem cell agency's new scientific advisory board recommends a number of changes at the enterprise, the board's bottom line is that the agency has had a "transformative" impact on stem cell science.

The conclusion from the panel, which was selected by the agency, was contained in a Power Point summary offered by the agency at its meeting here today. Here is an excerpt.

"The case that CIRM has been transformative in this exciting emerging field of  biomedical science seems self-evident to the SAB(scientific advisory board). The level of activity in this field in California is extraordinarily high and there are many excellent programs being supported by the CIRM that would have failed to be supported given the limited amounts of funding available for this field when CIRM was established. The program has yielded a large number of extremely well trained students and investigators supported directly or indirectly by the CIRM, there is a critical mass in a number of the major academic centers around California that has allowed it to compete internationally in this field, and the commercial environment for regenerative medicine in California has thrived as a result of CIRM intervention. 

"SAB noted that CIRM, despite its considerable achievements, had not received the attention and attribution that many equivalent funding bodies would have had for their contribution to successful science. SAB strongly suggests that CIRM ramps up its outreach activities, both to improve the California public’s awareness of CIRM’s uniqueness in the world, its successes so far, and the potential of stem cell research to advance treatment of diseases and injuries. Its brand recognition internationally and even nationally is limited and this should be corrected."

Wide-ranging Recommendations for California Stem Cell Agency

The California stem cell agency this morning released a Power Point summary of wide-ranging recommendations from its newly created scientific advisory board(SAB).

The recommendations will be discussed later today and again in December. Here is an excerpt from the lead recommendation.  The complete Power Point presentation can be found at the end of this item.

"SAB advises CIRM to identify, through a prioritization process, the top 6 to 8 projects, with clear relevance to the remit of CIRM’s stem cell mission, and to setaside the funding to ensure the projects can proceed to phase 1 and 2a clinical trials as rapidly as possible, without financial impediments. – Achieving clinical proof of concept is a key goal to achieve, to attract future potential investors and supporters of stem cell research, and has a strong chance of success, as long as CIRM advances the most promising clinical candidates “at speed”; this will require careful assessment / prioritization of portfolio.

"Preliminary management response: Management accepts this recommendation and will need to identify a process for selection of these projects that would include representatives from GWG(grant review group), CDAP(another agency advisory panel), and other external expertise as needed, and the amount of funding that would need to be set aside by the ICOC(CIRM directors). Recommendations will be developed for this priority group of projects as to where expertise and approach need to be modified to maximize the potential and to ensure rapid and effective progress. Management will provide separately a process to select these priority projects."

CIRM Scientific Advisory Board Recommendations

The Harsh Message at the California Stem Cell Agency

Grant reviewers have delivered a harsh message in the latest $243 million research round at the California stem cell agency – at least that is one way to look at it.

In effect, they told the governing board of the $3 billion enterprise that the overwhelming majority of applicants in its signature disease team round do not measure up, despite the fact that CIRM had early on partially vetted their efforts. Indeed, the reviewers said that the researchers deserve only $113 million instead of the full $243 million that was budgeted.

Obviously the results of the review can be interpreted in other ways as well. But the review outcome should raise some flags within the stem cell agency and its 29-member board, which meets tomorrow in Burlingame. It may not auger well for future rounds that also involve CIRM's newly energized drive to push research into the clinic.   

One interpretation of the review results could well be that CIRM's goals are unrealistic, that the agency is trying to move too fast for the normally glacial pace of research and development. Another interpretation is that the science is not good enough in California to accomplish what the agency is seeking to do, a view expressed by some in the early days of the nearly 9-year-old program. Another is that the reviewers themselves don't know enough or have failed to do their homework, which some of the rejected applicants have argued in their appeals. Yet another is that the CIRM review process is inadequate to the task of meeting CIRM's goals. And still another interpretation is that the normal peer review process on which CIRM's procedures are based is mightily flawed, a general contention argued by some(See here, here and here.)

Or quite possibly the result of the disease team reviews could reflect a combination of all of the above, to one degree or another.

Little is known about the substance of what goes on during the grant review process, aside from the staff-written review summaries. Even CIRM board members, who see only the summaries, have complained from time to time about not having enough information to make a good judgment on an application. Reviews are conducted behind closed doors. Information about the economic and professional interests of reviewers is withheld from the public by the stem cell agency.  

Here is a look, however, at what we do know. Initially the universe of applicants in this round totalled 36. That was the number that applied for planning grants for this round. Without a planning grant, they could not apply for a full $20 million award, with some exceptions. The exception process was controlled by CIRM President Alan Trounson, not reviewers. CIRM used the planning grants and the exception process not only to assist applicants but to winnow out weak applications.

Nineteen researchers won planning awards. With exceptions included and minus dropouts, 22 applied later for the big money. Out of the 22, only six were recommended for funding by reviewers, who are known more or less formally as the Grants Working Group. (See the four items at the end of this piece for a list of reviewers involved.)

In the past, reviewers have sometimes not approved sufficient applications to consume the entire amount budgeted for a round. But they have never produced a shortfall as great as in this case. It is all the more dramatic since this round carries a lot of weight for CIRM, which is pushing hard to commercialize research and fulfill at least part of the promises that were made to California voters in 2004 to win approval of creation of the stem cell agency.

One reflection of the unusual nature of the round is the record pace of researchers' appeals of negative decisions by reviewers. At least nine of the 15 rejected scientists are willing to say publicly that something is is not quite right in the review process, ranging from missing facts to inconsistencies in CIRM's endorsement of particular paths of research.

It is safe to say that CIRM directors tomorrow will pluck some applications out of the reject bin and increase the total awarded. But they should also examine the process to determine what generated this particular outcome. The Institute of Medicine, which is currently engaged in a $700,000 examination of CIRM, also might scrutinize this round with some care, given its size and importance to the California stem cell research effort.

10-05 Roster Specialists DTTD II

10-05 Roster GWG and PAs

10-05 ROSTER & SPECIALIST BIOS.docx

10-05 Roster - GRWG

Kerfuffle over NY Times Take on California's Stem Cell Program

Last week, the New York Times published an article that was critical of California's approach to funding scientific research, quickly prompting denunciations that called it a “hit piece” and an “unbelievable attack.”

We differ with those characterizations, some of which seem to stem from a misunderstanding of a comment in the Times about how the NIH is like a manager of a stock index fund, as opposed to California's narrower focus.

The Nov. 8 piece was written by Nicholas Wade, who has had a long and respectable career in science reporting. The article was carried in a special section on “prognostications” about what could be coming up in 2011 in science. The article was not intended as a “balanced” news story. Rather it was an analysis based on Wade's years of covering science. That distinction might have been clear in the print version of the section, but it was easily overlooked on the Web version of the Times. That led to some misunderstandings by readers based on comments that we have read.

Basically Wade said that California – as opposed to the NIH – has made a $6 billion bet (including interest) on a narrow field of science. He wrote,

“By allocating so much money to a single field, California is placing an enormous bet on a single horse, and the chances are substantial that its taxpayers will lose their collective shirt.”

Wade contrasted that approach to the NIH, which funds all sorts of scientific research, instead of just stem cells. He wrote,

“...(T)he National Institutes of Health and the National Science Foundation are like the managers of a stock index fund: they buy everything in the market, and the few spectacular winners make up for all the disasters.

“But just as index fund managers often go astray when they try to improve on the index’s performance by overweighting the stocks they favor, the government can go wrong when it tries to pick winners.”

Writing on his blog Nov. 9, UC Davis stem cell researcher Paul Knoepfler described Wade's article as a “hit piece.” Knoepfler said,

“The NY Times has allowed Mr. Wade to publish in essence an opinion piece smearing stem cell researchers in their Science section.

“NIH is incredibly strict and deliberate in what it funds. NIH funds approximately only the top 10-15% of all grant applications after thorough peer review, which is an extremely low percentage. This hardly reflects 'buying everything', but rather is just the opposite.”

It is clear that Wade's piece reflects his opinion and would not be carried on the front page of the NY Times as a news article. However, his broad-brush analogy about the NIH being akin to a manager of a stock index fund is on the mark. The NIH does not limit its funding to only one brand of research. It is certainly deliberate and approves a small fraction of applications, but those represent a broad range of approaches, just as an index fund for the entire stock market has oil, auto, tech, health, insurance, soap and other companies represented in its portfolio. If Wade were to carry his comments further, he might say that California has only bet on or invested in the biotech sector. That creates an investment risk, looking at it from a financial viewpoint.

Knoepfler also differs with Wade's assertion related to dubious claims involving stem cell research. Wade wrote,

“Stem cell researchers have created an illusion of progress by claiming regular advances in the 12 years since human embryonic stem cells were first developed. But a notable fraction of these claims have turned out to be wrong or fraudulent, and many others have amounted to yet another new way of getting to square one by finding better methods of deriving human embryonic stem cells.”

Knoepfler described that as an attack on embryonic stem cell research and researchers.

“He(Wade) says that us scientists have 'created an illusion of progress' with our claims and that a 'notable fraction of these claims have turned out to be wrong or fraudulent'. Wow. Can you please give me some facts to support such aggressive claims?”

Wade did not carry any evidence supporting his assertion but also carried this sentence,

“Stem cell scientists, while generally avoiding rash promises themselves, have allowed politicians to portray stem cells as a likely cure for all the major diseases.”

Stem cell research has indeed been susceptible to considerable hyperbole, much of it coming during the 2004 election campaign that created the California stem cell program. We are likely to see more as the stem cell agency becomes increasingly serious about asking voters for another $5 billion(actually perhaps $10 billion including interest), as early as 2012.

California patient advocate Don Reed weighed in with a comment on Knoepfler's blog. Reed described the Times article as an “unbelievable attack.” He said that the California stem cell agency has awarded $1 billion and “received” $1 billion in matching funds. In fact, the agency has not received anything remotely like that sum. It has required matching funds on some grants, notably lab construction projects, but that cash is ginned up by applicants. It is reasonable to assume that a goodly portion of those funds would have found their way to the respective institutions even without CIRM's matching requirements.

Wade also had this to say,

“Strangely, for a project that is aimed at regenerative medicine, the arbiters of stem cell research have largely neglected the free lesson that nature is offering as to how regenerative medicine could actually work. Many little animals, like newts and zebra fish, do regenerate parts of their bodies. But their recipe is the reverse of that presented by the advocates of stem cell therapy. Instead of taking a stem cell and trying to convert it into a well-behaved adult tissue, animals like the zebra fish start with the adult cell at the wound site, and walk it backward into a stemlike state from which a new limb grows.

“For the California Institute for Regenerative Medicine to invest its $3 billion in studying newts, rather than building new science buildings on every state campus, might seem the best way of understanding regeneration, but that would be hard to explain to California’s voters, who have been assured stem cell cures are just around the corner. Even if governments do better to avoid picking winners among basic research fields, they can play a necessary role in supporting specific scientific infrastructure that lies beyond the means of individual researchers or universities, like atom-smashers or the human genome project. But even these projects are not guaranteed success.”

Wade's bottom line?

“Basic research, the attempt to understand the fundamental principles of science, is so risky, in fact, that only the federal government is willing to keep pouring money into it. It is a venture that produces far fewer hits than misses.”